Investigation of rat exploratory behavior via evolving artificial neural networks.

PubMed

Costa, Ariadne de Andrade; Tinós, Renato

2016-09-01

Neuroevolution comprises the use of evolutionary computation to define the architecture and/or to train artificial neural networks (ANNs). This strategy has been employed to investigate the behavior of rats in the elevated plus-maze, which is a widely used tool for studying anxiety in mice and rats. Here we propose a neuroevolutionary model, in which both the weights and the architecture of artificial neural networks (our virtual rats) are evolved by a genetic algorithm. This model is an improvement of a previous model that involves the evolution of just the weights of the ANN by the genetic algorithm. In order to compare both models, we analyzed traditional measures of anxiety behavior, like the time spent and the number of entries in both open and closed arms of the maze. When compared to real rat data, our findings suggest that the results from the model introduced here are statistically better than those from other models in the literature. In this way, the neuroevolution of architecture is clearly important for the development of the virtual rats. Moreover, this technique allowed the comprehension of the importance of different sensory units and different number of hidden neurons (performing as memory) in the ANNs (virtual rats). Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of three chronic dialysis models.

PubMed

Peng, W X; Guo, Q Y; Liu, S M; Liu, C Z; Lindholm, B; Wang, T

2000-01-01

The chronic peritoneal dialysis model is important for understanding the pathophysiology of peritoneal transport and for studying biocompatibility of peritoneal dialysis solutions. In this study, we compared three different chronic peritoneal dialysis models. A peritoneal catheter was placed in 23 male Sprague-Dawley rats, 12 of which had an intact omentum (model 1) and 11 of which received an omentectomy (model 2). Seven other rats, without a catheter, received a daily intraperitoneal injection (model 3). Each rat received a daily infusion of 25 mL of 3.86% glucose dialysis solution either through the catheter (models 1 and 2) or through injection (model 3) for 4 weeks. Then, a 4-hour dwell study using 3.86% glucose solution with an intraperitoneal volume marker and frequent dialysate and blood sampling was performed in each rat. The intraperitoneal volume was significantly lower in all the dialysis groups as compared to a control group (n = 6) in which the rats had no chronic dialysate exposure. The peritoneal fluid absorption rate, as well as the direct lymphatic absorption rate, was significantly higher in the three dialysis groups as compared to the control group. In general, no significant differences were seen in any of the parameters among the three dialysis models. Owing to catheter obstruction, three rats in model 1 and four rats in model 2 were lost during dialysis. Histological examination showed no significant differences among the three dialysis groups. Our results suggest that omentectomy may not be necessary in the chronic peritoneal dialysis model when using dialysate infusion and no drainage. Based on the present study, we think that perhaps model 1 may be the method of choice to test new peritoneal dialysis solutions. However, owing to its simplicity, model 3 could also be used if great care is taken to avoid puncturing the intestine or injecting into the abdominal wall.

Pathological effects of obstructive apneas during the sleep cycle in an animal model of cerebral small vessel disease.

PubMed

Lloyd, Eric E; Durgan, David J; Martini, Sharyl R; Bryan, Robert M

2015-10-01

We tested the hypothesis that apneas during the sleep cycle exacerbate hypertension and accelerate changes that occur with cerebral small vessel disease. Obstructive sleep apnea was modeled by intermittent inflations of a chronically implanted tracheal balloon to occlude the airway during the sleep cycle (termed OSA) in spontaneously hypertensive stroke-prone (SHRSP) rats, a model of cerebral small vessel disease. SHRSP rats and their parent strain, Wistar Kyoto (WKY) rats, were exposed to OSA for 2 weeks (from 9 to 11 or from 18 to 20 weeks). At 9 weeks, hypertension was developing in the SHRSP rats and was firmly established by 18 weeks. OSA exposure increased systolic blood pressure in SHRSP rats by ≈30 mm Hg in both age groups compared with shams that were surgically prepared but not exposed to OSA (P<0.05). OSA exposure also increased systolic blood pressure in WKY rats by 20 and 37 mm Hg at 11 and 20 weeks, respectively (P<0.05). OSA exposure in SHRSP rats compromised blood-brain barrier integrity in white matter at both 11 and 20 weeks of age when compared with SHRSP sham rats (P<0.05). Microglia were activated in SHRSP rats exposed to OSA but not in sham rats at 11 weeks (P<0.05). At 20 weeks, microglia were activated in sham SHRSP rats (P<0.05) compared with WKY sham rats and were not further activated by OSA. Neither was blood-brain barrier integrity altered nor microglia activated in any of the WKY groups. We conclude that OSA accelerates the onset of the cerebral pathologies associated with cerebral small vessel disease in SHRSP, but not WKY, rats. © 2015 American Heart Association, Inc.

Selective binding of lectins to normal and neoplastic urothelium in rat and mouse bladder carcinogenesis models.

PubMed

Zupančič, Daša; Kreft, Mateja Erdani; Romih, Rok

2014-01-01

Bladder cancer adjuvant intravesical therapy could be optimized by more selective targeting of neoplastic tissue via specific binding of lectins to plasma membrane carbohydrates. Our aim was to establish rat and mouse models of bladder carcinogenesis to investigate in vivo and ex vivo binding of selected lectins to the luminal surface of normal and neoplastic urothelium. Male rats and mice were treated with 0.05 % N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in drinking water and used for ex vivo and in vivo lectin binding experiments. Urinary bladder samples were also used for paraffin embedding, scanning electron microscopy and immunofluorescence labelling of uroplakins. During carcinogenesis, the structure of the urinary bladder luminal surface changed from microridges to microvilli and ropy ridges and the expression of urothelial-specific glycoproteins uroplakins was decreased. Ex vivo and in vivo lectin binding experiments gave comparable results. Jacalin (lectin from Artocarpus integrifolia) exhibited the highest selectivity for neoplastic compared to normal urothelium of rats and mice. The binding of lectin from Amaranthus caudatus decreased in rat model and increased in mouse carcinogenesis model, indicating interspecies variations of plasma membrane glycosylation. Lectin from Datura stramonium showed higher affinity for neoplastic urothelium compared to the normal in rat and mouse model. The BBN-induced animal models of bladder carcinogenesis offer a promising approach for lectin binding experiments and further lectin-mediated targeted drug delivery research. Moreover, in vivo lectin binding experiments are comparable to ex vivo experiments, which should be considered when planning and optimizing future research.

Physiologically based kinetic modeling of bioactivation and detoxification of the alkenylbenzene methyleugenol in human as compared with rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Subeihi, Ala' A.A., E-mail: ala.alsubeihi@wur.nl; BEN-HAYYAN-Aqaba International Laboratories, Aqaba Special Economic Zone Authority; Spenkelink, Bert

2012-05-01

This study defines a physiologically based kinetic (PBK) model for methyleugenol (ME) in human based on in vitro and in silico derived parameters. With the model obtained, bioactivation and detoxification of methyleugenol (ME) at different doses levels could be investigated. The outcomes of the current model were compared with those of a previously developed PBK model for methyleugenol (ME) in male rat. The results obtained reveal that formation of 1′-hydroxymethyleugenol glucuronide (1′HMEG), a major metabolic pathway in male rat liver, appears to represent a minor metabolic pathway in human liver whereas in human liver a significantly higher formation of 1′-oxomethyleugenolmore » (1′OME) compared with male rat liver is observed. Furthermore, formation of 1′-sulfooxymethyleugenol (1′HMES), which readily undergoes desulfonation to a reactive carbonium ion (CA) that can form DNA or protein adducts (DA), is predicted to be the same in the liver of both human and male rat at oral doses of 0.0034 and 300 mg/kg bw. Altogether despite a significant difference in especially the metabolic pathways of the proximate carcinogenic metabolite 1′-hydroxymethyleugenol (1′HME) between human and male rat, the influence of species differences on the ultimate overall bioactivation of methyleugenol (ME) to 1′-sulfooxymethyleugenol (1′HMES) appears to be negligible. Moreover, the PBK model predicted the formation of 1′-sulfooxymethyleugenol (1′HMES) in the liver of human and rat to be linear from doses as high as the benchmark dose (BMD{sub 10}) down to as low as the virtual safe dose (VSD). This study shows that kinetic data do not provide a reason to argue against linear extrapolation from the rat tumor data to the human situation. -- Highlights: ► A PBK model is made for bioactivation and detoxification of methyleugenol in human. ► Comparison to the PBK model in male rat revealed species differences. ► PBK results support linear extrapolation from high to low dose and from rat to human.« less

Nonlinear identification of the total baroreflex arc: chronic hypertension model.

PubMed

Moslehpour, Mohsen; Kawada, Toru; Sunagawa, Kenji; Sugimachi, Masaru; Mukkamala, Ramakrishna

2016-05-01

The total baroreflex arc is the open-loop system relating carotid sinus pressure (CSP) to arterial pressure (AP). Its linear dynamic functioning has been shown to be preserved in spontaneously hypertensive rats (SHR). However, the system is known to exhibit nonlinear dynamic behaviors. The aim of this study was to establish nonlinear dynamic models of the total arc (and its subsystems) in hypertensive rats and to compare these models with previously published models for normotensive rats. Hypertensive rats were studied under anesthesia. The vagal and aortic depressor nerves were sectioned. The carotid sinus regions were isolated and attached to a servo-controlled piston pump. AP and sympathetic nerve activity were measured while CSP was controlled via the pump using Gaussian white noise stimulation. Second-order, nonlinear dynamics models were developed by application of nonparametric system identification to a portion of the measurements. The models of the total arc predicted AP 21-43% better (P < 0.005) than conventional linear dynamic models in response to a new portion of the CSP measurement. The linear and nonlinear terms of these validated models were compared with the corresponding terms of an analogous model for normotensive rats. The nonlinear gains for the hypertensive rats were significantly larger than those for the normotensive rats [-0.38 ± 0.04 (unitless) vs. -0.22 ± 0.03, P < 0.01], whereas the linear gains were similar. Hence, nonlinear dynamic functioning of the sympathetically mediated total arc may enhance baroreflex buffering of AP increases more in SHR than normotensive rats. Copyright © 2016 the American Physiological Society.

Effects of vitamin E on mercuric chloride-induced renal interstitial fibrosis in rats and the antioxidative mechanism.

PubMed

Tao, Yan-yan; Wang, Qing-lan; Yuan, Ji-li; Shen, Li; Liu, Cheng-hai

2011-02-01

To observe the effects of vitamin E (Vit E) on mercuric chloride (HgCl2)-induced renal interstitial fibrosis (RIF) in rats and discuss its antioxidative mechanism. A total of 32 Sprague-Dawley rats were randomly assigned to three groups: normal group, model group and Vit E group. RIF was induced by oral administration of HgCl(2) at a dose of 8 mg/kg body weight once a day for 9 weeks. Rats in Vit E group were administered with Vit E capsule at 100 mg/kg body weight, and rats in normal and model groups were treated with normal saline. At the end of the 9th week, rats were sacrificed and renal hydroxyproline (Hyp)'s trichrome and periodic acid-silver methenamine (PASM) staining. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and contents of glutathione (GSH) and malondialdehyde (MDA) in kidney tissue were tested with commercial kits. The expressions of nuclear factor-κB (NF-κB), inhibitor-κB (IκB), phospho-IκB (p-IκB) and tumor necrosis factor-α (TNF-α) were determined by Western blot. The expression of α-smooth muscle actin (α-SMA) was assayed by Western blot and immunofluorescent staining. Renal Hyp content, HE, Masson's trichrome and PASM staining results and α-SMA expression confirmed development of HgCl2-induced RIF in rats. Oxidative stress markers GSH, GSH-Px and MDA confirmed oxidative stress in RIF rats. Compared with model rats, rats in Vit E group had lower kidney Hyp content (P<0.01). GSH and MDA contents decreased significantly in Vit E group compared with model group (P<0.01). The expressions of NF-κB and IκB had no significant difference among all groups (P>0.05). In Vit E group, the expressions of p-IκB and TNF-α decreased significantly compared with model group (P<0.01). The expression of α-SMA in Vit E group was also decreased significantly compared with model group (P<0.01). Vit E has a protective effect on experimental RIF induced by HgCl(2) in rats and it is related to inhibition of lipid peroxidation, which involves blocking of NF-κB signaling pathway and the activation of cells producing extracellular matrix.

Biomarker and Drug Target Discovery Using Proteomics in a New Rat Model of Sepsis-Induced Acute Renal Failure

PubMed Central

Holly, Mikaela K.; Dear, James W.; Hu, Xuzhen; Schechter, Alan N.; Gladwin, Mark T.; Hewitt, Stephen M.; Yuen, Peter S.T.; Star, Robert A.

2008-01-01

Background Sepsis is one of the common causes of acute renal failure (ARF). The objective of this study was to identify new biomarkers and therapeutic targets. We present a new rat model of sepsis-induced ARF based on cecal ligation and puncture (CLP). We used this model to find urinary proteins which may be potential biomarkers and/or drug targets. Methods Aged rats were treated with fluids and antibiotics after CLP. Urinary proteins from septic rats without ARF and urinary proteins from septic rats with ARF were compared by difference in-gel electrophoresis (DIGE). Results CLP surgery elevated IL-6 and IL-10 serum cytokines and blood nitrite compared with sham-operated rats. However there was a range of serum creatinine values at 24 hrs (0.4–2.3 mg/dL) and only 24% developed ARF. Histology confirmed renal injury in these rats. 49% of rats did not develop ARF. Rats without ARF also had less liver injury. The mortality rate at 24 hrs was 27% but was increased by housing the post-surgery rats in metabolic cages. Creatinine clearance and urine output 2–8 hours after CLP was significantly reduced in rats which died within 24 hours. Using DIGE we identified changes in a number of urinary proteins including albumin, brush-border enzymes (eg., meprin-1-alpha) and serine protease inhibitors. The meprin-1-alpha inhibitor actinonin prevented ARF in aged mice. Conclusion In summary we describe a new rat model of sepsis-induced ARF which has a heterogeneous response similar to humans. This model allowed us to use DIGE to find changes in urinary proteins and this approach identified a potential biomarker and drug target – meprin-1-alpha. PMID:16760904

[Protective effect of emodin pretreatment in young rats with intrahepatic cholestasis].

PubMed

Xiong, Xiao-Li; Yan, Su-Qi; Qin, Huan; Zhou, Li-Shan; Zhang, Ling-Ling; Jiang, Zhi-Xia; Ding, Yan

2016-02-01

To investigate the protective effect of emodin in young rats with intrahepatic cholestasis. A total of 120 young Sprague-Dawley rats were randomly divided into control, model, and high-, medium-, and low-dose emodin groups, with 24 rats in each group. The rats in the control and model groups were given sodium carboxymethyl cellulose solution by gavage, while the other groups were given different doses of emodin solution by gavage. On the 5th day of experiment, alpha-naphthylisothiocyanate (ANIT, 50 mg/kg) was applied by gavage to establish the model of intrahepatic cholestasis in all groups except the control group. At 24, 48, and 72 hours after gavage, 8 rats in each group were sacrificed. Colorimetry was used to measure the serum levels of total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in each group, and hematoxylin-eosin staining was applied to observe the morphological changes of the liver under a light microscope at different time points. Compared with the control group, the model group had significantly increased serum levels of TBIL, DBIL, TBA, ALP, GGT, ALT, and AST at the 24-hour, 48-hour, and 72-hour time points (P<0.01). In the model group, the serum levels of TBIL, DBIL, TBA, ALT, and AST showed varying degrees of increase at 48 hours after establishment of model, compared with the values at 24 and 72 hours (P<0.05). At 24, 48, and 72 hours, the high-, medium-, and low-dose emodin groups had varying degrees of reductions in the serum levels of TBIL and TBA compared with the model group (P<0.05); the high- and low-dose emodin groups had significantly increased serum levels of TBA compared with the medium-dose emodin group (P<0.05). The model group had the most severe pathological changes at 48 hours. Compared with the model group, the high-, medium-, and low-dose emodin groups showed certain improvement in pathological changes of the liver at each time point, and the medium-dose emodin group had better improvement compared with the high- and low-dose emodin groups. Emodin can effectively improve ANIT-induced intrahepatic cholestasis in young rats, and medium-dose emodin shows the best effect.

Rapamycin protects the mitochondria against oxidative stress and apoptosis in a rat model of Parkinson's disease.

PubMed

Jiang, Jianhua; Jiang, Juean; Zuo, Yuanyi; Gu, Zhenlun

2013-04-01

Parkinson's disease (PD) is a neurodegenerative disease, in which oxidative stress and mitochondrial dysfunction are responsible for neuronal apoptosis. Rapamycin plays a crucial role in reducing oxidative stress and protecting the mitochondria. However, its protective role in PD has not yet been fully elucidated. In this study, we report that pre-treatment with rapamycin provides behavioral improvements, protects against the loss of dopaminergic neurons, and alleviates mitochondrial ultrastructural injuries in a rat model of PD. Peroxide levels were lower and antioxidant activities were higher in PD rats pre-treated with rapamycin compared to the PD rats pre-treated with the vehicle. Furthermore, pre-treatment with rapamycin significantly elevated the expression of anti-apoptotic markers and reduced the levels of pro-apoptotic markers compared to pre-treatment with the vehicle. In conclusion, our results demonstrated that rapamycin reduced oxidative stress and alleviated mitochondrial injuries in the 6-hydroxydopamine (6-OHDA)-induced rat model of PD, which may subsequently contribute to its anti-apoptotic effects. The ability of rapamycin to exhibit neuroprotection in a rat model of PD may be related to its antioxidant capabilities.

[Protective mechanism on the vascular pathological process in diabetes mellitus rats by Rheum officeinale].

PubMed

Tian, Feng-Sheng; Li, Zhen-Bin; Wang, Yuan-Song; Su, Xiu-Hai; Li, Wen-Dong; Wang, Xiao-Yun

2008-03-01

To explore the protective mechanism of officeihale on the vascular pathological process in diabetes mellitus (DM) rats. After the DM rat model was established, 24 DM rats were randomly divided into model group (12 DM rats) and Rheum officeinale group (12 DM rats). Rheum officeinale was orally given in 10 g kg(-1) per day, and the other two groups were given equal pure water. 8 weeks later, blood samples were collected to determine the level of nitric oxide (NO) and endothelin-1 (ET-1). Thoracic aortic rings was prepared to observe the inhibiting effect of Ach with different concentration on contraction caused by NE. Another part of aorta was made to observe the expression of ICAM-1 and VCAM-1 by method of SP immunohistochemistry staining, Rheum officeinale group obviously decreased the level of ET-1 and increased the NO compared with model group (P <0.05). The expression of ICAM-1 and VCAM-1 could be obviously inhibited in Rheum officeinale group compared with model group. (P <0.05). Rheum officeinale could decrease the level of ET-1 with increased the NO in diabetes rats, and inhibit the expression of ICAM-1 and VCAM-1, which may be mechanisms of protecting the endothelium of vessel in diabetes rats.

Naringin protects against bone loss in steroid-treated inflammatory bowel disease in a rat model.

PubMed

Li, Chengli; Zhang, Jun; Lv, Fang; Ge, Xingtao; Li, Gang

2018-07-15

We observed the effects of naringin on bone loss in glucocorticoid-treated inflammatory bowel disease (IBD) in a rat model. The IBD model was established in Sprague-Dawley rats by administering 5.0% dextran sodium sulfate. Dexamethasone (DEX) and naringin were given at the second week. Blood, colon and bone samples were collected for biomarker assay, histological analysis or microCT analysis. Superoxide dismutase, catalase and malonaldehyde were measured in bone. A significant decrease of procollagen type 1 N-terminal propeptide (P1NP) level was observed in DEX-treated IBD groups compared with the control (p < 0.05). P1NP levels were dose-dependently increased in the presence of naringin intervention. Bone loss and decreased bone biomechanical properties were observed in DEX-treated IBD rats compared with control rats (p < 0.01). Naringin intervention protected against bone loss and decreased bone biomechanical properties. Bone formation related gene mRNA expressions were significantly decreased in DEX-treated IBD rats compared with control rats. Naringin administration reversed the down-regulation of the expressions of those genes. Naringin treatment reduced the oxidative stress in bone from DEX-treated IBD rats. Our data indicated that naringin may have great potential for the treatment of bone loss in glucocorticoid-treated IBD patients via blocking oxidative stress and promoting bone formation. Copyright © 2018 Elsevier Inc. All rights reserved.

Development of a standardized laparoscopic caecum resection model to simulate laparoscopic appendectomy in rats

PubMed Central

2014-01-01

Background Laparoscopic appendectomy (LA) has become one of the most common surgical procedures to date. To improve and standardize this technique further, cost-effective and reliable animal models are needed. Methods In a pilot study, 30 Wistar rats underwent laparoscopic caecum resection (as rats do not have an appendix vermiformis), to optimize the instrumental and surgical parameters. A subsequent test study was performed in another 30 rats to compare three different techniques for caecum resection and bowel closure. Results Bipolar coagulation led to an insufficiency of caecal stump closure in all operated rats (Group 1, n = 10). Endoloop ligation followed by bipolar coagulation and resection (Group 2, n = 10) or resection with a LigaSure™ device (Group 3, n = 10) resulted in sufficient caecal stump closure. Conclusions We developed a LA model enabling us to compare three different caecum resection techniques in rats. In conclusion, only endoloop closure followed by bipolar coagulation proved to be a secure and cost-effective surgical approach. PMID:24934381

[Differential expression genes of bone tissues surrounding implants in diabetic rats by gene chip].

PubMed

Wang, Xin-xin; Ma, Yue; Li, Qing; Jiang, Bao-qi; Lan, Jing

2012-10-01

To compare mRNA expression profiles of bone tissues surrounding implants between normal rats and rats with diabetes using microarray technology. Six Wistar rats were randomly selected and divided into normal model group and diabetic group. Diabetic model condition was established by injecting Streptozotocin into peritoneal space. Titanium implants were implanted into the epiphyseal end of the rats' tibia. Bone tissues surrounding implant were harvested and sampled after 3 months to perform comprehensive RNA gene expression profiling, including 17983 for genome-wide association study.GO analysis was used to compare different gene expression and real-time PCR was used to confirm the results on core samples. The results indicated that there were 1084 differential gene expression. In the diabetic model, there were 352 enhanced expression genes, 732 suppressed expression genes. GO analysis involved 1154 different functional type. Osteoblast related gene expressions in bone tissue samples of diabetic rats were decreased, and lipid metabolism pathway related gene expression was increased.

Parenteral arginine impairs intestinal adaptation following massive small bowel resection in a rat model.

PubMed

Sukhotnik, Igor; Mogilner, Jorge G; Lerner, Aaron; Coran, Arnold G; Lurie, Michael; Miselevich, Iness; Shiloni, Eitan

2005-06-01

The nitric oxide precursor L-arginine (ARG) has been shown to influence intestinal structure and absorptive function. It is also well known that the route of administration modulates the effects of ARG. The present study evaluated the effects of parenteral ARG on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection and reanastomosis, SBS rats underwent a 75% small bowel resection, and SBS-ARG rats underwent a 75% small bowel resection and were treated with ARG given subcutaneously at a dose of 300 mug/kg, once daily, from days 3 to 14. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15 following operation. The SBS rats demonstrated a significant increase in jejunal and ileal bowel and mucosal weight, villus height and crypt depth, and cell proliferation index compared with the sham group. The SBS-ARG animals demonstrated lower ileal bowel and mucosal weights, jejunal mucosal DNA and ileal mucosal protein, and jejunal and ileal villus height and crypt depth compared with SBS animals. The SBS-ARG rats also had a lower cell proliferation index in both jejunum and ileum and a greater enterocyte apoptotic index in ileum compared with the SBS-untreated group. In conclusion, in a rat model of SBS, parenteral arginine inhibits structural intestinal adaptation. Decreased cell proliferation and increased apoptosis are the main mechanisms responsible for decreased cell mass.

Effect of subcutaneous insulin on intestinal adaptation in a rat model of short bowel syndrome.

PubMed

Sukhotnik, Igor; Mogilner, Jorge; Shamir, Raanan; Shehadeh, Naim; Bejar, Jacob; Hirsh, Mark; Coran, Arnold G

2005-03-01

Insulin has been shown to influence intestinal structure and absorptive function. The purpose of the present study was to evaluate the effects of parenteral insulin on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent bowel transection and reanastomosis, SBS rats underwent a 75% small bowel resection, and SBS-INS rats underwent a 75% small bowel resection and were treated with insulin given subcutaneously at a dose of 1 U/kg, twice daily, from day 3 through day 14. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15 following operation. SBS rats demonstrated a significant increase in jejunal and ileal bowel and mucosal weight, villus height and crypt depth, and cell proliferation index compared with the sham group. SBS-INS animals demonstrated higher jejunal and ileal bowel and mucosal weights, jejunal and ileal mucosal DNA and protein, and jejunal and ileal crypt depth compared with SBS animals. SBS-INS rats also had a greater cell proliferation index in both jejunum and ileum and a trend toward a decrease in enterocyte apoptotic index in jejunum and ileum compared with the SBS untreated group. In conclusion, parenteral insulin stimulates structural intestinal adaptation in a rat model of SBS. Increased cell proliferation is the main mechanism responsible for increased cell mass.

Effect of housing rats within a pyramid on stress parameters.

PubMed

Bhat, Surekha; Rao, Guruprasad; Murthy, K Dilip; Bhat, P Gopalakrishna

2003-11-01

The Giza pyramids of Egypt have been the subject of much research. Pyramid models with the same base to height ratio as of the Great Pyramid of Giza, when aligned on a true north-south axis, are believed to generate, transform and transmit energy. Research done with such pyramid models has shown that they induced greater relaxation in human subjects, promoted better wound healing in rats and afforded protection against stress-induced neurodegnerative changes in mice. The present study was done to assess the effects of housing Wistar rats within the pyramid on the status of oxidative damage and antioxidant defense in their erythrocytes and cortisol levels in their plasma. Rats were housed in cages under standard laboratory conditions. Cages were left in the open (normal control), under a wooden pyramid model (experimental rats) or in a cubical box of comparable dimensions (6 hr/day for 14 days). Erythrocyte malondialdehyde and plasma cortisol levels were significantly decreased in rats kept within the pyramid as compared to the normal control and those within the square box. Erythrocyte reduced glutathione levels, erythrocyte glutathione peroxidase and superoxide dismutase activities were significantly increased in the rats kept in the pyramid as compared to the other two groups. There was no significant difference in any of the parameters between the normal control and rats kept in the square box. The results showed that exposure of adult female Wistar rats to pyramid environment reduces stress oxidative stress and increases antioxidant defense in them.

Effects of aspirin and enoxaparin in a rat model of liver fibrosis.

PubMed

Li, Chen-Jie; Yang, Zhi-Hui; Shi, Xiao-Liu; Liu, De-Liang

2017-09-21

To examine the effects of aspirin and enoxaparin on liver function, coagulation index and histopathology in a rat model of liver fibrosis. METHODS Forty-five male Sprague-Dawley rats were randomly divided into the control group (n = 5) and model group (n = 40). Thioacetamide (TAA) was used to induce liver fibrosis in the model group. TAA-induced fibrotic rats received TAA continuously (n = 9), TAA + low-dose aspirin (n = 9), TAA + high-dose aspirin (n = 9) or TAA + enoxaparin (n = 9) for 4 wk. All rats were euthanized after 4 wk, and both hematoxylin-eosin and Masson staining were performed to observe pathological changes in liver tissue. Liver fibrosis was assessed according to the METAVIR score. Compared with untreated cirrhotic controls, a significant improvement in fibrosis grade was observed in the low-dose aspirin, high-dose aspirin and enoxaparin treated groups, especially in the high-dose aspirin treated group. Alanine aminotransferase and total bilirubin were higher, albumin was lower and both prothrombin time and international normalized ratio were prolonged in the four treatment groups compared to controls. No significant differences among the four groups were observed. Aspirin and enoxaparin can alleviate liver fibrosis in this rat model.

Bilateral Cavernous Nerve Crush Injury in the Rat Model: A Comparative Review of Pharmacologic Interventions.

PubMed

Haney, Nora M; Nguyen, Hoang M T; Honda, Matthew; Abdel-Mageed, Asim B; Hellstrom, Wayne J G

2018-04-01

It is common for men to develop erectile dysfunction after radical prostatectomy. The anatomy of the rat allows the cavernous nerve (CN) to be identified, dissected, and injured in a controlled fashion. Therefore, bilateral CN injury (BCNI) in the rat model is routinely used to study post-prostatectomy erectile dysfunction. To compare and contrast the available literature on pharmacologic intervention after BCNI in the rat. A literature search was performed on PubMed for cavernous nerve and injury and erectile dysfunction and rat. Only articles with BCNI and pharmacologic intervention that could be grouped into categories of immune modulation, growth factor therapy, receptor kinase inhibition, phosphodiesterase type 5 inhibition, and anti-inflammatory and antifibrotic interventions were included. To assess outcomes of pharmaceutical intervention on erectile function recovery after BCNI in the rat model. The ratio of maximum intracavernous pressure to mean arterial pressure was the main outcome measure chosen for this analysis. All interventions improved erectile function recovery after BCNI based on the ratio of maximum intracavernous pressure to mean arterial pressure results. Additional end-point analysis examined the corpus cavernosa and/or the major pelvic ganglion and CN. There was extreme heterogeneity within the literature, making accurate comparisons between crush injury and therapeutic interventions difficult. BCNI in the rat is the accepted animal model used to study nerve-sparing post-prostatectomy erectile dysfunction. However, an important limitation is extreme variability. Efforts should be made to decrease this variability and increase the translational utility toward clinical trials in humans. Haney NM, Nguyen HMT, Honda M, et al. Bilateral Cavernous Nerve Crush Injury in the Rat Model: A Comparative Review of Pharmacologic Interventions. Sex Med Rev 2018;6:234-241. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

The characterization of a full-thickness excision open foot wound model in n5-streptozotocin (STZ)-induced type 2 diabetic rats that mimics diabetic foot ulcer in terms of reduced blood circulation, higher C-reactive protein, elevated inflammation, and reduced cell proliferation.

PubMed

Yu, Caroline Oi-Ling; Leung, Kwok-Sui; Fung, Kwok-Pui; Lam, Francis Fu-Yuen; Ng, Ethel Sau-Kuen; Lau, Kit-Man; Chow, Simon Kwoon-Ho; Cheung, Wing-Hoi

2017-08-05

Delayed foot wound healing is a major complication attributed to hyperglycemia in type 2 diabetes mellitus (DM) patients, and these wounds may develop into foot ulcers. There are at least two types of DM wound models used in rodents to study delayed wound healing. However, clinically relevant animal models are not common. Most models use type 1 DM rodents or wounds created on the back rather than on the foot. An open full-thickness excision wound on the footpad of type 2 DM rats is more clinically relevant, but such a model has not yet been characterized systematically. The objective of this study was to investigate and characterize how DM affected a full-thickness excision open foot wound in n5-streptozotocin (n5-STZ)-induced type 2 DM rats. We hypothesized that elevated inflammation, reduced blood circulation, and cell proliferation due to hyperglycemia could delay the wound healing of DM rats. The wounds of DM rats were compared with those of non-DM rats (Ctrl) at Days 1 and 8 post wounding. The wound healing process of the DM rats was significantly delayed compared with that of the Ctrl rats. The DM rats also had higher C-reactive protein (CRP) and lower blood circulation and proliferating cell nuclear antigen (PCNA) in DM wounds. This confirmed that elevated inflammation and reduced blood flow and cell proliferation delayed foot wound healing in the n5-STZ rats. Hence, this open foot wound animal model provides a good approach to study the process of delayed wound healing.

The characterization of a full-thickness excision open foot wound model in n5-streptozotocin (STZ)-induced type 2 diabetic rats that mimics diabetic foot ulcer in terms of reduced blood circulation, higher C-reactive protein, elevated inflammation, and reduced cell proliferation

PubMed Central

Yu, Caroline Oi-Ling; Leung, Kwok-Sui; Fung, Kwok-Pui; Lam, Francis Fu-Yuen; Ng, Ethel Sau-Kuen; Lau, Kit-Man; Chow, Simon Kwoon-Ho; Cheung, Wing-Hoi

2017-01-01

Delayed foot wound healing is a major complication attributed to hyperglycemia in type 2 diabetes mellitus (DM) patients, and these wounds may develop into foot ulcers. There are at least two types of DM wound models used in rodents to study delayed wound healing. However, clinically relevant animal models are not common. Most models use type 1 DM rodents or wounds created on the back rather than on the foot. An open full-thickness excision wound on the footpad of type 2 DM rats is more clinically relevant, but such a model has not yet been characterized systematically. The objective of this study was to investigate and characterize how DM affected a full-thickness excision open foot wound in n5-streptozotocin (n5-STZ)-induced type 2 DM rats. We hypothesized that elevated inflammation, reduced blood circulation, and cell proliferation due to hyperglycemia could delay the wound healing of DM rats. The wounds of DM rats were compared with those of non-DM rats (Ctrl) at Days 1 and 8 post wounding. The wound healing process of the DM rats was significantly delayed compared with that of the Ctrl rats. The DM rats also had higher C-reactive protein (CRP) and lower blood circulation and proliferating cell nuclear antigen (PCNA) in DM wounds. This confirmed that elevated inflammation and reduced blood flow and cell proliferation delayed foot wound healing in the n5-STZ rats. Hence, this open foot wound animal model provides a good approach to study the process of delayed wound healing. PMID:28413186

Effects of Chailong Jieyu Pill on Behavior, Monoamine Neurotransmitters, and Corticosteroid Receptors in a Rat Model of Anxiety Disorder.

PubMed

Feng, Guang-Kui; Ma, Xian-Jun; Chen, Yin-Yi; Bian, Guang-Rong; Yang, Chao; Gu, Bao-Dong

2018-01-01

Chailong Jieyu Pill (CJP) is composed of Radix Bupleuri, Radix Scutellariae, Rhizoma Pinelliae Preparata, Radix Codonopsis, Radix Glycyrrhizae preparata , keel, Concha Ostreae, Concha Margaritifera Usta, Rhizoma Zingiberis Recens , and Fructus Jujubae . CJP has shown good clinical effects on improving anxiety disorders. However, as the mechanism underlying such benefits remains unclear, the aim of this study was to investigate the mechanism of action for CJP on anxiety-related behaviors in a rat model of anxiety disorder. After establishing a rat model of anxiety disorder using uncertain empty bottle stimulation, rats were divided into control, model, citalopram, low-dose CJP, and high-dose CJP groups. After 1 month of administration, effects of treatments on rat appearance, body weight, and open-field test scores were observed. In addition, hippocampal monoamine neurotransmitter (5-hydroxytryptamine, dopamine, and norepinephrine) contents were measured with an enzyme-linked immunosorbent assay, and mRNA expression of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) were measured with reverse transcription-polymerase chain reaction. CJP increased rat weight, and this effect was increased in the high-dose CJP group compared with the citalopram group ( P < 0.05). CJP also elevated open-field test scores compared with the citalopram group ( P < 0.05). While CJP decreased monoamine neurotransmitter contents in rat hippocampus, the regulatory effect of CJP on 5-hydroxytryptamine was reduced compared with citalopram ( P < 0.01). CJP upregulated GR mRNA expression in both low-dose ( P < 0.05) and high-dose ( P < 0.01) CJP groups, but only the latter significantly downregulated MR mRNA expression and showed enhanced effects compared with citalopram ( P < 0.05). Thus, CJP likely exerted its significant antianxiety effect by diminishing monoamine neurotransmitters and regulating mRNA expression of MR and GR in the hippocampus of our rat model of anxiety disorder.

Suprapubic Bladder Catheterization of Male Spinal-Cord–Injured Sprague–Dawley Rats

PubMed Central

Robinson, Mary A; Herron, Alan J; Goodwin, Bradford S; Grill, Raymond J

2012-01-01

The rat spinal-cord–injury (SCI) model is widely used to study the pathologic mechanisms that contribute to sensory and motor dysfunction in humans. This model is thought to mimic many of the negative outcomes experienced by humans after spinal contusion injury. We theorized that manual bladder expression contributed to the kidney and bladder lesions reported in previous studies using the rat SCI model. In the present study, rats were surgically implanted with bladder catheters after spinal contusion injury to provide continuous drainage of urine. After 72 h, the rats were euthanized and their kidneys and bladders examined histologically. BUN, serum creatinine, and urine protein were compared at 0 and 72 h after surgery. Kidney and bladder lesions were similar in SCI rats with and without implanted bladder catheters. BUN at 72 h was higher than baseline values in both groups, whereas serum creatinine was higher at 72 h compared with baseline values only in the catheterized rats. These findings indicate that suprapubic bladder catheterization does not reduce hydronephrosis in SCI rats and that the standard of care for bladder evacuation should continue to be manual expression of urine. PMID:22330872

Cafeteria diet is a robust model of human metabolic syndrome with liver and adipose inflammation: comparison to high-fat diet.

PubMed

Sampey, Brante P; Vanhoose, Amanda M; Winfield, Helena M; Freemerman, Alex J; Muehlbauer, Michael J; Fueger, Patrick T; Newgard, Christopher B; Makowski, Liza

2011-06-01

Obesity has reached epidemic proportions worldwide and reports estimate that American children consume up to 25% of calories from snacks. Several animal models of obesity exist, but studies are lacking that compare high-fat diets (HFD) traditionally used in rodent models of diet-induced obesity (DIO) to diets consisting of food regularly consumed by humans, including high-salt, high-fat, low-fiber, energy dense foods such as cookies, chips, and processed meats. To investigate the obesogenic and inflammatory consequences of a cafeteria diet (CAF) compared to a lard-based 45% HFD in rodent models, male Wistar rats were fed HFD, CAF or chow control diets for 15 weeks. Body weight increased dramatically and remained significantly elevated in CAF-fed rats compared to all other diets. Glucose- and insulin-tolerance tests revealed that hyperinsulinemia, hyperglycemia, and glucose intolerance were exaggerated in the CAF-fed rats compared to controls and HFD-fed rats. It is well-established that macrophages infiltrate metabolic tissues at the onset of weight gain and directly contribute to inflammation, insulin resistance, and obesity. Although both high fat diets resulted in increased adiposity and hepatosteatosis, CAF-fed rats displayed remarkable inflammation in white fat, brown fat and liver compared to HFD and controls. In sum, the CAF provided a robust model of human metabolic syndrome compared to traditional lard-based HFD, creating a phenotype of exaggerated obesity with glucose intolerance and inflammation. This model provides a unique platform to study the biochemical, genomic and physiological mechanisms of obesity and obesity-related disease states that are pandemic in western civilization today.

Effects of type 2 diabetes mellitus on the pharmacokinetics of berberine in rats.

PubMed

Jia, Yuzhen; Xu, Binger; Xu, Jisen

2017-12-01

Berberine is an active alkaloid isolated from Rhizoma coptidis [Coptis chinensis Franch. (Ranunculaceae)] that is widely used for the treatment of diabetes, hyperlipidemia and hypertension. However, the pharmacokinetics of berberine in normal rats and type 2 diabetes mellitus (T2DM) model rats are not clear. This study compares the pharmacokinetics of berberine between normal and T2DM model rats. The T2DM model rats were fed with high fat diet for 4 weeks, induced by low-dose (30 mg/kg) streptozotocin for 72 h and validated by determining the peripheral blood glucose level. Rats were orally treated with berberine at a dose of 20 mg/kg and then berberine concentration in rat plasma was determined by employing a sensitive and rapid LC-MS/MS method. The significantly different pharmacokinetic behaviour of berberine was observed between normal and T2DM model rats. When compared with the normal group, C max , t 1/2 and AUC (0- t ) of berberine were significantly increased in the model group (17.35 ± 3.24 vs 34.41 ± 4.25 μg/L; 3.95 ± 1.27 vs 9.29 ± 2.75 h; 151.21 ± 23.96 vs 283.81 ± 53.92 μg/h/L, respectively). In addition, oral clearance of berberine was significantly decreased in the model group (134.73 ± 32.15 vs 62.55 ± 16.34 L/h/kg). In T2DM model rats, the pharmacokinetic behaviour of berberine was significantly altered, which indicated that berberine dosage should be modified in T2DM patients.

Budesonide Attenuates Ventilator-induced Lung Injury in a Rat Model of Inflammatory Acute Respiratory Distress Syndrome.

PubMed

Gao, Wei; Ju, Ying-Nan

2016-05-01

Patients with acute respiratory distress syndrome (ARDS) are particularly susceptible to ventilator-induced lung injury (VILI). This study investigated the effect of budesonide on VILI in a rat model of inflammatory ARDS. Forty eight rats were randomized into three groups (n = 16 each): sham group (S), endotoxin/ventilation group (LV), endotoxin/ventilation/budesonide group (LVB). Rats in the S group received anesthesia only. Rats in the LV and LVB groups received endotoxin to simulate ARDS and were mechanically ventilated for 4 h (tidal volume 30 mL/kg). Rats in the LVB group received budesonide 1 mg, and rats in the LV group received saline in airway. PaO2/FiO2, lung wet-to-dry weight ratios, inflammatory factors in serum and bronchoalveolar lavage fluid (BALF), histopathologic analysis of lung tissue, and survival were examined. PaO2/FiO2 was significantly increased in rats in the LVB group compared to the LV group. Total cell count, macrophages, and neutrophils in BALF, and levels of intercellular adhesion molecule (ICAM)-1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-8 in BALF and serum were significantly decreased in rats in the LVB group compared to the LV group, whereas levels of IL-10 in BALF and serum were significantly increased. Histopathological changes of lung injury and apoptosis were reduced, and survival was increased in rats in the LVB group compared to the LV group. Budesonide ameliorated VILI in a rat model of inflammatory ARDS. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

[Protective effect of Saccharomyces boulardii against intestinal mucosal barrier injury in rats with nonalcoholic fatty liver disease].

PubMed

Liu, Y T; Li, Y Q; Wang, Y Z

2016-12-20

Objective: To investigate the protective effect of Saccharomyces boulardii against intestinal mucosal barrier injury in rats with nonalcoholic fatty liver disease (NAFLD). Methods: A total of 36 healthy male Sprague-Dawley rats with a mean body weight of 180±20 g were randomly divided into control group, model group, and treatment group, with 12 rats in each group, after adaptive feeding for 1 week. The rats in the control group were given basic feed, and those in the model group and treatment group were given high-fat feed. After 12 weeks of feeding, the treatment group was given Saccharomyces boulardii (75×10 8 CFU/kg/d) by gavage, and those in the control group and model group were given isotonic saline by gavage. At the 20th week, blood samples were taken from the abdominal aorta to measure the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), intestinal fatty acid binding protein (IFABP), tumor necrosis factor-α (TNF-α), and endotoxins. The liver pathological changes, intestinal histopathological changes, and expression of occludin in the intestinal mucosa were observed. Fecal samples were collected to measure the changes in Escherichia coli and Bacteroides. A one-way analysis of variance and the SNK test were used for comparison between multiple groups, and the rank sum test was used as the non-parametric test. Results: Compared with the control group, the model group had significantly higher body weight, liver mass, and liver index ( P < 0.05), and compared with the model group, the treatment group had significant reductions in body weight, liver mass, and liver index ( P < 0.05). The model group had significant increases in TG, ALT, and AST compared with the control group ( P < 0.05), the treatment group had a significant reduction in AST compared with the model group ( P < 0.05), and the treatment group had slight reductions in TG and ALT compared with the model group ( P > 0.05). Compared with the control group, the model group had significant increases in the levels of endotoxin, TNF-α, and IFABP ( P < 0.05), and the treatment group had significant reductions in the levels of endotoxin, TNF-α, and IFABP ( P < 0.05). Liver tissue staining showed that the model group had significantly increased hepatocyte steatosis compared with the control group ( P < 0.05), and that the treatment group had significantly reduced hepatocyte steatosis compared with the model group ( P < 0.05). The intestinal villi in the control group had ordered arrangement and a complete structure; in the model group, the intestinal villi were shortened with local shedding and a lack of ordered arrangement; compared with the model group, the treatment group had mild edema and ordered arrangements of the intestinal villi. The model group had a significantly reduced level of occludin protein compared with the control group ( P < 0.05), and the treatment group had a slight increase compared with the model group. The model group had a significantly increased number of Escherichia coli and a significantly reduced number of Bacteroides compared with the control group ( P < 0.05), and the treatment group had a significantly reduced number of Escherichia coli and a significantly increased number of Bacteroides compared with the model group ( P < 0.05). Conclusion: High-fat diet can successfully induce NAFLD in rats, and intervention with Saccharomyces boulardii can reduce body weight and improve hepatocyte steatosis. Saccharomyces boulardii can reduce endotoxemia in NAFLD rats and thus alleviate inflammatory response. Saccharomyces boulardii can also adjust the proportion of Escherichia coli and Bacteroides in the intestine of NAFLD rats.

A comparative study of approaches to compute the field distribution of deep brain stimulation in the Hemiparkinson rat model.

PubMed

Bohme, Andrea; van Rienen, Ursula

2016-08-01

Computational modeling of the stimulating field distribution during Deep Brain Stimulation provides an opportunity to advance our knowledge of this neurosurgical therapy for Parkinson's disease. There exist several approaches to model the target region for Deep Brain Stimulation in Hemi-parkinson Rats with volume conductor models. We have described and compared the normalized mapping approach as well as the modeling with three-dimensional structures, which include curvilinear coordinates to assure an anatomically realistic conductivity tensor orientation.

A comparative evaluation of the tissue responses associated with polymeric implants in the rat and mouse.

PubMed

Kidd, Kameha R; Dal Ponte, Donny B; Kellar, Robert S; Williams, Stuart K

2002-03-15

End product application is an important consideration when evaluating a material in an in vivo setting (Didisheim, Cardiovasc Pathol 1993;2:1S-2S). Small animal models allow high through-put evaluation of biocompatability. Previous preclinical evaluations have often used a rat subcutaneous model for the characterization of material-tissue interaction. Recent advances in genetic manipulation have provided mouse models with selective expression of a wide range of critical proteins. The rat model does not have many of the resources (i.e., knockouts, SCID, nude) that are present in mouse strains. The availability of these mice provides a resource to delineate the mechanisms regulating the healing associated with implants. However, before the mouse models can be used, they must be validated with respect to their ability to accurately assess tissue responses to materials. In this study the tissue responses after the implantation of expanded polytetrafluoroethylene (ePTFE) were compared between rat and mouse. Discs of ePTFE (30-microm internodal distance) were implanted in subcutaneous and epididymal fat tissue of rats (Sprague-Dawley) and mice (129-SVJ). After 5 weeks the samples were removed and evaluated for vascular density, inflammation, and fibrous encapsulation. No difference in the vessel density was observed within the peri-implant subcutaneous and adipose tissue or within the porous material. However, a significant difference was found in the number of activated macrophages and giant cells between these two species. Implants in the rat exhibited greater numbers of activated inflammatory cells in the peri-implant tissue. The data indicate that the mouse and rat provide a comparable model for evaluating angiogenesis and neovascularization associated with synthetic porous implants. Copyright 2001 John Wiley & Sons, Inc. J Biomed Mater Res 59: 682-689, 2002

Probiotics improve survival of septic rats by suppressing conditioned pathogens in ascites

PubMed Central

Liu, Da-Quan; Gao, Qiao-Ying; Liu, Hong-Bin; Li, Dong-Hua; Wu, Shang-Wei

2013-01-01

AIM: To investigate the benefits of probiotics treatment in septic rats. METHODS: The septic rats were induced by cecal ligation and puncture. The animals of control, septic model and probiotics treated groups were treated with vehicle and mixed probiotics, respectively. The mixture of probiotics included Bifidobacterium longum, Lactobacillus bulgaricus and Streptococcus thermophilus. We observed the survival of septic rats using different amounts of mixed probiotics. We also detected the bacterial population in ascites and blood of experimental sepsis using cultivation and real-time polymerase chain reaction. The severity of mucosal inflammation in colonic tissues was determined. RESULTS: Probiotics treatment improved survival of the rats significantly and this effect was dose dependent. The survival rate was 30% for vehicle-treated septic model group. However, 1 and 1/4 doses of probiotics treatment increased survival rate significantly compared with septic model group (80% and 55% vs 30%, P < 0.05). The total viable counts of bacteria in ascites decreased significantly in probiotics treated group compared with septic model group (5.20 ± 0.57 vs 9.81 ± 0.67, P < 0.05). The total positive rate of hemoculture decreased significantly in probiotics treated group compared with septic model group (33.3% vs 100.0%, P < 0.05). The population of Escherichia coli and Staphylococcus aureus in ascites of probiotics treated group were decreased significantly compared with that of septic model group (3.93 ± 0.73 vs 8.80 ± 0.83, P < 0.05; 2.80 ± 1.04 vs 5.39 ± 1.21, P < 0.05). With probiotics treatment, there was a decrease in the scores of inflammatory cell infiltration into the intestinal mucosa in septic animals (1.50 ± 0.25 vs 2.88 ± 0.14, P < 0.01). CONCLUSION: Escherichia coli and Staphylococcus aureus may be primary pathogens in septic rats. Probiotics improve survival of septic rats by suppressing these conditioned pathogens. PMID:23840152

Meat product based on porcine hearts and aortas ameliorates serum lipid profile and inflammation in hyperlipidemic rats

NASA Astrophysics Data System (ADS)

Chernukha, I. M.; Kotenkova, E. A.; Fedulova, L. V.

2017-09-01

The biological effect of porcine hearts and aortas in a hyperlipidemic rat model was confirmed. Porcine heart and aorta mixture in a 3:1 ratio was blended, canned and sterilized at 115°C and 0.23 Mpa for 40 min. Administration of experimental meat product to the animal model decreased total cholesterol, triglycerides and cholesterol low density lipoproteins by 31.8% (P<0.05), 28.2%, and 21.6% (P<0.05), respectively, compared to those of hyperlipidemic control rats, as well significantly reducing the serum atherogenic index by 41.3% (P<0.05) in rats fed the experimental meat product compared with hyperlipidemic control rats. Normalization of white blood cell populations was also detected. Monocyte and granulocyte counts in blood of rats fed the meat product decreased by 71.1% (P<0.05) and 57.6% (P<0.05) compared to those of the hyperlipidemic control animals. The granulocyte/leucocyte ratio was also reduced by an average of 38.6% (P<0.05) in rats fed the meat product compared with hyperlipidemic control rats. The data confirmed the hypolipidemic action of the sterilized meat product. Normalization of white blood cell populations led us to hypothesize an anti-inflammatory action of the new meat product, which, therefore, could be recommended as a part of maintenance therapy for people with lipid disorders or atherosclerosis.

Protection of estrogen in portal hypertension gastropathy: an experimental model.

PubMed

Morgan-Martins, Maria Isabel; Jacques, Simone Iahnig; Hartmann, Renata Minuzzo; Marques, Camila Moraes; Marroni, Cláudio Augusto; Marroni, Norma Possa

2011-01-01

Portal hypertension is a complication secondary to cirrhosis that is characterized by increased blood flow and/or vascular resistance in the portal system, causing the appearance of a hyperdynamic collateral circulation. Partial portal vein ligation is an experimental model used in rats to study the pathophysiological mechanisms involved in pre-hepatic portal hypertension. Estrogen E2 is an antioxidant molecule with various physiological actions. To evaluate the antioxidant activity of endogenous estrogen in an experimental model of partial portal vein ligation by comparing intact with castrated rats. Twenty Wistar rats, weighing on average 250 g were used and divided into four groups: sham-operated (SO); intact (I) with partial portal vein ligation (I + PPVL), castrated (C) and castrated with partial ligation of the vein (C + PPVL). Day 1: castration or sham-operation; day 7, PPVL surgery; on day 15 post-PPVL, portal pressure in the mesenteric vein of rats was measured on polygraph Letica. Lipid peroxidation in the stomach was assessed using the technique of thiobarbituric acid reactive substances and activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase. Statistical analysis was done with ANOVA - Student-Newman-Keuls (mean ± SE), and P<0.05 was considered as significant. Portal pressure was significantly increased in C + PPVL as compared to the other groups. There was no significant difference in the group of intact rats. TBARS showed significant damage in C and C + PPVL in relation to others. Antioxidant enzymes were significantly increased in the castrated rats with subsequent PPVL as compared to the other groups. We suggest that estrogen E2 plays a protective role in intact compared with castrated rats because it presents hydrophenolic radicals in its molecule, thus acting as an antioxidant in this experimental model.

Depression-related behavioural and neuroendocrine changes in the Spontaneously Diabetic Torii (SDT) fatty rat, an animal model of Type 2 Diabetes Mellitus.

PubMed

Sakimura, Katsuya; Maekawa, Tatsuya; Sasagawa, Kazuo; Ishii, Yukihito; Kume, Shin-Ichi; Ohta, Takeshi

2018-05-14

Depression is one of the most common psychiatric diseases and is commonly comorbid with type 1 or 2 diabetes mellitus (DM). However, the pathophysiology underlying the depressive state in DM remains poorly understood. Animal models are useful tools to investigate the association between depression and DM. In the present study we investigated whether the Spontaneously Diabetic Torii (SDT) fatty rat, a novel animal model of type 2 DM, shows depression-related features. We assessed depression-like behaviour, hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, and neurotransmitter levels in the brain. Behaviour was evaluated using a forced swimming test, and the HPA axis was evaluated with changes in plasma corticosterone levels after a swimming stress exposure or dexamethasone challenge. In addition, serotonin (5-hydroxytryptamine; 5-HT), noradrenaline, glutamate and γ-aminobutyric acid (GABA) concentrations in the frontal cortex, hippocampus and brain stem were measured. In the forced swimming test, SDT fatty rats exhibited increased duration of immobility compared with control Sprague-Dawley (SD) rats. Moreover, basal corticosterone levels were significantly elevated in SDT fatty compared with control SD rats. However, there were no stress-induced increases or changes in dexamethasone-induced suppression of corticosterone in SDT fatty compared with control SD rats. Furthermore, there were significant changes in 5-HT concentrations in the prefrontal cortex, and in GABA and glutamate concentrations in the hippocampus in SDT fatty compared with controls. The results of the present study suggest that the SDT fatty rat may be an appropriate model for diabetes with comorbid depression associated with neurotransmitter impairments and aberrant basal HPA hyperactivity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Effect of Ginkgo biloba extract on apoptosis of brain tissues in rats with acute cerebral infarction and related gene expression.

PubMed

Wu, C; Zhao, X; Zhang, X; Liu, S; Zhao, H; Chen, Y

2015-06-11

We investigated the effect of Ginkgo biloba extract on apoptosis of brain tissues in rats with acute cerebral infarction and apoptosis-related gene expression. Rat models of acute cerebral infarction were constructed using the suture method, and randomly divided into the control group, model, and treatment groups. In the treatment group, 4 mg/kg G. biloba extract was intravenously injected into the rat tail vein. Phosphate-buffered saline solution was injected in the model group. Seventy-two hours after treatment, rats were euthanized, and brain tissues were removed to analyze the changes in caspase-3, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) mRNA and protein levels, and variation in brain tissue cells' apoptosis indices was measured. Compared with the control group, the model and treatment groups showed significantly upregulated caspase-3, Bcl-2, and Bax mRNA and protein levels in brain tissues, but remarkably downregulated Bcl-2 mRNA and protein levels (P < 0.05). After treatment, in treatment group brain tissues, caspase-3 and Bax mRNA and protein levels were significantly lower than those in the model group, while Bcl-2 mRNA and protein levels were higher than that in the model group (P < 0.05). The model and treatment groups showed increased cell apoptosis indices of brain tissues compared to the control group; after treatment, the apoptosis index in the treatment group was significantly downregulated compared with that in the model group (P < 0.05). In conclusion, G. biloba extract significantly reduced apoptosis in rat brain tissue cells with acute cerebral infarction and thus protected brain tissues.

The intervention effect of zuogui pill on chronic kidney disease-mineral and bone disorder regulatory factor.

PubMed

Ma, Xiaohong; He, Liqun

2018-06-24

Chronic kidney disease-mineral and bone disorder (CKD-MBD) play a critical role in the pathogenesis of cardiovascular complications in patients with chronic kidney disease (CKD). Zuogui pill as a traditional Chinese herbal drug has been used for nourish kidney essence improve bone malnutrition of renal bone disease by regulating the metabolism of calcium and phosphorus and participating in osteoblast metabolism. In the present study, 5/6 nephrectomy rat model was used to reveal the mechanism of zuogui pill in treatment of CKD-MBD. Compared with sham rats, the levels of serum phosphorus, PTH, iPTH and creatinine were significantly decreased, while the serum calcium level was significantly increased, and the Cbfa1 protein level was significantly decreased and FGF23 protein level was significantly increased by Zuogui pill treatment. Compared with model rats, the BMD of rat was significantly increased by Zuogui pill treatment. Histological analysis revealed that the kidney injury of rats with CKD was significantly reduced by zuogui pill treatment. Compared with model rats, the CYP27B1 mRNA level was significantly increased, and the PTH mRNA level and NaPiIIa protein level were significantly decreased in the kidney by zuogui pill treatment. We inferred that zuogui pill exhibited potential therapeutic effects on CKD-MBD in the rats by regulating bone metabolism and nourish kidney. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Comparative pharmacokinetic and tissue distribution profiles of four major bioactive components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

PubMed

Yang, Tao; Liu, Shan; Wang, Chang-Hong; Tao, Yan-Yan; Zhou, Hua; Liu, Cheng-Hai

2015-10-10

Fuzheng Huayu recipe (FZHY) is a herbal product for the treatment of liver fibrosis approved by the Chinese State Food and Drug Administration (SFDA), but its pharmacokinetics and tissue distribution had not been investigated. In this study, the liver fibrotic model was induced with intraperitoneal injection of dimethylnitrosamine (DMN), and FZHY was given orally to the model and normal rats. The plasma pharmacokinetics and tissue distribution profiles of four major bioactive components from FZHY were analyzed in the normal and fibrotic rat groups using an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results revealed that the bioavailabilities of danshensu (DSS), salvianolic acid B (SAB) and rosmarinic acid (ROS) in liver fibrotic rats increased 1.49, 3.31 and 2.37-fold, respectively, compared to normal rats. There was no obvious difference in the pharmacokinetics of amygdalin (AMY) between the normal and fibrotic rats. The tissue distribution of DSS, SAB, and AMY trended to be mostly in the kidney and lung. The distribution of DSS, SAB, and AMY in liver tissue of the model rats was significantly decreased compared to the normal rats. Significant differences in the pharmacokinetics and tissue distribution profiles of DSS, ROS, SAB and AMY were observed in rats with hepatic fibrosis after oral administration of FZHY. These results provide a meaningful basis for developing a clinical dosage regimen in the treatment of hepatic fibrosis by FZHY. Copyright © 2015 Elsevier B.V. All rights reserved.

Motor Function and Dopamine Release Measurements in Transgenic Huntington’s Disease Model Rats

PubMed Central

Ortiz, Andrea N.; Osterhaus, Gregory L.; Lauderdale, Kelli; Mahoney, Luke; Fowler, Stephen C.; von Hörsten, Stephan; Riess, Olaf; Johnson, Michael A.

2013-01-01

Huntington’s disease (HD) is a fatal, genetic, neurodegenerative disorder characterized by deficits in motor and cognitive function. Here, we have quantitatively characterized motor deficiencies and dopamine release dynamics in transgenic HD model rats. Behavioral analyses were conducted using a newly-developed force-sensing runway and a previously-developed force-plate actometer. Gait disturbances were readily observed in transgenic HD rats at 12 to 15 months of age. Additionally, dopamine system challenge by ip injection of amphetamine also revealed that these rats were resistant to the expression of focused stereotypy compared to wild-type controls. Moreover, dopamine release, evoked by the application of single and multiple electrical stimulus pulses applied at different frequencies, and measured using fast-scan cyclic voltammetry at carbon-fiber microelectrodes, was diminished in transgenic HD rats compared to age-matched wild-type control rats. Collectively, these results underscore the potential contribution of dopamine release alterations to the expression of motor impairments in transgenic HD rats. PMID:22418060

The role of intestinal endotoxemia in a rat model of aluminum neurotoxicity

PubMed Central

Wang, Feng; Guo, Rui-Xia; Li, Wen-Xing; Yu, Bao-Feng; Han, Bai; Liu, Li-Xin; Han, De-Wu

2017-01-01

The present study aimed to investigate the effects of intestinal endotoxemia (IETM) in a rat model of aluminum neurotoxicity established by D-galactose and aluminum trichloride (AlCl3). Adult Wistar rats were administered D-galactose and AlCl3 to create the aluminum neurotoxicity model. The learning and memory abilities of the rats were subsequently observed using a Morris water maze test and the serum levels of lipopolysaccharide (LPS), tumor necrosis factor (TNF)-α, interleukin (IL)-1, diamine oxidase (DAO), glutamine (Gln) and glutaminase were measured. The expression of S-100β in the serum was detected using an enzyme-linked immunosorbent assay. The expression levels of the amyloid β-protein (Aβ) precursor (APP), presenilin 1 (PS1), β-site APP-cleaving enzyme (BACE), zona occludens protein (ZO)-1 and Aβ 1–40 in the brain of rats were detected via reverse-transcription polymerase chain reaction, western blotting and immunohistochemistry. The levels of LPS, TNF-α, IL-1, DAO, Gln and S-100β in serum and the mRNA and protein expression levels of APP, PS1, BACE and Aβ1-40 in the brain were markedly increased in the model rats compared with controls. The level of glutaminase in the serum and the expression of ZO-1 in the brain were decreased in the model rats compared with controls. IETM was present in the rat model of aluminum neurotoxicity established by D-galactose and AlCl3 and may be important in the development of this neurotoxicity. PMID:28627692

Postictal in situ MRS brain lactate in the rat kindling model.

PubMed

Maton, B M; Najm, I M; Wang, Y; Lüders, H O; Ng, T C

1999-12-10

To determine the temporal and spatial extent of the lactate (Lact) changes as correlated with seizure characteristics and EEG changes in the rat kindling model. Prior studies using MRS have detected cerebral Lact postictally in animal models of seizures and in patients with intractable focal epilepsy. We performed MRS in sham control rats (n = 4) and in rats stimulated in the right hippocampus at two different stages of the kindling and at three time points after the seizures: <2 hours (n = 8 and 5, stage 0 and stage 5), 2 to 3 hours (n = 5 and 6), and >3 hours (n = 4 and 2). Lact/creatine (Cr) and N-acetylaspartate (NAA)/Cr ratios were measured in six contiguous voxels (three left, three right) covering the hippocampi, anterior and posterior regions, and compared with EEG and ictal behavior. Lact/Cr ratios were measured at a very low level in the sham control rats and in the >3-hour group. In the <2-hour group, Lact/Cr increase was higher in stage-5 rats as compared with stage-0 rats (p = 0.001, unpaired t-test) and sham control rats when all the voxels were considered. Lact/Cr ratios were higher in the stimulated area as compared with all other brain areas in stage-0 rats (p = 0.05, paired t-test) but not in the stage-5 rats. Similar results with more inter-animal variability were measured in the 2- to 3-hour group. NAA/Cr ratios increased significantly after stage-0 kindling in the stimulated hippocampus but not after stage-5 kindling. Postictal Lact increase as assayed by MRS correlates with EEG and behavioral seizures and suggests that it would be an additional noninvasive technique for seizure localization during the presurgical evaluation of patients with intractable focal epilepsy.

[Adipose-derived stem cell transplantation promotes the expression of netrin-1 in the rat cortex after focal cerebral ischemia].

PubMed

Wang, Jiehua; Hong, Zhuquan; Pan, Ying; Li, Guoqian

2017-01-01

Objective To observe the effect of adipose-derived stem cells (ADSCs) transplantation on the expression of netrin-1 in rats after focal cerebral ischemia. Methods Male SD rats were randomly divided into control group, model group and ADSC group. ADSCs were harvested and purified. Focal cerebral ischemia models were established in rats by the suture method. ADSCs were injected into the lateral ventricle of ADSC group rats and the same does of PBS was given to model group rats. At day 4, 7 and 14 after reperfusion, six rats were sacrificed to remove the brain tissues at each time point. The expression of netrin-1 was detected by reverse-transcription PCR, Western blotting and immunohistochemistry. Results Compared with the control group, the expression of netrin-1 in the brain tissues of the model group increased after focal cerebral ischemia, reached the peak at 4 days, and the expression of netrin-1 was significantly higher than that of the control group at each time point. Compared with the model group, the expression of netrin-1 in the ADSC group increased further, reached the peak at 7 days, and the expression of netrin-1 in the ADSC group was significantly higher than that of the model group at each time point. Conclusion ADSC transplantation could up-regulate the expression of netrin-1, and promote axon regeneration and the recovery of neurological functions.

In Vivo Detection of the Effect of Electroacupuncture on “Zusanli” Acupoint in Rats with Adjuvant-Induced Arthritis through Optical Coherence Tomography

PubMed Central

Yang, Hui; Zhou, Yan; Wu, Xiuli; Su, Chengkang; Long, Jia; Lin, Jin

2016-01-01

This study aimed to investigate the effect of electroacupuncture (EA) treatment through optical coherence tomography (OCT) in vivo on rats with adjuvant-induced arthritis. OCT images were obtained from the ankle of the right hind paws of the rats in control, model, and EA groups before modelling and 1 day, 8 days, 15 days, 22 days, and 29 days after modelling. Results demonstrated that the OCT signal of the ankle of the right hind paws of the rats was indistinct compared to 1 day after modelling and before modelling in the EA group. In the EA group, the light averaged attenuation coefficients of the ankle tissues decreased as treatment duration was prolonged after EA was administered (3.43, 2.96, 2.61, 2.42, and 2.29 mm−1, resp.). There was a significant difference in attenuation coefficient decrease between the 29th d and the 1st d for EA group compared with control group (P < 0.01). This condition indicated that the light absorption of the ankle of the treated rats in the EA group decreased. Therefore, OCT can be used to monitor the effect of treatment on rats with arthritis in vivo. PMID:27981046

Sirolimus in kidney transplant donors and clinical and histologic improvement in recipients: rat model.

PubMed

Cicora, F; Lausada, N; Vasquez, D N; Cicora, P; Zalazar, G; Gonzalez, P; Palti, G; Raimondi, C

2010-01-01

Ischemia-reperfusion (I/R) injury is one of the risk factors for delayed graft function, acute rejection episodes, and impaired long-term allograft survival after kidney transplantation. This antigen-independent inflammatory process produces tissue damage. Isogeneic transplantation in a rat model is a useful method for study of nonimmunologic risk factors for kidney damage. To study the effect of sirolimus on I/R injury using only 1 dose of the drug in the donor. Eighteen rats were allocated to 3 groups of 6 rats each: sham group, control group, and rapamycin group. Improved renal function and systemic inflammatory response were observed in the rapamycin group compared with the control group (Deltaurea, Deltacreatinine, and DeltaC3, all P < .01). The number of apoptotic nuclei in the renal medulla in the control group was higher than in the rapamycin group (P < .01). Tubular damage was less severe in the rapamycin group compared with the control group (P < .01). Complement 3 and tumor necrosis factor-alpha expression in the kidney samples were significantly decreased when rapamycin was given to the donor rats (P > .01). Bcl-2 protein was upregulated in the rapamycin group compared with the control group (P < .01). Administration of rapamycin in donors attenuates the I/R injury process after kidney transplantation in a rat model.

[Protection and bidirectional effect of rhubarb anthraquinone and tannins for rats' liver].

PubMed

Qin, Lu-shan; Zhao, Hai-ping; Zhao, Yan-ling; Ma, Zhi-jiel; Zeng, Ling-na; Zhang, Ya-ming; Zhang, Ping; Yan, Dan; Bai, Zhao-fang; Li, Yue; Hao, Qing-xiu; Zhao, Kui-jun; Wang, Jia-bo; Xiao, Xiao-he

2014-06-01

To compare the bidirectional effect of rhubarb total anthraquinone (TA) and total tannins (TT) on rats' liver. One hundred rats were randomly divided into 10 groups, i.e., the blank group, the model group, the blank + high dose TA group, the blank +low dose TA group, the blank + high dose TT group, the blank + low dose TT group, the model + high dose TA group, the model + low dose TA group, the model +high dose TT group, and the model + low dose TT group, 10 in each group. The carbon tetrachloride (CCI4) was used to prepare the acute liver injury rat model. TA and TT of rhubarb (at 5.40 g crude drugs/kg and 14.69 g crude drugs/kg) were intragastrically administrated to rats in all groups except the blank group and the model group, once daily for 6 successive days.The general state of rats, biochemical indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), laminin (LN), hyaluronic acid (HA), transforming growth factor beta1 (TGF-beta1), as well pathological results of rat liver tissues. Finally the protection laws of TA and TT for rats' liver were analyzed using factor analysis. Compared with the blank control group, all biochemical indices increased in the blank group (P < 0.05, P < 0.01). HA also increased in the blank + high dose TA group; AST, ALT, and HA also increased in the blank +high dose TT group (P < 0.05). Compared with the model group, AST, ALT, ALP, HA, and TGF-beta1 significantly decreased in the model + low dose TA group, the model + high dose TA group, the model + low dose TT group (P < 0.05, P < 0.01). Serum AST, ALT, and ALP also decreased in the model + high dose TT group (P < 0.05, P < 0.01). Pathological results showed that mild swollen liver cells in the model + high dose TA group. Fatty degeneration and fragmental necrosis around the central veins occurred in the blank + high dose TA group. The pathological injury was inproved in the model +low dose TA group. Two common factors, liver fibrosis and liver cell injury, were extracted by using factor analysis. TA showed stronger improvement of the two common factors than TT. Rhubarb TA and TT showed protective and harmful effects on rats' liver. At an equivalent dosage, TA had better liver protection than TT. High dose TT played a role in liver injury to some extent.

Automated evaluation of liver fibrosis in thioacetamide, carbon tetrachloride, and bile duct ligation rodent models using second-harmonic generation/two-photon excited fluorescence microscopy.

PubMed

Liu, Feng; Chen, Long; Rao, Hui-Ying; Teng, Xiao; Ren, Ya-Yun; Lu, Yan-Qiang; Zhang, Wei; Wu, Nan; Liu, Fang-Fang; Wei, Lai

2017-01-01

Animal models provide a useful platform for developing and testing new drugs to treat liver fibrosis. Accordingly, we developed a novel automated system to evaluate liver fibrosis in rodent models. This system uses second-harmonic generation (SHG)/two-photon excited fluorescence (TPEF) microscopy to assess a total of four mouse and rat models, using chemical treatment with either thioacetamide (TAA) or carbon tetrachloride (CCl 4 ), and a surgical method, bile duct ligation (BDL). The results obtained by the new technique were compared with that using Ishak fibrosis scores and two currently used quantitative methods for determining liver fibrosis: the collagen proportionate area (CPA) and measurement of hydroxyproline (HYP) content. We show that 11 shared morphological parameters faithfully recapitulate Ishak fibrosis scores in the models, with high area under the receiver operating characteristic (ROC) curve (AUC) performance. The AUC values of 11 shared parameters were greater than that of the CPA (TAA: 0.758-0.922 vs 0.752-0.908; BDL: 0.874-0.989 vs 0.678-0.966) in the TAA mice and BDL rat models and similar to that of the CPA in the TAA rat and CCl 4 mouse models. Similarly, based on the trends in these parameters at different time points, 9, 10, 7, and 2 model-specific parameters were selected for the TAA rats, TAA mice, CCl 4 mice, and BDL rats, respectively. These parameters identified differences among the time points in the four models, with high AUC accuracy, and the corresponding AUC values of these parameters were greater compared with those of the CPA in the TAA rat and mouse models (rats: 0.769-0.894 vs 0.64-0.799; mice: 0.87-0.93 vs 0.739-0.836) and similar to those of the CPA in the CCl 4 mouse and BDL rat models. Similarly, the AUC values of 11 shared parameters and model-specific parameters were greater than those of HYP in the TAA rats, TAA mice, and CCl 4 mouse models and were similar to those of HYP in the BDL rat models. The automated evaluation system, combined with 11 shared parameters and model-specific parameters, could specifically, accurately, and quantitatively stage liver fibrosis in animal models.

Concentration change of DA, DOPAC, Glu and GABA in brain tissues in schizophrenia developmental model rats induced by MK-801.

PubMed

Liu, Yong; Tang, Yamei; Pu, Weidan; Zhang, Xianghui; Zhao, Jingping

2011-08-01

To explore the related neurobiochemical mechanism by comparing the concentration change of dopamine (DA), dihydroxy-phenyl acetic acid (DOPAC), glutamate (Glu), and γ-aminobutyric acid (GABA) in the brain tissues in schizophrenia (SZ) developmental model rats and chronic medication model rats. A total of 60 neonatal male Spragur-Dawley (SD) rats were randomly assigned to 3 groups at the postnatal day 6: an SZ developmental rat model group (subcutaneous injection with MK-801 at the postnatal day 7-10, 0.1 mg/kg, Bid), a chronic medication model group (intraperitoneal injection at the postnatal day 47-60, 0.2 mg/kg,Qd), and a normal control group (injection with 0.9% normal saline during the corresponding periods). DA, DOPAC, Glu, and GABA of the tissue homogenate from the medial prefrontal cortex (mPFC) and hippocampus were examined with Coularray electrochemic detection by high performance liquid chromatogram technique. The utilization rate of DA and Glu was calculated. Compared with the normal control group, the concentration of DA and DOPAC in the mPFC and the hippocampus in the SZ developmental model group significantly decreased (P<0.05), and the GABA concentration and Glu utilization rate in the mPFC also decreased (P<0.05). Compared with the chronic medication model group, the DA concentration of the mPFC in the SZ developmental group decreased (P<0.05), and the DOPAC concentration and the utility rate of DA in the hippocampus also decreased (P<0.01, P<0.05, respectively). The activities of DA, Glu and GABA system decrease in the mPFC and the DA system function reduces in the hippocampus of SZ developmental rats.

Comparative effects of Citrullus colocynthis, sunflower and olive oil-enriched diet in streptozotocin-induced diabetes in rats.

PubMed

Sebbagh, N; Cruciani-Guglielmacci, C; Ouali, F; Berthault, M-F; Rouch, C; Sari, D Chabane; Magnan, C

2009-06-01

Citrullus colocynthis (colocynth) seeds are traditionally used as antidiabetic medication in Mediterranean countries. The present study evaluated the differential effects of diets enriched with C. colocynthis, sunflower or olive oils on the pancreatic beta-cell mass in streptozotocin (STZ)-induced diabetes in rats. STZ injection induced rapid hyperglycaemia in all animals. However, 2 months later, hyperglycaemia was significantly less pronounced in the rats fed a C. colocynthis oil-enriched diet compared with other rat groups (7.9mM versus 12mM and 16mM with colocynth versus olive and sunflower oils, respectively). Assessment of insulin sensitivity using the homoeostasis model assessment (HOMA) method also indicated less insulin resistance in the rats fed a C. colocynthis oil-enriched diet versus the other rats. Finally, 2 months after STZ injection, the pancreatic beta-cell mass was similar in both the STZ-treated rats fed the colocynth oil-enriched diet and their controls fed the same diet. In contrast, the pancreatic beta-cell mass remained lower in the STZ-induced diabetic rats fed with olive oil- and sunflower oil-enriched diets compared with the C. colocynthis group. We conclude that C. colocynthis oil supplementation may have a beneficial effect by partly preserving or restoring pancreatic beta-cell mass in the STZ-induced diabetes rat model.

Effect on intensity of treadmill running on learning, memory and expressions of cell cycle-related proteins in rats with cerebral ischemia.

PubMed

Zhao, Ya-Ning; Li, Jian-Min; Chen, Chang-Xiang; Li, Shu-Xing; Xue, Cheng-Jing

2017-06-20

We discussed the intensity of treadmill running on learning, memory and expression of cell cycle-related proteins in rats with cerebral ischemia. Eighty healthy male SD rats were randomly divided into normal group, model group, intensity I group and intensity II group, with 20 rats in each group. The four-vessel occlusion method of Pulsinelli (4-VO) was used to induce global cerebral ischemia. Brain neuronal morphology was observed by hematoxylin-eosin (HE) staining at 3h, 6h, 24h and 48h after modeling, respectively. Hippocampal expressions of cyclin A and cyclin E were detected by immunohistochemistry. At 48h after modeling, the learning and memory performance of rats was tested by water maze experiment. Compared with the normal group, the other three groups had a significant reduction in surviving neurons, prolonging of escape latency and decreased number of passes over the former position of the platform (P<0.05). The number of surviving neurons and the number of passes over the former position of the platform were obviously lower in the model group than in intensity I group (P<0.05), but significantly higher compared with intensity II group (P<0.05). Escape latency of the model group was obviously prolonged as compared with intensity I group (P<0.05), but much shorter than that of intensity II group (P<0.05). Compared with the normal group, the expressions of cyclin A and cyclin E were significantly upregulated at different time points after modeling (P<0.05). The expression of the model group was higher than that of intensity I group, but lower than that of intensity II group (P<0.05). Moderate intensity of treadmill running can help protect brain neurons and improve learning and memory performance of rats with global cerebral ischemia. But high intensity of treadmill running has a negative impact, possibly through the regulation of cell cycle-related proteins in ischemia/reperfusion injury.

Kainic Acid-Induced Post-Status Epilepticus Models of Temporal Lobe Epilepsy with Diverging Seizure Phenotype and Neuropathology

PubMed Central

Bertoglio, Daniele; Amhaoul, Halima; Van Eetveldt, Annemie; Houbrechts, Ruben; Van De Vijver, Sebastiaan; Ali, Idrish; Dedeurwaerdere, Stefanie

2017-01-01

The aim of epilepsy models is to investigate disease ontogenesis and therapeutic interventions in a consistent and prospective manner. The kainic acid-induced status epilepticus (KASE) rat model is a widely used, well-validated model for temporal lobe epilepsy (TLE). As we noted significant variability within the model between labs potentially related to the rat strain used, we aimed to describe two variants of this model with diverging seizure phenotype and neuropathology. In addition, we evaluated two different protocols to induce status epilepticus (SE). Wistar Han (Charles River, France) and Sprague-Dawley (Harlan, The Netherlands) rats were subjected to KASE using the Hellier kainic acid (KA) and a modified injection scheme. Duration of SE and latent phase were characterized by video-electroencephalography (vEEG) in a subgroup of animals, while animals were sacrificed 1 week (subacute phase) and 12 weeks (chronic phase) post-SE. In the 12 weeks post-SE groups, seizures were monitored with vEEG. Neuronal loss (neuronal nuclei), microglial activation (OX-42 and translocator protein), and neurodegeneration (Fluorojade C) were assessed. First, the Hellier protocol caused very high mortality in WH/CR rats compared to SD/H animals. The modified protocol resulted in a similar SE severity for WH/CR and SD/H rats, but effectively improved survival rates. The latent phase was significantly shorter (p < 0.0001) in SD/H (median 8.3 days) animals compared to WH/CR (median 15.4 days). During the chronic phase, SD/H rats had more seizures/day compared to WH/CR animals (p < 0.01). However, neuronal degeneration and cell loss were overall more extensive in WH/CR than in SD/H rats; microglia activation was similar between the two strains 1 week post-SE, but higher in WH/CR rats 12 weeks post-SE. These neuropathological differences may be more related to the distinct neurotoxic effects of KA in the two rat strains than being the outcome of seizure burden itself. The divergences in disease progression and seizure outcome, in addition to the histopathological dissimilarities, further substantiate the existence of strain differences for the KASE rat model of TLE. PMID:29163349

Intermittent Fasting Pretreatment Prevents Cognitive Impairment in a Rat Model of Chronic Cerebral Hypoperfusion.

PubMed

Hu, Yuan; Yang, Ying; Zhang, Miao; Deng, Min; Zhang, Jun-Jian

2017-07-01

Background: Whether intermittent fasting (IF) pretreatment can prevent vascular cognitive dysfunction remains unknown to our knowledge. Objective: We investigated the effects and underlying mechanisms of IF pretreatment on cognitive dysfunction in a permanent 2-vessel occlusion (2VO) vascular dementia rat model. Methods: Male Wistar rats weighing 200 g were subjected to either IF or ad libitum feeding for 12 wk before 2VO surgery. Rats in the IF protocol underwent alternative-day feed deprivation (FD). Memory of the animals was assessed by using the Morris water maze (MWM) and the novel object recognition (NOR) test 6 wk after the surgery. After behavioral testing, malondialdehyde and glutathione concentrations, superoxide dismutase (SOD) activity, gene expression of antioxidative enzymes, inflammatory protein concentrations, and microglia density were determined in the hippocampus of rats. Results: 2-vessel occlusion operation ad libitum (2VO-AL) rats had significantly longer escape latencies on day 4 of the training phase and spent a lower percentage of time in the target quadrant (25% compared with 38% and 41%) in the MWM, and had lower discrimination ratios (47% compared with 65% and 67%) in the NOR test than 2-vessel operation and alternate-day feed deprivation (2VO-FD) and sham operation ad libitum (Sham-AL) rats, respectively ( P < 0.05). This indicates that IF helps to prevent vascular cognitive deficits. 2VO-AL rats also had higher malondialdehyde (3.54 compared with 2.15 and 1.66 nmol/mg protein) and lower glutathione concentrations (53.25 compared with 66.41 and 91.71 nmol/mg protein), lower SOD activity (100.1 compared with 133.3 and 138.5 U/mg protein), lower gene expression of antioxidative enzymes, higher expression of inflammatory proteins, and higher microglia density in the hippocampus than 2VO-FD and Sham-AL rats, respectively ( P < 0.05). This suggests that IF has antioxidative and anti-inflammatory effects. Conclusions: IF pretreatment provided sustained neuroprotection in a rat model of vascular dementia. These effects were associated with reduced oxidative stress and neuroinflammation. © 2017 American Society for Nutrition.

[The expression and significance of chemokines eotaxin and RANTES in the rat model of allergic rhinitis].

PubMed

Tian, Cuiling; Lei, Xiaoping; Shui, Minhong; Zhang, Yanhong; Jia, Qianwei; Tu, Jing; Lian, Gang; Tang, Siquan

2014-07-01

To explore the expression and significance of Eotaxin and RANTES in the rat model of allergic rhinitis (AR). 20 female SD rats in 6-7 weeks were randomly divided into control group and AR group (n = 10, respectively). AR rat model was made with ovalbumin stimulation. To detect pathological changes in mucosa and chemokine Eotaxin, RANTES in their nasal and lung tissues after execution. Compared with the control group, Lung EOS cell counted higher in AR group and the difference was significant (P < 0.01); the AR rats nasal mucosa and lung tissue of Eotaxin, RANTES expression was significantly increased (P < 0.01). There exist high expression of Eotaxin, RANTES, infiltration of eosinophils in nasal and lung tissue of model rats with allergic rhinitis, inferring that the upper and lower respiratory tract inflammatory response has obvious consistency.

Comparative Computational Modeling of Airflows and Vapor Dosimetry in the Respiratory Tracts of Rat, Monkey, and Human

PubMed Central

Corley, Richard A.

2012-01-01

Computational fluid dynamics (CFD) models are useful for predicting site-specific dosimetry of airborne materials in the respiratory tract and elucidating the importance of species differences in anatomy, physiology, and breathing patterns. We improved the imaging and model development methods to the point where CFD models for the rat, monkey, and human now encompass airways from the nose or mouth to the lung. A total of 1272, 2172, and 135 pulmonary airways representing 17±7, 19±9, or 9±2 airway generations were included in the rat, monkey and human models, respectively. A CFD/physiologically based pharmacokinetic model previously developed for acrolein was adapted for these anatomically correct extended airway models. Model parameters were obtained from the literature or measured directly. Airflow and acrolein uptake patterns were determined under steady-state inhalation conditions to provide direct comparisons with prior data and nasal-only simulations. Results confirmed that regional uptake was sensitive to airway geometry, airflow rates, acrolein concentrations, air:tissue partition coefficients, tissue thickness, and the maximum rate of metabolism. Nasal extraction efficiencies were predicted to be greatest in the rat, followed by the monkey, and then the human. For both nasal and oral breathing modes in humans, higher uptake rates were predicted for lower tracheobronchial tissues than either the rat or monkey. These extended airway models provide a unique foundation for comparing material transport and site-specific tissue uptake across a significantly greater range of conducting airways in the rat, monkey, and human than prior CFD models. PMID:22584687

Pulmonary Transcriptional Response to Ozone in Healthy and Cardiovascular Compromised Rat Models

EPA Science Inventory

The genetic cardiovascular disease (CVD) and associated metabolic impairments can influence the lung injury from inhaled pollutants. We hypothesized that comparative assessment of global pulmonary expression profile of healthy and CVD-prone rat models will provide mechanistic ins...

The Therapeutic Effect of Zuogui Wan in Gestational Diabetes Mellitus Rats

PubMed Central

Feng, Qianjin; Niu, Xin; Liu, Xinshe; Xu, Kaixia; Yang, Xiangzhu; Wang, Huifeng

2014-01-01

In this experiment, we established an animal model of gestational diabetes mellitus rats using streptozotocin. Using the rat model of GDM, the pregnant rats in 1-19d were divided into three groups: (1) Zuogui Wan gestational diabetes mellitus group (group I, n = 12), (2) gestational diabetes mellitus rats as the control group (group II, n = 11), and (3) rats of normal pregnancy group (group III, n = 11). Compared with gestational diabetes mellitus rats as the control group, Zuogui Wan can change the indexes of fasting blood glucose, body weight, total cholesterol, insulin, and metabolism cage index significantly in Zuogui Wan gestational diabetes mellitus group. We can conclude that Zuogui Wan has the therapeutic effect on gestational diabetes mellitus. PMID:25136475

Metabolic fingerprinting of joint tissue of collagen-induced arthritis (CIA) rat: In vitro, high resolution NMR (nuclear magnetic resonance) spectroscopy based analysis

PubMed Central

Srivastava, Niraj Kumar; Sharma, Shikha; Sharma, Rajkumar; Sinha, Neeraj; Mandal, Sudhir Kumar; Sharma, Deepak

2018-01-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease whose major characteristics persistent joint inflammation that results in joint destruction and failure of the function. Collagen-induced arthritis (CIA) rat is an autoimmune disease model and in many ways shares features with RA. The CIA is associated with systemic manifestations, including alterations in the metabolism. Nuclear magnetic resonance (NMR) spectroscopy-based metabolomics has been successfully applied to the perchloric acid extract of the joint tissue of CIA rat and control rat for the analysis of aqueous metabolites. GPC (Glycerophosphocholine), carnitine, acetate, and creatinine were important discriminators of CIA rats as compared to control rats. Level of lactate (significance; p = 0.004), alanine (p = 0.025), BCA (Branched-chain amino acids) (p = 0.006) and creatinine (p = 0.023) was significantly higher in CIA rats as compared to control rats. Choline (p = 0.038) and GPC (p = 0.009) were significantly reduced in CIA rats as compared to control rats. Choline to GPC correlation was good and negative (Pearson correlation = -0.63) for CIA rats as well as for control rats (Pearson correlation = -0.79). All these analyses collectively considered as metabolic fingerprinting of the joint tissue of CIA rat as compared to control rat. The metabolic fingerprinting of joint tissue of CIA rats was different as compared to control rats. The metabolic fingerprinting reflects inflammatory disease activity in CIA rats with synovitis, demonstrating that underlying inflammatory process drives significant changes in metabolism that can be measured in the joint tissue. Therefore, the outcome of this study may be helpful for understanding the mechanism of metabolic processes in RA. This may be also helpful for the development of advanced diagnostic methods and therapy for RA. PMID:29743863

Metabolic fingerprinting of joint tissue of collagen-induced arthritis (CIA) rat: In vitro, high resolution NMR (nuclear magnetic resonance) spectroscopy based analysis.

PubMed

Srivastava, Niraj Kumar; Sharma, Shikha; Sharma, Rajkumar; Sinha, Neeraj; Mandal, Sudhir Kumar; Sharma, Deepak

2018-01-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease whose major characteristics persistent joint inflammation that results in joint destruction and failure of the function. Collagen-induced arthritis (CIA) rat is an autoimmune disease model and in many ways shares features with RA. The CIA is associated with systemic manifestations, including alterations in the metabolism. Nuclear magnetic resonance (NMR) spectroscopy-based metabolomics has been successfully applied to the perchloric acid extract of the joint tissue of CIA rat and control rat for the analysis of aqueous metabolites. GPC (Glycerophosphocholine), carnitine, acetate, and creatinine were important discriminators of CIA rats as compared to control rats. Level of lactate (significance; p = 0.004), alanine (p = 0.025), BCA (Branched-chain amino acids) (p = 0.006) and creatinine (p = 0.023) was significantly higher in CIA rats as compared to control rats. Choline (p = 0.038) and GPC (p = 0.009) were significantly reduced in CIA rats as compared to control rats. Choline to GPC correlation was good and negative (Pearson correlation = -0.63) for CIA rats as well as for control rats (Pearson correlation = -0.79). All these analyses collectively considered as metabolic fingerprinting of the joint tissue of CIA rat as compared to control rat. The metabolic fingerprinting of joint tissue of CIA rats was different as compared to control rats. The metabolic fingerprinting reflects inflammatory disease activity in CIA rats with synovitis, demonstrating that underlying inflammatory process drives significant changes in metabolism that can be measured in the joint tissue. Therefore, the outcome of this study may be helpful for understanding the mechanism of metabolic processes in RA. This may be also helpful for the development of advanced diagnostic methods and therapy for RA.

Morphine sensitization as a model of mania: comparative study of the effects of repeated lithium or carbamazepine administration.

PubMed

Grappi, Silvia; Marchese, Giovanna; Secci, Maria Elena; De Montis, Maria Graziella; Gambarana, Carla; Scheggi, Simona

2011-10-01

Repeated unavoidable stress induces in rats decreased reactivity to avoidable stressors and an anhedonia-like condition that are reverted by long-term antidepressant treatments and regarded as models of core symptoms of depression. Morphine-sensitized rats present resilience to stress-induced behavioral deficits and, if hyporeactivity to stress models a depressive symptom, stress resistance can be regarded as a manic symptom. This hypothesis is supported by the observation that long-term lithium administration reinstates sensitivity to stress in sensitized rats. The first aim of the study was to examine the effects of carbamazepine, a standard antimanic treatment, on the stress resilience of sensitized rats, to further characterize morphine sensitization as a model of manic symptom. Carbamazepine administration abolished stress resilience but did not interfere with the expression of sensitization. The second aim of the study was to assess whether repeated carbamazepine treatment affected the dopaminergic and behavioral responses to a natural reward, a palatable food (vanilla sugar, VS), in non food-deprived sensitized and control rats and compare these possible effects with those of repeated lithium administration. Control and sensitized rats showed increased extraneuronal dopamine levels in the nucleus accumbens shell after VS consumption and competence to acquire an instrumental VS-sustained appetitive behavior (VAB). Repeated carbamazepine treatment abolished the dopaminergic response to VS consumption and disrupted the competence to acquire VAB in control rats. Lithium-treated rats showed a dopaminergic response to VS and easily acquired the appetitive behavior. In sensitized rats, neither carbamazepine nor lithium administration interfered with the dopaminergic response to VS and the acquisition of VAB. In summary, the effect of carbamazepine on the stress resilience of sensitized rats further supported the hypothesis that morphine sensitization might model some symptoms of mania. Moreover, in control rats carbamazepine treatment elicited an anhedonia-like condition that clearly distinguished the effects of this drug from those of lithium. Copyright © 2011 Elsevier Inc. All rights reserved.

Deficient prepulse inhibition of acoustic startle in Hooded-Wistar rats compared with Sprague-Dawley rats.

PubMed

van den Buuse, Maarten

2003-04-01

1. Prepulse inhibition of acoustic startle has been suggested as a model of sensorimotor gating and central sensory information processing. Prepulse inhibition is impaired in patients with schizophrenia and responses can be restored by antipsychotic drug treatment. In the present study, startle and prepulse inhibition of startle were compared in different rat strains. 2. Sprague-Dawley rats showed robust inhibition of startle responses by increasing intensities of prepulse delivered just before the startle stimulus. In contrast, at both 4 and 10 weeks of age, rats of the Hooded-Wistar line had markedly reduced prepulse inhibition, although startle responses were not different. 3. Treatment with the dopamine receptor agonist apomorphine (0.1 mg/kg) or the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 (0.1 mg/kg) caused disruption of prepulse inhibition in Sprague-Dawley rats. In Hooded-Wistar rats, apomorphine further reduced the already low level of prepulse inhibition, but MK-801 treatment had no significant effect. This suggests that the impaired prepulse inhibition in Hooded-Wistar rats could be caused by changes in glutamatergic activity and/or NMDA receptors in these rats. 4. In photocell cages, spontaneous exploratory activity and inner zone activity were significantly lower in Hooded-Wistar rats than in Sprague-Dawley rats. Similarly, on the elevated plus-maze, Hooded-Wistar rats showed a lower propensity to visit the open arms. In contrast, amphetamine (0.5 mg/kg)-induced locomotor hyperactivity, an animal model of psychosis, was enhanced in Hooded-Wistar rats. 5. These data suggest that the Hooded-Wistar line could be a useful genetic animal model to study the interaction of glutamatergic and dopaminergic mechanisms in anxiety and schizophrenia.

Inositol-requiring enzyme 1-mediated endoplasmic reticulum stress triggers apoptosis and fibrosis formation in liver cirrhosis rat models.

PubMed

Jiang, Tianpeng; Wang, Lizhou; Li, Xing; Song, Jie; Wu, Xiaoping; Zhou, Shi

2015-04-01

Long‑term and advanced cirrhosis is usually irreversible and often coincides with variceal hemorrhage or development of hepatocellular carcinoma; therefore, liver cirrhosis is a major cause of morbidity and mortality globally. The aim of the present study was to investigate the specific mechanism behind the formation of fibrosis or cirrhosis using rat models of hepatic fibrosis. The cirrhosis model was established by intraperitoneally administering dimethylnitrosamine to the rats. Hematoxylin and eosin staining was performed on the hepatic tissues of the rats to observe the fibrosis or cirrhosis, and western blot analysis was employed to detect α‑smooth muscle actin and desmin protein expression. Flow cytometric analysis was used to examine early and late apoptosis, and the protein and mRNA expression of endoplasmic reticulum (ER) stress-associated unfolded protein response (UPR) pathway proteins and apoptotic proteins [C/EBP homologous protein (CHOP) and caspase‑12] was detected by western blotting and the reverse-transcription polymerase chain reaction, respectively. The results indicated that the cirrhosis model was established successfully and that fibrosis was significantly increased in the cirrhosis model group compared with that in the normal control group. Flow cytometric analysis showed that early and late apoptosis in the cirrhosis model was significantly higher compared with that in the control group. The expression of the UPR pathway protein inositol-requiring enzyme (IRE) 1, as well as the expression of CHOP, was increased significantly in the cirrhotic rat tissues compared with that in the control group tissues (P<0.05). In conclusion, apoptosis was clearly observed in the hepatic tissue of cirrhotic rats, and the apoptosis was caused by activation of the ER stress-mediated IRE1 and CHOP.

[Influence of bear bile on rat hepatocarcinoma induced by diethylnitrosamine].

PubMed

Zhou, Jian-Yin; Yin, Zhen-Yu; Wang, Sheng-Yu; Yan, Jiang-Hua; Zhao, Yi-Lin; Wu, Duan; Liu, Zheng-Jin; Zhang, Sheng; Wang, Xiao-Min

2012-11-01

To investigate the influence of bear bile on rat hepatocarcinoma induced by diethylnitrosamine (DEN), a total of 40 rats were randomly divided into 4 groups: normal control group, model group, and two bear bile treatment groups. The rat liver cancer model was induced by breeding with water containing 100 mg x L(-1) DEN for 14 weeks. The rats of the bear bile groups received bear bile powder (200 or 400 mg x kg(-1)) orally 5 times per week for 18 weeks. The general condition and the body weight of rats were examined every day. After 18 weeks the activities of serum alanine transaminase (ALT), aspartate transaminase (AST) and total bilirubin (TBIL) were detected. Meanwhile, the pathological changes of liver tissues were observed after H&E staining. The expression of proliferative cell nuclear antigen (PCNA) and a-smooth muscle actin (alpha-SMA) in liver tissue were detected by immunohistochemical method. After 4 weeks the body weights of rats in normal group were significantly more than that in other groups (P < 0.05); and that in the two bile groups was significantly more than that in the model group. Compared with normal group, the level of serum glutamic-pyruvic transaminase and total bilirubin increased significantly in other groups; compared with model group, these two indexes decreased significantly in two bile groups. Hepatocellular carcinoma occurred in all rats except for normal group; there were classic cirrhosis and cancer in model group while there were mild cirrhosis and high differentiation in two bile groups. There were almost no expressions of PCNA and alpha-SMA in normal group while there were high expressions in model group; the two bile groups had some expressions but were inferior to the model group, and alpha-SMA reduced markedly. It indicated that bear bile restrained the development of liver cancer during DEN inducing rat hepatocarcinoma, which may be related to its depressing hepatic stellate cell activation and relieving hepatic lesion and cirrhosis.

Clopidogrel (Plavix) reduces the rate of thrombosis in the rat tuck model for microvenous anastomosis.

PubMed

Moore, Michael G; Deschler, Daniel G

2007-04-01

To evaluate the effect of clopidogrel on the rate of thrombosis in a rat model for venous microvascular failure. Forty rats were treated with clopidogrel or saline control via gastric gavage in a randomized, blinded fashion. After allowing for absorption and activation, each femoral vein was isolated and a venous "tuck" procedure was performed. The bleeding time and vessel patency were subsequently evaluated. The rate of vessel thrombosis was decreased in the clopidogrel-treated group compared to controls (7.9% vs 31.4%, P < 0.025). The bleeding time was longer in the clopidogrel-treated group compared to controls (250 +/- 100 seconds vs 173 +/- 59 seconds, P < 0.015). Clopidogrel decreased the rate of thrombosis in the rat model for venous microvascular failure. The use of clopidogrel may reduce the rate of venous thrombosis after free tissue transfer and may be indicated in select patients.

Negative learning bias is associated with risk aversion in a genetic animal model of depression.

PubMed

Shabel, Steven J; Murphy, Ryan T; Malinow, Roberto

2014-01-01

The lateral habenula (LHb) is activated by aversive stimuli and the omission of reward, inhibited by rewarding stimuli and is hyperactive in helpless rats-an animal model of depression. Here we test the hypothesis that congenital learned helpless (cLH) rats are more sensitive to decreases in reward size and/or less sensitive to increases in reward than wild-type (WT) control rats. Consistent with the hypothesis, we found that cLH rats were slower to switch preference between two responses after a small upshift in reward size on one of the responses but faster to switch their preference after a small downshift in reward size. cLH rats were also more risk-averse than WT rats-they chose a response delivering a constant amount of reward ("safe" response) more often than a response delivering a variable amount of reward ("risky" response) compared to WT rats. Interestingly, the level of bias toward negative events was associated with the rat's level of risk aversion when compared across individual rats. cLH rats also showed impaired appetitive Pavlovian conditioning but more accurate responding in a two-choice sensory discrimination task. These results are consistent with a negative learning bias and risk aversion in cLH rats, suggesting abnormal processing of rewarding and aversive events in the LHb of cLH rats.

Effects of Carnosine (Beta-Alanyl-L-Histidine) in an Experimental Rat Model of Acute Kidney Injury Due to Septic Shock

PubMed Central

Sahin, Sabiha; Donmez, Dilek Burukoglu

2018-01-01

Background Acute kidney injury (AKI) secondary to sepsis is a major cause of morbidity and mortality in the human intensive care unit (ICU). Kidney function and the histological findings of AKI were investigated in an experimental rat model with sepsis induced by cecal ligation and puncture (CLP) and compared with and without treatment with carnosine (beta-alanyl-L-histidine). Material/Methods Twenty-four Sprague-Dawley rats were randomly divided into three groups consisting eight rats in each: Group 1 – control; Group 2 – septic shock; and Group 3 – septic shock treated with carnosine. Femoral vein and artery catheterization were applied in all rats. Rats in Group 1 underwent laparotomy and catheterization. The other two groups with septic shock underwent laparotomy, CLP, catheterization, and bladder cannulation. Rats in Group 3 received an intraperitoneal (IP) injection of 250 mg/kg carnosine, 60 min following CLP. Rats were monitored for blood pressure, pulse rate, and body temperature to assess responses to postoperative sepsis, and 10 mL/kg saline replacement was administered. Twenty-four hours following CLP, rats were sacrificed, and blood and renal tissue samples were collected. Results Statistically significant improvements were observed in kidney function, tissue and serum malondialdehyde levels, routine blood values, biochemical indices, and in histopathological findings in rats in Group 3 who were treated with carnosine, compared with Group 2 exposed to septic shock without carnosine treatment. Conclusions Carnosine (beta-alanyl-L-histidine) has been shown to have beneficial effects in reducing AKI due to septic shock in a rat model of septicemia. PMID:29334583

Transcriptome profiling of visceral adipose tissue in a novel obese rat model, WNIN/Ob & its comparison with other animal models.

PubMed

Sakamuri, Siva Sankara Vara Prasad; Putcha, Uday Kumar; Veettil, Giridharan Nappan; Ayyalasomayajula, Vajreswari

2016-09-01

Adipose tissue dysfunction in obesity is linked to the development of type 2 diabetes and cardiovascular diseases. We studied the differential gene expression in retroperitoneal adipose tissue of a novel obese rat model, WNIN/Ob, to understand the possible underlying transcriptional changes involved in the development of obesity and associatedcomorbidities in this model. Four month old, male WNIN/Ob lean and obese rats were taken, blood was collected and tissues were dissected. Body composition analysis and adipose tissue histology were performed. Global gene expression in retroperitoneal adipose tissue of lean and obese rats was studied by microarray using Affymetrix GeneChips. One thousand and seventeen probe sets were downregulated and 963 probe sets were upregulated (more than two-fold) in adipose tissue of WNIN/Ob obese rats when compared to that of lean rats. Small nucleolar RNA (SnoRNA) made most of the underexpressed probe sets, whereas immune system-related genes werethe most overexpressed in the adipose tissues of obese rats. Genes coding for cytoskeletal proteinswere downregulated, whereas genes related to lipid biosynthesis were elevated in the adipose tissue of obese rats. Majority of the altered genes and pathways in adipose tissue of WNIN/Ob obese rats were similar to the observations in other obese animal models and human obesity. Based on these observations, it is proposed that WNIN/Ob obese rat model may be a good model to study the mechanisms involved in the development of obesity and its comorbidities. Downregulation of SnoRNA appears to be a novel feature in this obese rat model.

Effect of Qingnao tablet on blood viscosity of rat model of blood stasis induced by epinephrine

NASA Astrophysics Data System (ADS)

Xie, Guoqi; Hao, Shaojun; Ma, Zhenzhen; Liu, Xiaobin; Li, Jun; Li, Wenjun; Zhang, Zhengchen

2018-04-01

To establish a rat model of blood stasis with adrenaline (Adr) subcutaneous injection and ice bath stimulation. The effects of different doses on the blood viscosity of blood stasis model rats were observed. The rats were randomly divided into 6 groups: blank control group (no model), model group, positive control group, high, middle and low dose group. The whole blood viscosity and plasma viscosity were detected by blood viscosity instrument. Compared with the blank group, model group, high shear, low shear whole blood viscosity and plasma viscosity were significantly increased, TT PT significantly shortened, APTT was significantly prolonged, FIB increased significantly, indicating that the model was successful. Compared with the model group, can significantly reduce the Naoluotong group (cut, low cut). Qingnaopian high dose group (low cut), middle dose group (cut, low shear blood viscosity) (P<0.01), Can significantly reduce Naoluotong qingnaopian group, high dose group (P<0.01), plasma viscosity decreased qingnaopian plasma viscosity in low dose group (P<0.05). Conclusion: qingnaopian could improve the blood rheology of blood stasis mice abnormal index, decrease the blood viscosity, blood stasis has certain hemostatic effect.

Establishment of a rat and guinea pig aortic interposition graft model reveals model-specific patterns of intimal hyperplasia.

PubMed

Gregory, Elaine K; Vercammen, Janet M; Flynn, Megan E; Kibbe, Melina R

2016-12-01

Although the aortic interposition bypass model has been widely used to evaluate biomaterials for bypass grafting, there is no comprehensive description of the procedure or of the distribution of intimal hyperplasia that results. The objectives of this study were to (1) review and summarize approaches of aortic interposition grafting in animal models, (2) determine the pertinent anatomy for this procedure, (3) validate this model in the rat and guinea pig, and (4) compare the distribution of intimal hyperplasia that develops in each species. A literature search was performed in PubMed from 1980 to the present to analyze the use of anesthesia, anticoagulation, antiplatelet agents, graft material, suture, and anastomotic techniques. Using 10-week-old male Sprague-Dawley rats and Hartley guinea pigs, we established pertinent aortic anatomy, developed comparable models, and assessed complications for each model. At 30 days, the graft and associated aorta were explanted, intimal formation was assessed morphometrically, and cellularity was assessed via nuclear counting. We reviewed 30 articles and summarized the pertinent procedural findings. Upon establishing both animal models, key anatomic differences between the species that affect this model were noted. Guinea pigs have a much larger cecum, increased retroperitoneal fat, and lack the iliolumbar vessels compared with the rat. Surgical outcomes for the rat model included a 53% technical success rate and a 32% technical error rate. Surgical outcomes for the guinea pig model included a 69% technical success rate and a 31% technical error rate. These two species demonstrated unique distribution of intimal hyperplasia at 30 days. Intimal hyperplasia in the rat model was greatest at two areas, the proximal graft (5400 μm 2 ; P < .001) and distal graft (2800 μm 2 ; P < .04), whereas the guinea pig model developed similar intimal hyperplasia throughout the graft (4500-5100 μm 2 ; P < .01). In this report, we summarize the literature on the aortic interposition graft model, present a detailed description of the anatomy and aortic interposition graft procedure in the rat and guinea pig, and describe a unique distribution of intimal formation that results in both species. This information will be helpful when designing studies to evaluate novel graft materials in the future. Published by Elsevier Inc.

Structure-Activity Relationship Models for Rat Carcinogenesis and Assessing the Role Mutagens Play in Model Predictivity

PubMed Central

Carrasquer, C. Alex; Batey, Kaylind; Qamar, Shahid; Cunningham, Albert R.; Cunningham, Suzanne L.

2016-01-01

We previously demonstrated that fragment based cat-SAR carcinogenesis models consisting solely of mutagenic or non-mutagenic carcinogens varied greatly in terms of their predictive accuracy. This led us to investigate how well the rat cancer cat-SAR model predicted mutagens and non-mutagens in their learning set. Four rat cancer cat-SAR models were developed: Complete Rat, Transgender Rat, Male Rat, and Female Rat, with leave-one-out (LOO) validation concordance values of 69%, 74%, 67%, and 73%, respectively. The mutagenic carcinogens produced concordance values in the range of 69–76% as compared to only 47–53% for non-mutagenic carcinogens. As a surrogate for mutagenicity comparisons between single site and multiple site carcinogen SAR models was analyzed. The LOO concordance values for models consisting of 1-site, 2-site, and 4+-site carcinogens were 66%, 71%, and 79%, respectively. As expected, the proportion of mutagens to non-mutagens also increased, rising from 54% for 1-site to 80% for 4+-site carcinogens. This study demonstrates that mutagenic chemicals, in both SAR learning sets and test sets, are influential in assessing model accuracy. This suggests that SAR models for carcinogens may require a two-step process in which mutagenicity is first determined before carcinogenicity can be accurately predicted. PMID:24697549

Evaluation of an experimental rat model for comparative studies of bleaching agents.

PubMed

Cintra, Luciano Tavares Angelo; Benetti, Francine; Ferreira, Luciana Louzada; Rahal, Vanessa; Ervolino, Edilson; Jacinto, Rogério de Castilho; Gomes Filho, João Eduardo; Briso, André Luiz Fraga

2016-04-01

Dental materials in general are tested in different animal models prior to the clinical use in humans, except for bleaching agents. Objectives To evaluate an experimental rat model for comparative studies of bleaching agents, by investigating the influence of different concentrations and application times of H2O2 gel in the pulp tissue during in-office bleaching of rats' vital teeth. Material and Methods The right and left maxillary molars of 50 Wistar rats were bleached with 20% and 35% H2O2 gels, respectively, for 5, 10, 15, 30, or 45 min (n=10 rats/group). Ten animals were untreated (control). The rats were killed after 2 or 30 days, and the maxillae were examined by light microscopy. Inflammation was evaluated through histomorphometric analysis with inflammatory cell count in the coronal and radicular thirds of the pulp. Fibroblasts were also counted. Scores were attributed to odontoblastic layer and vascular changes. Tertiary dentin area and pulp chamber central area were measured histomorphometrically. Data were compared by analysis of variance and Kruskal-Wallis test (p<0.05). Results After 2 days, the amount of inflammatory cells increased in the coronal pulp occlusal third up to the 15-min application groups of each bleaching gel. In the groups exposed to each concentration for 30 and 45 min, the number of inflammatory cells decreased along with the appearance of necrotic areas. After 30 days, reduction on the pulp chamber central area and enlargement of the tertiary dentin area were observed, without the detection of inflammation areas. Conclusion The rat model of extracoronal bleaching showed to be adequate for studies of bleaching protocols, as it was possible to observe alterations in the pulp tissues and tooth structure caused by different concentrations and application periods of bleaching agents.

Visceral hypersensitive rats share common dysbiosis features with irritable bowel syndrome patients.

PubMed

Zhou, Xiao-Yan; Li, Ming; Li, Xia; Long, Xin; Zuo, Xiu-Li; Hou, Xiao-Hua; Cong, Ying-Zi; Li, Yan-Qing

2016-06-14

To evaluate gut microbial dysbiosis in two visceral hypersensitive models in comparison with irritable bowel syndrome (IBS) patients and to explore the extent to which these models capture the dysbiosis of IBS patients. Visceral hypersensitivity was developed using the maternal separation (MS) rat model and post-inflammatory rat model. The visceral sensitivity of the model groups and control group was evaluated using the abdominal withdraw reflex score and electromyography in response to graded colorectal distention. The 16S ribosomal RNA gene from fecal samples was pyrosequenced and analyzed. The correlation between dysbiosis in the microbiota and visceral hypersensitivity was calculated. Positive findings were compared to sequencing data from a published human IBS cohort. Dysbiosis triggered by neonatal maternal separation was lasting but not static. Both MS and post-inflammatory rat fecal microbiota deviated from that of the control rats to an extent that was larger than the co-housing effect. Two short chain fatty acid producing genera, Fusobacterium and Clostridium XI, were shared by the human IBS cohort and by the maternal separation rats and post-inflammatory rats, respectively, to different extents. Fusobacterium was significantly increased in the MS group, and its abundance positively correlated with the degree of visceral hypersensitivity. Porphyromonadaceae was a protective biomarker for both the rat control group and healthy human controls. The dysbiosis MS rat model and the post-inflammatory rat model captured some of the dysbiosis features of IBS patients. Fusobacterium, Clostridium XI and Porphyromonadaceae were identified as targets for future mechanistic research.

Antihyperalgesic Activity of Rhodiola rosea in a Diabetic Rat Model.

PubMed

Déciga-Campos, Myrna; González-Trujano, Maria Eva; Ventura-Martínez, Rosa; Montiel-Ruiz, Rosa Mariana; Ángeles-López, Guadalupe Esther; Brindis, Fernando

2016-02-01

Preclinical Research Rhodiola rosea L. (Crassulaceae) is used for enhancing physical and mental performance. Recent studies demonstrated that R. rosea had anti-inflammatory activity in animal models, for example, carrageenan- and nystatin-induced edema in rats, possibly by inhibiting phospholipase A2 and cyclooxygenases-1 and -2. In addition, R. rosea had antinociceptive activity in thermal and chemical pain tests as well as mechanical hyperalgesia. The purpose of the present study was to assess the antihyperalgesic effect of an ethanol extract of Rhodiola rosea (R. rosea) in a diabetic rat model. Rats were administered a single dose of streptozotocin (STZ; 50 mg/kg, i.p.) and hyperalgesia was evaluated four weeks later. Formalin-evoked (0.5%) flinching was increased in diabetic rats compared with nondiabetic controls Systemic (1-100 mg/kg, i.p.) and local (0.1-10 mg/paw into the dorsal surface of the right hind paw) administration of R. rosea ethanol extract dose-dependently reduced formalin-induced hyperalgesia in diabetic rats. The antihyperalgesic effect of R. rosea was compared with gabapentin. These results suggest that R. rosea ethanol extract may have potential as a treatment for diabetic hyperalgesia. © 2016 Wiley Periodicals, Inc.

[Effects of Anluohuaxianwan on transforming growth factor-β1 and related signaling pathways in rats with carbon tetrachloride-induced liver fibrosis].

PubMed

Lu, W; Gao, Y H; Wang, Z Z; Cai, Y S; Yang, Y Q; Miao, Y Q; Pei, F; Liu, X E; Zhuang, H

2017-04-20

Objective: The traditional Chinese medicine Anluohuaxianwan (ALHXW) has been used to treat liver fibrosis induced by chronic hepatitis B virus (HBV) infection. However, the anti-fibrosis mechanisms of ALHXW remain to be investigated. This study used a rat model of carbon tetrachloride (CCl(4))-induced liver fibrosis to explore the potential antifibrogenic mechanisms of ALHXW. Methods: Twenty-seven male Wistar rats were randomly assigned to control group, model group, and treatment group ( n = 9 per group). Rats in the model and treatment group were injected intraperitoneally with 40% CCl(4)(2 ml/kg), and rats in the control group were administered saline twice a week for 6 weeks. Starting at week 4 following model construction, rats in the treatment group received daily gavages with ALHXW solution (concentration 0.15 g/ml) daily, while rats in the control and model groups were given saline for a total of 6 weeks. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured from blood samples collected at the end of weeks 3, 6 and 9. Histopathological examination of liver tissue was performed to evaluate liver fibrosis at week 9. At the same time, the mRNA expression of TGF-β1 and Smads in liver tissues was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR), and TGF-β1 protein level in the liver was measured by Western blot. Inter-group comparison was performed using analysis of variance (ANOVA) when the continuous data were normally distributed and satisfied the homogeneity of variance; otherwise, nonparametric tests were used. Categorical data were compared between groups using nonparametric tests. Results: ALHXW markedly alleviated liver injury in the treatment group after 3 weeks of therapy as indicated by a significantly reduced level of ALT compared with the model group [(162.98 ± 73.14)U/L vs (322.52 ± 131.76)U/L, P = 0.047], and a 39.8% reduction in AST level compared with the model group[ (537.56 ± 306.06)U/L vs (892.98 ± 358.19)U/L, P = 0.053]. Moreover, at the end of the 6-week therapy, histopathological diagnosis showed that liver fibrosis was significantly reduced in the ALHXW-treated group compared with that in the model group ( P = 0.002). The relative expression of TGF-β1 mRNA and protein in the liver were significantly lower in ALHXW-treated rats than that in model rats (1.34 ± 0.31 vs 1.78 ± 0.45, P = 0.025; 0.39 ± 0.02 vs 0.57 ± 0.04, P = 0.003). Conclusion: ALHXW treatment can reverse CCl(4)-induced liver fibrosis in rats. Its mechanisms of anti-fibrosis may occur through the inhibition of TGF-β1 synthesis and TGF-β1/Smads signaling pathway, which in turn suppress the activation of hepatic stellate cells and thereby reverses fibrosis.

Effect of Combined Exercise Versus Aerobic-Only Training on Skeletal Muscle Lipid Metabolism in a Rodent Model of Type1 Diabetes.

PubMed

Dotzert, Michelle S; McDonald, Matthew W; Murray, Michael R; Nickels, J Zachary; Noble, Earl G; Melling, C W James

2017-12-04

Abnormal skeletal muscle lipid metabolism is associated with insulin resistance in people with type 1 diabetes. Although lipid metabolism is restored with aerobic exercise training, the risk for postexercise hypoglycemia is increased with this modality. Integrating resistance and aerobic exercise is associated with reduced hypoglycemic risk; however, the effects of this exercise modality on lipid metabolism and insulin resistance remain unknown. We compared the effects of combined (aerobic + resistance) versus aerobic exercise training on oxidative capacity and muscle lipid metabolism in a rat model of type 1 diabetes. Male Sprague-Dawley rats were divided into 4 groups: sedentary control (C), sedentary control + diabetes (CD), diabetes + high-intensity aerobic exercise (DAE) and diabetes + combined aerobic and resistance exercise (DARE). Following diabetes induction (20 mg/kg streptozotocin over five days), DAE rats ran for 12 weeks (5 days/week for 1 hour) on a motorized treadmill (27 m/min at a 6-degree grade), and DARE rats alternated daily between running and incremental weighted ladder climbing. After training, DAE showed reduced muscle CD36 protein content and lipid content compared to CD (p≤0.05). DAE rats also had significantly increased citrate synthase (CS) activity compared to CD (p≤0.05). DARE rats showed reduced CD36 protein content compared to CD and increased CS activity compared to CD and DAE rats (p≤0.05). DARE rats demonstrated increased skeletal muscle lipid staining, elevated lipin-1 protein content and insulin sensitivity (p≤0.05). Integration of aerobic and resistance exercise may exert a synergistic effect, producing adaptations characteristic of the "athlete's paradox," including increased capacity to store and oxidize lipids. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

[Impacts on urodynamic parameters and the protein expressions of M2 and M3 receptors of detrusor in the rats of detrusor hyperreflexia treated with ginger-salt-isolated moxibustion at "Shenque" (CV 8)].

PubMed

Liu, Yi; Wang, Xuerui; Li, Tianran; Lin, Liting; Shi, Guangxia; Fu, Yuanbo; Liu, Cunzhi

2017-04-12

To discuss the effects on detrusor hyperreflexia treated with ginger-salt-isolated moxibustion at "Shenque" (CV 8) and its mechanism. Thirty female adult SD rats were selected. The model of detrusor hyperreflexia was prepared with complete spinal transection at T 9 , of which, 20 rats were randomized into a model group (10 rats) and a moxibustion group (10 rats). A sham-operation group (10 rats) was set up for sham-spinal transection. In the moxibustion group, when urine incontinence occurred (about in 2 weeks of modeling), the ginger-salt-isolated moxibustion at "Shenque" (CV 8) was given, 3 moxa cones each time, once a day, continuously for 7 days. After treatment, in each group, the urodynamic parameters were determined, after which, the bladder detrusor was collected. Western blot was used to determine the protein expressions of M2 and M3 receptors. Compared with the sham-operation group, the micturition interval was shortened apparently ( P <0.01); the maximal bladder pressure was increased apparently ( P <0.01); the protein expression of M2 receptor in the detrusor was increased significantly ( P <0.05) and that of M3 receptor had no apparent change ( P >0.05) in the rats of the model group. Compared with the model group, the micturition interval was longer apparently ( P <0.01), the maximal bladder pressure was reduced apparently ( P <0.01), the protein expression of M2 receptor in the detrusor was reduced significantly ( P <0.05) and that of M3 receptor had no apparent change ( P >0.05) in the rats of the moxibustion group.Compared with the sham-operation group, the results of the above indicators were not different significantly in the moxibustion group (all P >0.05). The ginger-salt-isolated moxibustion at "Shenque" (CV 8) suppresses the overactive bladder in the rat with spinal transection and its effect mechanism is possibly relevant with reducing the protein expression of detrusor M2 and inhibiting the excessive contraction of the detrusor.

Heterogeneous Stock Rat: A Unique Animal Model for Mapping Genes Influencing Bone Fragility

PubMed Central

Alam, Imranul; Koller, Daniel L.; Sun, Qiwei; Roeder, Ryan K.; Cañete, Toni; Blázquez, Gloria; López-Aumatell, Regina; Martínez-Membrives, Esther; Vicens-Costa, Elia; Mont, Carme; Díaz, Sira; Tobeña, Adolf; Fernández-Teruel, Alberto; Whitley, Adam; Strid, Pernilla; Diez, Margarita; Johannesson, Martina; Flint, Jonathan; Econs, Michael J.; Turner, Charles H.; Foroud, Tatiana

2011-01-01

Previously, we demonstrated that skeletal mass, structure and biomechanical properties vary considerably among 11 different inbred rat strains. Subsequently, we performed quantitative trait loci (QTL) analysis in 4 inbred rat strains (F344, LEW, COP and DA) for different bone phenotypes and identified several candidate genes influencing various bone traits. The standard approach to narrowing QTL intervals down to a few candidate genes typically employs the generation of congenic lines, which is time consuming and often not successful. A potential alternative approach is to use a highly genetically informative animal model resource capable of delivering very high-resolution gene mapping such as Heterogeneous stock (HS) rat. HS rat was derived from eight inbred progenitors: ACI/N, BN/SsN, BUF/N, F344/N, M520/N, MR/N, WKY/N and WN/N. The genetic recombination pattern generated across 50 generations in these rats has been shown to deliver ultra-high even gene-level resolution for complex genetic studies. The purpose of this study is to investigate the usefulness of the HS rat model for fine mapping and identification of genes underlying bone fragility phenotypes. We compared bone geometry, density and strength phenotypes at multiple skeletal sites in HS rats with those obtained from 5 of the 8 progenitor inbred strains. In addition, we estimated the heritability for different bone phenotypes in these rats and employed principal component analysis to explore relationships among bone phenotypes in the HS rats. Our study demonstrates that significant variability exists for different skeletal phenotypes in HS rats compared with their inbred progenitors. In addition, we estimated high heritability for several bone phenotypes and biologically interpretable factors explaining significant overall variability, suggesting that the HS rat model could be a unique genetic resource for rapid and efficient discovery of the genetic determinants of bone fragility. PMID:21334473

Heterogeneous stock rat: a unique animal model for mapping genes influencing bone fragility.

PubMed

Alam, Imranul; Koller, Daniel L; Sun, Qiwei; Roeder, Ryan K; Cañete, Toni; Blázquez, Gloria; López-Aumatell, Regina; Martínez-Membrives, Esther; Vicens-Costa, Elia; Mont, Carme; Díaz, Sira; Tobeña, Adolf; Fernández-Teruel, Alberto; Whitley, Adam; Strid, Pernilla; Diez, Margarita; Johannesson, Martina; Flint, Jonathan; Econs, Michael J; Turner, Charles H; Foroud, Tatiana

2011-05-01

Previously, we demonstrated that skeletal mass, structure and biomechanical properties vary considerably among 11 different inbred rat strains. Subsequently, we performed quantitative trait loci (QTL) analysis in four inbred rat strains (F344, LEW, COP and DA) for different bone phenotypes and identified several candidate genes influencing various bone traits. The standard approach to narrowing QTL intervals down to a few candidate genes typically employs the generation of congenic lines, which is time consuming and often not successful. A potential alternative approach is to use a highly genetically informative animal model resource capable of delivering very high resolution gene mapping such as Heterogeneous stock (HS) rat. HS rat was derived from eight inbred progenitors: ACI/N, BN/SsN, BUF/N, F344/N, M520/N, MR/N, WKY/N and WN/N. The genetic recombination pattern generated across 50 generations in these rats has been shown to deliver ultra-high even gene-level resolution for complex genetic studies. The purpose of this study is to investigate the usefulness of the HS rat model for fine mapping and identification of genes underlying bone fragility phenotypes. We compared bone geometry, density and strength phenotypes at multiple skeletal sites in HS rats with those obtained from five of the eight progenitor inbred strains. In addition, we estimated the heritability for different bone phenotypes in these rats and employed principal component analysis to explore relationships among bone phenotypes in the HS rats. Our study demonstrates that significant variability exists for different skeletal phenotypes in HS rats compared with their inbred progenitors. In addition, we estimated high heritability for several bone phenotypes and biologically interpretable factors explaining significant overall variability, suggesting that the HS rat model could be a unique genetic resource for rapid and efficient discovery of the genetic determinants of bone fragility. Copyright © 2010 Elsevier Inc. All rights reserved.

Encapsulated Bifidobacteria reduced bacterial translocation in rats following hemorrhagic shock and resuscitation.

PubMed

Ruan, Xiangcai; Shi, Hanping; Xia, Gengfeng; Xiao, Ying; Dong, Jiaxi; Ming, Feiping; Wang, Shenming

2007-10-01

The aim of the present study was to determine the effects of peroral encapsulated Bifidobacteria on intestinal microflora, bacterial translocation (BT), plasma endotoxin, and ileal villi injury in a rat model of hemorrhagic shock. Sprague-Dawley rats were fed daily with three different diet supplements: phosphate buffered saline, Bifidobacteria (10(9) colon-forming units/day), or microencapsulated Bifidobacteria (10(9) colony-forming units/day). After 7 d of treatment, rats were anesthetized for hemorrhagic or sham shock. Then a laparotomy was performed to determine microbiological analysis of cecal content, BT to mesenteric lymph nodes, plasma endotoxin, and terminal ileal villous damage. In the hemorrhagic-shock model, rats pretreated with Bifidobacteria showed decreases in total aerobes in cecum, magnitude of total aerobes to BT, levels of plasma endotoxin, and percentage of ileal villous damage when compared with rats treated with phosphate buffered saline. Encapsulated Bifidobacteria induced greater decreases than intact Bifidobacteria in this model, except for no difference in percentage of ileal villous damage between the two groups. In addition, the incidence of BT was decreased in hemorrhagic rats pretreated with Bifidobacteria compared with control. However, the magnitude of total anaerobes and Bifidobacteria BT were similar among hemorrhagic-shocked rats receiving three different supplements. Bifidobacteria can be useful in preventing BT in hemorrhagic-shocked rats, and encapsulated Bifidobacteria can augment this effect further. Peroral administration of Bifidobacteria may be a favorable strategy to prevent sepsis and multiple organ dysfunction syndrome in hemorrhagic shock.

Study on the effects of parecoxib on hypothalamus orexin neuron of cerebral infarction rats.

PubMed

Li, F-T; Yao, C-H; Yao, L; Huo, Z-F; Liu, J

2018-03-01

To explore the effect of parecoxib on cerebral infarction in rats and the regulatory mechanism on hypothalamus orexin neurons (orexin) and protein expression. 60 SD male rats were randomly divided into sham operation group, model group and treatment group (20 rats in each group). Cerebral infarction model was established by modified Longa method. Rats in the treatment group were given parecoxib (2.5 mg kg-1) in tail by intravenous injection, while both the sham operation group and the model group were given the equal volume of sterile PBS solution in the tail vein. Continuous intervention of 72h was carried out in the three groups. Immunofluorescence staining and Western blot were used to detect the expression of orexin neurons and orexin protein in the hypothalamus of rats, respectively. Immunofluorescence staining showed that the number of orexin positive cells in the model group was significantly less than that in the sham-operated group (p < 0.01). After treatment intervention, the number of orexin positive cells in the hypothalamus was significantly increased compared to that in model group (p < 0.01). Western blot analysis showed that compared with sham operation group, the expression of orexin in the hypothalamus of model group was significantly decreased (p < 0.01), whereas the expression of orexin protein was significantly elevated after parecoxib intervention (p < 0.01). Parecoxib plays a therapeutic effect on cerebral infarction by up-regulating the orexin neuron.

Effect of Hua Yu Xiao Zheng decoction on the expression levels of vascular endothelial growth factor and angiopoietin-2 in rats with endometriosis.

PubMed

Chen, Zhen-Zhen; Gong, Xin

2017-12-01

The aims of the present study were to investigate the effects of a traditional Chinese medicine, Hua Yu Xiao Zheng (HYXZ) decoction, on surgically induced endometriosis in a rat model and to determine the possible underlying regulatory mechanisms. A total of 108 female Sprague-Dawley rats were divided into the control group (n=12) and endometriosis group (EM group; n=96), in which endometriosis was surgically induced in model rats by autotransplantation of endometrial tissues and 72 rats survived. After 3 weeks, the EM model rats were randomly divided into four subgroups (n=18), including the untreated model group, and three groups administered 7, 14 or 21 g/kg HYXZ decoction. Following 28 days of treatment, the associated proteins and genes of ectopic endometrial tissues were analyzed using immunohistochemistry, western blotting and quantitative polymerase chain reaction to investigate the underlying mechanisms. Compared with the model group, the size of the endometriotic implants decreased significantly in the HYXZ-treated groups. Furthermore, the expression levels of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) were significantly decreased in HYXZ-treated groups compared with the model group. These results indicate that HYXZ affected the inhibition of angiogenesis and decreased the endometriotic implant volumes and histopathological scores. The effectiveness of HYXZ may be partially attributed to the decrease of VEGF and Ang-2 expression levels in the ectopic endometrium.

Anti-migraine effect of Areca Catechu L. nut extract in bradykinin-induced plasma protein extravasation and vocalization in rats.

PubMed

Bhandare, Amol M; Vyawahare, Neeraj S; Kshirsagar, Ajay D

2015-08-02

Areca catechu Linn. (Arecaceae) nut is a popular folk remedy for the treatment of migraine in Kerala and Tamil Nadu states of India. This study was designed to investigate the effect of hydroalcoholic extract of A. catechu L. nut (ANE) treatment on migraine pain in rat models to strengthen its use as an anti-migraine therapy. Bradykinin (0.1 μmol/kg) injection in to left femoral vein of rat produced PPE which was measured with luminescence spectrometer. Vocalizations were produced in rats with 10 μg of bradykinin infusion into common carotid artery. Phonogram was recorded before, during and for 5min after bradykinin injection and sumatriptan was used as a standard anti-migraine drug. In both models, the ANE was orally administered at doses of 250 and 500 mg/kg, 60 min before bradykinin infusion. The PPE was reduced in both ANE treated groups of rats. The percent fluorescein was significantly increased in positive control group (97.00±1.7%; p<0.0001) compared to negative control (63.87±1.2%). With ANE treatments (250 and 500 mg/kg) PPE was significantly decreased to 88.88±1.4% (p<0.01) and 83.55±0.1% (p<0.0001) compared to positive control group, respectively. On the other hand in the model of vocalization, with 250 and 500 mg/kg ANE treatment, vocalization was significantly reduced to 33.33% and 16.66%, respectively, compared to saline treated rats. The reduction in vocalization is comparable to the reference drug sumatriptan. The findings provide the strong evidence for anti-migraine potential of ANE in rat models of migraine. In summary, therapeutic intervention with ANE treatment could be a promising strategy for prevention of migraine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Effect of Shugan Jianpi Recipe on LXRα/FAS signaling pathway mediated hepatocyte fatty deposits in NAFLD rats].

PubMed

Gong, Xiang-Wen; Yang-Qin-He; Yan, Hai-Zhen; Zhang, Yu-Pei; Huang, Jin; Xu, Yong-Jian; Zhang, Jin-Wen; Lin, Chun-Mei

2014-12-01

To explore the effect of Shugan Jianpi Recipe (SJR) on LXRα/FAS signaling pathway mediated hepatocyte fatty deposits in nonalcoholic fatty liver disease (NAFLD) rats. Totally 75 SPF grade male SD rats were randomly divided into 5 groups, i.e., the normal control group, the model group, the Shugan Recipe (SR) treatment groups, the Jianpi Recipe (JR) treatment group, and the SJR group. Except rats in the normal control group, the NAFLD rat model was duplicated using high fat diet (HFD). SR (Chaihu Shugan Powder) was administered to rats in the SR group. JR (Shenlin Baizhu Powder) was administered to rats in the JR group. SJR (Chaihu Shugan Powder plus Shenlin Baizhu Powder) was administered to rats in the SJR group. Changes of liver fat were analyzed using automatic biochemical analyzer. Liver cells were separated by low-speed centrifugation. Their activities and purities were identify using Typan blue and flow cytometry (FCM). Expression levels of LXRα and FAS mRNA in hepatocytes detected by Real-time quantitative PCR. Expression levels of LXRα and FAS protein were detected by Western blot. (1) Pathological results showed in the model group, hepatocytes were swollen with nucleus locating at the cell edge after oil red O staining; unequal sized small vacuoles could be seen inside cytoplasm. Some small vacuoles merged big vacuoles. All these indi- cated a NAFLD rat model was successfully established by high fat diet. Pathological structural changes could be impaired to some degree in all medicated groups, especially in the SR group. (2) Compared with the normal control group, expression levels of LXRα and FAS genes and proteins obviously increased in the model group (P < 0.01). Compared with the model group, their expression levels were obviously down-regulated in the JR group and the SR group (P < 0.01, P < 0.05). LXRα/FAS signaling pathway was an important signaling pathway for mediating lipid metabolism disorders of NAFLD rats. SJR could make hepatocyte fatty deposits tend to repair by adjusting the LXRα/FAS signaling pathway in NAFLD rats, which might be one of important mechanisms for SJR to prevent and cure NAFLD.

Memory deficiency, cerebral amyloid angiopathy, and amyloid-β plaques in APP+PS1 double transgenic rat model of Alzheimer's disease.

PubMed

Klakotskaia, Diana; Agca, Cansu; Richardson, Rachel A; Stopa, Edward G; Schachtman, Todd R; Agca, Yuksel

2018-01-01

Transgenic rat models of Alzheimer's disease were used to examine differences in memory and brain histology. Double transgenic female rats (APP+PS1) over-expressing human amyloid precursor protein (APP) and presenilin 1 (PS1) and single transgenic rats (APP21) over-expressing human APP were compared with wild type Fischer rats (WT). The Barnes maze assessed learning and memory and showed that both APP21 and APP+PS1 rats made significantly more errors than the WT rats during the acquisition phase, signifying slower learning. Additionally, the APP+PS1 rats made significantly more errors following a retention interval, indicating impaired memory compared to both the APP21 and WT rats. Immunohistochemistry using an antibody against amyloid-β (Aβ) showed extensive and mostly diffuse Aβ plaques in the hippocampus and dense plaques that contained tau in the cortex of the brains of the APP+PS1 rats. Furthermore, the APP+PS1 rats also showed vascular changes, including cerebral amyloid angiopathy with extensive Aβ deposits in cortical and leptomeningeal blood vessel walls and venous collagenosis. In addition to the Aβ accumulation observed in arterial, venous, and capillary walls, APP+PS1 rats also displayed enlarged blood vessels and perivascular space. Overall, the brain histopathology and behavioral assessment showed that the APP+PS1 rats demonstrated behavioral characteristics and vascular changes similar to those commonly observed in patients with Alzheimer's disease.

PP024. Effects of intravenous magnesium sulfate on the characteristics of eclamptic seizures induced by electrical stimuli in a rat preeclampsia/eclampsia model.

PubMed

Liu, Lei; Liu, Huishu; Huang, Qian; Brennecke, Shaun; Hu, Bihui

2013-04-01

Eclampsia is a serious complication of pregnancy and remains a leading cause of maternal mortality worldwide. Magnesium sulfate is commonly used in the prophylaxis and treatment of eclampsia. However, uncertainty remain regarding its anticonvulsant mechanism(s) of action. This study examined the effects of intravenous magnesium sulfate on the characteristics of eclamptic seizures in a rat preeclampsia/eclampsia model. All rats were implanted with stainless nickel-cadmium alloy bipolar electrodes one week before fertilization. Next, an experimental rat preeclampsia (PE) model was induced on gestational day 14 by anaesthetising rats and infusing over 1 hour into their tail veins lipopolysaccharide (LPS) (1.0μg/kg body weight) (with control rats receiving normal saline). The rats were then divided into three groups: a normal pregnancy (NP) group (n=6) which received a continuous infusion of saline; a control PE model group (n=7) (which had previously received the LPS treatment) which also received a continuous infusion of saline; and a treated PE model group (n=8) (which had previously received the LPS treatment) which received a continuous infusion of magnesium sulfate (60mg/kg/day). The continuous infusions in all three groups were delivered by implanted osmotic minipumps . Measurements were made of blood pressure, albuminuria, serum ALT, AST, and creatinine, BUN and serum magnesium concentrations. On gestational day 18, all experimental rats received a standardized electrical stimulus. Seizure activity was assessed using electroencephalogram (EEG) recordings. Terminations of pregnancy were performed on gestational day 21. Resorptions and pup birth weights were recorded. The pregnant LPS treated rats developed many features of human PE (e.g. hypertension, proteinuria, liver and kidney dysfunctions). The mean concentration of Mg(2+) in the magnesium sulfate therapy group (0.86±0.24mmol/L) was significantly higher (p<0.05) than in both the control PE model group (0.61±0.12mmol/L) and the NP group (0.62±0.09mmol/L). The magnesium sulfate therapy group had a significantly (p<0.05) increased latency period (21.7±8.9min) to evoke a full motor seizure compared to both the NP group (4.8±2.2min)and the control PE model group (3.3±1.4min), there being no significant difference (p>0.05) between the latency periods of the NP group and the control PE model group. Overall, the magnesium sulfate therapy regimen completely prevented seizure activity in 3/8 (37.5%) of the treated PE model rats compared to 6/6 (100%) of the NP rats and 7/7 (100%) of the control PE rats. The treated PE model group also had significantly (p<0.05) reduced seizure duration (26±4s) compared to both the NP (40±7s) and the control PE model (45±9s) groups. As well, there was a significantly (p<0.05) shorter EEG seizure amplitude change in the treated PE model group (58±6μv). In this rat preeclamsia/eclampsia model, the anticonvulsant characteristics of magnesium sulfate have been shown to include significantly increasing seizure latency period, reducing seizure duration and decreasing seizure EEG amplitude. Copyright © 2013. Published by Elsevier B.V.

Extracts of Bauhinia championii (Benth.) Benth. attenuate the inflammatory response in a rat model of collagen-induced arthritis.

PubMed

Xu, Wei; Huang, Mingqing; Zhang, Yuqin; Li, Huang; Zheng, Haiyin; Yu, Lishuang; Chu, Kedan; Lin, Yu; Chen, Lidian

2016-05-01

Rheumatoid arthritis is considered a serious public health problem, which is commonly treated with traditional Chinese or herbal medicine. The present study evaluated the effects of Bauhinia championii (Benth.) Benth. extraction (BCBE) on a type II collagen-induced arthritis (CIA) rat model. Wistar rats with CIA received either 125 or 500 mg/kg BCBE, after which, paw swelling was markedly suppressed compared with in the model group. In addition, BCBE significantly ameliorated pathological joint alterations, including synovial hyperplasia, and cartilage and bone destruction. The protein and mRNA expression levels of interleukin (IL)‑6, IL‑8, tumor necrosis factor‑α and nuclear factor‑κB in synovial tissue were determined by immunohistochemical staining, western blot analysis and reverse transcription‑polymerase chain reaction. The results demonstrated that the expression levels of these factors were significantly downregulated in the BCBE‑treated group compared with in the model group. These results indicated that BCBE may exert an inhibitory effect on the CIA rat model, and its therapeutic potential is associated with its anti-inflammatory action.

Extracts of Bauhinia championii (Benth.) Benth. attenuate the inflammatory response in a rat model of collagen-induced arthritis

PubMed Central

XU, WEI; HUANG, MINGQING; ZHANG, YUQIN; LI, HUANG; ZHENG, HAIYIN; YU, LISHUANG; CHU, KEDAN; LIN, YU; CHEN, LIDIAN

2016-01-01

Rheumatoid arthritis is considered a serious public health problem, which is commonly treated with traditional Chinese or herbal medicine. The present study evaluated the effects of Bauhinia championii (Benth.) Benth. extraction (BCBE) on a type II collagen-induced arthritis (CIA) rat model. Wistar rats with CIA received either 125 or 500 mg/kg BCBE, after which, paw swelling was markedly suppressed compared with in the model group. In addition, BCBE significantly ameliorated pathological joint alterations, including synovial hyperplasia, and cartilage and bone destruction. The protein and mRNA expression levels of interleukin (IL)-6, IL-8, tumor necrosis factor-α and nuclear factor-κB in synovial tissue were determined by immunohistochemical staining, western blot analysis and reverse transcription-polymerase chain reaction. The results demonstrated that the expression levels of these factors were significantly downregulated in the BCBE-treated group compared with in the model group. These results indicated that BCBE may exert an inhibitory effect on the CIA rat model, and its therapeutic potential is associated with its anti-inflammatory action. PMID:27035125

Substituted N-aryl-6-pyrimidinones: A new class of potent, selective, and orally active p38 MAP kinase inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Devadas, Balekudru; Selness, Shaun R.; Xing, Li

2012-02-28

A novel series of highly potent and selective p38 MAP kinase inhibitors was developed originating from a substituted N-aryl-6-pyrimidinone scaffold. SAR studies coupled with in vivo evaluations in rat arthritis model culminated in the identification of 10 with excellent oral efficacy. Compound 10 exhibited a significantly enhanced dissolution rate compared to 1, translating to a high oral bioavailability (>90%) in rat. In animal studies 10 inhibited LPS-stimulated production of tumor necrosis factor-{alpha} in a dose-dependent manner and demonstrated robust efficacy comparable to dexamethasone in a rat streptococcal cell wall-induced arthritis model.

Randomized structured triglycerides increase lymphatic absorption of tocopherol and retinol compared with the equivalent physical mixture in a rat model of fat malabsorption.

PubMed

Tso, P; Lee, T; DeMichele, S J

2001-08-01

Previously we demonstrated that the digestion, absorption and lymphatic transport of lipid and key essential fatty acids (EFA) from randomly interesterified fish oil/medium-chain structured triglycerides (STG) were significantly higher than an equivalent physical mixture (PM) in a normal lymph fistula rat model and in a rat model of lipid malabsorption caused by ischemia/reperfusion (I/R) injury. The goals of this study were to further explore the potential absorptive benefits of STG by comparing the intestinal absorption and lymphatic transport of tocopherol and retinol when delivered gastrically with either STG or PM under normal conditions and after I/R injury to the small bowel. Food-deprived male Sprague-Dawley rats were randomly assigned to two treatments (sham controls or I/R). Under halothane anesthesia, the superior mesenteric artery (SMA) was occluded for 20 min and then reperfused in I/R rats. The SMA was isolated but not occluded in control rats. In both groups, the mesenteric lymph duct was cannulated and a gastric tube was inserted. Each treatment group received 1 mL of the fish oil/MCT STG or PM (7 rats/group) along with (14)C-alpha-tocopherol and (3)H-retinol through the gastric tube followed by an infusion of PBS at 3 mL/h for 8 h. Lymph was collected hourly for 8 h. Under steady-state conditions, the amount of (14)C-alpha-tocopherol and (3)H-retinol transported into lymph was significantly higher in the STG-fed rats compared with those fed PM in both control and I/R groups. In addition, control and I/R rats given STG had earlier steady-state outputs of (14)C-alpha-tocopherol and (3)H-retinol and maintained approximately 30% higher outputs in lymph throughout the 8-h lymph collection period compared with rats given the PM. We conclude that STG provides the opportunity to potentiate improved absorption of fat-soluble vitamins under normal and malabsorptive states.

Oral L-glutamine administration attenuated cutaneous wound healing in Wistar rats.

PubMed

Goswami, Saurabh; Kandhare, Amit; Zanwar, Anand A; Hegde, Mahabaleshwar V; Bodhankar, Subhash L; Shinde, Sudhir; Deshmukh, Shahaji; Kharat, Ravindran

2016-02-01

The objective of this study was to evaluate the wound healing potential of L-glutamine in laboratory rats using excision and incision wound models. Excision wounds of size 500 mm(2) and depth 2 mm were made on the dorsal portion of male Wistar rats (230-250 g) and were used for the study of oral L-glutamine (1 g/kg) treatment on the rate of contraction of wound and epithelisation. Histological evaluation of wound tissue was also performed. Six-centimetre-long two linear-paravertebral incisions in male Wistar rats (230-250 g) were used to study the effect of L-glutamine (1 g/kg, p.o.) treatment on tensile strength, total protein and hydroxyproline content in the incision model. Oral administration of L-glutamine (1 g/kg) significantly decreased wound area, epithelisation period and wound index, whereas the rate of wound contraction significantly increased (P < 0·001) when compared with vehicle control rats in the excision wound model. Tensile strength, hydroxyproline content and protein level were significantly increased (P < 0·001) in L-glutamine (1 g/kg, p.o.)-treated rats when compared with vehicle control rats in the incision wound model. Histological evaluation of wound tissue from L-glutamine (1 g/kg, p.o.)-treated rats showed complete epithelialisation with new blood vessel formation and high fibrous tissues in the excision wound model. In conclusion, oral administration of l-glutamine (1 g/kg) promotes wound healing by acting on various stages of wound healing such as collagen synthesis, wound contraction and epithelialisation. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Evaluation of the effects of pulsed wave LLLT on tibial diaphysis in two rat models of experimental osteoporosis, as examined by stereological and real-time PCR gene expression analyses.

PubMed

Mohsenifar, Zhaleh; Fridoni, Mohammadjavad; Ghatrehsamani, Mahdi; Abdollahifar, Mohammad-amin; Abbaszadeh, Hojjatallah; Mostafavinia, Atarodalsadat; Fallahnezhad, Somaye; Asghari, Mohammadali; Bayat, Saba; Bayat, Mohammad

2016-05-01

Osteoporosis (OP) and osteoporotic fracture are major public health issues for society; the burden for the affected individual is also high. Previous studies have shown that pulsed wave low-level laser therapy (PW LLLT) has osteogenic effects. This study intended to evaluate the impacts of PW LLLT on the cortical bone of osteoporotic rats' tibias in two experimental models, ovariectomized and dexamethasone-treated. We divided the rats into four ovariectomized induced OP (OVX-d) and four dexamethasone-treated (glucocorticoid-induced OP, GIOP) groups. A healthy (H) group of rats was considered for baseline evaluations. At 14 weeks following ovariectomy, we subdivided the OVX-d rats into the following groups: (i) control which had OP, (ii) OVX-d rats treated with alendronate (1 mg/kg), (iii) OVX-d rats treated with LLLT, and (iv) OVX-d rats treated with alendronate and PW LLLT. The remaining rats received dexamethasone over a 5-week period and were also subdivided into four groups: (i) control rats treated with intramuscular (i.m.) injections of distilled water (vehicle), (ii) rats treated with subcutaneous alendronate injections (1 mg/kg), (iii) laser-treated rats, and (iv) rats simultaneously treated with laser and alendronate. The rats received alendronate for 30 days and underwent PW LLLT (890 nm, 80 Hz, 0.972 J/cm(2)) three times per week during 8 weeks. Then, the right tibias were extracted and underwent a stereological analysis of histological parameters and real-time polymerase chain reaction (RT-PCR). A significant increase in cortical bone volume (mm(3)) existed in all study groups compared to the healthy rats. There were significant decreases in trabecular bone volume (mm(3)) in all study groups compared to the group of healthy rats. The control rats with OP and rats from the vehicle group showed significantly increased osteoclast numbers compared to most other groups. Alendronate significantly decreased osteoclast numbers in osteoporotic rats. Concurrent treatments (compounded by PW LLLT and alendronate) produce the same effect on osteoporotic bone.

The Protective Effect of Melissa officinalis L. in Visceral Hypersensitivity in Rat Using 2 Models of Acid-induced Colitis and Stress-induced Irritable Bowel Syndrome: A Possible Role of Nitric Oxide Pathway.

PubMed

Dolatabadi, Fatemeh; Abdolghaffari, Amir H; Farzaei, Mohammad H; Baeeri, Maryam; Ziarani, Fatemeh S; Eslami, Majid; Abdollahi, Mohammad; Rahimi, Roja

2018-06-04

The aim of present study is to estimate the effects of Melissa officinalis L. (MO) on visceral hypersensitivity (VH), defecation pattern and biochemical factors in 2 experimental models of irritable bowel syndrome (IBS) and the possible role of nitric oxide. Two individual models of IBS were induced in male Wistar-albino rats. In the acetic acid model, the animals were exposed to rectal distension and abdominal withdrawal reflex, and the defecation patterns were determined. In the restraint stress model, the colons of rats were removed and the levels of TNF-α, myeloperoxidase, lipid peroxidation, and antioxidant powers were determined. Rats had been treated with MO, L-NG-nitroarginine methyl ester (L-NAME), aminoguanidine (AG), MO + AG, or MO + L-NAME in the mentioned experimental models. Hypersensitive response to rectal distension and more stool defecation in control rats have been observed in comparison to shams. MO-300 significantly reduced VH and defecation frequency in comparison to controls. VH and defecation pattern did not show significant change in AG + MO and L-NAME + MO groups compared to controls. Also, significant reduction in TNF-α, myeloperoxidase, TBARS, and an increase in antioxidant power in MO-300 was recorded compared to controls. AG + MO and L-NAME + MO groups showed a reverse pattern compared to MO-300. MO can ameliorate IBS by modulating VH and defecation patterns. Antioxidant and anti-inflammatory properties along with its effect on the nitrergic pathway seems to play important roles in its pharmacological activity.

Model based population PK-PD analysis of furosemide for BP lowering effect: A comparative study in primary and secondary hypertension.

PubMed

Shukla, Mahendra; Ibrahim, Moustafa M A; Jain, Moon; Jaiswal, Swati; Sharma, Abhisheak; Hanif, Kashif; Lal, Jawahar

2017-11-15

Though numerous reports have demonstrated multiple mechanisms by which furosemide can exert its anti-hypertensive response. However, lack of studies describing PK-PD relationship for furosemide featuring its anti-hypertensive property has limited its usage as a blood pressure (BP) lowering agent. Serum concentrations and mean arterial BP were monitored following 40 and 80mgkg -1 multiple oral dose of furosemide in spontaneously hypertensive rats (SHR) and DOCA-salt induced hypertensive (DOCA-salt) rats. A simultaneous population PK-PD relationship using E max model with effect compartment was developed to compare the anti-hypertensive efficacy of furosemide in these rat models. A two-compartment PK model with Weibull-type absorption and first-order elimination best described the serum concentration-time profile of furosemide. In the present study, post dose serum concentrations of furosemide were found to be lower than the EC 50 . The EC 50 predicted in DOCA-salt rats was found to be lower (4.5-fold), whereas the tolerance development was higher than that in SHR model. The PK-PD parameter estimates, particularly lower values of EC 50 , K e and Q in DOCA-salt rats as compared to SHR, pinpointed the higher BP lowering efficacy of furosemide in volume overload induced hypertensive conditions. Insignificantly altered serum creatinine and electrolyte levels indicated a favorable side effect profile of furosemide. In conclusion, the final PK-PD model described the data well and provides detailed insights into the use of furosemide as an anti-hypertensive agent. Copyright © 2017. Published by Elsevier B.V.

Noninvasive assessment of hepatic sinusoidal obstructive syndrome using acoustic radiation force impulse elastography imaging: A proof-of-concept study in rat models.

PubMed

Park, So Hyun; Lee, Seung Soo; Sung, Ji-Youn; Na, Kiyong; Kim, Hyoung Jung; Kim, So Yeon; Park, Beom Jin; Byun, Jae Ho

2018-05-01

To determine the feasibility of acoustic radiation force impulse (ARFI) elastography in the evaluation of hepatic sinusoidal obstruction syndrome (SOS) in rat models. Rat SOS models of various severities were created by monocrotaline gavage (n = 40) or by intraperitoneal injection of 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX) (n = 16). Liver shear-wave velocity (SWV) was measured using ARFI elastography. Liver samples were analysed for the SOS score, steatosis, lobular inflammation and fibrosis. The liver SWV was significantly elevated in the SOS models (1.29-2.24 m/s) compared with that of the matched control rats (1.01-1.09; p≤.09; veFor seven FOLFOX-treated rats which were longitudinally followed-up, the liver SWV significantly increased at 7 weeks (1.32±0.13 m/s) compared with the baseline (1.08±0.1 m/s, p=.015) and then significantly declined after a 2-week, treatment-free period (1.15±0.13 m/s; p=.048). Multivariate analysis revealed that the SOS score (p<.001) and lobular inflammation (p=.044) were independently correlated with the liver SWV. Liver SWV is elevated in SOS in proportion to the degree of sinusoidal injury and lobular inflammation in rat SOS models. ARFI elastography has potential as an examination for diagnosis, severity assessment and follow-up of SOS. • Liver SWV using ARFI elastography was significantly elevated in SOS rat. • Sinusoidal injury and lobular inflammation grades had correlation with liver SWV. • ARFI elastography has potential for diagnosis, severity assessment, and follow-up of SOS.

Respiratory Tract Lung Geometry and Dosimetry Model for Male Sprague-Dawley Rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Frederick J.; Asgharian, Bahman; Schroeter, Jeffry D.

2015-07-24

While inhalation toxicological studies of various compounds have been conducted using a number of different strains of rats, mechanistic dosimetry models have only had tracheobronchial (TB) structural data for Long-Evans rats, detailed morphometric data on the alveolar region of Sprague-Dawley rats and limited alveolar data on other strains. Based upon CT imaging data for two male Sprague-Dawley rats, a 15-generation, symmetric typical path model was developed for the TB region. Literature data for the alveolar region of Sprague-Dawley rats were analyzed to develop an eight-generation model, and the two regions were joined to provide a complete lower respiratory tract modelmore » for Sprague-Dawley rats. The resulting lung model was used to examine particle deposition in Sprague-Dawley rats and to compare these results with predicted deposition in Long-Evans rats. Relationships of various physiologic variables and lung volumes were either developed in this study or extracted from the literature to provide the necessary input data for examining particle deposition. While the lengths, diameters and branching angles of the TB airways differed between the two Sprague-Dawley rats, the predicted deposition patterns in the three major respiratory tract regions were very similar. Between Sprague-Dawley and Long-Evans rats, significant differences in TB and alveolar predicted deposition fractions were observed over a wide range of particle sizes, with TB deposition fractions being up to 3- to 4-fold greater in Sprague-Dawley rats and alveolar deposition being significantly greater in Long-Evans rats. Thus, strain-specific lung geometry models should be used for particle deposition calculations and interspecies dose comparisons.« less

Respiratory tract lung geometry and dosimetry model for male Sprague-Dawley rats.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Frederick J.; Asgharian, Bahman; Schroeter, Jeffry D.

2014-08-26

While inhalation toxicological studies of various compounds have been conducted using a number of different strains of rats, mechanistic dosimetry models have only had tracheobronchial (TB) structural data for Long-Evans rats, detailed morphometric data on the alveolar region of Sprague-Dawley rats and limited alveolar data on other strains. Based upon CT imaging data for two male Sprague-Dawley rats, a 15-generation, symmetric typical path model was developed for the TB region. Literature data for the alveolar region of Sprague-Dawley rats were analyzed to develop an eight-generation model, and the two regions were joined to provide a complete lower respiratory tract modelmore » for Sprague-Dawley rats. The resulting lung model was used to examine particle deposition in Sprague-Dawley rats and to compare these results with predicted deposition in Long-Evans rats. Relationships of various physiologic variables and lung volumes were either developed in this study or extracted from the literature to provide the necessary input data for examining particle deposition. While the lengths, diameters and branching angles of the TB airways differed between the two Sprague- Dawley rats, the predicted deposition patterns in the three major respiratory tract regions were very similar. Between Sprague-Dawley and Long-Evans rats, significant differences in TB and alveolar predicted deposition fractions were observed over a wide range of particle sizes, with TB deposition fractions being up to 3- to 4-fold greater in Sprague-Dawley rats and alveolar deposition being significantly greater in Long-Evans rats. Thus, strain-specific lung geometry models should be used for particle deposition calculations and interspecies dose comparisons.« less

Cocaine self-administration punished by i.v. histamine in rat models of high and low drug abuse vulnerability: Effects of saccharin preference, impulsivity, and sex

PubMed Central

Holtz, Nathan A.; Anker, Justin J.; Regier, Paul S.; Claxton, Alex; Carroll, Marilyn E.

2015-01-01

A key feature of substance use disorders is continued drug consumption despite aversive consequences. This has been modeled in the animal laboratory by pairing drug self-administration with electric shock, thereby punishing drug intake (Deroche-Gamonet et al. 2004). In the present experiments, we examined the effects of punishment on i.v. cocaine self-administration by adding histamine to the cocaine solution in three different animal models of high and low vulnerability to drug abuse: rats selectively bred for high (HiS) and low (LoS) saccharin consumption, rats selected for high (HiI) and low (LoI) impulsivity, and sex differences. Animals were allowed to self-administer cocaine (0.4 mg/kg/infusion) to establish a baseline of operant responding. Histamine (4.0 mg/kg/infusion) was then added directly into the cocaine solution and its consequent effects on self-administration were compared to baseline. The histamine + cocaine solution was then replaced with a cocaine-only solution, and the rats' operant responding was again measured and compared to baseline. Concurrent histamine exposure was effective in reducing cocaine consumption in all groups of rats; however, LoS and female rats took longer to return to baseline levels of cocaine consumption after histamine was removed compared to HiS and male rats. These data suggest the reduction of drug self-administration by aversive consequences may differ in groups that vary in drug use vulnerability, and these results may inform pharmacological strategies that enhance the negative aspects of drug consumption. PMID:23948673

Effects of high-fat diet and fructose-rich diet on obesity, dyslipidemia and hyperglycemia in the WBN/Kob-Leprfa rat, a new model of type 2 diabetes mellitus.

PubMed

Namekawa, Junichi; Takagi, Yoshiichi; Wakabayashi, Kaoru; Nakamura, Yuki; Watanabe, Ayaka; Nagakubo, Dai; Shirai, Mitsuyuki; Asai, Fumitoshi

2017-06-10

Obesity and type 2 diabetes mellitus (T2DM) are occurring at epidemic-like rates, and these epidemics appear to have emerged largely from changes in daily diet. In the present study, we compared effects of high-fat diet (HFD) and fructose-rich diet (FRD) in WBN/Kob-Lepr fa (WBKDF) rats that spontaneously develop obesity, dyslipidemia and T2DM. After a 4-week feeding of each diet, WBKDF-HFD and WBKDF-FRD rats exhibited aggravated obesity and dyslipidemia compared with WBKDF rats fed standard diet (STD). In contrast, hyperglycemia developed in WBKDF-STD rats was significantly inhibited in WBKDF-FRD rats, but not in WBKDF-HFD rats. The present study demonstrated that the 4-week feeding of HFD and FRD caused diet-induced obesity with a distinct phenotype in the glucose metabolism in WBKDF rats.

Effects of high-fat diet and fructose-rich diet on obesity, dyslipidemia and hyperglycemia in the WBN/Kob-Leprfa rat, a new model of type 2 diabetes mellitus

PubMed Central

NAMEKAWA, Junichi; TAKAGI, Yoshiichi; WAKABAYASHI, Kaoru; NAKAMURA, Yuki; WATANABE, Ayaka; NAGAKUBO, Dai; SHIRAI, Mitsuyuki; ASAI, Fumitoshi

2017-01-01

Obesity and type 2 diabetes mellitus (T2DM) are occurring at epidemic-like rates, and these epidemics appear to have emerged largely from changes in daily diet. In the present study, we compared effects of high-fat diet (HFD) and fructose-rich diet (FRD) in WBN/Kob-Leprfa (WBKDF) rats that spontaneously develop obesity, dyslipidemia and T2DM. After a 4-week feeding of each diet, WBKDF-HFD and WBKDF-FRD rats exhibited aggravated obesity and dyslipidemia compared with WBKDF rats fed standard diet (STD). In contrast, hyperglycemia developed in WBKDF-STD rats was significantly inhibited in WBKDF-FRD rats, but not in WBKDF-HFD rats. The present study demonstrated that the 4-week feeding of HFD and FRD caused diet-induced obesity with a distinct phenotype in the glucose metabolism in WBKDF rats. PMID:28442647

WNIN/GR-Ob - an insulin-resistant obese rat model from inbred WNIN strain.

PubMed

Harishankar, N; Vajreswari, A; Giridharan, N V

2011-09-01

WNIN/GR-Ob is a mutant obese rat strain with impaired glucose tolerance (IGT) developed at the National Institute of Nutrition (NIN), Hyderabad, India, from the existing 80 year old Wistar rat (WNIN) stock colony. The data presented here pertain to its obese nature along with IGT trait as evidenced by physical, physiological and biochemical parameters. The study also explains its existence, in three phenotypes: homozygous lean (+/+), heterozygous carrier (+/-) and homozygous obese (-/-). Thirty animals (15 males and 15 females) from each phenotype (+/+, +/-, -/-) and 24 lean and obese (6 males and 6 females) rats were taken for growth and food intake studies respectively. Twelve adult rats from each phenotype were taken for body composition measurement by total body electrical conductivity (TOBEC); 12 rats of both genders from each phenotype at different ages were taken for clinical chemistry parameters. Physiological indices of insulin resistance were calculated according to the homeostasis model assessment for insulin resistance (HOMA-IR) and also by studying U¹⁴C 2-deoxy glucose uptake (2DG). WNINGR-Ob mutants had high growth, hyperphagia, polydipsia, polyurea, glycosuria, and significantly lower lean body mass, higher fat mass as compared with carrier and lean rats. These mutants, at 50 days of age displayed abnormal response to glucose load (IGT), hyperinsulinaemia, hypertriglyceridaemia, hypercholesterolaemia and hyperleptinaemia. Basal and insulin-stimulated glucose uptakes by diaphragm were significantly decreased in obese rats as compared with lean rats. Obese rats of the designated WNIN/GR-Ob strain showed obesity with IGT, as adjudged by physical, physiological and biochemical indices. These indices varied among the three phenotypes, being lowest in lean, highest in obese and intermediate in carrier phenotypes thereby suggesting that obesity is inherited as autosomal incomplete dominant trait in this strain. This mutant obese rat model is easy to propagate, and can easily be transformed to frank diabetes model by dietary manipulation and thus can be used for screening anti-diabetic drugs.

Isolated Flinders Sensitive Line rats have decreased dopamine D2 receptor mRNA.

PubMed

Bjørnebekk, Astrid; Mathé, Aleksander A; Brené, Stefan

2007-07-02

Social isolation has profound effects on animal behavior and dopamine systems. We investigated the effect of social isolation on the dopamine receptor and neuropeptide mRNAs in the brain reward system in an animal model of depression, the Flinders Sensitive Line rats and Sprague-Dawley controls. We demonstrate that socially isolated but not group housed Flinders sensitive line rats had lower dopamine D2 receptor mRNA levels compared with Sprague-Dawley rats. Isolated and group housed Flinders Sensitive Line rats had higher levels of dopamine D1 receptor and substance P and enkephalin but not dynorphin mRNAs when compared with Sprague-Dawley rats. Our findings of decreased dopamine D2 receptor levels in socially isolated Flinders Sensitive Line rats suggest that low D2 receptor expression may play a role in pathophysiology of depression.

Surgery results in exaggerated and persistent cognitive decline in a rat model of the Metabolic Syndrome.

PubMed

Feng, Xiaomei; Degos, Vincent; Koch, Lauren G; Britton, Steven L; Zhu, Yinggang; Vacas, Susana; Terrando, Niccolò; Nelson, Jeffrey; Su, Xiao; Maze, Mervyn

2013-05-01

Postoperative cognitive decline can be reproduced in animal models. In a well-validated rat model of the Metabolic Syndrome, we sought to investigate whether surgery induced a more severe and persistent form of cognitive decline similar to that noted in preliminary clinical studies. In rats that had been selectively bred for low and high exercise endurance, the low capacity runners (LCR) exhibited features of Metabolic Syndrome (obesity, dyslipidemia, insulin resistance, and hypertension). Tibial fracture surgery was performed under isoflurane anesthesia in LCR and high capacity runner (HCR) rats and cognitive function was assessed postoperatively in a trace-fear conditioning paradigm and Morris Water Maze; non-operated rats were exposed to anesthesia and analgesia (sham). Group sizes were n = 6. On postoperative D7, LCR rats had shorter freezing times than postoperative HCR rats. Five months postoperatively, LCR rats had a flatter learning trajectory and took longer to locate the submerged platform than postoperative HCR rats; dwell-time in the target quadrant in a probe trial was shorter in the postoperative LCR compared to HCR rats. LCR and HCR sham rats did not differ in any test. Postoperatively, LCR rats diverged from HCR rats exhibiting a greater decline in memory, acutely, with persistent learning and memory decline, remotely; this could not be attributed to changes in locomotor or swimming performance. This Metabolic Syndrome animal model of surgery-induced cognitive decline corroborates, with high fidelity, preliminary findings of postoperative cognitive dysfunction in Metabolic Syndrome patients.

Visceral hypersensitive rats share common dysbiosis features with irritable bowel syndrome patients

PubMed Central

Zhou, Xiao-Yan; Li, Ming; Li, Xia; Long, Xin; Zuo, Xiu-Li; Hou, Xiao-Hua; Cong, Ying-Zi; Li, Yan-Qing

2016-01-01

AIM: To evaluate gut microbial dysbiosis in two visceral hypersensitive models in comparison with irritable bowel syndrome (IBS) patients and to explore the extent to which these models capture the dysbiosis of IBS patients. METHODS: Visceral hypersensitivity was developed using the maternal separation (MS) rat model and post-inflammatory rat model. The visceral sensitivity of the model groups and control group was evaluated using the abdominal withdraw reflex score and electromyography in response to graded colorectal distention. The 16S ribosomal RNA gene from fecal samples was pyrosequenced and analyzed. The correlation between dysbiosis in the microbiota and visceral hypersensitivity was calculated. Positive findings were compared to sequencing data from a published human IBS cohort. RESULTS: Dysbiosis triggered by neonatal maternal separation was lasting but not static. Both MS and post-inflammatory rat fecal microbiota deviated from that of the control rats to an extent that was larger than the co-housing effect. Two short chain fatty acid producing genera, Fusobacterium and Clostridium XI, were shared by the human IBS cohort and by the maternal separation rats and post-inflammatory rats, respectively, to different extents. Fusobacterium was significantly increased in the MS group, and its abundance positively correlated with the degree of visceral hypersensitivity. Porphyromonadaceae was a protective biomarker for both the rat control group and healthy human controls. CONCLUSION: The dysbiosis MS rat model and the post-inflammatory rat model captured some of the dysbiosis features of IBS patients. Fusobacterium, Clostridium XI and Porphyromonadaceae were identified as targets for future mechanistic research. PMID:27298564

Sivelestat sodium hydrate improves post-traumatic knee osteoarthritis through nuclear factor-κB in a rat model.

PubMed

Yu, Xiaofeng; Zhao, Lijun; Yu, Zhiping; Yu, Changzheng; Bi, Jianfei; Sun, Binglong; Cong, Haibo

2017-08-01

As a specific inhibitor of neutrophil elastase, sivelestat sodium hydrate has primarily been used in the treatment of acute lung injury caused by various factors since its approval in 2002. Sivelestat sodium hydrate also improves post-traumatic knee osteoarthritis (KOA), although its underlying mechanisms of action have yet to be elucidated. The aim of the current study was to determine if sivelestat sodium hydrate improves post-traumatic KOA through nuclear factor (NF)-κB in a rat model. Treatment with sivelestat sodium hydrate significantly inhibited the induction of structural changes and significantly increased the vertical episode count and ipsilateral static weight bearing of the joint in KOA rats (all P<0.01). Sivelestat sodium hydrate significantly inhibited tumor necrosis factor-α and interleukin-6 production, serum nitrite levels, inducible nitric oxide synthase protein expression and high mobility group box 1 (HMGB1) secretion in KOA rats compared with the model group (all P<0.01). Sivelestat sodium hydrate also significantly suppressed p50/p65 DNA binding activity and NF-κB and phosphorylated inhibitor of κB protein expression in the joints of KOA rats compared with the model group (all P<0.01). These results suggest that sivelestat sodium hydrate improves post-traumatic KOA through HMGB1 and NF-κB in rats.

Sivelestat sodium hydrate improves post-traumatic knee osteoarthritis through nuclear factor-κB in a rat model

PubMed Central

Yu, Xiaofeng; Zhao, Lijun; Yu, Zhiping; Yu, Changzheng; Bi, Jianfei; Sun, Binglong; Cong, Haibo

2017-01-01

As a specific inhibitor of neutrophil elastase, sivelestat sodium hydrate has primarily been used in the treatment of acute lung injury caused by various factors since its approval in 2002. Sivelestat sodium hydrate also improves post-traumatic knee osteoarthritis (KOA), although its underlying mechanisms of action have yet to be elucidated. The aim of the current study was to determine if sivelestat sodium hydrate improves post-traumatic KOA through nuclear factor (NF)-κB in a rat model. Treatment with sivelestat sodium hydrate significantly inhibited the induction of structural changes and significantly increased the vertical episode count and ipsilateral static weight bearing of the joint in KOA rats (all P<0.01). Sivelestat sodium hydrate significantly inhibited tumor necrosis factor-α and interleukin-6 production, serum nitrite levels, inducible nitric oxide synthase protein expression and high mobility group box 1 (HMGB1) secretion in KOA rats compared with the model group (all P<0.01). Sivelestat sodium hydrate also significantly suppressed p50/p65 DNA binding activity and NF-κB and phosphorylated inhibitor of κB protein expression in the joints of KOA rats compared with the model group (all P<0.01). These results suggest that sivelestat sodium hydrate improves post-traumatic KOA through HMGB1 and NF-κB in rats. PMID:28810618

Reliable critical sized defect rodent model for cleft palate research.

PubMed

Mostafa, Nesrine Z; Doschak, Michael R; Major, Paul W; Talwar, Reena

2014-12-01

Suitable animal models are necessary to test the efficacy of new bone grafting therapies in cleft palate surgery. Rodent models of cleft palate are available but have limitations. This study compared and modified mid-palate cleft (MPC) and alveolar cleft (AC) models to determine the most reliable and reproducible model for bone grafting studies. Published MPC model (9 × 5 × 3 mm(3)) lacked sufficient information for tested rats. Our initial studies utilizing AC model (7 × 4 × 3 mm(3)) in 8 and 16 weeks old Sprague Dawley (SD) rats revealed injury to adjacent structures. After comparing anteroposterior and transverse maxillary dimensions in 16 weeks old SD and Wistar rats, virtual planning was performed to modify MPC and AC defects dimensions, taking the adjacent structures into consideration. Modified MPC (7 × 2.5 × 1 mm(3)) and AC (5 × 2.5 × 1 mm(3)) defects were employed in 16 weeks old Wistar rats and healing was monitored by micro-computed tomography and histology. Maxillary dimensions in SD and Wistar rats were not significantly different. Preoperative virtual planning enhanced postoperative surgical outcomes. Bone healing occurred at defect margin leaving central bone void confirming the critical size nature of the modified MPC and AC defects. Presented modifications for MPC and AC models created clinically relevant and reproducible defects. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Cynanchum wilfordii Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia by Regulating 5α-Reductase and Androgen Receptor Activities in a Rat Model

PubMed Central

Lee, Gyuok; Shin, Jawon; Choi, Hakjoon; Jo, Ara; Pan, SangO; Bae, Donghyuck; Lee, Yongwook; Choi, Chulyung

2017-01-01

Benign prostatic hyperplasia (BPH) is characterized by uncontrolled proliferation of the prostate gland. Cynanchum wilfordii has been reported to improve sexual behavior in male rats. In this study, we investigated the protective effect of an aqueous extract of C. wilfordii (CWW) against BPH development in a testosterone-induced BPH rat model. The rats were divided into the following six groups: sham/vehicle; BPH/vehicle; BPH/finasteride; and three CWW doses (50, 100, and 200 mg/kg). After a 4-week treatment with CWW, the rats were euthanized at scheduled times, and their prostates were weighed, followed by a histopathological examination. Prostate growth inhibition rates in rats administered CWW 50, 100, and 200 mg/kg were 54.5%, 51.8%, and 50.1%, respectively. The BPH/CWW group showed decreased serum testosterone and dihydrotestosterone (DHT) levels compared to the BPH/vehicle group. Furthermore, the BPH/CWW group showed reduced prostate testosterone and DHT levels compared to the BPH/vehicle group. Mechanistically, the reverse transcription-polymerase chain reaction revealed downregulated mRNA expression levels of the androgen receptor, 5α-reductase, and B-cell lymphoma-2 (Bcl-2) in the BPH/CWW200 group compared with those in the testosterone-induced groups. In conclusion, these findings show the effectiveness of CWW in slowing the progression of testosterone-induced BPH in rats. PMID:28953224

[Effects of grain-sized moxibustion from 7 am to 9 am on circadian rhythm of inflammatory factor IL-6 in rats with rheumatoid arthritis].

PubMed

Ma, Wenbin; Liu, Xuguang; Qin, Yong; Zhou, Haiyan; Yang, Xin

2016-04-01

To explore the rhythm regulatory mechanism of interleukin-6 (IL-6) in the process of moxibustion for rheumatoid arthritis (RA). A total of 144 Sprague-Dawley (SD) rats were randomly divided into a blank group, a model group, a moxibustion group, a sham operation group, an operation group, an operation+moxibustion group, 24 rats in each one. Each group was divided into 4 time points (0:00 am, 6:00' am, 12:00 am, 6:00 pm), 6 rats in each time point. The Light-Dark 12 : 12 was given in all rats for light-dark cycle. Except the blank group, rats in the remaining groups were treated with intracutaneous injection of freund's complete adjuvant at right-side foot to establish the model of RA. After the model establishment, bilateral adrenal, glands were removed in the operation group and operation + moxibustion group, while those in the sham operation group were not removed with identical operation procedure. Rats in the moxibustion group and operation + moxibustion group were treated with grain-sized moxibustion from 7:00 am to 9:00 am at "Shenshu" (BL 23) and "Zusanli" (ST 36) once everyday, 6 times were taken as one session and 3 sessions were required tatclly, while rats in the remaining groups received identical fixation without moxibustion. The general health state and foot volume of rats were measured before model establishment, after establishment and after treatment. After treatment, rats were sacrificed at each time point to collect the blood sample and measure the content of IL-6 by using enzymne-immunoassay method. Compared with the blank group, the foot swelling in the model group was obviously increased (P<0. 05); the IL-6 maintained circadian rhythm (P<0. 05), but the peak phase had a backward trend, famplitude had an increased trend and the median was significantly lifted (P<0. 05). Compared with model group, !the foot swelling in the moxibustion group was obviously decreased (P<0. 05); the IL-6 maintained circadian. rhythm (P<0. 05), and the peak phase had a forward trend, amplitude had a decreased trend and the median was significantly reduced (P<0. 05). Compared with the moxibustion group, the foot swelling in the operation--moxibustion group was obviously increased (P < 0.05); the IL-6 maintained circadian rhythm (P < 0.5), but the peak phase moved forwrd, and the median was significantly elevated (P < 0.05). The IL-6 in plasma maintains significant pathological circadian rhythm in RA rats; with the complete hypothalamic-pituitary-adrenal axis, moxibustion is likely to regulate the circadian rhythm of IL-6 to play an important role of anti-inflammatory effect in RA rats.

Long term highly saturated fat diet does not induce NASH in Wistar rats

PubMed Central

Romestaing, Caroline; Piquet, Marie-Astrid; Bedu, Elodie; Rouleau, Vincent; Dautresme, Marianne; Hourmand-Ollivier, Isabelle; Filippi, Céline; Duchamp, Claude; Sibille, Brigitte

2007-01-01

Background Understanding of nonalcoholic steatohepatitis (NASH) is hampered by the lack of a suitable model. Our aim was to investigate whether long term high saturated-fat feeding would induce NASH in rats. Methods 21 day-old rats fed high fat diets for 14 weeks, with either coconut oil or butter, and were compared with rats feeding a standard diet or a methionine choline-deficient (MCD) diet, a non physiological model of NASH. Results MCDD fed rats rapidly lost weight and showed NASH features. Rats fed coconut (86% of saturated fatty acid) or butter (51% of saturated fatty acid) had an increased caloric intake (+143% and +30%). At the end of the study period, total lipid ingestion in term of percentage of energy intake was higher in both coconut (45%) and butter (42%) groups than in the standard (7%) diet group. No change in body mass was observed as compared with standard rats at the end of the experiment. However, high fat fed rats were fattier with enlarged white and brown adipose tissue (BAT) depots, but they showed no liver steatosis and no difference in triglyceride content in hepatocytes, as compared with standard rats. Absence of hepatic lipid accumulation with high fat diets was not related to a higher lipid oxidation by isolated hepatocytes (unchanged ketogenesis and oxygen consumption) or hepatic mitochondrial respiration but was rather associated with a rise in BAT uncoupling protein UCP1 (+25–28% vs standard). Conclusion Long term high saturated fat feeding led to increased "peripheral" fat storage and BAT thermogenesis but did not induce hepatic steatosis and NASH. PMID:17313679

The Anti-Inflammatory Effects of a Yin Zhi Huang Soup in an Experimental Autoimmune Prostatitis Rat Model

PubMed Central

Zhang, Xikui; Zhu, Weikun; Lu, Taikun; Chen, Jinchun; Zou, Qiang; Zheng, Qizhong; Chen, Junying; Jiang, Changming; Jin, Guanyu

2017-01-01

The present study aimed to investigate the therapeutic effects of the Chinese herbal medicine Yin Zhi Huang soup (YZS) in an experimental autoimmune prostatitis (EAP) rat model. In total, 48 rats were randomly divided into the following four groups (n = 12/group): saline group, pathological model group, Qianlietai group, and YZS group. We determined the average wet weight of the prostate tissue, the ratio of the wet weight of the prostate tissue to body weight, tumor necrosis factor-alpha (TNF-α) levels in the blood serum, the expression of inducible nitric oxide synthase (iNOS) in the rats' prostate tissues, and the pathological changes in the prostate tissue using light microscopy. YZS reduced the rats' prostate wet weight, the ratio of the prostate wet weight to body weight, and TNF-α levels in the blood serum and inhibited the expression of iNOS in the rats' prostate tissues (P < 0.05). Following YZS treatment, the pathological changes in the rats' prostates were improved compared with those in the model group (P < 0.05). Furthermore, YZS treatment reduced inflammatory changes in the prostate tissue. It also significantly suppressed proinflammatory cytokines, such as TNF-α, and chemokines, such as iNOS, in the rat model of EAP. PMID:29430255

The Anti-Inflammatory Effects of a Yin Zhi Huang Soup in an Experimental Autoimmune Prostatitis Rat Model.

PubMed

Deng, Longsheng; Zhang, Xikui; Zhu, Weikun; Lu, Taikun; Chen, Jinchun; Zou, Qiang; Zheng, Qizhong; Chen, Junying; Jiang, Changming; Jin, Guanyu

2017-01-01

The present study aimed to investigate the therapeutic effects of the Chinese herbal medicine Yin Zhi Huang soup (YZS) in an experimental autoimmune prostatitis (EAP) rat model. In total, 48 rats were randomly divided into the following four groups ( n = 12/group): saline group, pathological model group, Qianlietai group, and YZS group. We determined the average wet weight of the prostate tissue, the ratio of the wet weight of the prostate tissue to body weight, tumor necrosis factor-alpha (TNF- α ) levels in the blood serum, the expression of inducible nitric oxide synthase (iNOS) in the rats' prostate tissues, and the pathological changes in the prostate tissue using light microscopy. YZS reduced the rats' prostate wet weight, the ratio of the prostate wet weight to body weight, and TNF- α levels in the blood serum and inhibited the expression of iNOS in the rats' prostate tissues ( P < 0.05). Following YZS treatment, the pathological changes in the rats' prostates were improved compared with those in the model group ( P < 0.05). Furthermore, YZS treatment reduced inflammatory changes in the prostate tissue. It also significantly suppressed proinflammatory cytokines, such as TNF- α , and chemokines, such as iNOS, in the rat model of EAP.

Transgenic animal model for studying the mechanism of obesity-associated stress urinary incontinence.

PubMed

Wang, Lin; Lin, Guiting; Lee, Yung-Chin; Reed-Maldonado, Amanda B; Sanford, Melissa T; Wang, Guifang; Li, Huixi; Banie, Lia; Xin, Zhengcheng; Lue, Tom F

2017-02-01

To study and compare the function and structure of the urethral sphincter in female Zucker lean (ZL) and Zucker fatty (ZF) rats and to assess the viability of ZF fats as a model for female obesity-associated stress urinary incontinence (SUI). Two study arms were created: a ZL arm including 16-week-old female ZL rats (ZUC-Lepr fa 186; n = 12) and a ZF arm including 16-week-old female ZF rats (ZUC-Lepr fa 185; n = 12). I.p. insulin tolerance testing was carried out before functional study. Metabolic cages, conscious cystometry and leak point pressure (LPP) assessments were conducted. Urethral tissues were harvested for immunofluorescence staining to check intramyocellular lipid (IMCL) and sphincter muscle (smooth muscle and striated muscle) composition. The ZF rats had insulin resistance, a greater voiding frequency and lower LPP compared with ZL rats (P < 0.05), with more IMCL deposition localized in the urethral striated muscle fibres of the ZF rats (P < 0.05). The thickness of the striated muscle layer and the ratio of striated muscle to smooth muscle were lower in ZF than in ZL rats. Obesity impairs urethral sphincter function via IMCL deposition and leads to atrophy and distortion of urethral striated muscle. The ZF rats could be a consistent and reliable animal model in which to study obesity-associated SUI. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Exploring a post-traumatic stress disorder paradigm in Flinders sensitive line rats to model treatment-resistant depression I: bio-behavioural validation and response to imipramine.

PubMed

Brand, Sarel Jacobus; Harvey, Brian Herbert

2017-08-01

Co-morbid depression with post-traumatic stress disorder (PTSD) is often treatment resistant. In developing a preclinical model of treatment-resistant depression (TRD), we combined animal models of depression and PTSD to produce an animal with more severe as well as treatment-resistant depressive-like behaviours. Male Flinders sensitive line (FSL) rats, a genetic animal model of depression, were exposed to a stress re-stress model of PTSD [time-dependent sensitisation (TDS)] and compared with stress-naive controls. Seven days after TDS stress, depressive-like and coping behaviours as well as hippocampal and cortical noradrenaline (NA) and 5-hydroxyindoleacetic acid (5HIAA) levels were analysed. Response to sub-chronic imipramine treatment (IMI; 10 mg/kg s.c.×7 days) was subsequently studied. FSL rats demonstrated bio-behavioural characteristics of depression. Exposure to TDS stress in FSL rats correlated negatively with weight gain, while demonstrating reduced swimming behaviour and increased immobility versus unstressed FSL rats. IMI significantly reversed depressive-like (immobility) behaviour and enhanced active coping behaviour (swimming and climbing) in FSL rats. The latter was significantly attenuated in FSL rats exposed to TDS versus unstressed FSL rats. IMI reversed reduced 5HIAA levels in unstressed FSL rats, whereas exposure to TDS negated this effect. Lowered NA levels in FSL rats were sustained after TDS with IMI significantly reversing this in the hippocampus. Combining a gene-X-environment model of depression with a PTSD paradigm produces exaggerated depressive-like symptoms that display an attenuated response to antidepressant treatment. This work confirms combining FSL rats with TDS exposure as a putative animal model of TRD.

Obesity decreases serum selenium levels in DMBA-induced mammary tumor using Obese Zucker Rat Model

USDA-ARS?s Scientific Manuscript database

Recently, we reported that obese Zucker rats had increased susceptibility to DMBA-induced mammary tumors compared to lean Zucker rats. Several studies suggest that lower serum selenium may play an important role in increasing the risk of several types of cancers (e.g, colon, breast and prostate canc...

[Effects of quercetin on the learning and memory ability of neonatal rats with hypoxic-ischemic brain damage].

PubMed

Huang, Jing-Jing; Liu, Xuan; Wang, Xing-Qi; Yang, Li-Hua; Qi, Da-Shi; Yao, Rui-Qin

2012-06-01

To study the effects of quercetin, a flavonoid, on the learning and memory ability of 3-day-old neonatal rats with hypoxic-ischemic brain white matter damage (WMD). Sixty 3-day-old Sprague-Dawley rats were randomly divided into four groups: control, WMD model,and quercetin treatment groups (20 and 40 mg/kg). There were 15 rats in each group. Rats in the WMD model and the two quercetin treatment groups were subjected to right common carotid artery ligation followed by 2 hrs of exposure to 8% O2 to induce periventricular white matter injury. After the operation quercetin was administered daily in the two quercetin treatment groups for 6 weeks. Six weeks later, Morris water maze and open-field tests were carried out to test memory and learning ability as well as behavior and cognition. From the second day of training, escape latency in the Morris water maze test was more prolonged in the WMD model group than in the control group (P<0.01). The escape latency in the two quercetin treatment groups was shortened significantly compared with the WMD model group (P<0.05). The WMD model group crossed the original platform fewer times compared with the control and quercetin treatment groups (P<0.05). The open-field test indicated that the number of rearings increased and time spent in the centre was extended in the WMD model group compared with the control group. Compared with the WMD model group, the number of rearings was significantly reduced (P<0.05) and time spent in the centre was significantly shortened in the quercetin treatment groups (P<0.05). Quercetin treatment can improve memory and learning ability as well as cognitive ability in neonates with WMD, suggesting that quercetin protects against WMD resulting from hypoxia-ischemia.

Hydrogen-rich water attenuates experimental periodontitis in a rat model.

PubMed

Kasuyama, Kenta; Tomofuji, Takaaki; Ekuni, Daisuke; Tamaki, Naofumi; Azuma, Tetsuji; Irie, Koichiro; Endo, Yasumasa; Morita, Manabu

2011-12-01

Reactive oxygen species (ROS) contribute to the development of periodontitis. As molecular hydrogen can act as a scavenger of ROS, we examined the effects of treatment with hydrogen-rich water on a rat model of periodontitis. A ligature was placed around the maxillary molars for 4 weeks to induce periodontitis, and the animals were given drinking water with or without hydrogen-rich water. The rats with periodontitis which were treated with pure water showed a time-dependent increase in serum ROS level. Compared with the rats without periodontitis, the periodontitis-induced rats which were given pure water also showed polymorphonuclear leucocyte infiltration and alveolar bone loss at 4 weeks. Hydrogen-rich water intake inhibited an increase in serum ROS level and lowered expression of 8-hydroxydeoxyguanosine and nitrotyrosine in the periodontal tissue at 4 weeks. Such conditions prevented polymorphonuclear leucocyte infiltration and osteoclast differentiation following periodontitis progression. Furthermore, inflammatory signalling pathways, such as mitogen-activated protein kinases, were less activated in periodontal lesions from hydrogen-rich water-treated rats as compared with pure water-treated rats. Consuming hydrogen-rich water might be beneficial in suppressing periodontitis progression by decreasing gingival oxidative stress. © 2011 John Wiley & Sons A/S.

Impact of Parturition on Chemokine Homing Factor Expression in the Vaginal Distention Model of Stress Urinary Incontinence

PubMed Central

Lenis, Andrew T.; Kuang, Mei; Woo, Lynn L.; Hijaz, Adonis; Penn, Marc S.; Butler, Robert S.; Rackley, Raymond; Damaser, Margot S.; Wood, Hadley M.

2015-01-01

Purpose Human childbirth simulated by vaginal distention is known to increase the expression of chemokines and receptors involved in stem cell homing and tissue repair. We hypothesized that pregnancy and parturition in rats contributes to the expression of chemokines and receptors after vaginal distention. Materials and Methods We used 72 age matched female Lewis rats, including virgin rats with and without vaginal distention, and delivered rats with and without vaginal distention. Each rat was sacrificed immediately, or 3 or 7 days after vaginal distention and/or parturition, and the urethra was harvested. Relative expression of chemokines and receptors was determined by real-time polymerase chain reaction. Mixed models were used with the Bonferroni correction for multiple comparisons. Results Vaginal distention up-regulated urethral expression of CCL7 immediately after injury in virgin and postpartum rats. Hypoxia inducible factor-1α and vascular endothelial growth factor were up-regulated only in virgin rats immediately after vaginal distention. CD191 expression was immediately up-regulated in postpartum rats without vaginal distention compared to virgin rats without vaginal distention. CD195 was up-regulated in virgin rats 3 days after vaginal distention compared to virgin rats without vaginal distention. CD193 and CXCR4 showed delayed up-regulation in virgin rats 7 days after vaginal distention. CXCL12 was up-regulated in virgin rats 3 days after vaginal distention compared to immediately after vaginal distention. Interleukin-8 and CD192 showed no differential expression. Conclusions Vaginal distention results in up-regulation of the chemokines and receptors expressed during tissue injury, which may facilitate the spontaneous functional recovery previously noted. Pregnancy and delivery up-regulated CD191 and attenuated the expression of hypoxia inducible factor-1α and vascular endothelial growth factor in the setting of vaginal distention, likely by decreasing hypoxia. PMID:23022009

Neuropeptide S alters anxiety, but not depression-like behaviour in Flinders Sensitive Line rats: a genetic animal model of depression.

PubMed

Wegener, Gregers; Finger, Beate C; Elfving, Betina; Keller, Kirsten; Liebenberg, Nico; Fischer, Christina W; Singewald, Nicolas; Slattery, David A; Neumann, Inga D; Mathé, Aleksander A

2012-04-01

Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behaviour in rodents. However, little knowledge is available regarding the NPS system in depression-related behaviours, and whether NPS also exerts anxiolytic effects in an animal model of psychopathology. Therefore, the aim of this work was to characterize the effects of NPS on depression- and anxiety-related parameters, using male and female rats in a well-validated animal model of depression: the Flinders Sensitive Line (FSL), their controls, the Flinders Resistant Line (FRL), and Sprague-Dawley (SD) rats. We found that FSL showed greater immobility in the forced swim test (FST) than FRL, confirming their phenotype. However, NPS did not affect depression-related behaviour in any rat line. No significant differences in baseline anxiety levels between the FSL and FRL strains were observed, but FSL and FRL rats displayed less anxiety-like behaviour compared to SD rats. NPS decreased anxiety-like behaviour on the elevated plus-maze in all strains. The expression of the NPSR in the amygdala, periventricular hypothalamic nucleus, and hippocampus was equal in all male strains, although a trend towards reduced expression within the amygdala was observed in FSL rats compared to SD rats. In conclusion, NPS had a marked anxiolytic effect in FSL, FRL and SD rats, but did not modify the depression-related behaviour in any strain, in spite of the significant differences in innate level between the strains. These findings suggest that NPS specifically modifies anxiety behaviour but cannot overcome/reverse a genetically mediated depression phenotype.

A pectin-honey hydrogel prevents postoperative intraperitoneal adhesions in a rat model.

PubMed

Giusto, Gessica; Vercelli, Cristina; Iussich, Selina; Audisio, Andrea; Morello, Emanuela; Odore, Rosangela; Gandini, Marco

2017-02-17

Adhesions are a common postoperative surgical complication. Liquid honey has been used intraperitoneally to reduce the incidence of these adhesions. However, solid barriers are considered more effective than liquids in decreasing postoperative intra-abdominal adhesion formation; therefore, a new pectin-honey hydrogel (PHH) was produced and its effectiveness was evaluated in a rat cecal abrasion model. Standardized cecal/peritoneal abrasion was performed through laparotomy in 48 adult Sprague-Dawley rats to induce peritoneal adhesion formation. Rats were randomly assigned to a control (C) and treatment (T) group. In group T, PHHs were placed between the injured peritoneum and cecum. Animals were euthanized on day 15 after surgery. Adhesions were evaluated macroscopically and adhesion scores were recorded and compared between the two groups. Inflammation, fibrosis, and neovascularization were histologically graded and compared between the groups. In group C, 17 of 24 (70.8%) animals developed adhesions between the cecum and peritoneum, while in group T only 5 of 24 (20.8%) did (p = 0.0012). In group C, one rat had an adhesion score of 3, sixteen had scores of 2, and seven rats had scores of 0. In group T, four rats had adhesion scores of 2, one rat had an adhesion score of 1 and nineteen have score 0 (p = 0.0003). Significantly lower grades of inflammation, fibrosis, and neovascularization were seen in group T (p = 0.006, p = 0.001, p = 0.002, respectively). PHH is a novel absorbable barrier that is effective in preventing intra-abdominal adhesions in a cecal abrasion model in rats.

Assessing Anticalcification Treatments in Bioprosthetic Tissue by Using the New Zealand Rabbit Intramuscular Model

PubMed Central

Wright, Gregory A; Faught, Joelle M; Olin, Jane M

2009-01-01

The objective of this work was to demonstrate that the New Zealand White (NZW) rabbit intramuscular model can be used for detecting calcification in bioprosthetic tissue and to compare the calcification in the rabbit to that of native human valves. The rabbit model was compared with the commonly used Sprague–Dawley rat subcutaneous model. Eighteen rabbits and 18 rats were used to assess calcification in bioprosthetic tissue over time (7, 14, 30, and 90 d). The explanted rabbit and rat tissue discs were measured for calcium by using atomic absorption and Raman spectroscopy. Calcium deposits on the human valve explants were assessed by using Raman spectroscopy. The results showed that the NZW rabbit model is robust for detecting calcification in a shorter duration (14 d), with less infection complications, more space to implant tissue groups (thereby reducing animal use numbers), and a more metabolically and mechanically dynamic environment than the rat subcutaneous model . The human explanted valves and rabbit explanted tissue both showed Raman peaks at 960 cm−1 which is representative of hydroxyapatite. Hydroxyapatite is the final calcium and phosphate species in the calcification of bioprosthetic heart valves and rabbit intramuscular implants. The NZW rabbit intramuscular model is an effective model for assessing calcification in bioprosthetic tissue. PMID:19619417

Pretreatment with intravenous lipid emulsion reduces mortality from cocaine toxicity in a rat model.

PubMed

Carreiro, Stephanie; Blum, Jared; Hack, Jason B

2014-07-01

We compare the effects of intravenous lipid emulsion and normal saline solution pretreatment on mortality and hemodynamic changes in a rat model of cocaine toxicity. We hypothesize that intravenous lipid emulsion will decrease mortality and hemodynamic changes caused by cocaine administration compared with saline solution. Twenty male Sprague-Dawley rats were sedated and randomized to receive intravenous lipid emulsion or normal saline solution, followed by a 10 mg/kg bolus of intravenous cocaine. Continuous monitoring included intra-arterial blood pressure, pulse rate and ECG tracing. Endpoints included a sustained undetectable mean arterial pressure (MAP) or return to baseline MAP for 5 minutes. The log-rank test was used to compare mortality. A mixed-effect repeated-measures ANOVA was used to estimate the effects of group (intravenous lipid emulsion versus saline solution), time, and survival on change in MAP, pulse rate, or pulse pressure. In the normal saline solution group, 7 of 10 animals died compared with 2 of 10 in the intravenous lipid emulsion group. The survival rate of 80% (95% confidence interval 55% to 100%) for the intravenous lipid emulsion rats and 30% (95% confidence interval 0.2% to 58%) for the normal saline solution group was statistically significant (P=.045). Intravenous lipid emulsion pretreatment decreased cocaine-induced cardiovascular collapse and blunted hypotensive effects compared with normal saline solution in this rat model of acute lethal cocaine intoxication. Intravenous lipid emulsion should be investigated further as a potential adjunct in the treatment of severe cocaine toxicity. Copyright © 2013 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

[Effects of Salvianolate on Myosin Heavy Chain in Cardiomyocytes of Congestive Heart Failure Rats].

PubMed

Chen, Cheng; Zou, Xiang-gu; Qiu, Shan-dong; Chen, Hui; Chen, Yong-zhong; Lin, Xiu-ming

2015-07-01

To explore the effect of Salvianolate on myosin heavy chain (MHC) in cardiomyocytes of congestive heart failure (CHF) rats. Sixty male SD rats were divided into 6 groups according to random digit table, i.e., the normal control group (NCG), the model group, the Captopril group (CAG), the low dose Salvianolate group (LSG), the high dose Salvianolate group (HSG), the Captopril and high dose Salvianolate group (CSG), 10 in each group. CHF rat model was established with peritoneal injection of adriamycin in all rats except those in the NCG. Equal volume of normal saline was peritoneally injected to rats in the NCG, once per week for 6 successive weeks. Corresponding medication was started from the 5th week of injecting adriamycin. Rats in the CAG were administered with Captopril solution at the daily dose of 10 mg/kg by gastrogavage. Rats in the LSG and the HSG were administered with Salvianolate solution at the daily dose of 24.219 mg/kg and 48.438 mg/kg respectively by gastrogavage. Salvianolate was dissolved in 2 mL 5% glucose solution and administered by peritoneal injection. Rats in the CSG were peritoneally injected with high dose Salvianolate solution and administered with Captopril solution by gastrogavage. Two mL normal saline was peritoneally injected to rats in the model group, once per day for 8 successive weeks. Eight weeks later, the cardiac function and myocardial hypertrophy indices were detected by biological signal collecting and processing system. mRNA expression levels of alpha-MHC and beta-MHC in cardiac muscle were detected by fluorescence quantitative PCR. Expressions of protein kinase C (PKC) in cardiac muscle were detected by Western blot. Compared with the normal control group, heart mass index (HMI) and left ventricular mass index (LVMI) obviously increased in the model group (P < 0.01). Compared with the model group, HMI and LVMI decreased in HSG, CAG, and CSG groups (P < 0.05, P < 0.01). It was more obviously lowered in the CSG group than in the CAG group (P < 0.05). Compared with the NCG, the mRNA expression level of alpha-MHC in cardiac muscle decreased, the mRNA expression level of p-MHC and the expression of PKC in cardiac muscle increased in the model group (P < 0.01). Compared with the model group, the mRNA expression level of alpha-MHC in cardiac muscle was increased, and the mRNA expression level of beta-MHC and the expression of PKC in cardiac muscle were decreased in HSG, CAG, and CSG groups (P < 0.05, P < 0.01). There was statistical difference between the CSG group and the CAG group (P < 0.05). Salvianolate could up-regulate the mRNA expression level of alpha-MHC, and down-regulate the mRNA expression level of beta-MHC in cardiac muscle. Its mechanism might be related to decreasing the expression of PKC.

Effect of caffeic acid phenethyl ester on oxidant and anti-oxidant status of liver and serum in a rat model with acute methanol intoxication.

PubMed

Yazgan, Ü C; Elbey, B; Kuş, S; Baykal, B; Keskin, I; Yılmaz, A; Şahin, A

2017-05-01

Methanol toxicity is one of the major public health problems because it can cause severe morbidity and mortality. Methanol intoxication causes changes in the balance between the production of free radicals and antioxidant capacity. We aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on the total oxidant status, total antioxidant status (TAS), and oxidative stress index (OSI) parameters of the liver and the serum in a rat model of acute methanol intoxication. Rats were treated with intraperitoneal (i.p.) Methotrexate (MTX) for 7 days. On the 8th day, i.p. Methanol was administered in the methanol, ethanol and CAPE groups. Four hours after methanol treatment, ethanol was injected i.p. in the ethanol group; CAPE (i.p.) in the CAPE group; serum physiologic i.p. in other groups. After 8 hours, rats were killed and the serum and the liver samples were obtained for biochemical analyses. The OSI value was significantly higher in the methanol group compared to the ethanol and CAPE groups. Serum TAS levels of the methanol group were significantly different compared to the control group, but not compared to the MTX group. The amelioration of oxidative stress was greater in the CAPE group compared to the ethanol group but was not statistically significant. This study demonstrates that CAPE treatment ameliorates oxidative stress in the serum and liver in a rat model of acute methanol intoxication.

Postnatal treatment with metyrapone attenuates the effects of diet-induced obesity in female rats exposed to early-life stress.

PubMed

Murphy, Margaret O; Herald, Joseph B; Wills, Caleb T; Unfried, Stanley G; Cohn, Dianne M; Loria, Analia S

2017-02-01

Experimental studies in rodents have shown that females are more susceptible to exhibiting fat expansion and metabolic disease compared with males in several models of fetal programming. This study tested the hypothesis that female rat pups exposed to maternal separation (MatSep), a model of early-life stress, display an exacerbated response to diet-induced obesity compared with male rats. Also, we tested whether the postnatal treatment with metyrapone (MTP), a corticosterone synthase inhibitor, would attenuate this phenotype. MatSep was performed in WKY offspring by separation from the dam (3 h/day, postnatal days 2-14). Upon weaning, male and female rats were placed on a normal (ND; 18% kcal fat) or high-fat diet (HFD; 60% kcal fat). Nondisturbed littermates served as controls. In male rats, no diet-induced differences in body weight (BW), glucose tolerance, and fat tissue weight and morphology were found between MatSep and control male rats. However, female MatSep rats displayed increased BW gain, fat pad weights, and glucose intolerance compared with control rats (P < 0.05). Also, HFD increased plasma corticosterone (196 ± 51 vs. 79 ± 18 pg/ml, P < 0.05) and leptin levels (1.8 ± 0.4 vs. 1.3 ± 0.1 ng/ml, P < 0.05) in female MatSep compared with control rats, whereas insulin and adiponectin levels were similar between groups. Female control and MatSep offspring were treated with MTP (50 µg/g ip) 30 min before the daily separation. MTP treatment significantly attenuated diet-induced obesity risk factors, including elevated adiposity, hyperleptinemia, and glucose intolerance. These findings show that exposure to stress hormones during early life could be a key event to enhance diet-induced obesity and metabolic disease in female rats. Thus, pharmacological and/or behavioral inflection of the stress levels is a potential therapeutic approach for prevention of early life stress-enhanced obesity and metabolic disease. Copyright © 2017 the American Physiological Society.

Social stress contagion in rats: Behavioural, autonomic and neuroendocrine correlates.

PubMed

Carnevali, Luca; Montano, Nicola; Statello, Rosario; Coudé, Gino; Vacondio, Federica; Rivara, Silvia; Ferrari, Pier Francesco; Sgoifo, Andrea

2017-08-01

The negative emotional consequences associated with life stress exposure in an individual can affect the emotional state of social partners. In this study, we describe an experimental rat model of social stress contagion and its effects on social behaviour and cardiac autonomic and neuroendocrine functions. Adult male Wistar rats were pair-housed and one animal (designated as "demonstrator" (DEM)) was submitted to either social defeat stress (STR) by an aggressive male Wild-type rat in a separate room or just exposed to an unfamiliar empty cage (control condition, CTR), once a day for 4 consecutive days. We evaluated the influence of cohabitation with a STR DEM on behavioural, cardiac autonomic and neuroendocrine outcomes in the cagemate (defined "observer" (OBS)). After repeated social stress, STR DEM rats showed clear signs of social avoidance when tested in a new social context compared to CTR DEM rats. Interestingly, also their cagemate STR OBSs showed higher levels of social avoidance compared to CTR OBSs. Moreover, STR OBS rats exhibited a higher heart rate and a larger shift of cardiac autonomic balance toward sympathetic prevalence (as indexed by heart rate variability analysis) immediately after the first reunification with their STR DEMs, compared to the control condition. This heightened cardiac autonomic responsiveness habituated over time. Finally, STR OBSs showed elevated plasma corticosterone levels at the end of the experimental protocol compared to CTR OBSs. These findings demonstrate that cohabitation with a DEM rat, which has experienced repeated social defeat stress, substantially disrupts social behaviour and induces short-lasting cardiac autonomic activation and hypothalamic-pituitary-adrenal axis hyperactivity in the OBS rat, thus suggesting emotional state-matching between the OBS and the DEM rats. We conclude that this rodent model may be further exploited for investigating the neurobiological bases of negative affective sharing between social partners under chronic social stress conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of oral bioavailability of benzo[a]pyrene in soils using rat and swine and the implications for human health risk assessment.

PubMed

Duan, Luchun; Naidu, Ravi; Liu, Yanju; Dong, Zhaomin; Mallavarapu, Megharaj; Herde, Paul; Kuchel, Tim; Semple, Kirk T

2016-09-01

There are many uncertainties concerning variations in benzo[a]pyrene (B[a]P) soil guidelines protecting human health based on carcinogenic data obtained in animal studies. Although swine is recognised as being much more representative of the human child in terms of body size, gut physiology and genetic profile the rat/mice model is commonly used in practice. We compare B[a]P bioavailability using a rat model to that estimated in a swine model, to investigate the correlation between these two animal models. This may help reduce uncertainty in applying bioavailability to human health risk assessment. Twelve spiked soil samples and a spiked silica sand (reference material) were dosed to rats in parallel with a swine study. B[a]P bioavailability was estimated by the area under the plasma B[a]P concentration-time curve (AUC) and faecal excretion as well in the rats. Direct comparison between the two animal models was made for: firstly, relative bioavailability (RB) using AUC assay; and secondly, the two assays in the rat model. Both AUC and faecal excretion assays showed linear dose-response for the reference material. However, absolute bioavailability was significantly higher when using faecal excretion assay (p<0.001). In aged soils faecal excretion estimated based on solvent extraction was not accurate due to the form of non-extractable fraction through ageing. A significant correlation existed between the two models using RB for soil samples (RBrat=0.26RBswine+17.3, R(2)=0.70, p<0.001), despite the regression slope coefficient revealing that the rat model would underestimate RB by about one quarter compared to using swine. In the comparison employed in this study, an interspecies difference of four in RB using AUC assay was identified between the rat and swine models regarding pharmacokinetic differences, which supported the body weight scaling method recommended by US EPA. Future research should focus on the carcinogenic competency (pharmacodynamics) used in experiment animals and humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reconciled rat and human metabolic networks for comparative toxicogenomics and biomarker predictions

PubMed Central

Blais, Edik M.; Rawls, Kristopher D.; Dougherty, Bonnie V.; Li, Zhuo I.; Kolling, Glynis L.; Ye, Ping; Wallqvist, Anders; Papin, Jason A.

2017-01-01

The laboratory rat has been used as a surrogate to study human biology for more than a century. Here we present the first genome-scale network reconstruction of Rattus norvegicus metabolism, iRno, and a significantly improved reconstruction of human metabolism, iHsa. These curated models comprehensively capture metabolic features known to distinguish rats from humans including vitamin C and bile acid synthesis pathways. After reconciling network differences between iRno and iHsa, we integrate toxicogenomics data from rat and human hepatocytes, to generate biomarker predictions in response to 76 drugs. We validate comparative predictions for xanthine derivatives with new experimental data and literature-based evidence delineating metabolite biomarkers unique to humans. Our results provide mechanistic insights into species-specific metabolism and facilitate the selection of biomarkers consistent with rat and human biology. These models can serve as powerful computational platforms for contextualizing experimental data and making functional predictions for clinical and basic science applications. PMID:28176778

Effect of Jianweiyuyang granule on gastric ulcer recurrence and expression of VEGF mRNA in the healing process of gastric ulcer in rats.

PubMed

Dai, Xing-Ping; Li, Jia-Bang; Liu, Zhao-Qian; Ding, Xiang; Huang, Cheng-Hui; Zhou, Bing

2005-09-21

To investigate the effect of Jianweiyuyang (JWYY) granule on gastric ulcer recurrence and its mechanism in the treatment of gastric ulcer in rats. Gastric ulcer in rats was induced according to Okeba's method with minor modification and the recurrence model was induced by IL-1beta. The expression of vascular endothelial growth factor mRNA (VEGF mRNA) was examined by reverse transcription polymerase chain reaction in gastric ulcer and microvessel density (MVD) adjacent to the ulcer margin was examined by immunohistochemistry. MVD was higher in the JWYY treatment group (14.0+/-2.62) compared with the normal, model and ranitidine treatment groups (2.2+/-0.84, 8.8+/-0.97, 10.4+/-0.97) in rats (P<0.01). The expression level of VEGF mRNA in gastric tissues during the healing process of JWYY treatment group rats significantly increased compared with other groups (normal group: 0.190+/-0.019, model group: 0.642+/-0.034, ranitidine group: 0.790+/-0.037, P<0.01). JWYY granules can stimulate angiogenesis and enhance the expression of VEGF mRNA in gastric ulcer rats. This might be the mechanism for JWYY accelerating the ulcer healing, and preventing the recurrence of gastric ulcer.

Comparative analysis of two different models of swimming applied to pregnant rats born small for pregnant age.

PubMed

Corvino, Silvana B; Damasceno, Débora C; Sinzato, Yuri K; Netto, Aline O; Macedo, Nathália C D; Zambrano, Elena; Volpato, Gustavo T

2017-01-01

The aim of this study was to compare two models of swimming applied to pregnant rats born small for pregnancy age (SPA). Diabetes was chemically induced in adult female rats to develop an inadequate intrauterine environment, leading to birth of a SPA offspring. In adulthood, the female SPA rats were mated and submitted to different swimming programs. The exercise program 1 (Ex1) consisted of swimming for 15 minutes, followed by 15 minutes of rest and another 15 minutes of swimming, 3 days a week before and during pregnancy. Another program (Ex2) was applied during 60 minutes uninterrupted a day, 6 days/week during pregnancy. The pregnant rats presented no interference on body weight and glycemia. The rats submitted to Ex2 model showed decreased insulin and blood glucose levels by oral glucose tolerance test, and reduction in area under curve values. The offspring from dams submitted to both exercise protocols presented an increased rate of newborns SPA. However, the offspring from Ex2 dams showed percentage twice higher of newborns SPA than Ex1 offspring. Our data suggests that continuous exercise of 60 min/day ameliorated the enhanced peripheral insulin sensitivity in growth-restricted females. However, this protocol employed at pregnancy leads to intrauterine growth restriction.

Effect of streptozotocin-induced diabetes on left ventricular function in adult rats: an in vivo Pinhole Gated SPECT study

PubMed Central

Cosyns, Bernard; Droogmans, Steven; Weytjens, Caroline; Lahoutte, Tony; Van Camp, Guy; Schoors, Danny; Franken, Philippe R

2007-01-01

Background Recent studies have suggested that diabetes mellitus (DM) may cause left ventricular (LV) dysfunction directly resulting in increased susceptibility to heart failure. Using pinhole collimators and advances in data processing, gated SPECT was recently adapted to image the rat heart. The present study was aimed to assess this new imaging technique for quantifying LV function and remodeling from the Streptozotocin (STZ) rat model compared to controls. Methods Twenty one rats were randomly assigned to control or diabetic group. Six months after the induction of diabetes by STZ, Pinhole 99 m Tc-sestamibi gated SPECT was performed for determining rat LV volumes and function. Post-mortem histopathologic analysis was performed to evaluate the determinant of LV remodeling in this model. Results After six months, the normalized to body weight LV End-systolic volume was significantly different in diabetic rats compared to controls (0.46 ± 0.02 vs 0.33 ± 0.03 μL/g; p = 0.01). The normalized LV End-diastolic volume was also different in both groups (1.51 ± 0.03 vs 0.88 ± 0.05 μL/g; p = 0.001) and the normalized stroke volume was significantly higher in STZ-rats (1.05 ± 0.02 vs 0.54 ± 0.06 μL/g; p = 0.001). The muscular fibers were thinner at histology in the diabetic rats (0.44 ± 0.07 vs 0.32 ± 0.06 AU; p = 0.01). Conclusion Pinhole 99 m Tc-sestamibi gated SPECT can successfully be applied for the evaluation of cardiac function and remodeling in STZ-induced diabetic rats. In this model, LV volumes were significantly changed compared to a control population, leading to a LV dysfunction. These findings were consistent with the histopathological abnormalities. Finally, these data further suggest the presence of diabetes cardiomyopathy. PMID:17937784

A placebo-controlled efficacy study of the intravesical immunomodulators TMX-101 and TMX-202 in an orthotopic bladder cancer rat model.

PubMed

Falke, Johannes; Hulsbergen-van de Kaa, Christina A; Maj, Roberto; Oosterwijk, Egbert; Witjes, J Alfred

2018-05-16

TMX-101 and TMX-202 are formulations of toll-like receptor 7 (TLR-7) agonists, under investigation for the treatment of urothelial carcinoma. Our goal was to evaluate the efficacy of intravesical instillations of TMX-101 or TMX-202 in an orthotopic bladder cancer rat model. Four groups of 14 rats received an instillation with isogenic AY-27 tumor cells on day 0, starting tumor development. On day 2 and 5, the rats were treated with an intravesical instillation of TMX-101 0.1%, TMX-202 0.38%, vehicle solution or NaCl. On day 12 the rats were sacrificed and the bladders were evaluated histopathologically. No signs of toxicity were seen. The number of tumor-positive rats was 11 of 14 (79%) in the vehicle control group and in the NaCl control group, versus 9 of 14 (64%) in the TMX-101-treated group, and 8 of 14 (57%) in the TMX-20-treated group. The difference between tumor-bearing rats in the treated and control groups was not significant (p = 0.12). Bladder weight was significantly lower for TMX-202-treated rats compared to vehicle (p = 0.005). TMX-101 and TMX-202 are TLR-7 agonists with antitumor activity. Treatment with TMX-101 and TMX-202 resulted in less tumor-bearing rats compared to vehicle or saline control groups, although not statistically significant. In this aggressive bladder cancer model, a lower number of tumor-positive rats after treatment with TLR-7 agonists indicates activity for the treatment of non-muscle invasive bladder cancer.

Tio2-dopamine complex implanted unilaterally in the caudate nucleus improves motor activity and behavior function of rats with induced hemiparkinsonism.

PubMed

Vergara-Aragón, Patricia; Domínguez-Marrufo, Leonardo Eduardo; Ibarra-Guerrero, Patricia; Hernandez-Ramírez, Heidi; Hernández-Téllez, Beatriz; López-Martínez, Irma Elena; Sánchez-Cervantes, Ivonne; Santiago-Jacinto, Patricia; García-Macedo, Jorge Alberto; Valverde-Aguilar, Guadalupe; Santiago, Julio

2011-01-01

Parkinson's disease (PD) is characterized by malfunction of dopaminergic systems, and the current symptomatic treatment is to replace lost dopamine. For investigating mechanisms of pathogenesis and alternative treatments to compensate lack of dopamine (DA) activity in PD, the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD has been useful, these animals display apomorphine-induced contralateral rotational behavior, when they are examined after lesion. The purpose of this study was to assess Titania-dopamine (TiO2-DA) complexes implanted on the caudate nucleus for diminishing motor behavior alterations of the 6-OHDA rat model. Rats with 6-OHDA unilateral lesions received TiO2 alone or TiO2-DA implants, and were tested for open field (OF) gross motor crossing and rearing behaviors, and apomorphine-induced rotation (G) behavior. TiO2 complex have no effects on rearing OF and G behaviors, and a significant reducing effect on crossing motor behavior of normal rats compared to control non-treated rats throughout 56 days of observation. Interestingly, TiO2-DA treatment significant recovered motor crossing and rearing behaviors in 6-OHDA-lesioned rats, and diminished the G behaviors during 56 days of examination. Additionally, in the 6-OHDA-lesioned rats TiO2 treatment had a moderate recovering effect only on crossing behavior compared to lesioned non treated rats. Our results suggest that continuous release of dopamine in the caudate nucleus from TiO2-DA complex is capable of reversing gross motor deficits observed in the 6-OHDA-lesioned rat model of PD. Thistype of delivery system of DA represents a promising therapy for PD in humans.

[Effect of Electroacupuncture on Hypothalamus-Pituitary-Ovary (HPO) Axis in Rats with Peri-menopausal Depression].

PubMed

Jiang, Xi-Rong; Ren, Lu; Li, Chun-Ri

2017-02-25

To observe the effect of electroacupuncture (EA) on the hormones derived from the hypothalamus-pituitary-ovary (HPO) axis, so as to explore the neuroendocrine mechanism induced by EA on rats with perimenopausal depression disorder. Sixty female sprague-dawley rats were randomly divided into blank control group, model group, sham-operation (sham) group, clomipramine group, and electroacupuncture (EA) group, with 12 rats in each group. Perimenopausal depression model was established by bilateral ovariectomy combined with chronic unpredictable stimulation.The EA group received continuous treatment at "Baihui" (GV 20), "Shenshu" (BL 23) and "Sanyinjiao" (SP 6) once a day for 28 days. Estrous cycle and sucrose preference test were monitored, and serum estradiol (E 2 ), luteinizing hormone (LH), gonadotropin releasing hormone (GnRH), and β-endorphin (β-EP) were detected by ELISA. Compared to the blank control group, sugar water consumpution rates decreased in the model group and sham group ( P <0.05). Compared to the blank group and sham group, the serum LH and GnRH levels increased ( P <0.05), companied with lower serum E 2 and β-EP levels in the model group ( P <0.05). Compared to the model group, sugar water consumpution rates increased in the clomipramine group and EA group ( P <0.05), both were companied with decreased serum LH and GnRH levels ( P <0.05), and higher serum E 2 and β-EP levels ( P <0.05). Electroacupuncture can relieve the symptoms of rat with perimenopausal depression by regulating the hormone secretion in HPO axis.

[Effect of Cordyceps sinensis powder on renal oxidative stress and mitochondria functions in 5/6 nephrectomized rats].

PubMed

Zhang, Ming-hui; Pan, Ming-ming; Ni, Hai-feng; Chen, Jun-feng; Xu, Mn; Gong, Yu-xiang; Chen, Ping-sheng; Liu, Bi-cheng

2015-04-01

To observe the effect of Cordyceps sinensis (CS) powder on renal oxidative stress and mitochondria functions in 5/6 nephrectomized rats, and to primarily explore its possible mechanisms. Totally 30 male Sprague-Dawley rats were divided into the sham-operation group, the model group, and the treatment group by random digit table, 10 in each group. A chronic kidney disease (CKD) rat model was prepared by one step 5/6 nephrectomy. Rats in the treatment group were intragastrically administered with CS powder solution at the daily dose of 2 g/kg, once per day. Equal volume of double distilled water was intragastrically administered to rats in the sham-operation group and the model group. All medication lasted for 12 weeks. The general condition of rats, their body weight, blood pressure, 24 h proteinuria, urinary N-acetyl-β-D-glucosaminidase (NAG), serum creatinine (SCr) , and blood urea nitrogen (BUN) were assessed before surgery, at week 2, 4, 6, 8, 10, and 10 after surgery. Pathological changes of renal tissues were observed under light microscope. Morphological changes of mitochondria in renal tubular epithelial cells were observed under transmission electron microscope. Activities of antioxidant enzymes including reduced glutathione (GSH), manganese superoxide dismutase (MnSOD), and malondialdehyde (MDA) in fresh renal tissue homogenate were detected. Mitochondria of renal tissues were extracted to detect levels of mitochondrial membrane potential and changes of reactive oxygen species (ROS). And expressions of cytochrome-C (Cyto-C) and prohibitin in both mitochondria and cytoplasm of the renal cortex were also measured by Western blot. (1) Compared with the sham-operation group, body weight was significantly decreased at week 2 (P <0. 01), but blood pressure increased at week 4 (P <0. 05) in the model group. Compared with the model group, body weight was significantly increased at week 12 (P <0. 01), but blood pressure decreased at week 8 (P < 0. 01) in the treatment group. (2) Compared with the sham-operation group, 24 h proteinuria, urinary NAG, blood SCr and BUN significantly increased in the model group (all P <0. 01). Compared with the model group, blood and urinary biochemical indices all significantly decreased in the treatment group (all P <0. 01). (3) Results of pathological renal scoring: Glomerular sclerosis index, scoring for tubulointerstitial fibrosis, degree of tubulointerstitial inflammatory infiltration were all obviously higher in the model group than in the sham-operation group (all P <0. 01). All the aforesaid indices were more obviously improved in the treatment group than in the model group (all P <0. 01). (4) Compared with the sham-operation group, activities of MnSOD and GSH-Px were significantly reduced, but MDA contents obviously increased in the renal cortex of the model group (all P <0. 01). Compared with the model group, activities of MnSOD and GSH-Px obviously increased (P <0. 05, P <0. 01), but MDA contents obviously decreased in the renal cortex of the treatment group (P <0. 01). (5) Compared with the sham-operation group, the mitochondrial membrane potential significantly decreased, but ROS levels significantly increased in the model group (all P <0.01). Compared with the model group, mitochondrial transmembrane potential increased in the treatment group, thereby inhibiting the tendency of increased production of ROS (both P < 0. 01). (6) Results of Western blot showed that, compared with the sham-operation group, expression levels of mitochondrial Cyto-C and Prohibitin were significantly reduced in the renal cortex (P <0. 01), but significantly elevated in the cytoplasm of the model group (P <0. 01). Compared with the model group, each index was obviously improved in the treatment group with statistical difference (P <0. 05, P <0. 01). CS powder had renal protection, and its mechanism might partially depend on in- hibition of oxidative stress and protection for mitochondria.

Comparisons of Auricular Cartilage Tissues from Different Species.

PubMed

Chiu, Loraine L Y; Giardini-Rosa, Renata; Weber, Joanna F; Cushing, Sharon L; Waldman, Stephen D

2017-12-01

Tissue engineering of auricular cartilage has great potential in providing readily available materials for reconstructive surgeries. As the field of tissue engineering moves forward to developing human tissues, there needs to be an interspecies comparison of the native auricular cartilage in order to determine a suitable animal model to assess the performance of engineered auricular cartilage in vivo. Here, we performed interspecies comparisons of auricular cartilage by comparing tissue microstructure, protein localization, biochemical composition, and mechanical properties of auricular cartilage tissues from rat, rabbit, pig, cow, and human. Human, pig, and cow auricular cartilage have smaller lacunae compared to rat and rabbit cartilage ( P < .05). Despite differences in tissue microstructure, human auricular cartilage has similar biochemical composition to both rat and rabbit. Auricular cartilage from pig and cow, alternatively, display significantly higher glycosaminoglycan and collagen contents compared to human, rat, and rabbit ( P < .05). The mechanical properties of human auricular cartilage were comparable to that of all 4 animal species. This is the first study that compares the microstructural, biochemical, and mechanical properties of auricular cartilage from different species. This study showed that different experimental animal models of human auricular cartilage may be suitable in different cases.

The effect of the angiotensin II receptor, type 1 receptor antagonists, losartan and telmisartan, on thioacetamide-induced liver fibrosis in rats.

PubMed

Czechowska, G; Celinski, K; Korolczuk, A; Wojcicka, G; Dudka, J; Bojarska, A; Madro, A; Brzozowski, T

2016-08-01

It has been reported previously that the density of angiotensin II receptors is increased in the rat liver in experimentally-induced fibrosis. We hypothesized that pharmacological blockade of angiotensin receptors may produce beneficial effects in models of liver fibrosis. In this study, we used the widely used thioacetamide (TAA)-induced model of liver fibrosis (300 mg/L TAA ad libitum for 12 weeks). Rats received daily injections (i.p), lasting 4 weeks of the angiotensin II type 1 receptor antagonists, losartan 30 mg/kg (TAA + L) or telmisartan 10 mg/kg (TAA + T) and were compared to rat that received TAA alone. Chronic treatment with losartan and telmisartan was associated with a significant reduction in the activity of alkaline phosphatase, and decreased concentrations of tumor necrosis factor-alpha and transforming growth factor beta-1 compared to controls. We also found a significant reduction interleukin-6 in rats receiving telmisartan (P < 0.05) but not losartan. Both treatments increased the concentration of liver glutathione along with a concomitant decrease of GSSG compared to controls. In addition, increased paraoxonase 1 activity was observed in the serum of rats receiving telmisartan group compared to the TAA alone controls. Finally, histological evaluation of liver sections revealed losartan and telmisartan treatment was associated with reduced inflammation and liver fibrosis. Taken together, these results indicate that both telmisartan and losartan have anti-inflammatory and anti-oxidative properties in the TAA model of liver fibrosis. These finding add support to a growing body of literature indicating a potentially important role for the angiotensin system in liver fibrosis and indicate angiotensin antagonists may be useful agents for fibrosis treatment.

Soy Protein Alleviates Hypertension and Fish Oil Improves Diastolic Heart Function in the Han:SPRD-Cy Rat Model of Cystic Kidney Disease.

PubMed

Ibrahim, Naser H M; Thandapilly, Sijo J; Jia, Yong; Netticadan, Thomas; Aukema, Harold

2016-05-01

Abnormalities in cardiac structure and function are very common among people with chronic kidney disease, in whom cardiovascular disease is the major cause of death. Dietary soy protein and fish oil reduce kidney disease progression in the Han:SPRD-Cy model of cystic renal disease. However, the effects of these dietary interventions in preventing alterations in cardiac structure and function due to kidney disease (reno-cardiac syndrome) in a cystic kidney disease model are not known. Therefore, weanling Han:SPRD-Cy diseased (Cy/+) and normal (+/+) rats were given diets containing either casein or soy protein, and either soy or fish oil in a three-way design for 8 weeks. Diseased rats had larger hearts, augmented left ventricular mass, and higher systolic and mean arterial blood pressure compared to the normal rats. Assessment of cardiac function using two-dimensional guided M-mode and pulse-wave Doppler echocardiography revealed that isovolumic relaxation time was prolonged in the diseased compared to normal rats, reflecting a diastolic heart dysfunction, and fish oil prevented this elevation. Soy protein resulted in a small improvement in systolic and mean arterial pressure but did not improve diastolic heart function, while fish oil prevented diastolic heart dysfunction in this model of cystic kidney disease.

Evaluation of an experimental rat model for comparative studies of bleaching agents

PubMed Central

CINTRA, Luciano Tavares Angelo; BENETTI, Francine; FERREIRA, Luciana Louzada; RAHAL, Vanessa; ERVOLINO, Edilson; JACINTO, Rogério de Castilho; GOMES, João Eduardo; BRISO, André Luiz Fraga

2016-01-01

ABSTRACT Dental materials in general are tested in different animal models prior to the clinical use in humans, except for bleaching agents. Objectives To evaluate an experimental rat model for comparative studies of bleaching agents, by investigating the influence of different concentrations and application times of H2O2 gel in the pulp tissue during in-office bleaching of rats’ vital teeth. Material and Methods The right and left maxillary molars of 50 Wistar rats were bleached with 20% and 35% H2O2 gels, respectively, for 5, 10, 15, 30, or 45 min (n=10 rats/group). Ten animals were untreated (control). The rats were killed after 2 or 30 days, and the maxillae were examined by light microscopy. Inflammation was evaluated through histomorphometric analysis with inflammatory cell count in the coronal and radicular thirds of the pulp. Fibroblasts were also counted. Scores were attributed to odontoblastic layer and vascular changes. Tertiary dentin area and pulp chamber central area were measured histomorphometrically. Data were compared by analysis of variance and Kruskal-Wallis test (p<0.05). Results After 2 days, the amount of inflammatory cells increased in the coronal pulp occlusal third up to the 15-min application groups of each bleaching gel. In the groups exposed to each concentration for 30 and 45 min, the number of inflammatory cells decreased along with the appearance of necrotic areas. After 30 days, reduction on the pulp chamber central area and enlargement of the tertiary dentin area were observed, without the detection of inflammation areas. Conclusion The rat model of extracoronal bleaching showed to be adequate for studies of bleaching protocols, as it was possible to observe alterations in the pulp tissues and tooth structure caused by different concentrations and application periods of bleaching agents. PMID:27119766

Behavioral and hormonal responses to stress in binge-like eating prone female rats.

PubMed

Calvez, Juliane; Timofeeva, Elena

2016-04-01

Binge eating episodes are frequently stimulated by stress. We developed a model of binge eating proneness based on individual sensitivity of young female Sprague Dawley rats to significantly increase sucrose consumption in response to stress. The rats were subjected to unpredictable intermittent 1-h access to 10% sucrose. After the stabilization of sucrose intake, rats were assessed for consistency of higher (for binge-like eating prone, BEP) or lower (for binge-like eating resistant, BER) sucrose intake in response to unpredictable episodes of foot-shock stress. The objectives of this study included demonstrating face validity of the BEP model and determining if some of the features of this model were pre-existing before exposure to intermittent access to sucrose and repeated stress. The BEP rats consumed a larger (20%>BER) amount of sucrose in a discrete (1-h) period of time compared to the BER phenotype in non-stressful conditions and significantly increased sucrose intake (50%>BER) under stress. Conversely, stress did not affect sucrose intake in BER rats. BEP rats showed higher sucrose intake compared to BER rats at the beginning of darkness as well as during the light period when they were sated and not physically hungry. Analyses of the sucrose licking microstructure revealed that BEP rats had a high motivational drive to consume sucrose in non-stressful condition and an increased hedonic value of sucrose when they were exposed to stressful conditions. BEP rats consumed sucrose much more rapidly under stressful conditions compared to BER rats. Finally, BEP rats demonstrated compulsive-like intake of sucrose (assessed in the light-dark box) and a blunted stress-induced increase in plasma corticosterone levels. Body weight and chow intake were not different between the phenotypes. Before exposure to intermittent access to sucrose and repeated stress, the BEP rats showed no clear evidence for compulsive sucrose intake. However, from the first 1-h access to sucrose, the BEP rats exhibited sucrose overeating; and from the first exposure to stress before intermittent access to sucrose, the BEP rats showed a blunted increase in corticosterone plasma levels. Innate sucrose hyperconsumption and altered reactivity of the hypothalamo-pituitary adrenal (HPA) axis to stress may be involved in the development of binge-like eating. Increased perceived hedonic value of palatable food and an increased motivation to consume this food despite aversive conditions as well as deregulated reactivity of the HPA axis may contribute to stress-induced bingeing on sucrose in BEP rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Prevention of intra-abdominal adhesion by bi-layer electrospun membrane.

PubMed

Jiang, Shichao; Wang, Wei; Yan, Hede; Fan, Cunyi

2013-06-04

The aim of this study was to compare the anti-adhesion efficacy of a bi-layer electrospun fibrous membrane consisting of hyaluronic acid-loaded poly(ε-caprolactone) (PCL) fibrous membrane as the inner layer and PCL fibrous membrane as the outer layer with a single-layer PCL electrospun fibrous membrane in a rat cecum abrasion model. The rat model utilized a cecal abrasion and abdominal wall insult surgical protocol. The bi-layer and PCL membranes were applied between the cecum and the abdominal wall, respectively. Control animals did not receive any treatment. After postoperative day 14, a visual semiquantitative grading scale was used to grade the extent of adhesion. Histological analysis was performed to reveal the features of adhesion tissues. Bi-layer membrane treated animals showed significantly lower adhesion scores than control animals (p < 0.05) and a lower adhesion score compared with the PCL membrane. Histological analysis of the bi-layer membrane treated rat rarely demonstrated tissue adhesion while that of the PCL membrane treated rat and control rat showed loose and dense adhesion tissues, respectively. Bi-layer membrane can efficiently prevent adhesion formation in abdominal cavity and showed a significantly decreased adhesion tissue formation compared with the control.

Halofuginone can worsen liver fibrosis in bile duct obstructed rats.

PubMed

Van de Casteele, Marc; Roskams, Tania; Van der Elst, Ingrid; van Pelt, Jos F; Fevery, Johan; Nevens, Frederik

2004-10-01

Halofuginone (HF) is an antifibrotic agent in rat models of liver fibrosis caused by repetitive intoxications. A beneficial effect of HF on a biliary type of liver fibrosis has not been proven yet. Bile duct-obstructed rats were given HF from the moment of obstruction onwards and compared with no treatment. After 3 weeks, respectively, 6 weeks, aminopyrine breath test (ABT) and haemodynamic measurements including of portal pressure were carried out. Liver pieces were taken for Sirius red quantitative scoring, as well as for semiquantitative determinations of collagen type I and III RNA levels. ABT was significantly worse in HF-treated rats as compared with no treatment (P=0.02). Haemodynamic data and collagen type I and III determinations were not significantly different between groups. Biliary fibrosis scores were significantly higher in HF-treated rats as compared with no treatment (P=0.03). More Sirius red staining was associated with more proliferation of bile ductules. HF may worsen biliary fibrosis. This contrasts sharply with antifibrotic effects in other models of liver fibrosis. Distinctive cellular mechanisms in biliary fibrosis may explain this discrepancy. One should be cautious for chronic application of HF in man with cholestasis.

Expression and clinical significance of rhubarb on serum amylase and TNF-alpha of rat model of acute pancreatitis.

PubMed

Zhang, W F; Li, Z T; Fang, J J; Wang, G B; Yu, Y; Liu, Z Q; Wu, Y N; Zheng, S S; Cai, L

2017-01-01

The aim of this study was to evaluate the therapeutic effect of rhubarb extract on acute pancreatitis. Ninety-six healthy Sprague Dawley rats, weighing 301±5.12 g were randomly divided into 4 groups: sham surgery (group A), acute pancreatitis model (group B), acute pancreatitis with normal saline (group C), and acute pancreatitis model with rhubarb (group D). The levels of serum amylase (AMY) and TNF-α were measured at 1st, 6th, 12th and 24th hour after modeling, and the pancreatic tissue were used to observe the pathologic changes. Compared to the sham group, the serum AMY and serum tumor necrosis factor (TNF-α) levels were significantly increased in the other groups (p <0.05). Compared to the model group and the saline group, the serum AMY, serum TNF-α level and pathological changes of rats in the rhubarb group were significantly lower (p <0.05). The serum AMY and TNF-α levels increased in acute pancreatitis. The rhubarb reduced the serum AMY and TNF-α level in rats with acute pancreatitis and reduced the pathological changes of pancreas and other tissues.

Rat disc torsional mechanics: effect of lumbar and caudal levels and axial compression load.

PubMed

Espinoza Orías, Alejandro A; Malhotra, Neil R; Elliott, Dawn M

2009-03-01

Rat models with altered loading are used to study disc degeneration and mechano-transduction. Given the prominent role of mechanics in disc function and degeneration, it is critical to measure mechanical behavior to evaluate changes after model interventions. Axial compression mechanics of the rat disc are representative of the human disc when normalized by geometry, and differences between the lumbar and caudal disc have been quantified in axial compression. No study has quantified rat disc torsional mechanics. Compare the torsional mechanical behavior of rat lumbar and caudal discs, determine the contribution of combined axial load on torsional mechanics, and compare the torsional properties of rat discs to human lumbar discs. Cadaveric biomechanical study. Cyclic torsion without compressive load followed by cyclic torsion with a fixed compressive load was applied to rat lumbar and caudal disc levels. The apparent torsional modulus was higher in the lumbar region than in the caudal region: 0.081+/-0.026 (MPa/degrees, mean+/-SD) for lumbar axially loaded; 0.066+/-0.028 for caudal axially loaded; 0.091+/-0.033 for lumbar in pure torsion; and 0.056+/-0.035 for caudal in pure torsion. These values were similar to human disc properties reported in the literature ranging from 0.024 to 0.21 MPa/degrees. Use of the caudal disc as a model may be appropriate if the mechanical focus is within the linear region of the loading regime. These results provide support for use of this animal model in basic science studies with respect to torsional mechanics.

Unprovoked atrial tachyarrhythmias in aging spontaneously hypertensive rats: the role of the autonomic nervous system.

PubMed

Scridon, Alina; Gallet, Clément; Arisha, Moussa M; Oréa, Valérie; Chapuis, Bruno; Li, Na; Tabib, Alain; Christé, Georges; Barrès, Christian; Julien, Claude; Chevalier, Philippe

2012-08-01

Experimental models of unprovoked atrial tachyarrhythmias (AT) in conscious, ambulatory animals are lacking. We hypothesized that the aging, spontaneously hypertensive rat (SHR) may provide such a model. Baseline ECG recordings were acquired with radiotelemetry in eight young (14-wk-old) and eight aging (55-wk-old) SHRs and in two groups of four age-matched Wistar-Kyoto (WKY) rats. Quantification of AT and heart rate variability (HRV) analysis were performed based on 24-h ECG recordings in unrestrained rats. All animals were submitted to an emotional stress protocol (air-jet). In SHRs, carbamylcholine injections were also performed. Spontaneous AT episodes were observed in all eight aging SHRs (median, 91.5; range, 4-444 episodes/24 h), but not in young SHRs or WKY rats. HRV analysis demonstrated significantly decreased low frequency components in aging SHRs compared with age-matched WKY rats (P < 0.01) and decreased low/high frequency ratios in both young (P < 0.01) and aging (P = 0.01) SHRs compared with normotensive controls. In aging SHRs, emotional stress significantly reduced the number of arrhythmic events, whereas carbamylcholine triggered AT and significantly increased atrial electrical instability. This study reports the occurrence of unprovoked episodes of atrial arrhythmia in hypertensive rats, and their increased incidence with aging. Our results suggest that autonomic imbalance with relative vagal hyperactivity may be responsible for the increased atrial arrhythmogenicity observed in this model. We also provide evidence that, in this model, the sympatho-vagal imbalance preceded the occurrence of arrhythmia. These results indicate that aging SHRs may provide valuable insight into the understanding of atrial arrhythmias.

Effect of Zuogui Pill () on monoamine neurotransmitters and sex hormones in climacteric rats with panic attack.

PubMed

Li, Xiao-Yu; Wang, Xiao-Yun

2017-03-01

To explore the effects of Chinese medicine prescription Zuogui Pill (, ZGP) on monoamine neurotransmitters and sex hormones in climacteric rats with induced panic attacks. Forty-eight climacteric female rats were randomized into 6 groups with 8 rats in each group: the control group, the model group, the low-, medium- and high-dose ZGP groups and the alprazolam group. Rats in the low-, medium- and high-dose ZGP groups were administered 4.725, 9.45, or 18.9 g/kg ZGP by gastric perfusion, respectively. The alprazolam group was treated by gastric perfusion with 0.036 mg/kg alprazolam. The control and model groups were treated with distilled water. The animals were pretreated once daily for 8 consecutive weeks. The behaviors of rats in the open fifield test and the elevated T-maze (ETM) were observed after induced panic attack, and the levels of brain monoamine neurotransmitters and the plasma levels of sex hormones were measured. Compared with the control group, the mean ETM escape time and the levels of 5-hydroxytryptamine (5-HT) and noradrenalin (NE) of the model group were signifificantly reduced (P<0.05), Compared with the model group, the mean ETM escape time and the 5-HT and NE levels of all the ZGP groups increased signifificantly (P<0.05 or P<0.01). However, no signifificant difference was observed in the levels of sex hormones between the groups. Pretreatment with ZGP in climacteric rats may improve the behavior of panic attack, which may be related to increased 5-HT and NE in the brain.

[Effect of leptin on long-term spatial memory of rats with white matter damage in developing brain].

PubMed

Feng, Er-Cui; Jiang, Li

2017-12-01

To investigate the neuroprotective effect of leptin by observing its effect on spatial memory of rats with white matter damage in developing brain. A total of 80 neonatal rats were randomly divided into 3 groups: sham-operation (n=27), model (n=27) and leptin intervention (n=27). The rats in the model and leptin intervention groups were used to prepare a model of white matter damage in developing brain, and the rats in the leptin intervention group were given leptin (100 μg/kg) diluted with normal saline immediately after modelling for 4 consecutive days. The survival rate of the rats was observed and the change in body weight was monitored. When the rats reached the age of 21 days, the Morris water maze test was used to evaluate spatial memory. There was no significant difference in the survival rate of rats between the three groups (P>0.05). Within 10 days after birth, the leptin intervention group had similar body weight as the sham-operation group and significantly lower body weight than the model group (P<0.05); more than 10 days after birth, the leptin intervention group had rapid growth with higher body weight than the model and sham-operation groups (P>0.05). The results of place navigation showed that from the second day of experiment, there was a significant difference in the latency period between the three groups (P<0.05); from the fourth day of experiment, the leptin intervention group had a similar latency period as the sham-operation and a significantly shorter latency period than the model group (P<0.05). The results of space search experiment showed that compared with the sham-operation group, the model group had a significant reduction in the number of platform crossings and a significantly longer latency period (P<0.05); compared with the model group, the leptin intervention group had a significantly increased number of platform crossings and a significantly shortened latency period (P<0.05), while there was no significant difference between the leptin intervention and sham-operation groups. Leptin can alleviate spatial memory impairment of rats with white matter damage in developing brain. It thus exerts a neuroprotective effect, and is worthy of further research.

Exercise following a short immobilization period is detrimental to tendon properties and joint mechanics in a rat rotator cuff injury model.

PubMed

Peltz, Cathryn D; Sarver, Joseph J; Dourte, Leann M; Würgler-Hauri, Carola C; Williams, Gerald R; Soslowsky, Louis J

2010-07-01

Rotator cuff tears are a common clinical problem that can result in pain and disability. Previous studies in a rat model showed enhanced tendon to bone healing with postoperative immobilization. The objective of this study was to determine the effect of postimmobilization activity level on insertion site properties and joint mechanics in a rat model. Our hypothesis was that exercise following a short period of immobilization will cause detrimental changes in insertion site properties compared to cage activity following the same period of immobilization, but that passive shoulder mechanics will not be affected. We detached and repaired the supraspinatus tendon of 22 Sprague-Dawley rats, and the injured shoulder was immobilized postoperatively for 2 weeks. Following immobilization, rats were prescribed cage activity or exercise for 12 weeks. Passive shoulder mechanics were determined, and following euthanasia, tendon cross-sectional area and mechanical properties were measured. Exercise following immobilization resulted in significant decreases compared to cage activity in range of motion, tendon stiffness, modulus, percent relaxation, and several parameters from both a structurally based elastic model and a quasi-linear viscoelastic model. Therefore, we conclude that after a short period of immobilization, increased activity is detrimental to both tendon mechanical properties and shoulder joint mechanics, presumably due to increased scar production. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc

[Effect of grain-bean package, grain-bean package dietary fiber and single whole grain dietary fiber on dyslipidemia rats].

PubMed

Liu, Yang; Zhai, Chengkai; Sun, Guiju; Zhang, Hong; Jiang, Mingxia; Zhang, Haifeng; Guo, Junling; Lan, Xi

2014-05-01

To observe and compare the effects of grain-bean package, dietary fiber (DF) extracted from grain-bean package, and DF from grain corn on the blood lipids and fatty acid synthase (FAS) activity in high-fat, high-cholesterol feeding induced dyslipidemia rats, and observe its effects on regulation of sterol regulatory element protein-1c (SREBP-1c) mRNA expression in rat liver. Consolidation 50 SD rats of clean grade feeding adaptation for one week, randomly assigned into normal control group, hyperlipidemia model group, grain-bean package group, grain-bean package DF group and grain corn group. Feed with corresponding diets for 8 weeks, and measure the total cholesterol (TC), triglyceridaemia (TG), high density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), FAS, SREBP-1c mRNA of all groups. Compared with control group, TC, TG, FBG levels of hyperlipidemia model group were significantly increased (P < 0.05). Compared with model group, TC, TG, FBG levels of grain-bean package group, grain-bean package DF group were significantly decreased, HDL-C levels significantly increased, and activity of FAS, regulation of SREBP-1c were significantly decreased (P < 0.05). The Grain-bean package dietary fiber can improve blood lipids levels of dyslipidemia rats, and decrease FAS activity and SREBP-1c mRNA expression.

The comparison of methylene blue and vitamin E in prevention of abdominal postoperative adhesion formation in rat uterine horn models: Biochemical and histopathologic evaluation.

PubMed

Yildiz, Hamit; Durmus, Ali Said; Simsek, Halil; Yaman, Ihsan

2011-02-01

To compare the effects of vitamin E and 1% methylen blue solutions on prevention of experimentally induced adhesions in rats. Thirty seven female Spraque Dawley rats were randomized into four groups. First group was kept as sham operated group. An adhesion model was constituted on the left uterine horn of the other groups. The lesion areas of rats from the second, the third and the fourth groups were coated with 2 ml 0.9 % saline solution (C group), 10 mg vitamin E (VE group) and 1% methylen blue solutions (MB group), respectively. Histopathologically, adhesion scores, mononuclear cell infiltration, oedema and fibrosis were more prominent in the MB group compared with C and VE groups. There were no significant differences between the groups in tissue glutathione peroxidase (GPx), catalase (CAT) activities and glutation (GSH) level, these parameters were slightly increased in group with VE supplementation though. The administration of VE and MB significantly decreased NO (P<0.01) levels when compared to the C group. The level of malondialdehyde (MDA) in the VE group was significantly lower (P<0.05) than those of the Sh and C groups. Intraperitoneal methylen blue solutions treatments were more effective according to vitamin E in preventing the formation of intra-abdominal adhesion in a rat uterine horn model.

Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbestos: Effects at 18 Months Post Exposure###

EPA Science Inventory

Increased asbestosis, lung cancer, and mesothelioma rates are evident after exposures to Libby amphibole (LA). To support dosimetry model development and compare potency, a subchronic nose-only inhalation study (6 hr/d, 5 d/wk, 13 wk) was conducted in male F344 rats. Rats were ex...

Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbestos: Effects at 18 Months Post Exposure

EPA Science Inventory

Increased asbestosis, lung cancer, and mesothelioma rates are evident after exposures to Libby amphibole (LA). To support dosimetry model development and compare potency, a subchronic nose-only inhalation study (6 hr/d, 5 d/wk, 13 wk) was conducted in male F344 rats. Rats were ex...

Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbestos: Effects at 1 and 3 Months Post Exposure**

EPA Science Inventory

Increased asbestosis, lung cancer, and mesothelioma rates are evident after exposures to Libby amphibole (LA). To support dosimetry model development and compare potency, a subchronic nose-only inhalation exposure study (6 hr/d, 5 d/wk, 13 wk) was conducted in male F344 rats. Rat...

An automatic rat brain extraction method based on a deformable surface model.

PubMed

Li, Jiehua; Liu, Xiaofeng; Zhuo, Jiachen; Gullapalli, Rao P; Zara, Jason M

2013-08-15

The extraction of the brain from the skull in medical images is a necessary first step before image registration or segmentation. While pre-clinical MR imaging studies on small animals, such as rats, are increasing, fully automatic imaging processing techniques specific to small animal studies remain lacking. In this paper, we present an automatic rat brain extraction method, the Rat Brain Deformable model method (RBD), which adapts the popular human brain extraction tool (BET) through the incorporation of information on the brain geometry and MR image characteristics of the rat brain. The robustness of the method was demonstrated on T2-weighted MR images of 64 rats and compared with other brain extraction methods (BET, PCNN, PCNN-3D). The results demonstrate that RBD reliably extracts the rat brain with high accuracy (>92% volume overlap) and is robust against signal inhomogeneity in the images. Copyright © 2013 Elsevier B.V. All rights reserved.

Stress triggers anhedonia in rats bred for learned helplessness.

PubMed

Enkel, Thomas; Spanagel, Rainer; Vollmayr, Barbara; Schneider, Miriam

2010-05-01

Congenitally helpless (cLH) rats, a well-accepted model for depression, show reduced consumption of sweet solutions only under single-housing conditions, indicating anhedonia under stress. We investigated if anhedonic-like behaviour, measured by a reduction of sweetened-condensed milk (SCM) intake and the pleasure-attenuated startle response (PAS), could be induced by an electric foot-shock stress challenge in group-housed rats. After foot-shock stress, reduced SCM intake was observed in cLH rats compared to non-helpless (cNLH) rats. Furthermore, cLH rats also showed a decreased PAS, indicating deficient reward perception. In summary, we demonstrate that a predisposition for learned helplessness interacts with stress to trigger anhedonic-like behaviour in cLH rats. These findings further add to the validity of congenitally learned helplessness as an animal model of depression, since gene-environment interactions are considered to play a role in the etiology of this disorder.

Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats.

PubMed

Li, Peng; Huang, Pei-Pei; Yang, Yun; Liu, Chi; Lu, Yan; Wang, Fang; Sun, Wei; Kong, Xiang-Qing

2017-01-01

Li P, Huang P, Yang Y, Liu C, Lu Y, Wang F, Sun W, Kong X. Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats. J Appl Physiol 122: 121-129, 2017. First published October 14, 2016; doi:10.1152/japplphysiol.01019.2015-Sympathetic activity is enhanced in patients with essential or secondary hypertension, as well as in various hypertensive animal models. Therapeutic targeting of sympathetic activation is considered an effective antihypertensive strategy. We hypothesized that renal sympathetic denervation (RSD) attenuates hypertension and improves vascular remodeling and renal disease in the 2-kidney, 1-clip (2K1C) rat model. Rats underwent 2K1C modeling or sham surgery; then rats underwent RSD or sham surgery 4 wk later, thus resulting in four groups (normotensive-sham, normotensive-RSD, 2K1C-sham, and 2K1C-RSD). Norepinephrine was measured by ELISA. Echocardiography was used to assess heart function. Fibrosis and apoptosis were assessed by Masson and TUNEL staining. Changes in mean arterial blood pressure in response to hexamethonium and plasma norepinephrine levels were used to evaluate basal sympathetic nerve activity. The 2K1C modeling success rate was 86.8%. RSD reversed the elevated systolic blood pressure induced by 2K1C, but had no effect on body weight. Compared with rats in the 2K1C-sham group, rats in the 2K1C-RSD group showed lower left ventricular mass/body weight ratio, interventricular septal thickness in diastole, left ventricular end-systolic diameter, and left ventricular posterior wall thickness in systole, whereas fractional shortening and ejection fraction were higher. Right kidney apoptosis and left kidney hypertrophy were not changed by RSD. Arterial fibrosis was lower in animals in the 2K1C-RSD group compared with those in the 2K1C-sham group. RSD reduced plasma norepinephrine and basal sympathetic activity in rats in the 2K1C-RSD group compared with rats in the 2K1C-sham group. These results suggest a possible clinical efficacy of RSD for renovascular hypertension. The effects of renal sympathetic denervation (RSD) on hypertension, cardiac function, vascular fibrosis, and renal apoptosis were studied in the 2K1C rat model. Results showed that RSD attenuated hypertension, improved vascular remodeling, and reduced vascular fibrosis through decreased sympathetic activity in the 2K1C rat model, but it did not change the kidney size, renal apoptosis, or renal caspase-3 expression. These results could suggest possible clinical efficacy of RSD for renovascular hypertension. Copyright © 2017 the American Physiological Society.

[Study on the oxidative stress in the ovaries of a rat model of polycystic ovary].

PubMed

Gong, Jin; Wu, Dong-bo; Zhang, Lan-lan; Li, Jia; Zhao, Xing; Zhang, Dan

2015-03-01

To establish a pathological animal model of polycystic ovary (PCO) by letrozole in rats. Investigate whether PCO were mediated by the effect of oxidative stress by measuring oxidative stress levels in this cohort of rats with PCO, and proceed a new way of treatment for polycystic ovary syndrom (PCOS). 90 SD female rats aged 6 weeks were randomly divided into two groups, including a control group of 45 rats that received vehicle only [19% aqueous solution of carboxmethlycellulose (CMC), 1 mL/d] once daily orally (p.o.), and an experimental group of 45 rats, which were administered letrozole at concentrations of 1 mg/kg p.o. dissolved in 1% CMC (1 mL/d) once daily. The treatment period was 28 d. During this period, vaginal smears were collected daily for estrus cycle determination and body masses were measured every 7 d. On the day subsequent to the last letrozole dose administration, rats were killed; Uteri and ovaries were then excised and weighed for the calculation of organ indexes. Serum hormone levels, SHBG and histologic changes in the ovaries were examined. Then testosterone free index (FAD) was calculated. Oxidant status was evaluated by determination of ovarian total oxidant status (TOS), malondialdehyde (MDA) concentration and intracellular reactive oxygen species (ROS) level, while antioxidant status was evaluated by determination of total antioxidant status (TAS) and superoxide dismutase (SOD) concentration. Vaginal smear test showed the estrus cycle began to disappear from day 12 to day 15. A statistically significant difference in growth curves, ovarian weights, uterine weights and organ indexes between the groups were also observed. In rats with PCO serum testosterone (T), follicle-stimulating hormone (FSH) concentrations and free androgen index (FADI) were significantly increased compared with the control group (rats without PCO). However, rats with PCO had decreased levels of estrogen (E2), luteinizing hormone (LH), and progesterone (P) compared with the control group. In a rat model of PCO achieved via letrozole, it was found that the levels of TOS, MDA, oxidative stress index (OSI) and intracellular ROS were significantly increased, while the TAS level, SOD content were significantly decreased in the ovary homogenates (P<0.05). The results indicated that the PCOS pathological process significantly increased the oxidative stress production. PCO rat model successfully induced via letrozole, and it is a suitable model for study of ovarian lesions. Oxidative stress also contributes to the PCO rat model, the protective effect of antioxidant might provide a new insight into the potential therapeutic solution to PCOS.

Prime-, Stress- and Cue-Induced Reinstatement of Extinguished Drug-Reinforced Responding in Rats: Cocaine as the Prototypical Drug of Abuse

PubMed Central

Beardsley, Patrick M.; Shelton, Keith L.

2012-01-01

This unit describes the testing of rats in prime-, footshock- and cue-induced reinstatement procedures. Evaluating rats in these procedures enables the assessment of treatments on behavior thought to model drug relapse precipitated by re-contact with an abused drug (prime-induced), induced by stress (footshock-induced), or by stimuli previously associated with drug administration (cue-induced). For instance, levels of reinstatement under the effects of test compound administration could be compared to levels under vehicle administration to help identify potential treatments for drug relapse, or reinstatement levels of different rat strains could be compared to identify potential genetic determinants of perseverative drug-seeking behavior. Cocaine is used as a prototypical drug of abuse, and relapse to its use serves as the model in this unit, but other self-administered drugs could readily be substituted with little modification to the procedures. PMID:23093352

Cytochrome P450 dependent metabolism of the new designer drug 1-(3-trifluoromethylphenyl)piperazine (TFMPP). In vivo studies in Wistar and Dark Agouti rats as well as in vitro studies in human liver microsomes.

PubMed

Staack, Roland F; Paul, Liane D; Springer, Dietmar; Kraemer, Thomas; Maurer, Hans H

2004-01-15

1-(3-Trifluoromethylphenyl)piperazine (TFMPP) is a designer drug with serotonergic properties. Previous studies with male Wistar rats (WI) had shown, that TFMPP was metabolized mainly by aromatic hydroxylation. In the current study, it was examined whether this reaction may be catalyzed by cytochrome P450 (CYP)2D6 by comparing TFMPP vs. hydroxy TFMPP ratios in urine from female Dark Agouti rats, a model of the human CYP2D6 poor metabolizer phenotype (PM), male Dark Agouti rats, an intermediate model, and WI, a model of the human CYP2D6 extensive metabolizer phenotype. Furthermore, the human hepatic CYPs involved in TFMPP hydroxylation were identified using cDNA-expressed CYPs and human liver microsomes. Finally, TFMPP plasma levels in the above mentioned rats were compared. The urine studies suggested that TFMPP hydroxylation might be catalyzed by CYP2D6 in humans. Studies using human CYPs showed that CYP1A2, CYP2D6 and CYP3A4 catalyzed TFMPP hydroxylation, with CYP2D6 being the most important enzyme accounting for about 81% of the net intrinsic clearance, calculated using the relative activity factor approach. The hydroxylation was significantly inhibited by quinidine (77%) and metabolite formation in poor metabolizer genotype human liver microsomes was significantly lower (63%) compared to pooled human liver microsomes. Analysis of the plasma samples showed that female Dark Agouti rats exhibited significantly higher TFMPP plasma levels compared to those of male Dark Agouti rats and WI. Furthermore, pretreatment of WI with the CYP2D inhibitor quinine resulted in significantly higher TFMPP plasma levels. In conclusion, the presented data give hints for possible differences in pharmacokinetics in human PM and human CYP2D6 extensive metabolizer phenotype subjects relevant for risk assessment.

Sardine protein diet increases plasma glucagon-like peptide-1 levels and prevents tissue oxidative stress in rats fed a high-fructose diet.

PubMed

Madani, Zohra; Sener, Abdullah; Malaisse, Willy J; Dalila, Ait Yahia

2015-11-01

The current study investigated whether sardine protein mitigates the adverse effects of fructose on plasma glucagon‑like peptide-1 (GLP-1) and oxidative stress in rats. Rats were fed casein (C) or sardine protein (S) with or without high‑fructose (HF) for 2 months. Plasma glucose, insulin, GLP‑1, lipid and protein oxidation and antioxidant enzymes were assayed. HF rats developed obesity, hyperglycemia, hyperinsulinemia, insulin resistance and oxidative stress despite reduced energy and food intakes. High plasma creatinine and uric acid levels, in addition to albuminuria were observed in the HF groups. The S‑HF diet reduced plasma glucose, insulin, creatinine, uric acid and homeostasis model assessment‑insulin resistance index levels, however increased GLP‑1 levels compared with the C‑HF diet. Hydroperoxides were reduced in the liver, kidney, heart and muscle of S‑HF fed rats compared with C‑HF fed rats. A reduction in liver, kidney and heart carbonyls was observed in S‑HF fed rats compared with C‑HF fed rats. Reduced levels of nitric oxide (NO) were detected in the liver, kidney and heart of the S‑HF fed rats compared with C‑HF fed rats. The S diet compared with the C diet reduced levels of liver hydroperoxides, heart carbonyls and kidney NO. The S‑HF diet compared with the C‑HF diet increased the levels of liver and kidney superoxide dismutase, liver and muscle catalase, liver, heart and muscle glutathione peroxidase and liver ascorbic acid. The S diet prevented and reversed insulin resistance and oxidative stress, and may have benefits in patients with metabolic syndrome.

Effects of primary and recurrent sacral chordoma on the motor and nociceptive function of hindlimbs in rats: an orthotopic spine model.

PubMed

Sarabia-Estrada, Rachel; Ruiz-Valls, Alejandro; Shah, Sagar R; Ahmed, A Karim; Ordonez, Alvaro A; Rodriguez, Fausto J; Guerrero-Cazares, Hugo; Jimenez-Estrada, Ismael; Velarde, Esteban; Tyler, Betty; Li, Yuxin; Phillips, Neil A; Goodwin, C Rory; Petteys, Rory J; Jain, Sanjay K; Gallia, Gary L; Gokaslan, Ziya L; Quinones-Hinojosa, Alfredo; Sciubba, Daniel M

2017-08-01

OBJECTIVE Chordoma is a slow-growing, locally aggressive cancer that is minimally responsive to conventional chemotherapy and radiotherapy and has high local recurrence rates after resection. Currently, there are no rodent models of spinal chordoma. In the present study, the authors sought to develop and characterize an orthotopic model of human chordoma in an immunocompromised rat. METHODS Thirty-four immunocompromised rats were randomly allocated to 4 study groups; 22 of the 34 rats were engrafted in the lumbar spine with human chordoma. The groups were as follows: UCH1 tumor-engrafted (n = 11), JHC7 tumor-engrafted (n = 11), sham surgery (n = 6), and intact control (n = 6) rats. Neurological impairment of rats due to tumor growth was evaluated using open field and locomotion gait analysis; pain response was evaluated using mechanical or thermal paw stimulation. Cone beam CT (CBCT), MRI, and nanoScan PET/CT were performed to evaluate bony changes due to tumor growth. On Day 550, rats were killed and spines were processed for H & E-based histological examination and immunohistochemistry for brachyury, S100β, and cytokeratin. RESULTS The spine tumors displayed typical chordoma morphology, that is, physaliferous cells filled with vacuolated cytoplasm of mucoid matrix. Brachyury immunoreactivity was confirmed by immunostaining, in which samples from tumor-engrafted rats showed a strong nuclear signal. Sclerotic lesions in the vertebral body of rats in the UCH1 and JHC7 groups were observed on CBCT. Tumor growth was confirmed using contrast-enhanced MRI. In UCH1 rats, large tumors were observed growing from the vertebral body. JHC7 chordoma-engrafted rats showed smaller tumors confined to the bone periphery compared with UCH1 chordoma-engrafted rats. Locomotion analysis showed a disruption in the normal gait pattern, with an increase in the step length and duration of the gait in tumor-engrafted rats. The distance traveled and the speed of rats in the open field test was significantly reduced in the UCH1 and JHC7 tumor-engrafted rats compared with controls. Nociceptive response to a mechanical stimulus showed a significant (p < 0.001) increase in the paw withdrawal threshold (mechanical hypalgesia). In contrast, the paw withdrawal response to a thermal stimulus decreased significantly (p < 0.05) in tumor-engrafted rats. CONCLUSIONS The authors developed an orthotopic human chordoma model in rats. Rats were followed for 550 days using imaging techniques, including MRI, CBCT, and nanoScan PET/CT, to evaluate lesion progression and bony integrity. Nociceptive evaluations and locomotion analysis were performed during follow-up. This model reproduces cardinal signs, such as locomotor and sensory deficits, similar to those observed clinically in human patients. To the authors' knowledge, this is the first spine rodent model of human chordoma. Its use and further study will be essential for pathophysiology research and the development of new therapeutic strategies.

Comparative Analysis of Mechanical Properties of PWV, NO and Ascending Aorta between WHY Rats and SHR Rats.

PubMed

Yu, Bo; Xu, De-Jun; Sun, Huan; Yang, Kun; Luo, Min

2015-09-01

The aim of this study was to compare and analyze the tensile mechanical properties of the ascending aorta (AA) in Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs), for the purpose of providing a biomechanical basis for hypertension prevention. Pulse wave velocities (PWV) and serum nitric oxide (NO) concentrations were determined in 6-month-old WKY rats and SHRs (n = 21, n = 21, respectively). Then, 20 AAs from each group were obtained for longitudinal tensile testing. The maximum stress, maximum strain, and strain at a tensile stress of 16 Kpa were greater in WKY rats than in SHRs (p < 0.05). The aortic elastic modulus and PWV value were greater in SHRs than in WKY rats (p < 0.05 for both), while NO concentrations were lower in the SHR group than in the WKY group (p < 0.05). The AA tensile mechanical properties differed between the WKY rats and SHRs, and the tensile mechanical properties of the SHR model had changed. Ascending aorta; Hypertension; Mechanical properties; Pulse wave velocity; SHR rats; WKY rats.

Comparison of Allogeneic and Syngeneic Rat Glioma Models by Using MRI and Histopathologic Evaluation.

PubMed

Biasibetti, Elena; Valazza, Alberto; Capucchio, Maria T; Annovazzi, Laura; Battaglia, Luigi; Chirio, Daniela; Gallarate, Marina; Mellai, Marta; Muntoni, Elisabetta; Peira, Elena; Riganti, Chiara; Schiffer, Davide; Panciani, Pierpaolo; Lanotte, Michele

2017-03-01

Research in neurooncology traditionally requires appropriate in vivo animal models, on which therapeutic strategies are tested before human trials are designed and proceed. Several reproducible animal experimental models, in which human physiologic conditions can be mimicked, are available for studying glioblastoma multiforme. In an ideal rat model, the tumor is of glial origin, grows in predictable and reproducible patterns, closely resembles human gliomas histopathologically, and is weakly or nonimmunogenic. In the current study, we used MRI and histopathologic evaluation to compare the most widely used allogeneic rat glioma model, C6-Wistar, with the F98-Fischer syngeneic rat glioma model in terms of percentage tumor growth or regression and growth rate. In vivo MRI demonstrated considerable variation in tumor volume and frequency between the 2 rat models despite the same stereotactic implantation technique. Faster and more reproducible glioma growth occurred in the immunoresponsive environment of the F98-Fischer model, because the immune response is minimized toward syngeneic cells. The marked inability of the C6-Wistar allogeneic system to generate a reproducible model and the episodes of spontaneous tumor regression with this system may have been due to the increased humoral and cellular immune responses after tumor implantation.

Evaluation of an experimental rat model for comparative studies of bleaching agents.

PubMed

Cintra, Luciano Tavares Angelo; Benetti, Francine; Ferreira, Luciana Lousada; Rahal, Vanessa; Ervolino, Edilson; Jacinto, Rogério de Castilho; Gomes Filho, João Eduardo; Briso, André Luiz Fraga

2016-01-01

Dental materials, in general, are tested in different animal models prior to their clinical use in humans, except for bleaching agents. To evaluate an experimental rat model for comparative studies of bleaching agents by investigating the influence of different concentrations and application times of H2O2 gel in the pulp tissue during in-office bleaching of rats' vital teeth. The right and left maxillary molars of 50 Wistar rats were bleached with 20% and 35% H2O2 gels, respectively, for 5, 10, 15, 30, or 45 min (n=10 rats/group). Ten animals (control) were untreated. The rats were killed after 2 or 30 days, and the maxillae were examined by light microscopy. Inflammation was evaluated by histomorphometric analysis with inflammatory cell counting in the coronal and radicular thirds of the pulp. The counting of fibroblasts was also performed. Scores were attributed to the odontoblastic layer and to vascular changes. The tertiary dentin area and the pulp chamber central area were histomorphometrically measured. Data were compared by the analysis of variance and the Kruskal-Wallis test (p<0.05). After 2 days, the amount of inflammatory cells increased in the occlusal third of the coronal pulp until the time of 15 min for both concentrations of bleaching gels. In 30 and 45 min groups of each concentration, the number of inflammatory cells decreased along with the appearance of necrotic areas. After 30 days, a reduction in the pulp chamber central area and an enlargement of tertiary dentin area were observed without the detection of inflammation areas. The rat model of extra coronal bleaching showed to be adequate for bleaching protocols studies, as it was possible to observe alterations in the pulp tissues and in the tooth structure caused by different concentrations and periods of application of bleaching agents.

The chemopreventive activity of the histone deacetylase inhibitor tributyrin in colon carcinogenesis involves the induction of apoptosis and reduction of DNA damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heidor, Renato; Advanced Research Center in Food Science and Nutrition; Furtado, Kelly Silva

2014-04-15

The chemopreventive activity of the histone deacetylase inhibitor (HDACi) tributyrin (TB), a prodrug of butyric acid (BA), was evaluated in a rat model of colon carcinogenesis. The animals were treated with TB (TB group: 200 mg/100 g of body weight, b.w.) or maltodextrin (MD isocaloric control group: 300 mg/100 g b.w.) daily for 9 consecutive weeks. In the 3rd and 4th weeks of treatment, the rats in the TB and MD groups were given DMH (40 mg/kg b.w.) twice a week. After 9 weeks, the animals were euthanized, and the distal colon was examined. Compared with the control group (MDmore » group), TB treatment reduced the total number of aberrant crypt foci (ACF; p < 0.05) as well as the ACF with ≥ 4 crypts (p < 0.05), which are considered more aggressive, but not inhibited the formation of DMH-induced O6-methyldeoxyguanosine DNA adducts. The TB group also showed a higher apoptotic index (p < 0.05) and reduced DNA damage (p < 0.05) compared with MD group. TB acted as a HDACi, as rats treated with the prodrug of BA had higher levels of histone H3K9 acetylation compared with the MD group (p < 0.05). TB administration resulted in increased colonic tissue concentrations of BA (p < 0.05) compared with the control animals. These results suggest that TB can be considered a promising chemopreventive agent for colon carcinogenesis because it reduced the number of ACF, including those that were more aggressive. Induction of apoptosis and reduction of DNA damage are cellular mechanisms that appear to be involved in the chemopreventive activity of TB. - Highlights: • Tributyrin is a chemopreventive agent for rat colon aberrant crypt foci. • Tributyrin increased apoptosis in an experimental rat colon carcinogenesis model. • Tributyrin treatment in a rat colon carcinogenesis model decreased DNA damage. • Tributyrin treatment induced H3K9 acetylation in a rat colon carcinogenesis model.« less

Influence of manual therapy on functional mobility after joint injury in a rat model.

PubMed

Ruhlen, Rachel L; Snider, Eric J; Sargentini, Neil J; Worthington, Bart D; Singh, Vineet K; Pazdernik, Vanessa K; Johnson, Jane C; Degenhardt, Brian F

2013-10-01

Animal models can be used to investigate manual therapy mechanisms, but testing manipulation in animal models is problematic because animals cannot directly report their pain. To develop a rat model of inflammatory joint injury to test the efficacy of manual therapy in reducing nociception and restoring function. The authors induced acute inflammatory joint injury in rats by injecting carrageenan into the ankle and then measured voluntary running wheel activity in treated and untreated rats. Treatments included manual therapy applied to the ankle and knee of the injured limb and several analgesic medications (eg, morphine, ketorolac, prednisone). Intra-articular injection of carrageenan to the ankle produced significant swelling (diameter of the ankle increased by 64% after injection; P=.004) and a robust reduction in voluntary running wheel activity (running distance reduced by 91% compared with controls; P<.001). Injured rats gradually returned to running levels equal to controls over 10 days. Neither manual therapy nor analgesic medications increased running wheel activity relative to untreated rats. Voluntary running wheel activity appears to be an appropriate functional measure to evaluate the impact of an acute inflammatory joint injury. However, efforts to treat the injury did not restore running relative to untreated rats.

A novel animal model of dysphagia following stroke.

PubMed

Sugiyama, Naoto; Nishiyama, Eiji; Nishikawa, Yukitoshi; Sasamura, Takashi; Nakade, Shinji; Okawa, Katsumasa; Nagasawa, Tadashi; Yuki, Akane

2014-02-01

Patients who have an ischemic stroke are at high risk of swallowing disorders. Aspiration due to swallowing disorders, specifically delayed trigger of the pharyngeal stage of swallowing, predisposes such patients to pneumonia. In the present study, we evaluated swallowing reflex in a rat model of transient middle cerebral artery occlusion (tMCAO), which is one of the most common experimental animal models of cerebral ischemia, in order to develop a novel animal model of dysphagia following ischemic stroke. A swallowing reflex was elicited by a 10-s infusion of distilled water (DW) to the pharyngolaryngeal region in the tMCAO rat model. Swallowing reflex was estimated using the electromyographic activity of the mylohyoid muscle from 1 to 3 weeks after surgery. Two weeks after tMCAO, the number of swallows significantly decreased and the onset latency of the first swallow was prolonged compared with that of the sham group. The number of swallows in rats significantly increased by infusions of 10 mM citric acid and 0.6 μM capsaicin to the pharyngolaryngeal region compared with the number from infusion of DW. It has been reported that sensory stimulation of the pharyngolaryngeal region with citric acid, capsaicin, and L-menthol ameliorates hypofunction of pharyngeal-stage swallowing in dysphagia patients. Therefore, the tMCAO rat model may show some of the symptoms of pharyngeal-stage swallowing disorders, similar to those in patients with ischemic stroke. This rat tMCAO model has the potential to become a novel animal model of dysphagia following stroke that is useful for development of therapeutic methods and drugs.

The toxicosis of Embellisia fungi from locoweed (Oxytropis lambertii) is similar to locoweed toxicosis in rats.

PubMed

McLain-Romero, J; Creamer, R; Zepeda, H; Strickland, J; Bell, G

2004-07-01

Locoweeds cause significant livestock poisoning and economic loss in the western United States. The toxicity of Embellisia sp. fungi isolated from locoweed was compared with locoweed toxicity using the rat as a model. Rats were fed diets containing locoweed, fungus and alfalfa, or alfalfa. Locoweed- and fungus-fed rats consumed swainsonine-containing food at approximately 1.3 mg x kg(-1) x d(-1), gained less weight (P = 0.001) and ate less than controls. Swainsonine is the principal agent responsible for inducing locoism in animals. The concentrations of alkaline phosphatase and aspartate aminotransferase enzymes were greater (P < 0.05) in serum of locoweed- and fungus-fed rats compared with control rats. Similar intracellular vacuolation was observed in renal, pancreatic, and hepatic tissues of rats that consumed either locoweed or fungus. Rats that ate locoweed or Embellisia fungi displayed indistinguishable toxicity symptoms. The Embellisia fungi from locoweed can induce toxicity without the plants. Locoism management strategies need to involve management of the Embellisia fungi.

[Effectiveness of cultured Cordyceps sinensis combined with glucocorticosteroid on pulmonary fibrosis induced by bleomycin in rats].

PubMed

Xu, Huijuan; Li, Shiyue; Lin, Yunen; Liu, Rong; Gu, Yingying; Liao, Dongjiang

2011-08-01

To study the treatment effects of cultured Cordyceps sinensis combined with glucocorticosteroid on experimental pulmonary fibrosis in rats induced by bleomycin. Fifty rats were randomly divided into five groups, including control group, model group, cultured C. sinensis groups, prednisone group, cultured C. sinensis combined with prednisone group. On experimental day 0, the rats were respectively intratracheally instilled with bleomycin, and rats in the control group and model group with the same volume of normal saline. One day after the injection, cultured C. sinensis and glucocorticosteroid was respectively given to rats daily by gastric gavage, while the same volume of normal saline was given to those in the control group and model group. On 28th d, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. Histological changes of the lungs were evaluated by HE stain, Masson's trichrome stain. Collagen content of the lung tissue was assessed by hydroxyprolin concentration. Lung expression of CTGF protein was assessed by immunohistochemistry. The level of TGF-beta1 protein was measured by ELISA. Compared to model group, pulmonary fibrosis were alleviated in cultured C. sinensis and prednisone group, and CTGF expression, Hydroxyproline concentrations and protein TGF-beta1 were decreased. The combination effect of C. sinensis and prednisone group is augmented compared with using C. sinensis or prednisone group alone. The cultured C. sinensis and prednisone alleviates pulmonary fibrosis, and the combination use of both drugs has synergia effects in anti-fibrous degeneration.

Comparison of two cannulation methods for assessment of intracavernosal pressure in a rat model

PubMed Central

Luo, Lianmin; Wang, Jiamin; Li, Ermao; Luo, Jintai; Liu, Luhao; Wan, ShawPong

2018-01-01

Intracavernous pressure (ICP) measurement is a well-established technique for assessing the erectile function, which was performed by cannulating either crus or shaft of the penis. However, there are no studies concerning the experimental performance of the two cannulation sites yet. The aim of this study was to compare the measuring outcomes using two different cannulation sites. To validate the capacity of our study, both normal and the castration-induced erectile dysfunction rat models were conducted. Fifty adult male Sprague-Dawley rats were randomized equally into two groups: an intact group and a castration group. Five rats from each group firstly underwent different stimulation parameters to detect the optimal erectile responses. The residual rats in each group were further assigned into two subgroups (n = 10 per subgroup) according to two different cannulation sites (crus or shaft of the corpus cavernosum). The ICP values were compared between groups after different interventions. The optimal parameters for mean maximum ICP were recorded at 2.5V and a frequency of 15 Hz. The rats under the two different cannulation sites tended to show similar ICP values in both the intact and the castration groups. However, the success rate in monitoring ICP was significantly higher in the groups cannulating into the shaft of the penis compared to the crus (100% vs. 70%; P = 0.02). Our data suggested that the method of cannulation into the penile shaft could serve as a better alternative for the ICP measurement in rats. PMID:29486011

The rat: a laboratory model for studies of the diving response

PubMed Central

Gan, Qi; Juric, Rajko

2010-01-01

Underwater submersion in mammals induces apnea, parasympathetically mediated bradycardia, and sympathetically mediated peripheral vasoconstriction. These effects are collectively termed the diving response, potentially the most powerful autonomic reflex known. Although these physiological responses are directed by neurons in the brain, study of neural control of the diving response has been hampered since 1) it is difficult to study the brains of animals while they are underwater, 2) feral marine mammals are usually large and have brains of variable size, and 3) there are but few references on the brains of naturally diving species. Similar responses are elicited in anesthetized rodents after stimulation of their nasal mucosa, but this nasopharyngeal reflex has not been compared directly with natural diving behavior in the rat. In the present study, we compared hemodynamic responses elicited in awake rats during volitional underwater submersion with those of rats swimming on the water's surface, rats involuntarily submerged, and rats either anesthetized or decerebrate and stimulated nasally with ammonia vapors. We show that the hemodynamic changes to voluntary diving in the rat are similar to those of naturally diving marine mammals. We also show that the responses of voluntary diving rats are 1) significantly different from those seen during swimming, 2) generally similar to those elicited in trained rats involuntarily “dunked” underwater, and 3) generally different from those seen from dunking naive rats underwater. Nasal stimulation of anesthetized rats differed most from the hemodynamic variables of rats trained to dive voluntarily. We propose that the rat trained to dive underwater is an excellent laboratory model to study neural control of the mammalian diving response, and also suggest that some investigations may be done with nasal stimulation of decerebrate preparations to decipher such control. PMID:20093670

Characterization of beta-cell mass and insulin resistance in diet-induced obese and diet-resistant rats.

PubMed

Paulsen, Sarah J; Jelsing, Jacob; Madsen, Andreas N; Hansen, Gitte; Lykkegaard, Kirsten; Larsen, Leif K; Larsen, Philip J; Levin, Barry E; Vrang, Niels

2010-02-01

The selectively bred diet-induced obese (DIO) and diet-resistant (DR) rats represent a polygenetic animal model mimicking most clinical variables characterizing the human metabolic syndrome. When fed a high-energy (HE) diet DIO rats develop visceral obesity, dyslipidemia, hyperinsulinemia, and insulin resistance but never frank diabetes. To improve our understanding of the underlying cause for the deteriorating glucose and insulin parameters, we have investigated possible adaptive responses in DIO and DR rats at the level of the insulin-producing beta-cells. At the time of weaning, DR rats were found to have a higher body weight and beta-cell mass compared to DIO rats, and elevated insulin and glucose responses to an oral glucose load. However, at 2.5 months of age, and for the remaining study period, the effect of genotype became evident: the chow-fed DIO rats steadily increased their body weight and beta-cell mass, as well as insulin and glucose levels compared to the DR rats. HE feeding affected both DIO and DR rats leading to an increased body weight and an increased beta-cell mass. Interestingly, although the beta-cell mass in DR rats and chow-fed DIO rats appeared to constantly increase with age, the beta-cell mass in the HE-fed DIO rats did not continue to do so. This might constitute part of an explanation for their reduced glucose tolerance. Collectively, the data support the use of HE-fed DIO rats as a model of human obesity and insulin resistance, and accentuate its relevance for studies examining the benefit of pharmaceutical compounds targeting this disease complex.

[Comparative analysis of the maternal motivation expression in WAG/Rij and Wistar rats in the place preference and open field tests].

PubMed

Dobriakova, Iu V; Tanaeva, K K; Dubynin, V A; Sarkisova, K Iu

2014-01-01

Maternal behavior in females of WAG/Rij and Wistar rats was compared in the place preference test from 2 to 8 days after delivery, as well as in the open field test from 4 to 6 days after delivery. In females of WAG/Rij rats compared with females of Wistar rats weaker expression of maternal motivation has been revealed in both tests: they spend less time in the compartment associated with pups. Moreover, in females of WAG/Rij rats, number of approaches to pups, number of pup-carryings and time spent with pups (time of contacts) were less than in females of Wistar rats. Reduced maternal motivation in females of WAG/Rij rats in the place preference test persisted in repeated testing, while in the open field test it was detected only in the first testing, indicating higher reliability of the place preference test for revealing inter-strain differences in the expression of maternal motivation. It is supposed that weaker expression of maternal behavior and preference is due to hypo-function of the mesolimbic dopaminergic bran system in WAG/Rij rats as a genetic model of depression associated with absence epilepsy.

Structural changes of gut microbiota in a rat non-alcoholic fatty liver disease model treated with a Chinese herbal formula.

PubMed

Yin, Xiaochen; Peng, Jinghua; Zhao, Liping; Yu, Yunpeng; Zhang, Xu; Liu, Ping; Feng, Qin; Hu, Yiyang; Pang, Xiaoyan

2013-05-01

Accumulating evidence indicates that disruption of the gut microbiota by a high-fat diet (HFD) may play a pivotal role in the progression of metabolic disorders such as non-alcoholic fatty liver disease (NAFLD). In this study, the structural changes of gut microbiota were analyzed in an HFD-induced NAFLD rat model during treatment with an ancient Chinese herbal formula (CHF) used in clinical practice -Qushi Huayu Fang. CHF treatment significantly reduced body weight, alleviated hepatic steatosis, and decreased the content of triglycerides and free fatty acids in the livers of the rats. Gut microbiota of treated and control rats were profiled with polymerase chain reaction-denaturing gradient gel electrophoresis and bar-coded pyrosequencing of the V3 region of 16S rRNA genes. Both analyses indicated that the CHF-treated group harbored significantly different gut microbiota from that of model rats. Partial least squares discriminant analysis and taxonomy-based analysis were further employed to identify key phylotypes responding to HFD and CHF treatment. Most notably, the genera Escherichia/Shigella, containing opportunistic pathogens, were significantly enriched in HFD-fed rats compared to controls fed normal chow (P<0.05) but they decreased to control levels after CHF treatment. Collinsella, a genus with short chain fatty acid producers, was significantly elevated in CHF-treated rats compared to HFD-fed rats (P<0.05). The results revealed that the bacterial profiles of HFD-induced rats could be modulated by the CHF. Elucidation of these differences in microbiota composition provided a basis for further understanding the pharmacological mechanism of the CHF. Copyright © 2013 Elsevier GmbH. All rights reserved.

Colorectal distension-induced pseudoaffective changes as indices of nociception in the anesthetized female rat: morphine and strain effects on visceral sensitivity.

PubMed

Sivarao, Digavalli V; Langdon, Shaun; Bernard, Christopher; Lodge, Nicholas

2007-01-01

Colorectal distension of a sufficient intensity evokes several characteristic postural, visceromotor and cardiovascular reflexes in conscious rats that have been extensively utilized for testing putative visceral analgesics. The neural circuitry for these reflexes is encompassed within the spinobulbar region and continues to be robust even after decerebration. Yet, these are not consistently replicated in anesthetized animals, presumably due to medullary depression. In the following studies, we tested the hypothesis that a carefully chosen anesthetic regimen can replicate the pattern of pseudoaffective responses seen in awake animals. Female rats were anesthetized with methohexital sodium and equipped with arterial and venous catheters, a colorectal balloon and abdominal wire electrodes. Subsequent anesthesia was maintained with urethane. Colorectal distension produced clear changes in visceromotor and cardiovascular indices that not only mimicked responses to distension seen in conscious rats, but also importantly, showed a comparable stimulus sensitivity and stability. Morphine (ED(50), 0.17 mg/kg, iv) was highly efficacious in attenuating response in a dose-dependent and naloxone-selective manner. Using this model, we compared three commonly used rat strains (Wistar, Wistar-Kyoto and Sprague-Dawley) for distension-mediated responses. Whereas Wistar-Kyoto rats were significantly hyper-responsive to distension, the sensory threshold for distension was nearly identical across strains. Thus, we report an anesthetized female rat model that replicates characteristic responses associated with visceral pain in conscious rats and its modulation by known factors like analgesia and strain. These findings provide a simple insensate model for testing novel visceral analgesics while eliminating postoperative recovery and motion-related artifact typically associated with colorectal distension studies in conscious rats. Thus, a viable and humane alternative to visceral nociception studies in conscious animals is offered.

Developmental stress elicits preference for methamphetamine in the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder.

PubMed

Womersley, Jacqueline S; Mpeta, Bafokeng; Dimatelis, Jacqueline J; Kellaway, Lauriston A; Stein, Dan J; Russell, Vivienne A

2016-06-17

Developmental stress has been hypothesised to interact with genetic predisposition to increase the risk of developing substance use disorders. Here we have investigated the effects of maternal separation-induced developmental stress using a behavioural proxy of methamphetamine preference in an animal model of attention-deficit/hyperactivity disorder, the spontaneously hypertensive rat, versus Wistar Kyoto and Sprague-Dawley comparator strains. Analysis of results obtained using a conditioned place preference paradigm revealed a significant strain × stress interaction with maternal separation inducing preference for the methamphetamine-associated compartment in spontaneously hypertensive rats. Maternal separation increased behavioural sensitization to the locomotor-stimulatory effects of methamphetamine in both spontaneously hypertensive and Sprague-Dawley strains but not in Wistar Kyoto rats. Our findings indicate that developmental stress in a genetic rat model of attention-deficit/hyperactivity disorder may foster a vulnerability to the development of substance use disorders.

[C1q/tumor necrosis factor related protein 6 (CTRP6) is involved in gentamicin-induced acute kidney injury in rats].

PubMed

Li, Rong; Yang, Xiaoxia; Yu, Yan; Zhou, Meilan; Tian, Xiujuan; Feng, Shidong; Wang, Hanmin

2016-11-01

Objective To explore the role of the anti-inflammatory cytokine C1q/tumor necrosis factor related protein 6 (CTRP6) in gentamicin-induced acute kidney injury in rats. Methods SD rats were divided into 5 groups including control group, model group and the other 3 experimental groups. The rats in model group and experimental groups were subcutaneously injected with gentamicin at the dose of 400 mg/(kg.d) for consecutive 2 days to induce acute renal injury. Two days before gentamicin injection, the rats in the 3 experimental groups were given pAd-CTRP6 at the doses of 0.5, 5 and 50 mg/kg, respectively. The serum levels of blood urea nitrogen (BUN) and creatinine (Cr) were respectively assayed with picric acid colorimetry and ultraviolet spectrophotometry; ELISA was used to detect serum CTRP6 content and the production of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) in the kidney homogenate; Western blotting was performed to detect the expressions of CTRP6, caspase-1 and pyrin domain containing 3 (NLRP3) proteins in the renal tissues of rats. Results Compared with control group, serum BUN and Cr contents increased in the model rats; the secretion of inflammatory factors IL-1β and TNF-α, as well as the expressions of caspase-1 and NLRP3 were also enhanced in the model group. Compared with the model group, serum BUN and Cr contents decreased in the experimental groups; the secretion of IL-1β and TNF-α, as well as the expressions of caspase-1 and NLRP3 were also attenuated in the experimental groups. Moreover, with the increase of the injection dosage of pAd-CTRP6, the suppressive effect was gradually strengthened. Conclusion CTRP6 can attenuate gentamicin-induced acute renal injury in rats in a dose-dependent manner.

Differences in Retinal Structure and Function between Aging Male and Female Sprague-Dawley Rats are Strongly Influenced by the Estrus Cycle

PubMed Central

Chaychi, Samaneh; Polosa, Anna; Lachapelle, Pierre

2015-01-01

Purpose Biological sex and age are considered as two important factors that may influence the function and structure of the retina, an effect that might be governed by sexual hormones such as estrogen. The purpose of this study was to delineate the influence that biological sex and age exert on the retinal function and structure of rodents and also clarify the effect that the estrus cycle might exert on the retinal function of female rats. Method The retinal function of 50 normal male and female albino Sprague-Dawley (SD) rats was investigated with the electroretinogram (ERG) at postnatal day (P) 30, 60, 100, 200, and 300 (n = 5–6 male and female rats/age). Following the ERG recording sessions, retinal histology was performed in both sexes. In parallel, the retinal function of premenopausal and menopausal female rats aged P540 were also compared. Results Sex and age-related changes in retinal structure and function were observed in our animal model. However, irrespective of age, no significant difference was observed in ERG and retinal histology obtained from male and female rats. Notwithstanding the above we did however notice that between P60 and P200 there was a gradual increase in ERG amplitudes of female rats compared to males. Furthermore, the ERG of premenopausal female rats aged 18 months old (P540) was larger compared to age-matched menopausal female rats as well as that of male rats. Conclusion Our results showed that biological sex and age can influence the retinal function and structure of albino SD rats. Furthermore, we showed that cycled female rats have better retinal function compared to the menopausal female rats suggesting a beneficial effect of the estrus cycle on the retinal function. PMID:26317201

[Therapeutic effects and mechanisms of Opuntia dillenii Haw on atherosclerosis of rats].

PubMed

Wang, Yu-chun; Qi, Zhan-peng; Liu, Zhen-zhong; Li, Tao; Cui, Hong-xia; Wang, Bao-qing; Chi, Na

2015-04-01

The research aimed to investigate the therapeutic effects and mechanisms of Opuntia dillenii Haw polysaccharide (OPS) on atherosclerosis of rats. First atherosclerotic rat models were established by high-fat and high-calcium diet. Thirty days later, the rats were treated with low dosage of OPS (0.2 g x kg(-1) x d(-1)) or high dosage of OPS (0.4 g x kg(-1) x d(-1)) by intraperitoneal injection for 60 days continuously. At the end of treatment, thoracic aorta rings were prepared and vasorelaxation of rat thoracic aorta in different experiment groups were determined by using 620M multi wire myograph system in vitro. Blood and livers of rats were collected. Then plasma levels of total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) of rats were separately determined using whole automatic biochemical analyzer; protein level of hepatic apolipoprotein B (ApoB) and that of hepatic diglyceride acyltransferase (Dgat1) were measured by Western Blot technique. Results showed that the ability of rat thoracic aorta to relax decreased markedly in the model group compared with that in the normal group, and significant differences existed in vasorelaxation ratios induced by different concentrations of carbamylcholine chloride (Carb) between these two groups (P < 0.01). After OPS treatment, the ability of rat thoracic aorta to relax improved markedly, the vasorelaxation ratios induced by Carb at 5 and 10 μmol x L(-1) were respectively 0.34 ± 0.08 and 0.62 ± 0.15 in the group treated with low dosage of OPS, while the ratios induced by Carb at 1 and 5 μmol x L(-1) were respectively 0.54 ± 0.08 and 0.98 ± 0.02 in the group treated with high dosage of OPS, which were all significantly different with those in the model group (P < 0.01). Plasma contents of TC, TG and LDL reduced significantly by the treatments both with low and high dosages of OPS compared with those in the model group (P < 0.01). Protein level of hepatic ApoB and that of hepatic Dgat1 decreased significantly after the treatment with high dosage of OPS compared with those in the model group (P < 0.01). These results indicate that OPS can markedly improve the vasorelaxation of thoracic aorta of atherosclerotic rats and has significant anti-atherosclerotic effect; inhibiting the expression of ApoB and Dgat1 and thus decreasing the amounts of TC, LDL and TG serving as one of the molecular mechanisms of its antiatherosclerosis effect.

[Effects of the scalp acupuncture at baihui (DU20) through qubin (GB7) on the expressions of GDNF VEGF in the brain tissue of rats with acute intracerebral hemorrhage].

PubMed

Zhang, Guo-Wei; Zou, Wei; Liu, Fang

2012-09-01

To observe the effects of the scalp acupuncture at Baihui (DU20) through Qubin (GB7) on the expressions of glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF) in the brain tissue of rats with acute intracerebral hemorrhage (AICH). Totally 150 healthy male Wistar rats were used to prepare the intracerebral hemorrhage (ICH) model. They were randomly divided into the model group, the acupuncture group, and the Western medicine group, 50 in each group. Rats in each group were then randomly divided into five subgroups, i. e., 6 h, day 1, day 2, day 3, and day 7, 10 in each subgroup. Another 10 normal rats were recruited as the blank control group. Rats in the acupuncture group were acupunctured at Baihui (DU20) through Qubin (GB7) on the lesion side. Rats in the Western medicine group were administered with aniracetam diluent 1 mL by gastrogavage, 3 times daily. Rats in the model group were bound the same way as those in the acupuncture group 30 min daily, and then administered with normal saline 1 mL by gastrogavage, 3 times daily. The expressions of GDNF and VEGF in the brain tissue of the rats in each group were detected using in situ hybridization and immunohistochemical methods. Compared with the blank control group, the number of GDNF positive cells in the model group increased at 6 h-3 days, and the number of VEGF positive cells in the model group increased at each time point, showing statistical difference (P<0.01). The numbers of GDNF positive cells increased in the acupuncture group at each time point, showing statistical difference when compared with those of the model group and the Western medicine group (P<0.01). There was no statistical difference between the model group and the Western medicine group at each time point (P>0.05). Compared with the model group, the number of VEGF positive cells in the acupuncture group decreased at 6 h -3 days. The VEGF positive cells increased at day 7 and were higher than that of the Western medicine group, showing statistical difference (P<0.01). The scalp acupuncture at Baihui (DU20) through Qubin (GB7) played the role of nerves remodeling in AICH possibly through promoting the expression of endogenous GDNF and early inhibiting the expression of VEGF in the AICH. This method possibly had favorable bidirectional regulation effects in AICH. Its therapeutic effects were superior to Aniracetam.

Effects of Chinese herbal medicine Yinsiwei compound on spatial learning and memory ability and the ultrastructure of hippocampal neurons in a rat model of sporadic Alzheimer disease.

PubMed

Diwu, Yong-chang; Tian, Jin-zhou; Shi, Jing

2011-02-01

To study the effects of Chinese herbal medicine Yinsiwei compound (YSW) on spatial learning and memory ability in rats with sporadic Alzheimer disease (SAD) and the ultrastructural basis of the hippocampal neurons. A rat model of SAD was established by intracerebroventricular injection of streptozotocin. The rats were divided into six groups: sham-operation group, model group, donepezil control group, and YSW low, medium and high dose groups. Drug interventions were started on the 21st day after modeling and each treatment group was given the corresponding drugs by gavage for two months. Meanwhile, the model group and the sham-operation group were given the same volume of distilled water by gavage once a day for two months. The Morris water maze was adopted to test spatial learning and memory ability of the rats. The place navigation test and the spatial probe test were conducted. The escape latency, total swimming distance and swimming time in the target quadrant of the rats were recorded. Also, the hippocampus tissues of rats were taken out and the ultrastructure of hippocampus neurons were observed by an electron microscope. In the place navigation test, compared with the model group, the mean escape latency and the total swimming distance of the donepezil group and the YSW low, medium and high dose groups were significantly shortened (P<0.05 or P<0.01). In the space probe test, the swimming time of each treatment group in the target quadrant was significantly longer than that of the model group (P<0.05 or P<0.01). For most of the test period, the donepezil group had no significant change compared with the YSW low, medium and high dose groups, respectively. The ultrastructure of the hippocampus neurons under the electron microscope also confirmed the efficacy of the drug treatment. Chinese herbal medicine YSW compound can improve spatial learning and memory impairment of rats with SAD. The ultrastructural basis may be that it can protect the microtubule structures of hippocampal neurons and prevent nerve axons from being damaged.

Green tea polyphenols reduce body weight in rats by modulating obesity-related genes.

PubMed

Lu, Chuanwen; Zhu, Wenbin; Shen, Chwan-Li; Gao, Weimin

2012-01-01

Beneficial effects of green tea polyphenols (GTP) against obesity have been reported, however, the mechanism of this protection is not clear. Therefore, the objective of this study was to identify GTP-targeted genes in obesity using the high-fat-diet-induced obese rat model. A total of three groups (n = 12/group) of Sprague Dawley (SD) female rats were tested, including the control group (rats fed with low-fat diet), the HF group (rats fed with high-fat diet), and the HF+GTP group (rats fed with high-fat diet and GTP in drinking water). The HF group increased body weight as compared to the control group. Supplementation of GTP in the drinking water in the HF+GTP group reduced body weight as compared to the HF group. RNA from liver samples was extracted for gene expression analysis. A total of eighty-four genes related to obesity were analyzed using PCR array. Compared to the rats in the control group, the rats in the HF group had the expression levels of 12 genes with significant changes, including 3 orexigenic genes (Agrp, Ghrl, and Nr3c1); 7 anorectic genes (Apoa4, Cntf, Ghr, IL-1β, Ins1, Lepr, and Sort); and 2 genes that relate to energy expenditure (Adcyap1r1 and Adrb1). Intriguingly, the HF+GTP group restored the expression levels of these genes in the high-fat-induced obese rats. The protein expression levels of IL-1β and IL-6 in the serum samples from the control, HF, and HF+GTP groups confirmed the results of gene expression. Furthermore, the protein expression levels of superoxide dismutase-1 (SOD1) and catechol-O-methyltransferase (COMT) also showed GTP-regulated protective changes in this obese rat model. Collectively, this study revealed the beneficial effects of GTP on body weight via regulating obesity-related genes, anti-inflammation, anti-oxidant capacity, and estrogen-related actions in high-fat-induced obese rats.

Green Tea Polyphenols Reduce Body Weight in Rats by Modulating Obesity-Related Genes

PubMed Central

Lu, Chuanwen; Zhu, Wenbin; Shen, Chwan-Li; Gao, Weimin

2012-01-01

Beneficial effects of green tea polyphenols (GTP) against obesity have been reported, however, the mechanism of this protection is not clear. Therefore, the objective of this study was to identify GTP-targeted genes in obesity using the high-fat-diet-induced obese rat model. A total of three groups (n = 12/group) of Sprague Dawley (SD) female rats were tested, including the control group (rats fed with low-fat diet), the HF group (rats fed with high-fat diet), and the HF+GTP group (rats fed with high-fat diet and GTP in drinking water). The HF group increased body weight as compared to the control group. Supplementation of GTP in the drinking water in the HF+GTP group reduced body weight as compared to the HF group. RNA from liver samples was extracted for gene expression analysis. A total of eighty-four genes related to obesity were analyzed using PCR array. Compared to the rats in the control group, the rats in the HF group had the expression levels of 12 genes with significant changes, including 3 orexigenic genes (Agrp, Ghrl, and Nr3c1); 7 anorectic genes (Apoa4, Cntf, Ghr, IL-1β, Ins1, Lepr, and Sort); and 2 genes that relate to energy expenditure (Adcyap1r1 and Adrb1). Intriguingly, the HF+GTP group restored the expression levels of these genes in the high-fat-induced obese rats. The protein expression levels of IL-1β and IL-6 in the serum samples from the control, HF, and HF+GTP groups confirmed the results of gene expression. Furthermore, the protein expression levels of superoxide dismutase-1 (SOD1) and catechol-O-methyltransferase (COMT) also showed GTP-regulated protective changes in this obese rat model. Collectively, this study revealed the beneficial effects of GTP on body weight via regulating obesity-related genes, anti-inflammation, anti-oxidant capacity, and estrogen-related actions in high-fat-induced obese rats. PMID:22715380

WenTong HuoXue Cream Can Inhibit the Reduction of the Pain-Related Molecule PLC-β3 in the Dorsal Root Ganglion of a Rat Model of Diabetic Peripheral Neuropathy

PubMed Central

Feng, Chengcheng; Xu, Lijuan; Guo, Shiyun; Chen, Qian; Shen, Yuguo; Zang, Deng

2018-01-01

WenTong HuoXue Cream (WTHX-Cream) has been shown to effectively alleviate clinical symptoms of diabetic peripheral neuropathy (DPN). This study investigated the gene and protein expression of the pain-related molecule PLC-β3 in the dorsal root ganglion (DRG) of DPN rats. 88 specific pathogen-free male Wistar rats were randomly divided into placebo (10 rats) and DPN model (78 rats) groups, and the 78 model rats were used to establish the DPN model by intraperitoneal injection of streptozotocin and were then fed a high-fat diet for 8 weeks. These rats were randomly divided into the model group, the high-, medium-, and low-dose WTHX-Cream + metformin groups, the metformin group, the capsaicin cream group, and the capsaicin cream + metformin group. After 4 weeks of continuous drug administration, the blood glucose, body weight, behavioral indexes, and sciatic nerve conduction velocity were measured. The pathological structure of the DRG and the sciatic nerve were observed. PLC-β3 mRNA and protein levels in the DRG of rats were measured. Compared with the model group, the high-dose WTHX-Cream group showed increased sciatic nerve conduction velocity, improved sciatic nerve morphological changes, and increased expression of PLC-β3 mRNA and protein in the DRG. This study showed that WTHX-Cream improves hyperalgesia symptoms of DPN by inhibiting the reduction of PLC-β3 mRNA and protein expression in the diabetic DRG of DPN rats. PMID:29599806

WenTong HuoXue Cream Can Inhibit the Reduction of the Pain-Related Molecule PLC-β3 in the Dorsal Root Ganglion of a Rat Model of Diabetic Peripheral Neuropathy.

PubMed

Feng, Chengcheng; Xu, Lijuan; Guo, Shiyun; Chen, Qian; Shen, Yuguo; Zang, Deng; Ma, Li

2018-01-01

WenTong HuoXue Cream (WTHX-Cream) has been shown to effectively alleviate clinical symptoms of diabetic peripheral neuropathy (DPN). This study investigated the gene and protein expression of the pain-related molecule PLC- β 3 in the dorsal root ganglion (DRG) of DPN rats. 88 specific pathogen-free male Wistar rats were randomly divided into placebo (10 rats) and DPN model (78 rats) groups, and the 78 model rats were used to establish the DPN model by intraperitoneal injection of streptozotocin and were then fed a high-fat diet for 8 weeks. These rats were randomly divided into the model group, the high-, medium-, and low-dose WTHX-Cream + metformin groups, the metformin group, the capsaicin cream group, and the capsaicin cream + metformin group. After 4 weeks of continuous drug administration, the blood glucose, body weight, behavioral indexes, and sciatic nerve conduction velocity were measured. The pathological structure of the DRG and the sciatic nerve were observed. PLC- β 3 mRNA and protein levels in the DRG of rats were measured. Compared with the model group, the high-dose WTHX-Cream group showed increased sciatic nerve conduction velocity, improved sciatic nerve morphological changes, and increased expression of PLC- β 3 mRNA and protein in the DRG. This study showed that WTHX-Cream improves hyperalgesia symptoms of DPN by inhibiting the reduction of PLC- β 3 mRNA and protein expression in the diabetic DRG of DPN rats.

Long-term characterization of the diet-induced obese and diet-resistant rat model: a polygenetic rat model mimicking the human obesity syndrome.

PubMed

Madsen, Andreas Nygaard; Hansen, Gitte; Paulsen, Sarah Juel; Lykkegaard, Kirsten; Tang-Christensen, Mads; Hansen, Harald S; Levin, Barry E; Larsen, Philip Just; Knudsen, Lotte Bjerre; Fosgerau, Keld; Vrang, Niels

2010-09-01

The availability of useful animal models reflecting the human obesity syndrome is crucial in the search for novel compounds for the pharmacological treatment of obesity. In the current study, we have performed an extensive characterization of the obesity syndrome in a polygenetic animal model, namely the selectively bred diet-induced obese (DIO) and diet-resistant (DR) rat strains. We show that they constitute useful models of the human obesity syndrome. DIO and DR rats were fed either a high-energy (HE) or a standard chow (Chow) diet from weaning to 9 months of age. Metabolic characterization including blood biochemistry and glucose homeostasis was examined at 2, 3, 6, and 9 months of age. Furthermore, in 6-month-old HE-fed DIO rats, the anti-obesity effects of liraglutide and sibutramine were examined in a 28-day study. Only HE-fed DIO rats developed visceral obesity, hyperleptinemia, hyperinsulinemia, and dyslipidemia, and showed a worsening of glucose tolerance over time. In line with the hyperlipidemic profile, a severe hepatic fat infiltration was observed in DIO rats at 6 months of age. The effects of liraglutide and sibutramine were tested in 6-month-old DIO rats. Both compounds effectively reduced food intake and body weight in DIO rats. Liraglutide furthermore improved glucose tolerance when compared with sibutramine. Our data highlights the usefulness of a polygenetic animal model for screening of compounds affecting food intake, body weight, and glucose homeostasis. Furthermore, the results underscore the effectiveness of GLP-1 mimetics both as anti-diabetes and anti-obesity agents.

miR-494 up-regulates the PI3K/Akt pathway via targetting PTEN and attenuates hepatic ischemia/reperfusion injury in a rat model.

PubMed

Su, Song; Luo, De; Liu, Xiangdong; Liu, Jiang; Peng, Fangyi; Fang, Cheng; Li, Bo

2017-10-31

A rat HIRI model was constructed and treated with an intraperitoneal injection of agomir- miR-494 or agomir-NC (negative control) for 7 days after the surgery. The pathophysiological changes in sham-operated rats, HIRI, HIRI + agomir- miR-494 , and HIRI + agomir-NC were compared. The effect of miR-494 was also assessed in an H 2 O 2 -induced apoptosis model. Hepatic AML12 cells were transfected with mimics NC or miR-494 mimics, followed by 6-h H 2 O 2 treatment. Cell proliferation and apoptosis were detected by CCK8 assay and flow cytometry, respectively. Further, the miR-494 target gene was identified by luciferase reporter assay, and verified both in vitro and in vivo experiments. The activity of AKT pathway was further analyzed in vivo by Western blot. HIRI + agomir- miR-494 rats exhibited significantly higher miR-494 expression, lower serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and glutamate dehydrogenase (GLDH) level, lower hepatic MDA, TOA, and OSI, alleviated hepatic necrosis, reduced hepatocyte apoptosis, and decreased expression of apoptosis-related proteins, when compared with HIRI + agomir-NC rats ( P <0.05 or 0.01). After H 2 O 2 treatment, AML-12 cells transfected with miR-494 mimics had significantly higher proliferation and lower apoptosis rate compared with mimics NC group ( P <0.01). PTEN was identified as an miR-494 target gene. PTEN expression was significantly down-regulated in AML12 cells transfected with miR-494 mimics, and was up-regulated by treatment of miR-494 inhibitor ( P <0.01). Moreover, HIRI + agomir- miR-494 rats exhibited significantly lower PTEN expression, and higher p-AKT, p-mTOR, and p-p70S6K levels compared with HIRI + agomir-NC rats. Therefore, miR-494 protected rats against hepatic ischemia/reperfusion (I/R) injury through down-regulating its downstream target gene PTEN , leading to the activation of PI3K/AKT signaling pathway. © 2017 The Author(s).

Metabolite Profiling Reveals the Effect of Dietary Rubus coreanus Vinegar on Ovariectomy-Induced Osteoporosis in a Rat Model.

PubMed

Lee, Mee Youn; Kim, Hyang Yeon; Singh, Digar; Yeo, Soo Hwan; Baek, Seong Yeol; Park, Yoo Kyoung; Lee, Choong Hwan

2016-01-26

The study was aimed at exploring the curative effects of Rubus coreanus (RC) vinegar against postmenopausal osteoporosis by using ovariectomized rats as a model. The investigations were performed in five groups: sham, ovariectomized (OVX) rats without treatment, low-dose RC vinegar (LRV)-treated OVX rats, high-dose RC vinegar (HRV)-treated OVX rats and alendronate (ALEN)-treated OVX rats. The efficacy of RC vinegar was evaluated using physical, biochemical, histological and metabolomic parameters. Compared to the OVX rats, the LRV and HRV groups showed positive effects on the aforementioned parameters, indicating estrogen regulation. Plasma metabolome analysis of the groups using gas chromatography-time of flight mass spectrometry (GC-TOF-MS) and ultra-performance liquid chromatography quadrupole-TOF-MS (UPLC-Q-TOF-MS) with multivariate analysis revealed 19 and 16 metabolites, respectively. Notably, the levels of butyric acid, phenylalanine, glucose, tryptophan and some lysophosphatidylcholines were marginally increased in RC vinegar-treated groups compared to OVX. However, the pattern of metabolite levels in RC vinegar-treated groups was found similar to ALEN, but differed significantly from that in sham group. The results highlight the prophylactic and curative potential of dietary vinegar against postmenopausal osteoporosis. RC vinegar could be an effective natural alternative for the prevention of postmenopausal osteoporosis.

Insulin Effects on Glucose Tolerance, Hypermetabolic Response, and Circadian-metabolic Protein Expression in a Rat Burn and Disuse Model

DTIC Science & Technology

2014-04-23

laboratory, body mass, GTT, and protein expression values for fasted healthy rats subjected to housing in metabolic cages, the stress of sham and GTT...in IBH rats compared with VBH and CC. Insulin was withheld for 24 h, and rats were fasted 10 h in preparation for the procedure. Glucose tolerance...timeline. Animals were fasted for 10 h prior to testing, which was performed on day 7 or 8 for cage control rats and day 14 for insulin and vehicle

[Effect of acupuncture on pattern-visual evoked potential in rats with monocular visual deprivation].

PubMed

Yan, Xing-Ke; Dong, Li-Li; Liu, An-Guo; Wang, Jun-Yan; Ma, Chong-Bing; Zhu, Tian-Tian

2013-08-01

To explore electrophysiology mechanism of acupuncture for treatment and prevention of visual deprivation effect. Eighteen healthy 15-day Evans rats were randomly divided into a normal group, a model group and an acupuncture group, 6 rats in each one. Deprivation amblyopia model was established by monocular eyelid suture in the model group and acupuncture group. Acupuncture was applied at "Jingming" (BL 1), "Chengqi" (ST 1), "Qiuhou" (EX-HN 7) and "Cuanzhu" (BL 2) in the acupuncture group. The bilateral acupoints were selected alternately, one side for a day, and totally 14 days were required. The effect of acupuncture on visual evoked potential in different spatial frequencies was observed. Under three different kinds of spatial frequencies of 2 X 2, 4 X 4 and 8 X 8, compared with normal group, there was obvious visual deprivation effect in the model group where P1 peak latency was delayed (P<0.01) while N1 -P1 amplitude value was decreased (P<0.01). Compared with model group, P1 peak latency was obviously ahead of time (P<0.01) while N1-P1 amplitude value was increased (P<0.01) in the acupuncture group, there was no statistical significance compared with normal group (P>0.05). Under spatial frequency of 4 X 4, N1-P1 amplitude value was maximum in the normal group and acupuncture group. With this spatial frequency the rat's eye had best resolving ability, indicating it could be the best spatial frequency for rat visual system. The visual system has obvious electrophysiology plasticity in sensitive period. Acupuncture treatment could adjust visual deprivation-induced suppression and slow of visual response in order to antagonism deprivation effect.

The effects of virgin coconut oil on bone oxidative status in ovariectomised rat.

PubMed

Abujazia, Mouna Abdelrahman; Muhammad, Norliza; Shuid, Ahmad Nazrun; Soelaiman, Ima Nirwana

2012-01-01

Virgin coconut oil (VCO) was found to have antioxidant property due to its high polyphenol content. The aim of this study was to investigate the effect of the virgin coconut oil on lipid peroxidation in the bone of an osteoporotic rat model. Normal female Sprague-Dawley rats aged 3 months old were randomly divided into 4 groups, with 8 rats in each group: baseline, sham, ovariectomised (OVX) control group, and OVX given 8% VCO in the diet for six weeks. The oxidative status of the bone was assessed by measuring the index of lipid peroxidation, which is malondialdehyde (MDA) concentration, as well as the endogenous antioxidant enzymes glutathione peroxidase (GPX) and superoxide dismutase (SOD) in the tibia at the end of the study. The results showed that there was a significant decrease in MDA levels in the OVX-VCO group compared to control group. Ovariectomised rats treated with VCO also had significantly higher GPX concentration. The SOD level seemed to be increased in the OVX-VCO group compared to OVX-control group. In conclusion, VCO prevented lipid peroxidation and increased the antioxidant enzymes in the osteoporotic rat model.

The Effects of Virgin Coconut Oil on Bone Oxidative Status in Ovariectomised Rat

PubMed Central

Abujazia, Mouna Abdelrahman; Muhammad, Norliza; Shuid, Ahmad Nazrun; Soelaiman, Ima Nirwana

2012-01-01

Virgin coconut oil (VCO) was found to have antioxidant property due to its high polyphenol content. The aim of this study was to investigate the effect of the virgin coconut oil on lipid peroxidation in the bone of an osteoporotic rat model. Normal female Sprague-Dawley rats aged 3 months old were randomly divided into 4 groups, with 8 rats in each group: baseline, sham, ovariectomised (OVX) control group, and OVX given 8% VCO in the diet for six weeks. The oxidative status of the bone was assessed by measuring the index of lipid peroxidation, which is malondialdehyde (MDA) concentration, as well as the endogenous antioxidant enzymes glutathione peroxidase (GPX) and superoxide dismutase (SOD) in the tibia at the end of the study. The results showed that there was a significant decrease in MDA levels in the OVX-VCO group compared to control group. Ovariectomised rats treated with VCO also had significantly higher GPX concentration. The SOD level seemed to be increased in the OVX-VCO group compared to OVX-control group. In conclusion, VCO prevented lipid peroxidation and increased the antioxidant enzymes in the osteoporotic rat model. PMID:22927879

Comparison of plutonium systemic distribution in rats and dogs with published data in humans.

PubMed

Melo, Dunstana R; Weber, Waylon; Doyle-Eisele, Melanie; Guilmette, Raymond A

2014-11-01

This manuscript compares the behavior of monomeric (239)Pu(4+)-citrate injected intravenously in rats and dogs with a comparison of available humans' data. The experimental design for these two studies consisted of eight groups sacrificed at predetermined time-points post exposure. All organs and tissues as well as daily urinary and fecal excretion were analyzed. Liver and skeleton were the organs with the highest (239)Pu uptake in both species; 76% in dogs and 70% in rats at 24 hours (h) post IV administration. By the end of the study (28 days, d), the activity in skeleton and liver was 85% in dogs and 65% in rats. The urinary excretion function seems to be similar for rats, dogs and humans but the daily fecal to urinary excretion ratio differs between species. A rapid clearance from the liver of rats was observed compared to dogs. Skeleton-to-liver ratios are variable between species. Urinary and fecal excretion patterns for dogs are consistent with human data, indicating that dogs seem to represent better the (239)Pu behavior in humans. The data confirm that the better animal model to evaluate the efficacy of (239)Pu chelating compounds is the canine model.

MR brain volumetric measurements are predictive of neurobehavioral impairment in the HIV-1 transgenic rat.

PubMed

Casas, Rafael; Muthusamy, Siva; Wakim, Paul G; Sinharay, Sanhita; Lentz, Margaret R; Reid, William C; Hammoud, Dima A

2018-01-01

HIV infection is known to be associated with brain volume loss, even in optimally treated patients. In this study, we assessed whether dynamic brain volume changes over time are predictive of neurobehavorial performance in the HIV-1 transgenic (Tg) rat, a model of treated HIV-positive patients. Cross-sectional brain MRI imaging was first performed comparing Tg and wild type (WT) rats at 3 and 19 months of age. Longitudinal MRI and neurobehavioral testing of another group of Tg and WT rats was then performed from 5 to 23 weeks of age. Whole brain and subregional image segmentation was used to assess the rate of brain growth over time. We used repeated-measures mixed models to assess differences in brain volumes and to establish how predictive the volume differences are of specific neurobehavioral deficits. Cross-sectional imaging showed smaller whole brain volumes in Tg compared to WT rats at 3 and at 19 months of age. Longitudinally, Tg brain volumes were smaller than age-matched WT rats at all time points, starting as early as 5 weeks of age. The Tg striatal growth rate delay between 5 and 9 weeks of age was greater than that of the whole brain. Striatal volume in combination with genotype was the most predictive of rota-rod scores and in combination with genotype and age was the most predictive of total exploratory activity scores in the Tg rats. The disproportionately delayed striatal growth compared to whole brain between 5 and 9 weeks of age and the role of striatal volume in predicting neurobehavioral deficits suggest an important role of the dopaminergic system in HIV associated neuropathology. This might explain problems with motor coordination and executive decisions in this animal model. Smaller brain and subregional volumes and neurobehavioral deficits were seen as early as 5 weeks of age, suggesting an early brain insult in the Tg rat. Neuroprotective therapy testing in this model should thus target this early stage of development, before brain damage becomes irreversible.

The effect of combined photobiomodulation and metformin on open skin wound healing in a non-genetic model of type II diabetes.

PubMed

Asghari, Mohammadali; Kanonisabet, Ali; Safakhah, Mandanad; Azimzadeh, Zahra; Mostafavinia, Ataroalsadat; Taheri, Soudabeh; Amini, Abdollah; Ghorishi, Seyed Kamran; JalaliFiroozkohi, Reza; Bayat, Sahar; Bayat, Mohammad

2017-04-01

This study intended to examine the combined influences of photobiomodulation (PBM) and metformin on the microbial flora and biomechanical parameters of wounds in a non-genetic model of type II diabetes mellitus (TII DM). We induced a non-genetic model of TII DM in 20 rats by feeding them a 10% fructose solution for 2weeks followed by an injection of streptozotocin (STZ, 40mg/kg). After 21days from the injection of STZ, we induced one full-thickness skin wound in each of the diabetic rats. We randomly divided the rats into four groups: i) placebo; ii) pulsed wave laser (890nm, 80Hz, 0.324J/cm 2 ); iii) metformin; and iv) laser+metformin. Rats received daily intraperitoneal injections of metformin (50mg/kg). On days 7and 15 we inspected the microbial flora of each wound. On day 15 we obtained a standard sample from each healing wound for biomechanical analyses. PBM significantly decreased colony-forming units (CFUs) 7days after wound infliction compared to the placebo group (LSD test, p=0.012). Metformin significantly enhanced the biomechanical property (stress high load) of the wounds compared to the placebo group (LSD test, p=0.028). We observed the same significant result for PBM compared to the placebo group (LSD test, p=0.047). PBM significantly accelerated the wound healing process and significantly reduced CFUs of bacteria in a non-genetic rat model of TII DM. Copyright © 2017 Elsevier B.V. All rights reserved.

Xiao Yao San Improves Depressive-Like Behaviors in Rats with Chronic Immobilization Stress through Modulation of Locus Coeruleus-Norepinephrine System.

PubMed

Ding, Xiu-Fang; Zhao, Xiao-Hua; Tao, Yang; Zhong, Wei-Chao; Fan, Qin; Diao, Jian-Xin; Liu, Yuan-Liang; Chen, Yu-Yao; Chen, Jia-Xu; Lv, Zhi-Ping

2014-01-01

Most research focuses on the hypothalamic-pituitary-adrenal (HPA) axis, hypothalamus-pituitary-thyroid (HPT) axis, and hypothalamus-pituitary-gonadal (HPGA) axis systems of abnormalities of emotions and behaviors induced by stress, while no studies of Chinese herbal medicine such as Xiao Yao San (XYS) on the mechanisms of locus coeruleus-norepinephrine (LC-NE) system have been reported. Therefore, experiments were carried out to observe mechanism of LC-NE system in response to chronic immobilization stress (CIS) and explore the antidepressant effect of XYS. Rat model was established by CIS. LC morphology in rat was conducted. The serum norepinephrine (NE) concentrations and NE biosynthesis such as tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), and corticotrophin-releasing-factor (CRF) in LC were determined. Results showed that there were no discernible alterations in LC in rats. The serum NE concentrations, positive neurons, mean optical density (MOD), and protein levels of TH, DBH, and CRF in model group were significantly increased compared to the control group. But XYS-treated group displayed a significantly decreased in NE levels and expressions of TH, DBH, and CRF compared to the model group. In conclusion, CIS can activate LC-NE system to release NE and then result in a significant decrease in rats. XYS treatment can effectively improve depressive-like behaviors in rats through inhibition of LC-NE neurons activity.

Xiao Yao San Improves Depressive-Like Behaviors in Rats with Chronic Immobilization Stress through Modulation of Locus Coeruleus-Norepinephrine System

PubMed Central

Ding, Xiu-Fang; Zhao, Xiao-Hua; Tao, Yang; Zhong, Wei-Chao; Fan, Qin; Diao, Jian-Xin; Liu, Yuan-Liang; Chen, Yu-Yao; Chen, Jia-Xu; Lv, Zhi-Ping

2014-01-01

Most research focuses on the hypothalamic-pituitary-adrenal (HPA) axis, hypothalamus-pituitary-thyroid (HPT) axis, and hypothalamus-pituitary-gonadal (HPGA) axis systems of abnormalities of emotions and behaviors induced by stress, while no studies of Chinese herbal medicine such as Xiao Yao San (XYS) on the mechanisms of locus coeruleus-norepinephrine (LC-NE) system have been reported. Therefore, experiments were carried out to observe mechanism of LC-NE system in response to chronic immobilization stress (CIS) and explore the antidepressant effect of XYS. Rat model was established by CIS. LC morphology in rat was conducted. The serum norepinephrine (NE) concentrations and NE biosynthesis such as tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), and corticotrophin-releasing-factor (CRF) in LC were determined. Results showed that there were no discernible alterations in LC in rats. The serum NE concentrations, positive neurons, mean optical density (MOD), and protein levels of TH, DBH, and CRF in model group were significantly increased compared to the control group. But XYS-treated group displayed a significantly decreased in NE levels and expressions of TH, DBH, and CRF compared to the model group. In conclusion, CIS can activate LC-NE system to release NE and then result in a significant decrease in rats. XYS treatment can effectively improve depressive-like behaviors in rats through inhibition of LC-NE neurons activity. PMID:25610478

A comparison of the biocompatibility of phosphate-buffered saline and dianeal 3.86% in the rat model of peritoneal dialysis.

PubMed

Wieczorowska-Tobis, K; Polubinska, A; Breborowicz, A; Oreopoulos, D G

2001-01-01

Phosphate-buffered saline (PBS), an isotonic solution with a physiologic pH can be considered an example of a biocompatible dialysis fluid. This study compared the biocompatibility of PBS with that of Dianeal 3.86% (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.), using a model of peritoneal dialysis in the rat. In an acute experiment, after catheter implantation, rats were infused on day 1 with PBS, on day 5 with standard dialysis solution (Dianeal 3.86%), and on day 7 again with PBS. When rats were injected with Dianeal 3.86%, the inflammatory reaction was suppressed as compared with PBS. The cell count was lower with Dianeal (-85%, p < 0.001), the neutrophil:macrophage ratio in dialysate was 80% lower (p < 0.01), total protein concentration in the Dianeal dialysate was 73% lower (p < 0.01), and the dialysate nitrite level was 45% lower (p < 0.01). In a chronic experiment, after catheter implantation, rats were dialyzed for four weeks with PBS or with Dianeal 3.86%. At the end of the study, a 1-hour peritoneal equilibration test (PET) was performed. As evaluated on a semiquantitative scale, macroscopic changes in the peritoneum were more severe in rats exposed to PBS than in those exposed to Dianeal 3.86% (8.6 +/- 3.2 vs 5.2 +/- 2.6, p < 0.05). The thickness of the visceral peritoneum was comparable in both groups; but, in PBS-treated rats, the peritoneal interstitium contained more inflammatory cells and more new vessels. During the 1-hour PET, peritoneal permeability to water and solutes was comparable in the two groups. Despite a more physiologic composition, PBS is a less biocompatible peritoneal dialysis solutions than is standard, acidic, hypertonic dialysis solution.

Altered Sleep Patterns and Physiologic Characteristics in Spontaneous Dwarf Rats

PubMed Central

Andersen, Monica L; Lee, Kil S; Guindalini, Camila; Leite, Waldemarks A; Bignotto, Magda; Tufik, Sergio

2009-01-01

Spontaneous dwarf rats are a useful experimental model for studying various biologic events associated with pituitary dwarfism. Dwarf rats occurred serendipitously in our colony of Wistar rats during experimental breeding. This study aimed to describe the sleep pattern and physiologic characteristics of these rats compared with normal-sized adult rats. Because growth hormone can attenuate the upregulation of ceruloplasmin expression caused by acute inflammation, we also assessed the basal levels of serum ceruloplasmin in these animals. At 90 d of age, body weight and length were significantly lower in dwarf rats relative to normal rats. Dwarves had lower concentrations of serum testosterone and growth hormone, but progesterone was unchanged. Corticosterone levels did not differ between groups. During the light period, the percentage of sleep time recorded and duration of slow-wave sleep did not differ between groups. However, compared with controls, dwarf rats had marked fragmentation of sleep and less paradoxical sleep. During the dark phase, sleep patterns in dwarf rats were within the normal range. Immunoblotting data showed that the levels of ceruloplasmin in serum were lower in dwarf rats. Our findings provide insight into pathologic processes related to growth hormone deficiency. PMID:19712574

Comparison of colony stimulation factors on in vitro rat and human neutrophil function.

PubMed

Wheeler, J G; Huffine, M E; Childress, S; Sikes, J

1994-01-01

The effects of rhCSFs on in vitro polymorphonuclear leukocyte (PMN) function were studied in Sprague-Dawley neonatal and adult rats and adult and umbilical cord derived human PMN to compare species response. Following in vitro exposure to buffer or rhCSFs (50-100 micrograms/ml), PMN oxidative burst, chemotactic activity and adherence protein expression were measured. RhG-CSF increased the oxidative burst of adult rat PMN as measured by chemiluminescence and altered CD11b/CD18 in resting neonatal rat but not adult rat cells. RhGM-CSF had no effect on adult rat PMN function in vitro, but led to modest changes in adult rat PMN diapedesis across rat peritoneum. No responses were noted to rhM-CSF. Human PMN responded best to GM-CSF (particularly in the neonate), intermediately to G-CSF and none to M-CSF. These experiments show that the profile of cytokine effects is not similar in adult and neonatal rat PMN when compared to human cells. The diversity of actions in other species must be considered when using rhCSFs in animal models.

The effects of PEP-1-FK506BP on dry eye disease in a rat model.

PubMed

Kim, Dae Won; Lee, Sung Ho; Ku, Sae Kwang; Lee, Ji Eun; Cha, Hyun Ju; Youn, Jong Kyu; Kwon, Hyeok Yil; Park, Jong Hoon; Park, Eun Young; Cho, Sung-Woo; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

2015-03-01

As FK506 binding proteins (FK506BPs) are known to play an important role in the regulation of a variety of biological processes related to cell survival, this study was designed to examined the protective effects of FK506 binding protein 12 (FK506BP) on low humidity air flow induced dry eye in a rat model using transduced PEP-1-FK506BP. After the topical application of PEP-1-FK506BP, tear volumes were markedly increased and significant prevention of cornea damage was observed compared with dry eye rats. Further, immunohistochemical analysis demonstrated that PEP-1-FK506BP markedly prevented damage to the cornea, the bulbar conjunctiva, and the palpebral conjunctiva epithelial lining compared with dry eye rats. In addition, caspase-3 and PARP expression levels were found to be decreased. These results demonstrated that topical application of PEP-1-FK506BP significantly ameliorates dry eye injury in an animal model. Thus, we suggest that PEP-1-FK506BP can be developed as a new ophthalmic drop to treat dry eye diseases.

Antifibrotic effect of total flavonoids of Astmgali Radix on dimethylnitrosamine-induced liver cirrhosis in rats.

PubMed

Cheng, Yang; Mai, Jing-Yin; Wang, Mei-Feng; Chen, Gao-Feng; Ping, Jian

2017-01-01

To study the effect of total flavonoids of Astmgali Radix (TFA) on liver cirrhosis induced with dimethylnitrosamine (DMN) in rats, and the effect on peroxisome proliferator-activated receptor γ (PPARγ), uncoupling protein 2 (UCP2) and farnesoid X receptor (FXR). Fifty-three Sprague-Dawley rats were randomly divided into a control group (10 rats) and a DMN group (43 rats). Rats in the DMN group were given DMN for 4 weeks and divided randomly into a model group (14 rats), a low-dosage TFA group (14 rats) and a high-dosage TFA group (15 rats) in the 3rd week. Rats were given TFA for 4 weeks at the dosage of 15 and 30 mg/kg in the low- and high-TFA groups, respectively. At the end of the experiment blood and liver samples were collected. Serum liver function and liver tissue hydroxyproline content were determined. hematoxylin-eosin (HE), Sirus red and immunohistochemical stainings of collagen I, smooth muscle actin (α-SMA) was conducted in paraffinembedded liver tissue slices. Real time polymerase chain reaction (PCR) was adopted to determine PPARγ, UCP2 and FXR mRNA levels. Western blot was adopted to determine protein levels of collagen I, α-SMA, PPARγ, UCP2 and FXR. Compared with the model group, TFA increased the ratio of liver/body weight (low-TFA group P<0.05, high-TFA group P<0.01), improved liver biochemical indices (P<0.01 for ALT, AST, GGT in both groups, P<0.05 for albumin and TBil in the high-TFA group) and reduced liver tissue hydroxproline content (P<0.01 in both groups) in treatment groups significantly. HE staining showed that TFA alleviated liver pathological changes markedly and Sirus red staining showed that TFA reduced collagen deposition, alleviated formation and extent of liver pseudolobule. Collagen I and α-SMA immunohistochemical staining showed that staining area and extent markedly decreased in TFA groups compared with the model group. TFA could increase PPARγ, it regulated target UCP2, and FXR levels significantly compared with the model group (in the low-TFA group all P<0.05, in the high group all P<0.01). TFA could improve liver function, alleviate liver pathological changes, and reduce collagen deposition and formation of liver pseudolobule in rats with liver cirrhosis. The antifibrotic effect of TFA was through regulating PPARγ signal pathway and the interaction with FXR.

Rat Disc Torsional Mechanics: Effect of Lumbar and Caudal Levels and Axial Compression Load

PubMed Central

Elliott, Dawn M; Espinoza Orías, Alejandro A; Malhotra, Neil R

2009-01-01

Background Context Rat models with altered loading are used to study disc degeneration and mechano-transduction. Given the prominent role of mechanics in disc function and degeneration, it is critical to measure mechanical behavior in order to evaluate changes following model interventions. Axial compression mechanics of the rat disc are representative of the human disc when normalized by geometry, and differences between the lumbar and caudal disc have been quantified in axial compression. No study has quantified rat disc torsional mechanics. Purpose Compare the torsional mechanical behavior of rat lumbar and caudal discs, determine the contribution of combined axial load on torsional mechanics, and compare the torsional properties of rat discs to human lumbar discs. Study Design Cadaveric biomechanical study. Methods Cyclic torsion without compressive load followed by cyclic torsion with a fixed compressive load was applied to rat lumbar and caudal disc levels. Results The apparent torsional modulus was higher in the lumbar region than in the caudal region,: 0.081±0.026 (MPa/°, Mean±SD) for lumbar axially loaded; 0.066±0.028 caudal axially loaded; 0.091±0.033 for lumbar in pure torsion; and 0.056±0.035 for caudal in pure torsion. These values were similar to human disc properties reported in the literature ranging from 0.024 to 0.21 MPa/°. Conclusions Use of the caudal disc as a model may be appropriate if the mechanical focus is within the linear region of the loading regime. These results provide support for use of this animal model in basic science studies with respect to torsional mechanics. PMID:18495544

A novel intracerebral hemorrhage-induced rat model of neurogenic voiding dysfunction: Analysis of lower urinary tract function

PubMed Central

CHO, YOUNG-SAM; KO, IL-GYU; KIM, CHANG-JU; KIM, KHAE-HAWN

2015-01-01

Neurogenic lower urinary tract dysfunction (NLUTD) is a major problem in patients with various neurological disorders, and may result in debilitating symptoms and serious complications, including chronic renal failure and recurrent urinary tract infections. Clinically, stroke is associated with voiding dysfunction. However, lower urinary tract function evaluation in an intracerebral hemorrhage (ICH) model has not, to the best of our knowledge, been reported. Therefore, in the present study, lower urinary tract function in ICH-induced rats was investigated and the results were compared with those obtained in normal rats. The effects of ICH on peripheral bladder function and central micturition centers [medial preoptic area, ventrolateral gray, pontaine micturition center and spinal cord (lumbar 4 (L4)-L5)] were also examined. Adult female Sprague-Dawley rats were divided into two groups: Control ICH-induced. Induction of ICH in the hippocampal CA1 region was performed using a stereotaxic frame and type IV collagenase. The effects of ICH on the central micturition centers were investigated by simultaneously determining the extent of neuronal activation (c-Fos) and nerve growth factor (NGF) expression, and assessing voiding function (urodynamically using cystometry). The results revealed that induction of ICH significantly enhanced bladder contraction pressure and time, while simultaneously reducing voiding pressure and time. Furthermore, the c-Fos and NGF expression levels in the neuronal voiding centers were significantly increased in the rats with induced ICH as compared with the control rats. Therefore, this ICH-induced NLUTD rat model may be a more appropriate method to analyze NLUTD in stroke patients than a cerebral infarction model, as the former more accurately reflects the nature of the hemorrhage in the two types of stroke. PMID:25954993

Transdifferentiated rat pancreatic progenitor cells (AR42J-B13/H) respond to phenobarbital in a rat hepatocyte-specific manner.

PubMed

Osborne, M; Haltalli, M; Currie, R; Wright, J; Gooderham, N J

2016-07-01

Phenobarbital (PB) is known to produce species-specific effects in the rat and mouse, being carcinogenic in certain mouse strains, but only in rats if treated after a DNA damaging event. PB treatment in the rat and mouse also produces disparate effects on cell signalling and miRNA expression profiles. These responses are induced by short term and prolonged PB exposure, respectively, with the latter treatments being difficult to examine mechanistically in primary hepatocytes due to rapid loss of the original hepatic phenotype and limited sustainability in culture. Here we explore the rat hepatocyte-like B13/H cell line as a model for hepatic response to PB exposure in both short-term and longer duration treatments. We demonstrate that PB with Egf treatment in the B13/H cells resulted in a significant increase in Erk activation, as determined by the ratio of phospho-Erk to total Erk, compared to Egf alone. We also show that an extended treatment with PB in the B13/H cells produces a miRNA response similar to that seen in the rat in vivo, via the time-dependent induction of miR-182/96. Additionally, we confirm that B13/H cells respond to Car activators in a typical rat-specific manner. These data suggest that the B13/H cells produce temporal responses to PB that are comparable to those reported in short-term primary rat hepatocyte cultures and in the longer term are similar to those in the rat in vivo. Finally, we also show that Car-associated miR-122 expression is decreased by PB treatment in B13/H cells, a PB-induced response that is common to the rat, mouse and human. We conclude that the B13/H cell system produces a qualitative response comparable to the rat, which is different to the response in the mouse, and that this model could be a useful tool for exploring the functional consequences of PB-sensitive miRNA changes and resistance to PB-mediated tumours in the rat. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Pharmacodynamic and pharmacokinetic studies and prostatic tissue distribution of fosfomycin tromethamine in bacterial prostatitis or normal rats.

PubMed

Fan, L; Shang, X; Zhu, J; Ma, B; Zhang, Q

2018-05-02

In this study, we assessed the therapeutic effects of fosfomycin tromethamine (FT) in a bacterial prostatitis (BP) rat model. The BP model was induced by Escherichia coli and was demonstrated after 7 days microbiologically and histologically. Then, 25 BP rats selected were randomly divided into five treatment groups: model group, positive group, FT-3 day group, FT-7 day group and FT-14 day group. Ventral lobes of prostate from all animals were removed, and the serum samples were collected at the end of the experiments. Microbiological cultures and histological findings of the prostate samples demonstrated reduced bacterial growth and improved inflammatory responses in FT-treatment groups compared with the model group, indicating that FT against prostatic infection induced by E. coli showed good antibacterial effects. Moreover, plasma pharmacokinetics and prostatic distribution of fosfomycin were studied and compared in BP and normal rats. The concentrations of fosfomycin in samples were analysed by liquid chromatography-tandem mass spectrometry. There were no differences in plasma pharmacokinetic parameters between two groups. But significantly higher penetration of fosfomycin into prostatic tissues was found in BP rats. We therefore suggested that FT had a good therapeutic effect on BP and it might be used in curing masculine reproductive system diseases. © 2018 Blackwell Verlag GmbH.

Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats.

PubMed

Kelly, Karen B; Kennelly, John P; Ordonez, Marta; Nelson, Randal; Leonard, Kelly; Stabler, Sally; Gomez-Muñoz, Antonio; Field, Catherine J; Jacobs, René L

2016-09-23

Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet.

Timing in a Variable Interval Procedure: Evidence for a Memory Singularity

PubMed Central

Matell, Matthew S.; Kim, Jung S.; Hartshorne, Loryn

2013-01-01

Rats were trained in either a 30s peak-interval procedure, or a 15–45s variable interval peak procedure with a uniform distribution (Exp 1) or a ramping probability distribution (Exp 2). Rats in all groups showed peak shaped response functions centered around 30s, with the uniform group having an earlier and broader peak response function and rats in the ramping group having a later peak function as compared to the single duration group. The changes in these mean functions, as well as the statistics from single trial analyses, can be better captured by a model of timing in which memory is represented by a single, average, delay to reinforcement compared to one in which all durations are stored as a distribution, such as the complete memory model of Scalar Expectancy Theory or a simple associative model. PMID:24012783

lncRNA NONRATT021972 siRNA Decreases Diabetic Neuropathic Pain Mediated by the P2X3 Receptor in Dorsal Root Ganglia.

PubMed

Peng, Haiying; Zou, Lifang; Xie, Jinyan; Wu, Hong; Wu, Bing; Zhu, Gaochun; Lv, Qiulan; Zhang, Xi; Liu, Shuangmei; Li, Guilin; Xu, Hong; Gao, Yun; Xu, Changshui; Zhang, Chunping; Wang, Shouyu; Xue, Yun; Liang, Shangdong

2017-01-01

Long noncoding RNAs (lncRNAs) participate in physiological and pathophysiological processes. Type 2 diabetes mellitus (T2DM) accounts for more than 90 % of all cases of diabetes mellitus (DM). Diabetic neuropathic pain (DNP) is a common complication of T2DM. The aim of this study was to investigate the effects of lncRNA NONRATT021972 small interference RNA (siRNA) on DNP mediated by the P2X 3 receptor in dorsal root ganglia (DRG). These experiments showed that the expression levels of NONRATT021972 in DRG were increased in the T2DM rat model (intraperitoneal injection of STZ with 30 mg/kg). The concentration of NONRATT021972 in T2DM patient serum was higher compared to control healthy subjects. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in T2DM rats were lower compared to control rats. MWT and TWL in T2DM rats treated with NONRATT021972 siRNA were higher compared with those in T2DM rats. The expression levels of the P2X 3 protein and messenger RNA (mRNA) of T2DM rat DRG were higher compared to the control, while those in T2DM rats treated with NONRATT021972 siRNA were significantly lower compared to T2DM rats. The level of tumor necrosis factor-α (TNF-α) in the serum of T2DM rats treated with NONRATT021972 siRNA was significantly decreased compared with T2DM rats. NONRATT021972 siRNA inhibited the phosphorylation and activation of ERK1/2 in T2DM DRG. Thus, NONRATT021972 siRNA treatment may suppress the upregulated expression and activation of the P2X 3 receptor and reduce the hyperalgesia potentiated by the pro-inflammatory cytokine TNF-α in T2DM rats.

Effects on the tumor specific growth factor and tumor necrosis factor α in rats' precancerous lesion of primary hepatocellular carcinoma by direct moxibustion at Ganshu (BL 18) acupoint.

PubMed

Wang, Pei; Zhu, Jiang; Xie, Xi-Liang; Sui, Ming-He; Zhang, Qiu-Ju; Jia, Wen-Rui; Xin, Si-Yuan; Liu, Yang; Hou, Zhong-Wei

2016-07-01

To investigate the effect of direct moxibustion at Ganshu (BL18) on the serum concentrations of tumor specific growth factor (TSGF) and tumor necrosis factor α (TNF-α) in a rat model with precancerous lesion of primary hepatocellular carcinoma (HCC), so as to explore the mechanism of moxibustion underlying improvement of HCC. Sixty male Wistar rats were randomly divided into control group (n=10), model group (n=20), prevention group 1 (n=15) and prevention group 2 (n=15). The normal rats were injected with physiological saline as blank control. At the same time, the rats of other three groups were injected with diethylnitrosamine to establish the HCC model. Direct moxibustion with grain-sized moxa was applied to bilateral Ganshu acupoint of the rats in the prevention group 1 (1 treatment course, 20 days) and prevention group 2 (2 treatment courses, 40 days), 5 doses for each acupoint, 0.5 mg/dose, once every other day. At each time point (before model establishment, the end of 1st course prevention, the end of 2nd course prevention and the end of model establishment), serum levels of TSGF and TNF-α were detected using enzyme-linked immunosorbent assay. Compared with the control group, there was a remarkably increase of serum TSGF and TNF-α contents in the model group at the end of the experiment (P<0.05). At the end of the 1st course of direct moxibustion, the contents of serum TSGF and TNF-α of rats in the prevention group 1 were significantly increased compared with that of the model group (P<0.05). At the end of the 2nd course of direct moxibustion, serum TSGF and TNF-α levels of rats in the model group were higher than the normal group with significantly difference (P<0.05), and the levels of TSGF and TNF-α in the prevention group 2 were significantly reduced in comparison with the model group (P<0.05). It was possible that direct moxibustion could inhibit precancerous lesion and postpone hepatocarcinogenesis, and the therapeutic effect of two courses were better than one course.

Seroma Formation in Rat Latissimus Dorsi Resection in the Presence of Biologics: The Role of Quilting.

PubMed

Hurwitz, Zachary M; Ignotz, Ronald A; Rowin, Craig; Freniere, Brian B; Lalikos, Janice F; Dunn, Raymond M

2015-09-01

Seroma formation is a well-recognized complication associated with many operative procedures. Despite its ubiquity, a lack of definitive scientific understanding of the etiology, natural history, and biochemistry of seromas remains. We endeavored to create and examine seromas in a rat model in the setting of commonly used biologic implants and to examine the role of quilting sutures/mechanical fixation in mitigating seroma development. Female Sprague-Dawley rats were assigned to either Quilting or Nonquilting groups then subdivided into one of 3 porcine dermal implant groups (Permacol Surgical Implant, Strattice Reconstructive Tissue Matrix, or XCM Biologic Tissue Matrix) or control group. A 5-cm midline back incision was made, the skin reflected and the latissimus dorsi muscle resected bilaterally. Implants were sutured into the surgical bed using a running suture. The skin of nonquilted rats was closed with a running subcuticular suture. Quilted rats underwent placement of absorbable quilting sutures spaced 2 cm apart between the skin and underlying implant or muscle before skin closure. Postoperatively, rats were monitored for seroma formation with fluid aspirated as needed. At 28 or 90 days, rats were euthanized. Seroma and implants were examined grossly and under light microscopy. Of nonquilted rats, 42/54 (78%) developed seromas compared with 19/46 (41%) of quilted rats (P < 0.05), defined by bursa cavity present at necropsy. When a biologic implant was present, 28/35 (80%) of nonquilted rats developed seromas compared with 12/33 (36%) of quilted rats (P < 0.05). In the control group, 14/19 (74%) of nonquilted rats developed seromas compared with 7/13 (54%) of quilted rats. This difference was not statistically significant. Bursa presence was confirmed histologically in all cases, with no difference in bursa character seen between groups. This study confirms a reliable rat model of seroma formation, with most of the rats exhibiting at least subclinical seromas. There was no difference in seroma formation rate in the presence of biologic implants, and no differences in bursa character between implants. Mechanical fixation with quilting sutures decreased seroma rate significantly in all subgroups. All rats with seromas at necropsy had histological evidence of a bursa with no difference in appearance between groups.

Shock wave therapy effectively attenuates inflammation in rat carotid artery following endothelial denudation by balloon catheter.

PubMed

Shao, Pei-Lin; Chiu, Chaw-Chi; Yuen, Chun-Man; Chua, Sarah; Chang, Li-Teh; Sheu, Jiunn-Jye; Sun, Cheuk-Kwan; Wu, Chiung-Jen; Wang, Ching-Jen; Yip, Hon-Kan

2010-01-01

This study investigates the effectiveness of extracorporeal shock wave (ECSW) in ameliorating inflammatory mediator expression and neointimal formation in a rat model of vascular injury. Male Sprague-Dawley rats with left carotid artery (LCA) injury induced by balloon dilatation (BD; group 1) were compared with group 2 [LCA injury plus ECSW-181 (defined as 181 total shocks given in LCA at 0.011 mJ/mm(2)) on day 2 post-LCA injury], and group 3 (normal controls). The rats in each group were further divided into 3 subgroups (n = 6, each) that were sacrificed on postoperative day 3, 7 and 14, respectively. The results demonstrated that, compared to groups 2 and 3, group 1 had significantly increased cellular expression of CD40, interleukin-18, and connexin 43 at each analyzed time point (all p < 0.001). Additionally, LCCA macrophage (CD68) recruitment was substantially increased in group 1 compared to groups 2 and 3 (all p < 0.001). Furthermore, LCA neointimal proliferation and media thickness were markedly higher in group 1 than in groups 2 and 3 on days 7 and 14 post-BD (all p < 0.001). ECSW markedly attenuates inflammatory responses, proliferation of neointima and smooth muscle cells in a rat vascular injury model.

Rodent growth, behavior, and physiology resulting from flight on the Space Life Sciences-1 mission

NASA Technical Reports Server (NTRS)

Jahns, G.; Meylor, J.; Fast, T.; Hawes, N.; Zarow, G.

1992-01-01

A rodent-based spaceflight study is conducted to investigate physiological changes in rats vs humans and the effects of changes in the design of the Research Animal Holding Facility (RAHF) and the Animal Enclosure Module (AEM). Rats were housed in the AEM and the RAHF, and controls were kept in identical flight hardware on earth subjected to the same flight-environmental profile. Biosamples and organ weights are taken to compare the rats before and after flight, and food/water intake are also compared. Weight gain, body weight, and food consumptions in the flight rats are significantly lower than corresponding values for the control subjects. Flight rats tend to have smaller postexperiment spleens and hearts, and flight rats consumed more water in the AEM than in the RAHF. The rodents' behavior is analogous to humans with respect to physiological and reconditioning effects, showing that the rat is a good model for basic research into the effects of spaceflight on humans.

Reduced incidence of stress ulcer in germ-free Sprague Dawley rats.

PubMed

Paré, W P; Burken, M I; Allen, E D; Kluczynski, J M

1993-01-01

Recent findings with respect to the role of spiral gram-negative bacteria in peptic ulcer disease have stimulated interest in discerning the role of these agents in stress ulcer disease. We tested the hypothesis that a standard restraint-cold ulcerogenic procedure would fail to produce ulcers in axenic rats. Axenic, as well as normal Sprague Dawley rats, were exposed to a cold-restraint procedure. The germ-free condition was maintained throughout the study in the axenic rats. Axenic rats had significantly fewer ulcers as compared to normal rats exposed to the standard cold-restraint procedure, as well as handling control rats. The data represent the first report suggesting a microbiologic component in the development of stress ulcer using the rat model.

Sirolimus-eluting Biodegradable Poly-l-Lactic Acid Stent to Suppress Granulation Tissue Formation in the Rat Urethra.

PubMed

Kim, Kun Yung; Park, Jung-Hoon; Kim, Do Hoon; Tsauo, Jiaywei; Kim, Min Tae; Son, Woo-Chan; Kang, Sung-Gwon; Kim, Dong-Hyun; Song, Ho-Young

2018-01-01

Purpose To investigate the use of sirolimus-eluting biodegradable stents (SEBSs) to suppress granulation tissue formation after stent placement in a rat urethral model. Materials and Methods All experiments were approved by the animal research committee. A total of 36 male Sprague-Dawley rats were randomized into three equal groups after biodegradable stent placement. Group A received control biodegradable stents. Groups B and C received stents coated with 90 µg/cm 2 and 450 µg/cm 2 sirolimus, respectively. Six rats in each group were sacrificed after 4 weeks; the remaining rats were sacrificed after 12 weeks. The therapeutic effectiveness of SEBSs was assessed by comparing the results of retrograde urethrography and histologic examination. Analysis of variance with post hoc comparisons was used to evaluate statistical differences. Results SEBS placement was technically successful in all rats. Urethrographic and histologic examinations revealed significantly less granulation tissue formation at both time points in the rats receiving SEBSs (groups B and C) compared with those that received control stents (group A) (P < .05 for all). There were no significant differences in urethrographic and histologic findings between groups B and C (P > .05 for all). However, the mean number of epithelial layers in group B was higher than that in group C at 4 weeks after stent placement (P < .001). Apoptosis increased in group C compared with groups A and B (P < .05 for all). Conclusion The use of SEBSs suppressed granulation tissue formation secondary to stent placement in a rat urethral model; local therapy with SEBSs may be used to decrease stent-related granulation tissue formation. © RSNA, 2017.

LncRNAs expression in adjuvant-induced arthritis rats reveals the potential role of LncRNAs contributing to rheumatoid arthritis pathogenesis.

PubMed

Jiang, Hui; Qin, Xiu-Juan; Li, Wei-Ping; Ma, Rong; Wang, Ting; Li, Zhu-Qing

2016-11-15

Long non-coding RNAs (LncRNAs) are an important class of widespread molecules involved in diverse biological functions, which are exceptionally expressed in numerous types of diseases. Currently, limited study on LncRNA in rheumatoid arthritis (RA) is available. In this study, we aimed to identify the specifically expressed LncRNA that are relevant to adjuvant-induced arthritis (AA) in rats, and to explore the possible molecular mechanisms of RA pathogenesis. To identify LncRNAs specifically expressed in rheumatoid arthritis, the expression of LncRNAs in synoviums of rats from the model group (n=3) was compared with that in the control group (n=3) using Arraystar Rat LncRNA/mRNA microarray and real-time polymerase chain reaction (RT-PCR). Up to 260 LncRNAs were found to be differentially expressed (≥1.5-fold-change) in the synoviums between AA model and the normal rats (170 up-regulated and 90 down-regulated LncRNAs in AA rats compared with normal rats). Coding-non-coding gene co-expression networks (CNC network) were drawn based on the correlation analysis between the differentially expressed LncRNAs and mRNAs. Six LncRNAs, XR_008357, U75927, MRAK046251, XR_006457, DQ266363 and MRAK003448, were selected to analyze the relationship between LncRNAs and RA via the CNC network and GO analysis. Real-time PCR result confirmed that the six LncRNAs were specifically expressed in the AA rats. These results revealed that clusters of LncRNAs were uniquely expressed in AA rats compared with controls, which manifests that these differentially expressed LncRNAs in AA rats might play a vital role in RA development. Up-regulation or down-regulation of the six LncRNAs might contribute to the molecular mechanism underlying RA. To sum up, our study provides potential targets for treatment of RA and novel profound understanding of the pathogenesis of RA. Copyright © 2016. Published by Elsevier B.V.

Comparative effects of torasemide and furosemide on gap junction proteins and cardiac fibrosis in a rat model of dilated cardiomyopathy.

PubMed

Watanabe, Kenichi; Sreedhar, Remya; Thandavarayan, Rajarajan A; Karuppagounder, Vengadeshprabhu; Giridharan, Vijayasree V; Antony, Shanish; Harima, Meilei; Nakamura, Masahiko; Suzuki, Kenji; Suzuki, Hiroshi; Sone, Hirohito; Arumugam, Somasundaram

2017-03-01

Cardiac fibrosis is the major hallmark of adverse cardiac remodeling in chronic heart failure (CHF) and its therapeutic targeting might help against cardiac dysfunction during chronic conditions. Diuretic agents are potentially useful in these cases, but their effects on the cardiac fibrosis pathogenesis are yet to be identified. This study was designed to identify and compare the effects of diuretic drugs torasemide and furosemide on cardiac fibrosis in a rat model of dilated cardiomyopathy induced by porcine cardiac myosin mediated experimental autoimmune myocarditis. Gap junction proteins, connexin-43 and N-cadherin, expressions were downregulated in the hearts of CHF rats, while torasemide treatment has upregulated their expression. Western blotting and immunohistochemical analysis for various cardiac fibrosis related proteins as well as histopathological studies have shown that both drugs have potential anti-fibrotic effects. Among them, torasemide has superior efficacy in offering protection against adverse cardiac remodeling in the selected rat model of dilated cardiomyopathy. In conclusion, torasemide treatment has potential anti-fibrotic effect in the hearts of CHF rats, possibly via improving the gap junction proteins expression and thereby improving the cell-cell interaction in the heart. © 2016 BioFactors, 43(2):187-194, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

Mechanism of Mongolian medical warm acupuncture in treating insomnia by regulating miR-101a in rats with insomnia.

PubMed

Bo, Agula; Si, Lengge; Wang, Yuehong; Bao, Lidao; Yuan, Hongwei

2017-07-01

MicroRNAs (miRNAs or miRs) and the target genes before and after warm acupuncture at the genetic level were assessed, and the cytokines and neurotransmitters related to insomnia were studied. Male Sprague-Dawley rats were used to create PCPA insomnia rat models and randomly divided into the normal, model, warm acupuncture, and drug groups. The Dinghui Acupoint, Heyi Acupoint, and Xin Acupoint were inserted in the Mongolian medicine warm acupuncture group. The differential expression profile of microRNA in the brain tissue of the insomnia rats was determined before and after Mongolian medicine warm acupuncture for establishment of miR-101a mimics and inhibitor. qPCR was used to detect the expression level of miR-101a. Western blotting was used to detect the expression level of PAX8. The rats receiving Mongolian medicine warm acupuncture had 141 miRNAs with differential expression compared with the normal rats. The expression level of miR-101a in the cells of the hippocampus of the insomnia rats transfected with miR-101a mimics increased significantly at 72 h (P<0.05). The activity of the neuronal cells transfected with miR-101a inhibitor increased significantly at 72 h (P<0.05). The western blotting result indicated that the expression of the PAX8 protein in the neuronal cells of the insomnia model rats was inhibited and downregulated significantly at 72 h after addition of miR-101a mimics compared with that in the scramble added group (P<0.01). The levels of the interleukins IL-1, IL-2, and IL-6 and the tumor necrosis factor-α in the hypothalamus, hippocampus, and prefrontal cortex decreased significantly compared with those in the blank control group (P<0.05). The levels of noradrenaline, dopamine, and glutamic decreased significantly following warm acupuncture or western medicine treatment (P<0.05). In conclusion, this study demonstrates that the upregulation of miR-101a in the rats treated with warm acupuncture is directly associated with PAX8 regulation.

Mechanism of Mongolian medical warm acupuncture in treating insomnia by regulating miR-101a in rats with insomnia

PubMed Central

Bo, Agula; Si, Lengge; Wang, Yuehong; Bao, Lidao; Yuan, Hongwei

2017-01-01

MicroRNAs (miRNAs or miRs) and the target genes before and after warm acupuncture at the genetic level were assessed, and the cytokines and neurotransmitters related to insomnia were studied. Male Sprague-Dawley rats were used to create PCPA insomnia rat models and randomly divided into the normal, model, warm acupuncture, and drug groups. The Dinghui Acupoint, Heyi Acupoint, and Xin Acupoint were inserted in the Mongolian medicine warm acupuncture group. The differential expression profile of microRNA in the brain tissue of the insomnia rats was determined before and after Mongolian medicine warm acupuncture for establishment of miR-101a mimics and inhibitor. qPCR was used to detect the expression level of miR-101a. Western blotting was used to detect the expression level of PAX8. The rats receiving Mongolian medicine warm acupuncture had 141 miRNAs with differential expression compared with the normal rats. The expression level of miR-101a in the cells of the hippocampus of the insomnia rats transfected with miR-101a mimics increased significantly at 72 h (P<0.05). The activity of the neuronal cells transfected with miR-101a inhibitor increased significantly at 72 h (P<0.05). The western blotting result indicated that the expression of the PAX8 protein in the neuronal cells of the insomnia model rats was inhibited and downregulated significantly at 72 h after addition of miR-101a mimics compared with that in the scramble added group (P<0.01). The levels of the interleukins IL-1, IL-2, and IL-6 and the tumor necrosis factor-α in the hypothalamus, hippocampus, and prefrontal cortex decreased significantly compared with those in the blank control group (P<0.05). The levels of noradrenaline, dopamine, and glutamic decreased significantly following warm acupuncture or western medicine treatment (P<0.05). In conclusion, this study demonstrates that the upregulation of miR-101a in the rats treated with warm acupuncture is directly associated with PAX8 regulation. PMID:28672928

Exposure to low level of arsenic and lead in drinking water from Antofagasta city induces gender differences in glucose homeostasis in rats.

PubMed

Palacios, Javier; Roman, Domingo; Cifuentes, Fredi

2012-08-01

Populations chronically exposed to arsenic in drinking water often have increased prevalence of diabetes mellitus. The purpose of this study was to compare the glucose homeostasis of male and female rats exposed to low levels of heavy metals in drinking water. Treated groups were Sprague-Dawley male and female rats exposed to drinking water from Antofagasta city, with total arsenic of 30 ppb and lead of 53 ppb for 3 months; control groups were exposed to purified water by reverse osmosis. The two treated groups in both males and females showed arsenic and lead in the hair of rats. The δ-aminolevulinic acid dehydratase was used as a sensitive biomarker of arsenic toxicity and lead. The activity of δ-aminolevulinic acid dehydratase was reduced only in treated male rats, compared to the control group. Treated males showed a significantly sustained increase in blood glucose and plasma insulin levels during oral glucose tolerance test compared to control group. The oral glucose tolerance test and the homeostasis model assessment of insulin resistance demonstrated that male rats were insulin resistant, and females remained sensitive to insulin after treatment. The total cholesterol and LDL cholesterol increased in treated male rats vs. the control, and triglyceride increased in treated female rats vs. the control. The activity of intestinal Na+/glucose cotransporter in male rats increased compared to female rats, suggesting a significant increase in intestinal glucose absorption. The findings indicate that exposure to low levels of arsenic and lead in drinking water could cause gender differences in insulin resistance.

Effects of Menthol-Containing Artificial Tears on Tear Stimulation and Ocular Surface Integrity in Normal and Dry Eye Rat Models.

PubMed

Ahn, Somin; Eom, Youngsub; Kang, Boram; Park, Jungboung; Lee, Hyung Keun; Kim, Hyo Myung; Song, Jong Suk

2018-05-01

To evaluate the effects of menthol-containing artificial tears on tear stimulation and ocular surface integrity in normal and dry eye rat models. A total of 54 male Lewis rats were used. The levels of tear secretion and tear MUC5AC concentrations were compared between the menthol-containing artificial tear-treated group (menthol group) and the vehicle-treated group (vehicle group). The groups were compared after a single instillation to evaluate the immediate effects, and after repeated instillation (five times a day for 5 days) to evaluate the longer-term effects. Tear lactate dehydrogenase (LDH) activity was measured to evaluate eye drop instillation-induced ocular surface damage. The effects of menthol-containing artificial tears were also evaluated in a dry eye rat model. After a single instillation of menthol-containing artificial tears, tear secretion increased from 4.37 (±0.75) mm at baseline to 7.37 (±1.60) mm. However, after repeated instillations, the effects of tear stimulation decreased. The tear MUC5AC concentration was significantly lower in the menthol group than in the vehicle group after a single instillation, but not after repeated instillation. However, the tear LDH concentration was significantly increased in the menthol group after repeated instillation. In the dry eye rat model, the extent of menthol-induced tear stimulation was reduced. Menthol-containing artificial tears increased tear secretion, but lowered the tear MUC5AC concentration. Menthol-induced tear stimulation was reduced after repeated instillation for 5 days and in the dry eye rat model. Conversely, repeated instillation of menthol-induced ocular surface damage, resulting in increased tear LDH activity.

[Protective effect of Tanreqing injection on acute hepatic injury induced by CCl4 in rats].

PubMed

Lei, Yang; Zhou, Ai-Min; Guo, Tao; Tan, Ye; Tao, Yan-Yan; Liu, Cheng-Hai

2013-04-01

To observe the protective effect of Tanreqing injection(TRQ) on carbon tetrachloride-induced acute hepatic injury in rats. Rats were randomly divided into the normal group and the model group, and injected subcutaneously with 100% CCl4 5 mL x kg(-1) to establish the single CCl4 infection model, in order to observe the changes in rat liver injury after 3 h and 6 h. Subsequently, the multiple CCl4 infection liver injury model was reproduced by subcutaneously injecting 100% CCl4 (5 mL x kg(-1)), 50% CCl4 olive oil solution (2 mL x kg(-1)) and then 20% CCl4 olive oil solution (2 mL x kg(-1)). At 6 h after the first CCl4 injection, the rats were divided into six groups: the model group, the control group, the diammonium glycyrrhizinate-treated group, and TRQ high, middle and low dose groups. They were injected through caudal veins, while a normal control group was set up. Their weight and liver-body ratio were observed. Hepatic inflammation was observed with HE staining. Assay kits were adopted to detect ALT, AST, T. Bil, D. Bil, CHE, TBA, gamma-GT and Alb. According to the single injection model, serum AST and T. Bil of model rats were obviously increased at 6 h after single subcutaneous injection of CCl4, with disordered lobular structure in liver tissues, notable swollen liver cells and remarkable liver injury. According to the results of the multiple injection pharmacological experiment, compared with the normal group, the model group had higher serum ALT, AST, and gamma-GT activities (P < 0. 05), TBA and T. Bil contents (P < 0.05) and lower CHE activity (P < 0.05). HE staining showed disorganized lobular structure in liver tissues and notable ballooning degeneration in liver cells. Compared with the model group, TRQ high and middle dose groups and the diammonium glycyrrhizinate-treated group showed significant charges in serum liver function and inflammation in liver cells. Specifically, TRQ high and middle dose groups were superior to the diammonium glycyrrhizinate-treated group. Tanreqing injection has significant protective effect on CCl4-induced acute hepatic injury in rats.

Comparison of Allogeneic and Syngeneic Rat Glioma Models by Using MRI and Histopathologic Evaluation

PubMed Central

Biasibetti, Elena; Valazza, Alberto; Capucchio, Maria T; Annovazzi, Laura; Battaglia, Luigi; Chirio, Daniela; Gallarate, Marina; Mellai, Marta; Muntoni, Elisabetta; Peira, Elena; Riganti, Chiara; Schiffer, Davide; Panciani, Pierpaolo; Lanotte, Michele

2017-01-01

Research in neurooncology traditionally requires appropriate in vivo animal models, on which therapeutic strategies are tested before human trials are designed and proceed. Several reproducible animal experimental models, in which human physiologic conditions can be mimicked, are available for studying glioblastoma multiforme. In an ideal rat model, the tumor is of glial origin, grows in predictable and reproducible patterns, closely resembles human gliomas histopathologically, and is weakly or nonimmunogenic. In the current study, we used MRI and histopathologic evaluation to compare the most widely used allogeneic rat glioma model, C6-Wistar, with the F98-Fischer syngeneic rat glioma model in terms of percentage tumor growth or regression and growth rate. In vivo MRI demonstrated considerable variation in tumor volume and frequency between the 2 rat models despite the same stereotactic implantation technique. Faster and more reproducible glioma growth occurred in the immunoresponsive environment of the F98-Fischer model, because the immune response is minimized toward syngeneic cells. The marked inability of the C6-Wistar allogeneic system to generate a reproducible model and the episodes of spontaneous tumor regression with this system may have been due to the increased humoral and cellular immune responses after tumor implantation. PMID:28381315

Comparison of the antibacterial effect of silver sulfadiazine 1%, mupirocin 2%, Acticoat and octenidine dihydrochloride in a full-thickness rat burn model contaminated with multi drug resistant Acinetobacter baumannii.

PubMed

Selçuk, Caferi Tayyar; Durgun, Mustafa; Ozalp, Burhan; Tekin, Alicem; Tekin, Recep; Akçay, Cemal; Alabalık, Ulaş

2012-12-01

In this study, our aim is to compare the efficacy of different topical antibacterial agents in a rat model contaminated with a multi drug resistant (MDR) standard Acinetobacter baumannii strain. The study was carried out on 40 Sprague-Dawley rats of 250-300 g each. For the purposes of this study, the rats were divided into 5 groups, with 8 rats in each group: Group 1 control; Group 2 silver sulfadiazine; Group 3 mupirocin; Group 4 Acticoat group; and Group 5 octenidine dihydrochloride group. Following to the formation of the full-thickness burn areas in rats, the MDR A. baumannii standard strain was inoculated into the burned area. The rats in all the groups were sacrificed at the end of the 10th day and subjected to histopathological and microbiological evaluation. In the histopathological evaluation, the lowest inflammatory cell response and bacterial density in the eschar and muscle tissues were observed in the Acticoat group. While these results were found to be statistically significant compared to the silver sulfadiazine group, only the bacterial density in the muscle tissue was found as significant in comparison to the mupirocin and octenidine groups. In the microbiological evaluation, the lowest growth in the muscle tissue culture among all the groups was observed in the Acticoat group. The growth in the eschar tissue culture was significantly lower in the Acticoat and octenidine groups in comparison to the silver sulfadiazine group. At the end of the study, it has been observed that Acticoat was effective both in eschar and muscle, while octenidine was effective in eschar tissues in a rat burn model contaminated with MDR A. baumannii. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

Mu-Opioid (MOP) receptor mediated G-protein signaling is impaired in specific brain regions in a rat model of schizophrenia.

PubMed

Szűcs, Edina; Büki, Alexandra; Kékesi, Gabriella; Horváth, Gyöngyi; Benyhe, Sándor

2016-04-21

Schizophrenia is a complex mental health disorder. Clinical reports suggest that many patients with schizophrenia are less sensitive to pain than other individuals. Animal models do not interpret schizophrenia completely, but they can model a number of symptoms of the disease, including decreased pain sensitivities and increased pain thresholds of various modalities. Opioid receptors and endogenous opioid peptides have a substantial role in analgesia. In this biochemical study we investigated changes in the signaling properties of the mu-opioid (MOP) receptor in different brain regions, which are involved in the pain transmission, i.e., thalamus, olfactory bulb, prefrontal cortex and hippocampus. Our goal was to compare the transmembrane signaling mediated by MOP receptors in control rats and in a recently developed rat model of schizophrenia. Regulatory G-protein activation via MOP receptors were measured in [(35)S]GTPγS binding assays in the presence of a highly selective MOP receptor peptide agonist, DAMGO. It was found that the MOP receptor mediated activation of G-proteins was substantially lower in membranes prepared from the 'schizophrenic' model rats than in control animals. The potency of DAMGO to activate MOP receptor was also decreased in all brain regions studied. Taken together in our rat model of schizophrenia, MOP receptor mediated G-proteins have a reduced stimulatory activity compared to membrane preparations taken from control animals. The observed distinct changes of opioid receptor functions in different areas of the brain do not explain the augmented nociceptive threshold described in these animals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

PDGF-α stimulates intestinal epithelial cell turnover after massive small bowel resection in a rat.

PubMed

Sukhotnik, Igor; Mogilner, Jorge G; Pollak, Yulia; Blumenfeld, Shiri; Bejar, Jacob; Coran, Arnold G

2012-06-01

Numerous cytokines have been shown to affect epithelial cell differentiation and proliferation through epithelial-mesenchymal interaction. Growing evidence suggests that platelet-derived growth factor (PDGF) signaling is an important mediator of these interactions. The purpose of this study was to evaluate the effect of PDGF-α on enterocyte turnover in a rat model of short bowel syndrome (SBS). Male rats were divided into four groups: Sham rats underwent bowel transection, Sham-PDGF-α rats underwent bowel transection and were treated with PDGF-α, SBS rats underwent a 75% bowel resection, and SBS-PDGF-α rats underwent bowel resection and were treated with PDGF-α. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined at euthanasia. Illumina's Digital Gene Expression analysis was used to determine PDGF-related gene expression profiling. PDGF-α and PDGF-α receptor (PDGFR-α) expression was determined by real-time PCR. Western blotting was used to determine p-ERK, Akt1/2/3, bax, and bcl-2 protein levels. SBS rats demonstrated a significant increase in PDGF-α and PDGFR-α expression in jejunum and ileum compared with sham animals. SBS-PDGF-α rats demonstrated a significant increase in bowel and mucosal weight, villus height, and crypt depth in jejunum and ileum compared with SBS animals. PDGF-α receptor expression in crypts increased in SBS rats (vs. sham) and was accompanied by an increased cell proliferation following PDGF-α administration. A significant decrease in cell apoptosis in this group was correlated with lower bax protein levels. In conclusion, in a rat model of SBS, PDGF-α stimulates enterocyte turnover, which is correlated with upregulated PDGF-α receptor expression in the remaining small intestine.

The corpus cavernosum after treatment with dutasteride or finasteride: A histomorphometric study in a benign prostatic hyperplasia rodent model.

PubMed

Da Silva, Marcello H A; Costa, Waldemar S; B Sampaio, Francisco J; De Souza, Diogo B

2018-06-08

Erectile dysfunction is a common side effect of finasteride and dutasteride treatments. The objective of this study was to investigate the structural changes in the penis using a benign prostatic hyperplasia (BPH) rodent model treated with dutasteride or finasteride. Sixty male rats were divided into the following groups: C, untreated control rats; C + D, control rats receiving dutasteride; C + F, control rats receiving finasteride; H, untreated spontaneously hypertensive rats (SHRs); H + D, SHRs treated with dutasteride; and H + F, SHRs treated with finasteride. Treatments were performed for 40 days, and penises were collected immediately thereafter. The organs were analyzed using histomorphometric methods to determine the cross-sectional penile area, as well as the surface density (Sv) of smooth muscle fibers, connective tissue, elastic system fibers, and sinusoidal spaces of the corpus cavernosum. The results were compared using a one-way ANOVA with Bonferroni's posttest. Groups C + D and C + F had a significantly smaller penile cross-sectional area, but more elastic system fiber Sv compared to Group C. Group C + D showed less smooth muscle Sv, and Group H showed more connective tissue but a smaller sinusoidal space Sv in the corpus cavernosum compared to Group C. Groups H + D and H + F had less smooth muscle Sv than Group H. Group H + D also had more connective tissue and elastic system fiber Sv than Group H. Both dutasteride and finasteride promoted penile modifications in the control rat penis, although this affect was greater in Group H animals. In this rodent model, dutasteride was the drug that most affected the corpus cavernosum.

Cannabinoids increase conditioned ultrasonic vocalisations and cat odour avoidance in rats: strain differences in drug-induced anxiety.

PubMed

Arnold, Jonathon C; Dielenberg, Robert A; McGregor, Iain S

2010-10-23

Genetic disposition modulates the psychoactive effects of cannabis. Cannabinoids have a greater impact on brain regions that subserve anxiety in Wistar compared to Lewis strain rats. Here we aim to show that this correlates with strain differences in cannabinoid-induced anxiety-related behaviour. Lewis and Wistar rats were administered vehicle or the synthetic cannabinoid receptor agonist, CP 55,940 (10, 25 and 50μg/kg) before testing in the conditioned ultrasonic vocalization (USV), cat odour avoidance or open area avoidance models. Animals were placed in a chamber in which they had previously received footshock. Wistar but not Lewis rats re-exposed under the influence of all CP 55,940 doses emitted significantly more USVs than vehicle-treated rats. In the cat odour avoidance model, rats were exposed to cat odour and given the opportunity to hide in a small box. In Wistar but not Lewis rats, 50μg/kg of CP 55,940 magnified hiding behaviour promoted by cat odour exposure. Animals were also tested in the open area avoidance model which occurred in the same arena as the predatory avoidance model but without cat odour. In Wistar, but not Lewis rats, 25 and 50μg/kg of CP 55,940 increased the avoidance of the open space. CP 55,940 increased anxiety-related behaviour in Wistar rats but not Lewis rats providing a model to dissect the genetic basis of cannabinoid-induced anxiety. We show for the first time that cannabinoids magnify conditioned USVs and cat odour avoidance behaviour dependent on the strain being tested. Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.

A new minimal-stress freely-moving rat model for preclinical studies on intranasal administration of CNS drugs.

PubMed

Stevens, Jasper; Suidgeest, Ernst; van der Graaf, Piet Hein; Danhof, Meindert; de Lange, Elizabeth C M

2009-08-01

To develop a new minimal-stress model for intranasal administration in freely moving rats and to evaluate in this model the brain distribution of acetaminophen following intranasal versus intravenous administration. Male Wistar rats received one intranasal cannula, an intra-cerebral microdialysis probe, and two blood cannulas for drug administration and serial blood sampling respectively. To evaluate this novel model, the following experiments were conducted. 1) Evans Blue was administered to verify the selectivity of intranasal exposure. 2) During a 1 min infusion 10, 20, or 40 microl saline was administered intranasally or 250 microl intravenously. Corticosterone plasma concentrations over time were compared as biomarkers for stress. 3) 200 microg of the model drug acetaminophen was given in identical setup and plasma, and brain pharmacokinetics were determined. In 96% of the rats, only the targeted nasal cavity was deeply colored. Corticosterone plasma concentrations were not influenced, neither by route nor volume of administration. Pharmacokinetics of acetaminophen were identical after intravenous and intranasal administration, although the Cmax in microdialysates was reached a little earlier following intravenous administration. A new minimal-stress model for intranasal administration in freely moving rats has been successfully developed and allows direct comparison with intravenous administration.

White matter atrophy and myelinated fiber disruption in a rat model of depression.

PubMed

Gao, Yuan; Ma, Jing; Tang, Jing; Liang, Xin; Huang, Chun-Xia; Wang, San-Rong; Chen, Lin-Mu; Wang, Fei-Fei; Tan, Chuan-Xue; Chao, Feng-Lei; Zhang, Lei; Qiu, Xuan; Luo, Yan-Min; Xiao, Qian; Du, Lian; Xiao, Qian; Tang, Yong

2017-06-01

Brain imaging and postmortem studies have indicated that white matter abnormalities may contribute to the pathology and pathogenesis of depression. However, until now, no study has quantitatively investigated white matter changes in depression in rats. The current study used the chronic unpredictable stress (CUS) model of depression. Body weight and sucrose preference test (SPT) scores were assessed weekly. Upon successfully establishing the CUS animal model, all animals were tested using the SPT and the open field test (OFT). Then, transmission electron microscopy and unbiased stereological methods were used to investigate white matter changes in the rats. Compared with the control group, the body weight and sucrose preference of the CUS rats were significantly decreased (p < .001, p < .001, respectively). In the OFT, the total time spent and the total distance traveled in the inner area by the CUS rats were significantly lower than those of the control group (p = .002, p = .001, respectively). The stereological results revealed that white matter volume, the total volume, and the total length and mean diameter of myelinated fibers in the white matter of the CUS rats were significantly decreased compared to the control rats (p = .042, p = .038, p = .035, p = .019, respectively). The results of this study suggested that white matter atrophy and disruption of myelinated fibers in the white matter may contribute to the pathophysiology underlying depression, which might provide new targets for the development of novel therapeutic interventions for depression. © 2017 Wiley Periodicals, Inc.

Biomechanics of Two External Fixator Devices Used in Rat Femoral Fractures.

PubMed

Osagie-Clouard, Liza; Kaufmann, Joshua; Blunn, Gordon; Coathup, Melanie; Pendegrass, Catherine; Meeson, Richard; Briggs, Timothy; Moazen, Mehran

2018-05-04

The use of external fixators allows for the direct investigation of newly formed interfragmentary bone, and the radiographic evaluation of the fracture. We validated the results of a finite element model with the in vitro stiffness' of two widely used external fixator devices used for in vivo analysis of fracture healing in rat femoral fractures with differing construction (Ti alloy ExFix1 and PEEK ExFix2). Rat femoral fracture fixation was modelled using two external fixators. For both constructs an osteotomy of 2.75 mm was used, and offset maintained at 5 mm. Tufnol, served as standardized substitutes for rat femora. Constructs were loaded under axial compression and torsion. Overall axial and torsional stiffness were compared between the in vitro models and FE results. FE models were also used to compare the fracture movement and overall pattern of von Mises stress across the external fixators. In vitro axial stiffness of ExFix1 was 29.26 N/mm ± 3.83 compared to ExFix2 6.31 N/mm ± 0.67 (p* < 0.05). Torsional stiffness of ExFix1 was 47.5 Nmm/° ± 2.71 compared to ExFix2 at 19.1 Nmm/° ± 1.18 (p* < 0.05). FE results predicted similar comparative ratios between the ExFix1 and 2 as the in vitro studies. FE results predicted considerably larger interfragmentary motion in the ExFix2 comparing to ExFix1. We demonstrated significant differences in the stiffness' of the two external fixators as one would expect from such variable designs; yet, importantly we validated the utility of an FE model for the analysis and prediction of changes in fracture mechanics dependent on fixator choice. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Electrophysiological characterization of spinal neurons in different models of diabetes type 1- and type 2-induced neuropathy in rats.

PubMed

Schuelert, N; Gorodetskaya, N; Just, S; Doods, H; Corradini, L

2015-04-16

Diabetic polyneuropathy (DPN) is a devastating complication of diabetes. The underlying pathogenesis of DPN is still elusive and an effective treatment devoid of side effects presents a challenge. There is evidence that in type-1 and -2 diabetes, metabolic and morphological changes lead to peripheral nerve damage and altered central nociceptive transmission, which may contribute to neuropathic pain symptoms. We characterized the electrophysiological response properties of spinal wide dynamic range (WDR) neurons in three diabetic models. The streptozotocin (STZ) model was used as a drug-induced model of type-1 diabetes, and the BioBreeding/Worcester (BB/Wor) and Zucker diabetic fatty (ZDF) rat models were used for genetic DPN models. Data were compared to the respective control group (BB/Wor diabetic-resistant, Zucker lean (ZL) and saline-injected Wistar rat). Response properties of WDR neurons to mechanical stimulation and spontaneous activity were assessed. We found abnormal response properties of spinal WDR neurons in all diabetic rats but not controls. Profound differences between models were observed. In BB/Wor diabetic rats evoked responses were increased, while in ZDF rats spontaneous activity was increased and in STZ rats mainly after discharges were increased. The abnormal response properties of neurons might indicate differential pathological, diabetes-induced, changes in spinal neuronal transmission. This study shows for the first time that specific electrophysiological response properties are characteristic for certain models of DPN and that these might reflect the diverse and complex symptomatology of DPN in the clinic. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Further Characterization of the Predictive Validity of the Brattleboro Rat Model for Antipsychotic Efficacy

PubMed Central

Feifel, D.; Shilling, P. D.; Melendez, G.

2014-01-01

Our laboratory and others have reported that Brattleboro (BRAT) rats, a Long Evans (LE) strain with a single gene mutation, have inherent deficits in prepulse inhibition (PPI) homologous to those observed in schizophrenia patients and that these deficits are reversed by antipsychotic drugs (APDs). To further evaluate the potential predictive validity of BRAT rat PPI for APDs, we compared the effects of acute subcutaneous administration of the typical APD chlorpromazine to that of three psychotropic drugs without antipsychotic efficacy, the antidepressant imipramine, the anxiolytic diazepam and the anticonvulsant mood stabilizer valproic acid on male and female BRAT rat PPI. Male and female BRAT rats exhibited baseline (saline treatment) PPI that was not different from each other (21.1 % and 21.3 %, respectively) and low compared to those historically exhibited by LE rats (approximately 59 %). Chlorpromazine facilitated PPI in male and female BRAT rats, whereas imipramine, diazepam, and valproic acid had no significant effect on PPI. These results suggest that PPI in the BRAT rat responds specifically to drugs with APD efficacy but not psychotropic drugs of different therapeutic families. PMID:21106605

Effects of Sex and Stress on Trigeminal Neuropathic Pain-Like Behavior in Rats.

PubMed

Korczeniewska, Olga Anna; Khan, Junad; Tao, Yuanxiang; Eliav, Eli; Benoliel, Rafael

2017-01-01

To investigate the effects and interactions of sex and stress (provoked by chronic restraint [RS]) on pain-like behavior in a rat model of trigeminal neuropathic pain. The effects of sex and RS (carried out for 14 days as a model for stress) on somatosensory measures (reaction to pinprick, von Frey threshold) in a rat model of trigeminal neuropathic pain were examined. The study design was 2 × 4, with surgery (pain) and sham surgery (no pain) interacting with male restrained (RS) and unrestrained (nRS) rats and female RS and nRS rats. A total of 64 Sprague Dawley rats (32 males and 32 females) were used. Half of the animals in each sex group underwent RS, and the remaining half were left unstressed. Following the RS period, trigeminal neuropathic pain was induced by unilateral infraorbital nerve chronic constriction injury (IOCCI). Half of the animals in the RS group and half in the nRS group (both males and females) were exposed to IOCCI, and the remaining halves to sham surgery. Elevated plus maze (EPM) assessment and plasma interferon gamma (IFN-γ) levels were used to measure the effects of RS. Analysis of variance (ANOVA) was used to assess the effects of stress, sex, and their interactions on plasma IFN-γ levels, changes in body weight, EPM parameters, tactile allodynia, and mechanohyperalgesia. Pairwise comparisons were performed by using Tukey post hoc test corrected for multiple comparisons. Both male and female RS rats showed significantly altered exploratory behavior (as measured by EPM) and had significantly lower plasma IFN-γ levels than nRS rats. Rats exposed to RS gained weight significantly slower than the nRS rats, irrespective of sex. Following RS but before surgery, RS rats showed significant bilateral reductions in von Frey thresholds and significantly increased pinprick response difference scores compared to nRS rats, irrespective of sex. From 17 days postsurgery, RSIOCCI rats showed significantly reduced von Frey thresholds and significantly increased pinprick response difference scores compared to nRS-IOCCI rats, and the von Frey thresholds were significantly lower in females than in males. RS-sham females-but not RS-sham males-developed persistently reduced thresholds and increased pinprick response difference scores. RS produced an increased bilateral sensitivity to stimuli applied to the vibrissal pad following infraorbital nerve injury, irrespective of sex. This observed sensitivity subsequently persisted in RS-sham female rats but not in RS-sham male rats. Stress induced a significant but moderate increase in pain-like behavior in female rats compared to male rats. RS had no significant sex effects on IFN-γ levels, EPM parameters, or body weight gain. This suggests that stress may have a selective effect on pain-like behavior in both sexes, but the possible mechanisms are unclear.

Development and initial characterization of a novel ghrelin receptor CRISPR/Cas9 knockout wistar rat model.

PubMed

Zallar, L J; Tunstall, B J; Richie, C T; Zhang, Y J; You, Z B; Gardner, E L; Heilig, M; Pickel, J; Koob, G F; Vendruscolo, L F; Harvey, B K; Leggio, L

2018-01-30

Ghrelin, a stomach-derived hormone implicated in numerous behaviors including feeding, reward, stress, and addictive behaviors, acts by binding to the growth hormone secretagogue receptor (GHSR). Here, we present the development, verification, and initial characterization of a novel GHSR knockout (KO) Wistar rat model created with CRISPR genome editing. Using CRISPR/Cas9, we developed a GHSR KO in a Wistar background. Loss of GHSR mRNA expression was histologically verified using RNAscope in wild-type (WT; n = 2) and KO (n = 2) rats. We tested the effects of intraperitoneal acyl-ghrelin administration on food consumption and plasma growth hormone (GH) concentrations in WT (n = 8) and KO (n = 8) rats. We also analyzed locomotion, food consumption, and body fat composition in these animals. Body weight was monitored from early development to adulthood. The RNAscope analysis revealed an abundance of GHSR mRNA expression in the hypothalamus, midbrain, and hippocampus in WTs, and no observed probe binding in KOs. Ghrelin administration increased plasma GH levels (p = 0.0067) and food consumption (p = 0.0448) in WT rats but not KOs. KO rats consumed less food overall at basal conditions and weighed significantly less compared with WTs throughout development (p = 0.0001). Compared with WTs, KOs presented higher concentrations of brown adipose tissue (BAT; p = 0.0322). We have verified GHSR deletion in our KO model using histological, physiological, neuroendocrinological, and behavioral measures. Our findings indicate that GHSR deletion in rats is not only associated with a lack of response to ghrelin, but also associated with decreases in daily food consumption and body growth, and increases in BAT. This GHSR KO Wistar rat model provides a novel tool for studying the role of the ghrelin system in obesity and in a wide range of medical and neuropsychiatric disorders.

Association between renal iron accumulation and renal interstitial fibrosis in a rat model of chronic kidney disease.

PubMed

Naito, Yoshiro; Fujii, Aya; Sawada, Hisashi; Oboshi, Makiko; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Morisawa, Daisuke; Eguchi, Akiyo; Hirotani, Shinichi; Masuyama, Tohru

2015-07-01

Iron accumulation is associated with the pathophysiology of chronic kidney disease (CKD). Renal fibrosis is a final common feature that contributes to the progression of CKD; however, little is known about the association between renal iron accumulation and renal interstitial fibrosis in CKD. Here we investigate the effects of iron chelation on renal interstitial fibrosis in a rat model of CKD. CKD was induced by 5/6 nephrectomy in Sprague-Dawley rats. At 8 weeks after operation, 5/6 nephrectomized rats were administered an oral iron chelator, deferasirox (DFX), in chow for 8 weeks. Other CKD rats were given a normal diet. Sham-operative rats given a normal diet served as a control. CKD rats exhibited hypertension, glomerulosclerosis and renal interstitial fibrosis. Iron chelation with DFX did not change hypertension and glomerulosclerosis; however, renal interstitial fibrosis was attenuated in CKD rats. Consistent with these findings, renal gene expression of collagen type III and transforming growth factor-β was increased in CKD rats compared with the controls, while iron chelation suppressed these increments. In addition, a decrease in vimentin along an increase in E-cadherin in renal gene expression was observed in CKD rats with iron chelation. CKD rats also showed increased CD68-positive cells in the kidney, whereas its increase was attenuated by iron deprivation. Similarly, increased renal gene expression of CD68, tumor necrosis factor-α and monocyte chemoattractant protein-1 was suppressed in CKD rats with iron chelation. Renal iron accumulation seems to be associated with renal interstitial fibrosis in a rat model of CKD.

A physiologically based model of chromium kinetics in the rat.

PubMed

O'Flaherty, E J

1996-05-01

A physiologically based model of chromium kinetics in rats has been developed. The general structure of the model is similar to that of a model of lead kinetics in rats. Like lead chromium exchanges between plasma and the bone surfaces in contact with plasma, and also like lead, although with much lower efficiency, it can become incorporated into actively mineralizing bone. Both processes are included in the model. Parallel absorption and disposition schemes for chromium(VI) and chromium(III) are linked in the model by reduction processes occurring throughout the body, including the lung and gastrointestinal tract. Examination of a number of data sets from studies in which chromium salts were administered to rats intravenously, orally, or by intratracheal instillation established that intravenous administration, on the one hand, and oral or pulmonary administration, on the other hand, result in different disposition patterns. The model was calibrated based on published oral and intratracheal kinetic studies in rats given soluble chromium(III) and chromium(VI) salts. In the most complete of these studies, chromium concentrations were monitored in individual tissues for 42 days following intratracheal administration of a soluble chromium(VI) salt. Inclusion in the model of a urinary excretion delay was necessary in order to fit excretion data from two other intratracheal studies. Model predictions of blood chromium concentrations are compared with the results of a published kinetic study in which rats were administered a soluble chromium(VI) salt by inhalation.

Preliminary Characterization of a Leptin Receptor Knockout Rat Created by CRISPR/Cas9 System.

PubMed

Bao, Dan; Ma, Yuanwu; Zhang, Xu; Guan, Feifei; Chen, Wei; Gao, Kai; Qin, Chuan; Zhang, Lianfeng

2015-11-05

Leptin receptor, which is encoded by the diabetes (db) gene and is highly expressed in the choroid plexus, regulatesenergy homeostasis, the balance between food intake and energy expenditure, fertility and bone mass. Here, using CRISPR/Cas9 technology, we created the leptin receptor knockout rat. Homozygous leptin receptor null rats are characterized by obesity, hyperphagia, hyperglycemia, glucose intolerance, hyperinsulinemia and dyslipidemia. Due to long-term poor glycemic control, the leptin receptor knockout rats also develop some diabetic complications such as pancreatic, hepatic and renal lesions. In addition, the leptin receptor knockout rats show a significant decrease in bone volume and bone mineral density of the femur compared with their wild-type littermates. Our model has rescued some deficiency of the existing rodent models, such as the transient hyperglycemia of db/db mice in the C57BL/6J genetic background and the delayed onset of glucose intolerance in the Zucker rats, and it is proven to be a useful animal model for biomedical and pharmacological research on obesity and diabetes.

Effects of enteral arginine supplementation on the structural intestinal adaptation in a rat model of short bowel syndrome.

PubMed

Sukhotnik, Igor; Lerner, Aaron; Sabo, Edmund; Krausz, Michael M; Siplovich, Leonardo; Coran, Arnold G; Mogilner, Jorge; Shiloni, Eitan

2003-07-01

The nitric oxide precursor L-arginine (ARG) has been shown to influence intestinal morphology and intestinal absorptive function. The purpose of the present study was to determine the effect of enteral ARG supplementation on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Thirty male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection, SBS rats underwent 75% small bowel resection, and SBS-ARG rats underwent bowel resection and were treated with ARG given in the drinking water (2%). Parameters of intestinal adaptation, enterocyte proliferation and enterocyte apoptosis were determined on day 14 following operation. We have demonstrated that SBS-ARG animals had a lower jejunal and ileal mucosal weight, jejunal mucosal DNA and protein, ileal mucosal protein, jejunal villus height, jejunal and ileal crypt depth, and enterocyte proliferation index and a greater enterocyte apoptosis compared to SBS untreated animals. We conclude that in a rat model of SBS enteral L-arginine inhibits structural intestinal adaptation. Possible mechanism for this effect may be decreased cell proliferation and increased cell apoptosis.

Hypophosphatemia occurs with insulin administration during refeeding by total parenteral nutrition in rats.

PubMed

Kawamura, Hiromi; Tanaka, Sarasa; Uenami, Yuri; Tani, Mariko; Ishitani, Midori; Morii, Saeko; Sakaue, Motoyoshi; Ito, Mikiko

2018-01-01

Refeeding syndrome (RFS) is characterized by the metabolic and clinical changes that occur following aggressive nutritional supplementation in malnourished patients. Hypophosphatemia is the hallmark of RFS and is key to its prevention and treatment in clinical practice. However, the mechanism of hypophosphatemia during RFS is unclear because of the lack of an animal model. In this study, we developed a rat RFS model as a first step to clarifying the molecular mechanism. After establishing the parenteral route, rats were fasted for 5 days and refeeding was started using total parenteral nutrition. The animals were infused with a high calorie solution with or without insulin administration. Results showed that plasma phosphate levels did not decrease in rats infused with the high calorie solution alone;in contrast, a 20% reduction compared to baseline was observed in rats administered insulin. In addition, rats infused with the high calorie solution containing added phosphate did not present with hypophosphatemia. Thus, we developed a rat RFS model with hypophosphatemia by tube feeding and insulin administration, and demonstrated the importance of phosphate in preventing refeeding hypophosphatemia. J. Med. Invest. 65:50-55, February, 2018.

Evaluation of two techniques of partial urethral obstruction in the male rat model of bladder outlet obstruction.

PubMed

Melman, Arnold; Tar, Moses; Boczko, Judd; Christ, George; Leung, Albert C; Zhao, Weixin; Russell, Robert G

2005-11-01

To perform a comparison to determine which of two methods of partial urethral ligation produces the most consistent outcome and fewest side effects. Such a study has not been previously reported. Partial urethral ligation is a means of causing reproducible bladder outlet obstruction. In the male rat model, partial urethral obstruction can be performed either by perineal incision and bulbous urethral ligation or retropubic incision and midprostatic obstruction. Fifteen male Sprague-Dawley rats were studied. Five were selected for bulbous urethral obstruction through a perineal incision, five for midprostatic obstruction using a retropubic approach, and five for a sham operation through a perineal incision. The operative time was shorter and morbidity lower with the perineal approach compared with the retropubic approach. Inflammation or infection, or both, were seen in the prostate, bladder, proximal urethra, ureters, and kidneys in the rats in which a midprostatic obstruction was performed. The proximal urethra and prostate were mildly inflamed in those rats that underwent bulbous obstruction. Sham-operated rats exhibited mild prostatitis only. The perineal approach to the bulbous urethra is the method of choice for creating a partial urethral obstruction model of bladder outlet obstruction in the male rat.

Cross-sectional and longitudinal small animal PET shows pre and post-synaptic striatal dopaminergic deficits in an animal model of HIV.

PubMed

Sinharay, Sanhita; Lee, Dianne; Shah, Swati; Muthusamy, Siva; Papadakis, Georgios Z; Zhang, Xiang; Maric, Dragan; Reid, William C; Hammoud, Dima A

2017-12-01

In vivo imaging biomarkers of various HIV neuropathologies, including dopaminergic dysfunction, are still lacking. Towards developing dopaminergic biomarkers of brain involvement in HIV, we assessed the pre and postsynaptic components of the dopaminergic system in the HIV-1 transgenic rat (Tg), a well-characterized model of treated HIV+ patients, using small-animal PET imaging. Fifteen to 18 month-old Tg and wild type (WT) rats were imaged with both [18F]-FP-CMT, a dopamine transporter (DAT) ligand (n=16), and [18F]-Fallypride, a D2/D3 dopamine receptor (D2/D3DR) ligand (n=16). Five to 8 month-old Tg and WT rats (n=18) were also imaged with [18F]-FP-CMT. A subset of animals was imaged longitudinally at 7 and 17 months of age. Multiplex immunohistochemistry staining for DAT, tyrosine hydroxylase, D2DR, D3DR , GFAP, Iba1 and NeuN was performed on a subgroup of the scanned animals. [18F]-FP-CMT and [18F]-Fallypride binding potential (BP ND ) values were significantly lower in 15-18 month-old Tg compared to age-matched WT rats (p<0.0001 and 0.001, respectively). [18F]-FP-CMT BP ND values in 5-8 month-old rats, however, were not significantly different. Longitudinal age-related decrease in [18F]-FP-CMT BP ND was exacerbated in the Tg rat. Immunohistochemistry showed decreased staining of dopaminergic markers in Tg rats. Rats with higher serum gp120 had lower mean BP ND values for both ligands. We found presynaptic and postsynaptic dopaminergic dysfunction/loss in older Tg compared to WT rats. We believe this to be related to neurotoxicity of viral proteins present in the Tg rats' serum and brain. Our findings confirm prior reports of neurobehavioral abnormalities suggestive of dopaminergic dysfunction in this model. They also suggest similarities between the Tg rat and HIV+ patients as far as dopaminergic dysfunction. The Tg rat, along with the above-described quantitative PET imaging biomarkers, can have a role in the evaluation of HIV neuroprotective therapies prior to human translation. Published by Elsevier Inc.

Fused pulmonary lobes is a rat model of human Fraser syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kiyozumi, Daiji; Nakano, Itsuko; Takahashi, Ken L.

Highlights: {yields} Fused pulmonary lobes (fpl) mutant rats exhibit similar phenotypes to Fraser syndrome. {yields} The fpl gene harbors a nonsense mutation in Fraser syndrome-associated gene Frem2. {yields} Fpl mutant is defined as a first model of human Fraser syndrome in rats. -- Abstract: Fused pulmonary lobes (fpl) is a mutant gene that is inherited in an autosomal recessive manner and causes various developmental defects, including fusion of pulmonary lobes, and eyelid and digit anomalies in rats. Since these developmental defects closely resemble those observed in patients with Fraser syndrome, a recessive multiorgan disorder, and its model animals, we investigatedmore » whether the abnormal phenotypes observed in fpl/fpl mutant rats are attributable to a genetic disorder similar to Fraser syndrome. At the epidermal basement membrane in fpl/fpl mutant neonates, the expression of QBRICK, a basement membrane protein whose expression is attenuated in Fraser syndrome model mice, was greatly diminished compared with control littermates. Quantitative RT-PCR analyses of Fraser syndrome-related genes revealed that Frem2 transcripts were markedly diminished in QBRICK-negative embryos. Genomic DNA sequencing of the fpl/fpl mutant identified a nonsense mutation that introduced a stop codon at serine 2005 in Frem2. These findings indicate that the fpl mutant is a rat model of human Fraser syndrome.« less

[Effect of qihuang decoction on mRNA expressions of Bcl-2, Bax, and Caspase-3, 9 in intestinal mucosa epithelium of ischemia/reperfusion injured rats].

PubMed

Yu, Qing-Sheng; Yu, Hong-Liang; Pan, Jin-Fang

2011-02-01

To observe the effect of Qihuang Decoction (QHD) on mRNA expression of apoptosis genes Bcl-2, Bax, and signal transduction molecules Caspase-3, 9 in intestinal mucosa epithelium of ischemia/ reperfusion (I/R) injured rats. Forty Wistar rats were randomized equally into 4 groups, the control group, the model group, the glutamine group, and the QHD group. Rats in the latter two groups were gastric infused with glutamine and QHD respectively for 3 days, but saline was infused instead to rats in the control group and model group. After then, except those in the control group intervened only by sham operation, rats were made into I/R injured model by 45 min occlusion of superior mesenteric artery followed by 1 h reperfusion. Immediately after modeling, mRNA expressions of Bcl-2, Bax, Caspase-3, and Caspase-9 in intestinal mucosa epithelium of rats were detected by reverse transcription-polymerase chain reaction (RT-PCR). Compared with the control group, mRNA expressions of Bcl-2, Bax, Caspase-3 and Caspase-9 were higher in the other three groups (P < 0.05). Compared with the model group, Bcl-2 mRNA expression was higher, while the expressions of the other three indices were lower in both the glutamine group and the QHD group (P < 0.05); and comparisons between the glutamine group and the QHD group showed a more depressed Bax mRNA expression (0.281 +/- 0.087 vs 0.350 +/- 0.053) and higher Bcl-2/Bax ratio (1.648 vs 1. 374) in the QHD group. QHD can reduce the I/R injury in the intestinal mucosa epithelium by inhibiting the cell apoptosis. The mechanism may be correlated with increased Bcl-2 mRNA expressions and decreased mRNA expressions of Bax, Caspase-3 and Caspase-9.

Exploring human disease using the Rat Genome Database.

PubMed

Shimoyama, Mary; Laulederkind, Stanley J F; De Pons, Jeff; Nigam, Rajni; Smith, Jennifer R; Tutaj, Marek; Petri, Victoria; Hayman, G Thomas; Wang, Shur-Jen; Ghiasvand, Omid; Thota, Jyothi; Dwinell, Melinda R

2016-10-01

Rattus norvegicus, the laboratory rat, has been a crucial model for studies of the environmental and genetic factors associated with human diseases for over 150 years. It is the primary model organism for toxicology and pharmacology studies, and has features that make it the model of choice in many complex-disease studies. Since 1999, the Rat Genome Database (RGD; http://rgd.mcw.edu) has been the premier resource for genomic, genetic, phenotype and strain data for the laboratory rat. The primary role of RGD is to curate rat data and validate orthologous relationships with human and mouse genes, and make these data available for incorporation into other major databases such as NCBI, Ensembl and UniProt. RGD also provides official nomenclature for rat genes, quantitative trait loci, strains and genetic markers, as well as unique identifiers. The RGD team adds enormous value to these basic data elements through functional and disease annotations, the analysis and visual presentation of pathways, and the integration of phenotype measurement data for strains used as disease models. Because much of the rat research community focuses on understanding human diseases, RGD provides a number of datasets and software tools that allow users to easily explore and make disease-related connections among these datasets. RGD also provides comprehensive human and mouse data for comparative purposes, illustrating the value of the rat in translational research. This article introduces RGD and its suite of tools and datasets to researchers - within and beyond the rat community - who are particularly interested in leveraging rat-based insights to understand human diseases. © 2016. Published by The Company of Biologists Ltd.

An ex vivo rat eye model to aid development of high-resolution retina imaging devices for rodents

NASA Astrophysics Data System (ADS)

van Oterendorp, Christian; Martin, Keith R.; Zhong, Jiang Jian; Diaz-Santana, Luis

2010-09-01

High resolution in vivo retinal imaging in rodents is becoming increasingly important in eye research. Development of suitable imaging devices currently requires many lengthy animal procedures. We present an ex vivo rat model eye with fluorescently labelled retinal ganglion cells (RGC) and nerve fibre bundles that reduces the need for animal procedures while preserving key properties of the living rat eye. Optical aberrations and scattering of four model eyes and eight live rat eyes were quantified using a Shack-Hartmann sensor. Fluorescent images from RGCs were obtained using a prototype scanning laser ophthalmoscope. The wavefront aberration root mean square value without defocus did not significantly differ between model and living eyes. Higher order aberrations were slightly higher but RGC image quality was comparable to published in vivo work. Overall, the model allows a large reduction in number and duration of animal procedures required to develop new in vivo retinal imaging devices.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Corley, Richard A.; Kabilan, Senthil; Kuprat, Andrew P.

Coupling computational fluid dynamics (CFD) with physiologically based pharmacokinetic (PBPK) models is useful for predicting site-specific dosimetry of airborne materials in the respiratory tract and elucidating the importance of species differences in anatomy, physiology, and breathing patterns. Historically, these models were limited to discrete regions of the respiratory system. CFD/PBPK models have now been developed for the rat, monkey, and human that encompass airways from the nose or mouth to the lung. A PBPK model previously developed to describe acrolein uptake in nasal tissues was adapted to the extended airway models as an example application. Model parameters for each anatomicmore » region were obtained from the literature, measured directly, or estimated from published data. Airflow and site-specific acrolein uptake patterns were determined under steadystate inhalation conditions to provide direct comparisons with prior data and nasalonly simulations. Results confirmed that regional uptake was dependent upon airflow rates and acrolein concentrations with nasal extraction efficiencies predicted to be greatest in the rat, followed by the monkey, then the human. For human oral-breathing simulations, acrolein uptake rates in oropharyngeal and laryngeal tissues were comparable to nasal tissues following nasal breathing under the same exposure conditions. For both breathing modes, higher uptake rates were predicted for lower tracheo-bronchial tissues of humans than either the rat or monkey. These extended airway models provide a unique foundation for comparing dosimetry across a significantly more extensive range of conducting airways in the rat, monkey, and human than prior CFD models.« less

Intra-arterial catheter system to repeatedly deliver mesenchymal stem cells in a rat renal failure model.

PubMed

Katsuoka, Yuichi; Ohta, Hiroki; Fujimoto, Eisuke; Izuhara, Luna; Yokote, Shinya; Kurihara, Sho; Yamanaka, Shuichiro; Tajiri, Susumu; Chikaraish, Tatsuya; Okano, Hirotaka J; Yokoo, Takashi

2016-04-01

Mesenchymal stem cell therapy in renal failure is rarely used because of low rates of cell engraftment after systemic delivery. Repeated intra-arterial cell administration may improve results; however, no current delivery method permits repeated intra-arterial infusions in a rat model. In this study, we developed an intra-arterial delivery system for repeated stem cell infusion via the aorta, catheterizing the left femoral artery to the suprarenal aorta under fluoroscopic guidance in rats with adenosine-induced renal failure. First, we compared our intra-arterial catheter system (C group, n = 3) with tail vein injection (V group, n = 3) for engraftment efficacy, using mesenchymal stem cells from luciferase transgenic rats. Rats were infused with the cells and euthanized the following day; we performed cell-tracking experiments using a bioluminescence imaging system to assess the distribution of the infused cells. Second, we assessed the safety of the system over a 30-day period in a second group of six rats receiving infusions every 7 days. Cells infused through our delivery system efficiently engrafted into the kidney, compared with peripheral venous infusion. In five of the six rats in the safety study, the delivery system remained patent for at least 9 days (range, 9-24 days). Complications became evident only after 10 days. Our intra-arterial catheter system was effective in delivering cells to the kidney and permitted repeated injection of cells.

Ferulic acid alleviates symptoms of preeclampsia in rats by upregulating vascular endothelial growth factor.

PubMed

Gong, Weiyan; Wan, Jipeng; Yuan, Qing; Man, Quanzhan; Zhang, Xiaojing

2017-10-01

Preeclampsia is a complication affecting pregnant women worldwide, which leads to maternal and fetal morbidity and mortality. In this study, we evaluated the efficacy of ferulic acid (FA) on an N ω -nitro-L-arginine methyl ester hydrochloride (L-NAME) induced rat model of preeclampsia. L-NAME was administered to pregnant rats to induce preeclampsia. 48 rats were divided into three experimental groups (n=16 each): control group, preeclampsia group and preeclampsia with FA treatment (preeclampsia+FA). Physiological characteristics such as urine volume, total urine protein and blood pressure were assessed. Expressions levels of urinary nephrin and podocin mRNAs were analyzed by RT-PCR. Levels of renal vascular endothelial growth factor (VEGF), renal soluble fms-like tyrosine kinase-1 (sFlt-1) and serum placenta growth factor (PlGF) were also examined. Urine volume, total urine protein and blood pressure were markedly increased in preeclampsia group rats compared to control (P<.05), which were then significantly reduced in preeclampsia+FA group (P<.05). Expressions of urinary nephrin and podocin mRNAs, levels of VEGF, sFlt-1 and PlGF were also reversed in preeclampsia+FA group compared to preeclampsia rats (P<.05). We hereby report for the first time, FA alleviates preeclampsia symptoms in a rat preeclampsia model, supporting its potential value in treating preeclampsia. © 2017 John Wiley & Sons Australia, Ltd.

Enhancement of Wound Healing by the Traditional Chinese Medicine Herbal Mixture Sophora flavescens in a Rat Model of Perianal Ulceration

PubMed Central

XU, XIAOPING; LI, XIAOHUA; ZHANG, LEI; LIU, ZHAOHUI; PAN, YUAN; CHEN, DONG; BIN, DONGHUA; DENG, QUN; SUN, YU; HOFFMAN, M. ROBERT; YANG, ZHIJIAN; YUAN, HONG

2017-01-01

Background/Aim: Hemorrhoidectomy is often associated with significant postoperative complications that may result in slow wound healing. The traditional Chinese medicine (TCM) compound Sophora flavescens (CSF) has shown efficacy on many inflammatory disorders. The aim of the present study was to examine the efficacy of CSF on wound healing in a rat model of perianal ulceration. Materials and Methods: A rat model of perianal ulceration was induced by subcutaneous injection of 75% glacial acetic acid. The animals with induced perianal ulcer received topical treatment of low, medium, and high doses of CFS twice daily. Potassium permanganate (PP); 0.02%) was given to the animals for comparison. Macroscopic and histological assessments of the ulcerated area were performed after treatment. The expression of pro-inflammatory cytokines prostaglandin E2 (PGE2) and interleukin-8 (IL-8) was detected by immunohistochemical analysis. Results: Topical administration of medium- and high-dose CSF significantly enhanced perianal ulcer healing as compared to the untreated control (p<0.05). The macroscopic ulceration score was significantly reduced only in the high-dose CSF-treated group as compared to the control (p<0.01). All doses of CSF and PP ameliorated histological damages in the rats with induced perianal ulceration. High-dose CSF or PP significantly reduced the expression of PGE2 and IL-8 as compared to the control (p<0.01). No treatment-related toxicity was found in either the CSF- or the PP-treated mice. Conclusion: CSF enhances wound healing in a rat model of perianal ulceration. The inhibitory effect of CSF on pro-inflammatory cytokines PGE2 and IL-8 may be involved in the mechanism of enhanced wound-healing. PMID:28652418

Enhancement of Wound Healing by the Traditional Chinese Medicine Herbal Mixture Sophora flavescens in a Rat Model of Perianal Ulceration.

PubMed

Xu, Xiaoping; Li, Xiaohua; Zhang, Lei; Liu, Zhaohui; Pan, Yuan; Chen, Dong; Bin, Donghua; Deng, Qun; Sun, Y U; Hoffman, Robert M; Yang, Zhijian; Yuan, Hong

2017-01-01

Hemorrhoidectomy is often associated with significant postoperative complications that may result in slow wound healing. The traditional Chinese medicine (TCM) compound Sophora flavescens (CSF) has shown efficacy on many inflammatory disorders. The aim of the present study was to examine the efficacy of CSF on wound healing in a rat model of perianal ulceration. A rat model of perianal ulceration was induced by subcutaneous injection of 75% glacial acetic acid. The animals with induced perianal ulcer received topical treatment of low, medium, and high doses of CFS twice daily. Potassium permanganate (PP); 0.02%) was given to the animals for comparison. Macroscopic and histological assessments of the ulcerated area were performed after treatment. The expression of pro-inflammatory cytokines prostaglandin E 2 (PGE 2 ) and interleukin-8 (IL-8) was detected by immunohistochemical analysis. Topical administration of medium- and high-dose CSF significantly enhanced perianal ulcer healing as compared to the untreated control (p<0.05). The macroscopic ulceration score was significantly reduced only in the high-dose CSF-treated group as compared to the control (p<0.01). All doses of CSF and PP ameliorated histological damages in the rats with induced perianal ulceration. High-dose CSF or PP significantly reduced the expression of PGE 2 and IL-8 as compared to the control (p<0.01). No treatment-related toxicity was found in either the CSF- or the PP-treated mice. CSF enhances wound healing in a rat model of perianal ulceration. The inhibitory effect of CSF on pro-inflammatory cytokines PGE 2 and IL-8 may be involved in the mechanism of enhanced wound-healing. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Myrtol ameliorates cartilage lesions in an osteoarthritis rat model.

PubMed

Ying, Binbin; Maimaiti, Abudu Kelimujiang; Song, Donghui; Zhu, Songsong

2015-01-01

The aim of this study is to evaluate the effects of myrtol standardized on cartilage lesions in osteoarthritis (OA) rats. Fifty-six healthy Sprague-Dawley rats were randomly divided into sham group (13 rats) and OA model group (43 rats) with interior meniscus excision. Then serum estradiol (E2) and glycosaminoglycan (GAG) content in cartilage tissue were measured by radioimmunoassay and toluidine blue staining, respectively. After that, the model rats were randomly divided into low dose myrtol (LDM) group, middle dose myrtol (MDM) group and high dose myrtol (HDM) group (10 rats in each group) with treatment of 450 mg/kg, 300 mg/kg and 150 mg/kg myrtol, respectively. Then, Mankin scores were used to evaluate lesion extent of knee joint cartilage. Expression of tumor necrosis factor α (TNF-α), transforming growth factor β1 (TGF-β1), interleukin (IL)-6, Bax and Bcl-2 were investigated using PCR gel electrophoresis method. Mankin cores were lower in sham group and myrtol group than in model group. There were statistically significant differences (P < 0.01) between sham group and model group in expression of TNF-α, TGF-β1, IL-6, Bax and Bcl-2 in the cartilage tissue. Myrtol significantly reduced the expression of TNF-α, IL-6 and Bax, and increased the expression of TGF-β1 and Bcl-2 in myrtol group, comparing with those in model group (P < 0.01). Myrtol could down-regulate the expression of TNF-α, IL-6 and Bax, and up-regulate the expression of TGF-β1 and Bcl-2. Myrtol standardized is a promising drug to ameliorate knee cartilage lesions in the OA rat model.

Effect of baculovirus P35 protein on apoptosis in brain tissue of rats with acute cerebral infarction.

PubMed

Ji, J F; Ma, X H

2015-08-10

We explored the effect of baculovirus P35 protein on apoptosis in the brain tissue of rats with acute cerebral infarction (ACI). A rat model of middle cerebral artery infarction was created. The rats were randomly divided into sham, model, and treatment groups. Baculovirus P35 protein was injected into the intracranial arteries of the treatment group rats. The rats in the model group were given an equal volume of phosphate-buffered saline. The rats were sacrificed after 72 h and the brain tissue was separated. The levels of caspase-3, Bcl-2, and Bax mRNA, the brain cell apoptosis index, and the infarct size were determined. After 72 h, the levels of caspase-3 and Bax mRNA in the model and treatment groups were significantly greater than in the sham group, and the levels of Bcl-2 mRNA were significantly smaller (P < 0.05). The levels of caspase-3 and Bax mRNA were significantly lower in the treatment group than in the model group, and the level of Bcl-2 mRNA was significantly greater (P < 0.05). Compared with the sham group, the brain tissue apoptosis index and the cerebral infarction area increased significantly in the model and treatment groups (P < 0.05). The brain tissue apoptosis index and cerebral infarction area in the treatment group were significantly lower than in the model group (P < 0.05). Baculovirus P35 protein can effectively inhibit brain cell apoptosis in rats with ACI. It delayed apoptosis and necrosis in subjects with ACI tissue and had a protective effect on brain tissue.

Effects of voluntary exercise on anxiety-like behavior and voluntary morphine consumption in rat pups borne from morphine-dependent mothers during pregnancy.

PubMed

Haydari, Sakineh; Miladi-Gorji, Hossein; Mokhtari, Amin; Safari, Manouchehr

2014-08-22

Exposure to morphine during pregnancy produced long-term effects in offspring behaviors. Recent studies have shown that voluntary exercise decreases the severity of anxiety behaviors in both morphine-dependent and withdrawn rats. Thus, the aims of the present study were to examine whether maternal exercise decreases prenatal dependence-induced anxiety and also, voluntary consumption of morphine in animal models of craving in rat pups. Pregnant rats were made dependent by chronic administration of morphine in drinking water simultaneously with access to a running wheel that lasted at least 21 days. Then, anxiety-like behaviors using the elevated plus-maze (EPM) and voluntary consumption of morphine using a two-bottle choice paradigm (TBC) were tested in male rat pups. The results showed that the rat pups borne from exercising morphine-dependent mothers exhibited an increase in EPM open arm time (P<0.0001) and entries (P<0.05) as compared with the sedentary groups. In animal models of craving showed that voluntary consumption of morphine in the rat pups borne from exercising morphine-dependent mothers was less in the second (P<0.032) and third (P<0.014) periods of intake as compared with the sedentary group. This study showed that maternal exercise decreases the severity of the anxiogenic-like behaviors and voluntary consumption of morphine in rat pups. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Evaluation of an experimental rat model for comparative studies of bleaching agents

PubMed Central

Cintra, Luciano Tavares Angelo; Benetti, Francine; Ferreira, Luciana Lousada; Rahal, Vanessa; Ervolino, Edilson; Jacinto, Rogério de Castilho; Gomes, João Eduardo; Briso, André Luiz Fraga

2016-01-01

ABSTRACT Dental materials, in general, are tested in different animal models prior to their clinical use in humans, except for bleaching agents. Objectives To evaluate an experimental rat model for comparative studies of bleaching agents by investigating the influence of different concentrations and application times of H2O2 gel in the pulp tissue during in-office bleaching of rats’ vital teeth. Material and methods The right and left maxillary molars of 50 Wistar rats were bleached with 20% and 35% H2O2 gels, respectively, for 5, 10, 15, 30, or 45 min (n=10 rats/group). Ten animals (control) were untreated. The rats were killed after 2 or 30 days, and the maxillae were examined by light microscopy. Inflammation was evaluated by histomorphometric analysis with inflammatory cell counting in the coronal and radicular thirds of the pulp. The counting of fibroblasts was also performed. Scores were attributed to the odontoblastic layer and to vascular changes. The tertiary dentin area and the pulp chamber central area were histomorphometrically measured. Data were compared by the analysis of variance and the Kruskal-Wallis test (p<0.05). Results After 2 days, the amount of inflammatory cells increased in the occlusal third of the coronal pulp until the time of 15 min for both concentrations of bleaching gels. In 30 and 45 min groups of each concentration, the number of inflammatory cells decreased along with the appearance of necrotic areas. After 30 days, a reduction in the pulp chamber central area and an enlargement of tertiary dentin area were observed without the detection of inflammation areas. Conclusion The rat model of extra coronal bleaching showed to be adequate for bleaching protocols studies, as it was possible to observe alterations in the pulp tissues and in the tooth structure caused by different concentrations and periods of application of bleaching agents. PMID:27008262

Intrinsic neurophysiological properties of hilar ectopic and normotopic dentate granule cells in human temporal lobe epilepsy and a rat model.

PubMed

Althaus, A L; Sagher, O; Parent, J M; Murphy, G G

2015-02-15

Hilar ectopic dentate granule cells (DGCs) are a salient feature of aberrant plasticity in human temporal lobe epilepsy (TLE) and most rodent models of the disease. Recent evidence from rodent TLE models suggests that hilar ectopic DGCs contribute to hyperexcitability within the epileptic hippocampal network. Here we investigate the intrinsic excitability of DGCs from humans with TLE and the rat pilocarpine TLE model with the objective of comparing the neurophysiology of hilar ectopic DGCs to their normotopic counterparts in the granule cell layer (GCL). We recorded from 36 GCL and 7 hilar DGCs from human TLE tissue. Compared with GCL DGCs, hilar DGCs in patient tissue exhibited lower action potential (AP) firing rates, more depolarized AP threshold, and differed in single AP waveform, consistent with an overall decrease in excitability. To evaluate the intrinsic neurophysiology of hilar ectopic DGCs, we made recordings from retrovirus-birthdated, adult-born DGCs 2-4 mo after pilocarpine-induced status epilepticus or sham treatment in rats. Hilar DGCs from epileptic rats exhibited higher AP firing rates than normotopic DGCs from epileptic or control animals. They also displayed more depolarized resting membrane potential and wider AP waveforms, indicating an overall increase in excitability. The contrasting findings between disease and disease model may reflect differences between the late-stage disease tissue available from human surgical specimens and the earlier disease stage examined in the rat TLE model. These data represent the first neurophysiological characterization of ectopic DGCs from human hippocampus and prospectively birthdated ectopic DGCs in a rodent TLE model. Copyright © 2015 the American Physiological Society.

Hematopoiesis in antiorthostatic, hypokinesic rats

NASA Technical Reports Server (NTRS)

Dunn, C. D. R.; Johnson, P. C.; Lange, R. D.

1983-01-01

Rats exposed to antiorthostatic, hypokinesia showed the following effects which are comparable to those seen in man during or after space flight: weight loss, reduced food and water consumption, transient increases in peripheral hematocrit and RBC count, decreasing MCV and reduced reticulocyte count. In addition, the hemoglobin P50 was shifted to the right. A significant shortening of RBC t1/2 was only seen after suspension. Changes in leukocyte and platelet numbers in suspended rats were also comparable to those in man during space flight, but leukocyte PHA sensitivity in rats showed no consistent alteration. The results demonstrate that this model reproduces many of the hematological effects of space flight and has potential as a tool in understanding the hematopoietic response to zero gravity.

Intermittent Administration of Parathyroid Hormone [1-34] Prevents Particle-Induced Periprosthetic Osteolysis in a Rat Model.

PubMed

Bi, Fanggang; Shi, Zhongli; Zhou, Chenhe; Liu, An; Shen, Yue; Yan, Shigui

2015-01-01

We examined whether intermittent administration of parathyroid hormone [1-34] (PTH[1-34]; 60 μg/kg/day) can prevent the negative effects of titanium (Ti) particles on implant fixation and periprosthetic osteolysis in a rat model. Eighteen adult male rats (12 weeks old, bones still growing) received intramedullary Ti implants in their bilateral femurs; 6 rats from the blank group received vehicle injections, and 12 rats from the control group and PTH treatment group received Ti particle injections at the time of operation and intra-articular injections 2 and 4 weeks postoperatively. Six of the rats that received Ti particles from the PTH group also received PTH[1-34] treatment. Six weeks postoperatively, all specimens were collected for assessment by X-ray, micro-CT, biomechanical, scanning electron microscopy (SEM), and dynamic histomorphometry. A lower BMD, BV/TV, Tb.N, maximal fixation strength, and mineral apposition rate were observed in the control group compared to the blank group, demonstrating that a periprosthetic osteolysis model had been successfully established. Administration of PTH[1-34] significantly increased the bone mineral density of the distal femur, BV/TV, Tb.N, Tb.Th, Tb.Sp, Con.D, SMI, and maximal fixation strength in the PTH group compared to that in the control group. SEM revealed higher bone-implant contact, thicker lamellar bone, and larger trabecular bone area in the PTH group than in the control group. A higher mineral apposition rate was observed in the PTH group compared to both the blank and control groups. These findings imply that intermittent administration of PTH[1-34] prevents periprosthetic osteolysis by promoting bone formation. The effects of PTH[1-34] were evaluated at a suprapharmacological dosage to the human equivalent in rats; therefore, additional studies are required to demonstrate its therapeutic potential in periprosthetic osteolysis.

The effects of pentoxifylline adminstration on fracture healing in a postmenopausal osteoporotic rat model

PubMed Central

Vashghani Farahani, Mohammad Mahdi; Ahadi, Reza; Abdollahifar, Mohammadamin

2017-01-01

Previous studies report positive effects of pentoxifylline (PTX) alone or in combination with other drugs on some pathologic bone diseases as well as an ability to accelerate osteogensis and fracture healing in both animal models and human patients. The aim of this present study was to evaluate the effects of PTX administration on Hounsfield unit and bone strength at catabolic response (bone resorbing) of a fracture in an experimental rat model of ovariectomy induced osteoporosis (OVX-D). Thirty adult female rats were divided into groups as follows: 1 (OVX, control, no treatment); 2 (OVX, sham: daily distilled water); 3 (OVX, daily alendronate: 3 mg/kg); 4 (OVX, twice daily 100 mg/kg PTX) and 5 (OVX, PTX+alenderonate). OVX was induced by bilateral ovariectomy in all rats. A complete standardized osteotomy of the right femur was made after 3.5 months. PTX and alendronate treatments were performed for eight weeks. Then, rats were euthanized and had its right femur subjected to computerized tomography scanning for measuring Hounsfield unit; eventually, the samples were sent for a three point bending test for evaluation of the bone strength. Administration of PTX with 200 mg/kg and alendronate alone and in combination showed no significant alteration in Hounsfield unit and biomechanical properties of repairing callus of the complete osteotomy compared with the control group. Results showed increased bending stiffness and stress high load mean values of repairing complete osteotomy in PTX-treated rats compared to the control OVX-D. PMID:28400835

[Phosphorylation of protein kinase C in cerebrospinal fluid-contacting nucleus modulates the inflammatory pain in rats].

PubMed

Zhou, Fang; Wang, Jia-You; Tian, En-Qi; Zhang, Li-Cai

2015-12-25

The present study was aimed to investigate the role of cerebrospinal fluid-contacting nucleus (CSF-CN) neurons in modulation of inflammatory pain and underlying mechanism. The inflammatory pain model was made by subcutaneous injection of the complete Freund's adjuvant (CFA) into the left hind paw of rats. The phosphorylation level of PKC (p-PKC) was examined by Western blot. Thermal withdrawal latency (TWL) of the rats was measured to assess inflammatory pain. The results showed that, compared with the sham controls, the inflammatory pain model rats showed shortened TWL on day 1, 3, and 7 after CFA injection, as well as increased level of p-PKC in CSF-CN neurons at 24 h after CFA injection. The administration of GF109203X, a PKC inhibitor, into lateral ventricle decreased the level of p-PKC protein expression and increased TWL in the model rats. These results suggest that blocking the PKC pathway in CSF-CN neurons may be an effective way to reduce or eliminate the inflammatory pain.

The olfactory bulbectomized rat model is not an appropriate model for studying depression based on morphological/stereological studies of the hippocampus.

PubMed

Yurttas, Canan; Schmitz, Christoph; Turgut, Mehmet; Strekalova, Tatyana; Steinbusch, Harry W M

2017-09-01

Bilateral olfactory bulbectomy (OBX) has been used as an animal model for major depression that results in behavioral, neurochemical, and neuroendocrinological changes were reversed by chronic treatment with antidepressants, including fluoxetine. However, both etiological and construct validities are lacking in OBX for rats. In the present study, we investigated the morphological changes in the hippocampi of rats undergoing OBX that were treated with fluoxetine (10mg/kg, p.o. once daily for 4 and 12 weeks) using stereological techniques. Our results revealed that OBX caused a reduction in the volumes of the CA1/2, CA3, and dentate gyrus regions 4 weeks after OBX without fluoxetine treatment. With fluoxetine treatment, these reductions were achieved 12 weeks after OBX and the volumes were comparable to normal control rats. Nevertheless, fluoxetine treatment did not reverse neuron loss in all hippocampal regions 12 weeks after OBX. Therefore, we suggest that the OBX rat model should not be used to detect the antidepressant activity of various pharmacological agents such as fluoxetine. Copyright © 2017 Elsevier Inc. All rights reserved.

Enhanced intestinal epithelial cell proliferation in diabetic rats correlates with β-catenin accumulation.

PubMed

Dorfman, Tatiana; Pollak, Yulia; Sohotnik, Rima; Coran, Arnold G; Bejar, Jacob; Sukhotnik, Igor

2015-09-01

The Wnt/β-catenin signaling cascade is implicated in the control of stem cell activity, cell proliferation, and cell survival of the gastrointestinal epithelium. Recent evidence indicates that the Wnt/β-catenin pathway is activated under diabetic conditions. The purpose of this study was to evaluate the role of Wnt/β-catenin signaling during diabetes-induced enteropathy in a rat model. Male rats were divided into three groups: control rats received injections of vehicle; diabetic rats received injections of one dose of streptozotocin (STZ); and diabetic-insulin rats received injections of STZ and were treated with insulin given subcutaneously at a dose of 1 U/kg twice daily. Rats were killed on day 7. Wnt/β-catenin-related genes and expression of proteins was determined using real-time PCR, western blotting, and immunohistochemistry. Among 13 genes identified by real-time PCR, seven genes were upregulated in diabetic rats compared with control animals including the target genes c-Myc and Tcf4. Diabetic rats also showed a significant increase in β-catenin protein compared with control animals. Treatment of diabetic rats attenuated the stimulating effect of diabetes on intestinal cell proliferation and Wnt/β-catenin signaling. In conclusion, enhanced intestinal epithelial cell proliferation in diabetic rats correlates with β-catenin accumulation. © 2015 Society for Endocrinology.

Sildenafil Attenuates Hepatocellular Injury after Liver Ischemia Reperfusion in Rats: A Preliminary Study

PubMed Central

Savvanis, Spyridon; Nastos, Constantinos; Tasoulis, Marios-Konstantinos; Papoutsidakis, Nikolaos; Demonakou, Maria; Karmaniolou, Iosifina; Arkadopoulos, Nikolaos; Smyrniotis, Vassilios; Theodoraki, Kassiani

2014-01-01

We evaluated the role of sildenafil in a rat liver ischemia-reperfusion model. Forty male rats were randomly allocated in four groups. The sham group underwent midline laparotomy only. In the sildenafil group, sildenafil was administered intraperitoneally 60 minutes before sham laparotomy. In the ischemia-reperfusion (I/R) group, rats were subjected to 45 minutes of hepatic ischemia followed by 120 minutes of reperfusion, while in the sild+I/R group rats were subjected to a similar pattern of I/R after the administration of sildenafil, 60 minutes before ischemia. Two hours after reperfusion, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured and histopathological examination of the lobes subjected to ischemia as well as TUNEL staining for apoptotic bodies was performed. Additionally, myeloperoxidase (MPO) activity and the expression of intercellular adhesion molecule-1 (ICAM-1) were analyzed. Serum markers of hepatocellular injury were significantly lower in the sild+I/R group, which also exhibited lower severity of histopathological lesions and fewer apoptotic bodies, as compared to the I/R group. The I/R group showed significantly higher MPO activity and higher expression of ICAM-1, as compared to the sild+I/R group. Use of sildenafil as a preconditioning agent in a rat model of liver I/R exerted a protective effect. PMID:24999378

A randomized study to assess the efficacy of herbal product to prevent cisplatin-induced nephrotoxicity in a rat model.

PubMed

Kucuk, Eyup Veli; Bindayi, Ahmet; Mese, Meral; Gulcu Bulmus, Funda; Parmaksiz, Ergun; Cetinel, Ali Cihangir; Bicik Bahcebasi, Zerrin; Sarica, Kemal

2017-10-03

This study aimed to investigate the protective effect and antioxidant activity of an herbal product that made from multiple plants in a rat model of kidney dysfunction induced by intraperitoneal cisplatin. Twenty-four rats were divided into four different groups namely: Group 1 - control healthy animals without any specific medication, Group 2 - Herbal product only 5 mg/kg, Group 3 - cisplatin only and Group 4 - Herbal product 5 mg/kg + cisplatin. Evaluation of our findings demonstrated a significant (p = 0.017) reduction in Catalase activities and a significant increase (p = 0.001) in renal tissue Malondialdehyde levels in cisplatin- treated rats when compared with the control group. Also, Glutathion and Glutathione peroxidase content revealed significant (p = 0.031) reduction in renal tissues of cisplatintreated rats compared with the control group. Pre-treatment of rats with the herbal product ameliorated these cisplatininduced changes of the antioxidant enzymes. No statistically significant changes were demonstrated in Superoxide dismutase activities in the tissue specimens of any group. This potent antioxidant herbal medicine was found to have potential antioxidant activity, which may in turn to be effective in the protection of kidney tissue resulting from cisplatin application. Therefore, much attention should be given to the possible role of natural dietary antioxidants for protecting the kidney.

Lipid changes in hepatic microsomes and its relationship to P-nitrophenol glucuronidation in an experimental model of portal hypertension.

PubMed

Ghanem, C; Ghisolfi, C; Marabotto, L; Ouviña, G; Rubio, M; Perazzo, J; Lemberg, A; Bengochea, L

1997-10-01

The liver is responsible for the most important metabolic pathway of non polar compounds. The aim of the present work was to study the p-nitrophenol glucuronidation and its relationship with lipidic composition of microsomal membrane in a model of hepatic portal hypertension and hepatocellular damage induced by monocrotaline. A global increment in liver microsomal phospholipids as well as changes in the phospholipid pattern (phosphatidylethanolamine and sphingomyelin increased up to 156 +/- 13 and 195 +/- 14% respectively) were detected in monocrotaline intoxicated rats when it were compared to control rats. The microsomal cholesterol content showed a decrease in monocrotaline intoxicated rats. (4.1 +/- 0.7 against 6.6 +/- 1.5 micrograms/mg of microsomal protein, in control rats). When p-nitrophenol activity was measured, Km from monocrotaline intoxicated rats was 0.137 mM, and Vmax was 2.9 nmol of p-nitrophenol/mg microsomal protein since in control group Km was 0.322 mM, and Vmax was 4.5 nmol of p-nitrophenol/mg microsomal protein. It is concluded that monocrotaline intoxicated rats showed a different behavior in the kinetics of p-nitrophenol UDP-glucuronyltransferase, as well as a different microsomal lipidic profile, when compared to control group.

Cardiac dysfunction in the diabetic rat: quantitative evaluation using high resolution magnetic resonance imaging.

PubMed

Loganathan, Rajprasad; Bilgen, Mehmet; Al-Hafez, Baraa; Alenezy, Mohammed D; Smirnova, Irina V

2006-04-04

Diabetes is a major risk factor for cardiovascular disease. In particular, type 1 diabetes compromises the cardiac function of individuals at a relatively early age due to the protracted course of abnormal glucose homeostasis. The functional abnormalities of diabetic myocardium have been attributed to the pathological changes of diabetic cardiomyopathy. In this study, we used high field magnetic resonance imaging (MRI) to evaluate the left ventricular functional characteristics of streptozotocin treated diabetic Sprague-Dawley rats (8 weeks disease duration) in comparison with age/sex matched controls. Our analyses of EKG gated cardiac MRI scans of the left ventricle showed a 28% decrease in the end-diastolic volume and 10% increase in the end-systolic volume of diabetic hearts compared to controls. Mean stroke volume and ejection fraction in diabetic rats were decreased (48% and 28%, respectively) compared to controls. Further, dV/dt changes were suggestive of phase sensitive differences in left ventricular kinetics across the cardiac cycle between diabetic and control rats. Thus, the MRI analyses of diabetic left ventricle suggest impairment of diastolic and systolic hemodynamics in this rat model of diabetic cardiomyopathy. Our studies also show that in vivo MRI could be used in the evaluation of cardiac dysfunction in this rat model of type 1 diabetes.

Resveratrol Reduces the Incidence of Portal Vein System Thrombosis after Splenectomy in a Rat Fibrosis Model

PubMed Central

Xu, Meng; Xue, Wanli; Ma, Zhenhua; Bai, Jigang

2016-01-01

Purpose. To investigate the preventive effect of resveratrol (RES) on the formation of portal vein system thrombosis (PVST) in a rat fibrosis model. Methods. A total of 64 male SD rats, weighing 200–300 g, were divided into five groups: Sham operation, Splenectomy I, Splenectomy II, RES, and low molecular weight heparin (LMWH), with the former two groups as nonfibrosis controls. Blood samples were subjected to biochemical assays. Platelet apoptosis was measured by flow cytometry. All rats were euthanized for PVST detection one week after operation. Results. No PVST occurred in nonfibrosis controls. Compared to Splenectomy II, the incidences of PVST in RES and LMWH groups were significantly decreased (both p < 0.05). Two rats in LMWH group died before euthanasia due to intra-abdominal hemorrhage. In RES group, significant decreases in platelet aggregation, platelet radical oxygen species (ROS) production, and increase in platelet nitric oxide (NO) synthesis and platelet apoptosis were observed when compared with Splenectomy II (all p < 0.001), while in LMWH group only significant decrease in platelet aggregation was observed. Conclusion. Prophylactic application of RES could safely reduce the incidence of PVST after splenectomy in cirrhotic rat. Regulation of platelet function and induction of platelet apoptosis might be the underlying mechanisms. PMID:27433290

[Effects of Tongluo Xingnao effervescent tablets on blood rheology, iNOS, VEGF and LDH-5 in MID rats].

PubMed

Ren, Xiang-Yi; Hu, Yong; Wei, Jiang-Ping; Fu, Wen-Jun; Xu, Shi-Jun; Wang, Yong-Yan

2016-03-01

The study was to explore effects of Tongluo Xingnao effervescent tablets on the blood rheology, iNOS, VEGF and LDH-5 in multi-infarct dementia(MID) model rats. Establish MID model rats were induced by microthrombosis, from which 50 successful model rats were randomly divided into five groups, such as the model control group, the dihydroergotoxine mesylate tablets(hydergine) group(0.7 mg•kg⁻¹), Tongluo Xingnao effervescent tablets high-dose, medium-dose and low-dose groups(7.56, 3.78, 1.89 g•kg⁻¹). Another ten rats in the sham group were randomly selected as the parallel control group. Each group was orally administered with drugs for 90 days. The learning and memory ability was evaluated with the Morris water maze test, while the whole blood viscosity and the erythrocyte aggregation index derived from abdominal aorta were measured in different shear rates. In addition, the levels of VEGF and iNOS in the serum were determined by ELISA kits. The expression of LDH-5 in hippocampus of rats was measured with immunohistochemistry and image quantitative analysis. The result showed that Tongluo Xingnao effervescent tablets notably decreased the escape latency of MID model rats, increased times of entering into the escape platform and prolonged retention time in medium ring, meanwhile the whole blood viscosity in MID model rats was also notably reduced in four shear rates, i.e. 1, 5, 30, 200 S⁻¹, erythrocyte aggregation index, serum VEGF and iNOS, and average optical density value of LDH-5, with a statistically significant differences compared with the model control group (P<0.05). In conclusion, Tongluo Xingnao effervescent tablets could improve the ability of learning and memory of MID model rats and the blood rheology, reduce the level of iNOS, VEGF and the expression of LDH-5, and then improved the brain energy supply. Copyright© by the Chinese Pharmaceutical Association.

Transgenic rat model of childhood-onset dermatitis by overexpressing telomerase reverse transcriptase (TERT).

PubMed

Kaneko, Ryosuke; Sato, Atsuko; Hamada, Shun; Yagi, Takeshi; Ohsawa, Ichiro; Ohtsuki, Mamitaro; Kobayashi, Eiji; Hirabayashi, Masumi; Murakami, Takashi

2016-08-01

Childhood-onset dermatitis is one of the most common skin disorders in children. Although various mouse models that mirror aspects of dermatitis have become available, there is still a need for an animal model that develops dermatitis in childhood and is more suitable for performing tissue transplantation experiments. There is emerging evidence that peripheral blood T lymphocytes from patients with dermatitis have significantly increased telomerase activity. Here, we developed telomerase reverse transcriptase (TERT)-expressing transgenic (Tg) rats that spontaneously developed eczematous skin inflammation in childhood. Newborn TERT-Tg rats developed visible dermatitis in 56 % of cases, and the skin lesions microscopically showed spongiosis and acanthosis with infiltration of lymphocytes, eosinophils and mast cells. TERT-Tg rats with dermatitis exhibited increased CD4 (2.5-fold) and CD8 (fivefold) T cell numbers compared with dermatitis-free TERT-Tg rats. Stronger TERT activity was observed in the peripheral lymphocytes of dermatitis-positive TERT-Tg rats than those of dermatitis-free TERT-Tg rats. RT-PCR analysis revealed that IL-4 was markedly elevated in the spleen of dermatitis-positive TERT-Tg rats, and that interferon-gamma was increased in the dermatitis lesions. Moreover, skin grafting of TERT-Tg rats with dermatitis onto T cell-deficient nude rats demonstrated that the inflamed skin lesions could not be maintained. Taken together, the results suggest that TERT activation in T lymphocytes is one of the potential predisposing factors for dermatitis. Moreover, our results demonstrated that the TERT-Tg rats mirror aspects of human childhood-onset dermatitis and that these animals represent a potential animal model system for studying childhood-onset dermatitis.

Comparative study of the organisation and phenotypes of bladder interstitial cells in human, mouse and rat.

PubMed

Gevaert, Thomas; Neuhaus, Jochen; Vanstreels, Els; Daelemans, Dirk; Everaerts, Wouter; Der Aa, Frank Van; Timmermans, Jean-Pierre; Roskams, Tania; Steiner, Clara; Pintelon, Isabel; De Ridder, Dirk

2017-12-01

With most research on interstitial cells (IC) in the bladder being conducted on animal models, it remains unclear whether all structural and functional data on IC from animal models can be translated to the human context. This prompted us to compare the structural and immunohistochemical properties of IC in bladders from mouse, rat and human. Tissue samples were obtained from the bladder dome and subsequently processed for immunohistochemistry and electron microscopy. The ultrastructural properties of IC were compared by means of electron microscopy and IC were additionally characterized with single/double immunohistochemistry/immunofluorescence. Our results reveal a similar organization of the IC network in the upper lamina propria (ULP), the deep lamina propria (DLP) and the detrusor muscle in human, rat and mouse bladders. Furthermore, despite several similarities in IC phenotypes, we also found several obvious inter-species differences in IC, especially in the ULP. Most remarkably in this respect, ULP IC in human bladder predominantly displayed a myoid phenotype with abundant presence of contractile micro-filaments, while those in rat and mouse bladders showed a fibroblast phenotype. In conclusion, the organization of ULP IC, DLP IC and detrusor IC is comparable in human, rat and mouse bladders, although several obvious inter-species differences in IC phenotypes were found. The present data show that translating research data on IC in laboratory animals to the human setting should be carried out with caution.

[Hydrogen-rich saline attenuates hyperalgesia and reduces cytokines in rats with post-herpetic neuralgia via activating autophagy].

PubMed

Ma, Hongtao; Chen, Hongguang; Dong, Aili; Wang, Yanyan; Bian, Yingxue; Xie, Keliang

2017-02-01

To investigate the role of autophagy in hydrogen-rich saline attenuating post-herpetic neuralgia( PHN) in rats. A total of 100 male SD rats were randomly divided into the five groups( n = 20) : control group,PHN group,PHN group treated with hydrogen-rich saline( PHN-H2group),PHN group treated with hydrogen-rich saline and3-MA( PHN-H2-3-MA group),PHN group treated with hydrogen-rich saline and rapamycin( PHN-H2-Rap group). PHN models were established by varicella-zoster virus( VZV) inoculation. After modeling,15 mg / kg 3-MA or 10 mg / kg rapamycin were intraperitoneally injected in corresponding rats with PHN once two days for 3 times. Hydrogen-rich saline( 10 m L / kg)was injected intraperitoneally twice a day for 7 consecutive days in PHN-H2 group,PHN-H2-3-MA group and PHN-H2-Rap group after VZV injection. The paw withdrawal thresholds( PWT) of 50 rats were detected at 3,7,14 and 21 days after modeling. Spinal cord enlargements of the other 50 rats were collected to examine tumor necrosis factor α( TNF-α),interleukine 1β( IL-1β) and IL-6 by ELISA and autophagy protein microtubule-associated protein 1 light chain 3( LC3),beclin 1and P62 by Western blotting. Compared with the control group,the rats in the PHN group presented with decreased PWT,increased levels of TNF-α,IL-1β,IL-6,LC3Ⅱ and beclin 1,and down-regulated P62 expression. Compared with PHN group,the rats in the PHN-H2 group and PHN-H2-Rap group showed increased PWT,decreased levels of TNF-α,IL-1β and IL-6,further up-regulated expressions of LC3 and beclin 1 as wel as P62 expression. Compared with PHN-H2 group,the rats in the PHN-H2-3-MA group had reduced PWT,elevated expressions of TNF-α,IL-1β and IL-6,suppressed expressions of LC3 and beclin 1,and enhanced p62 expression. Hydrogen-rich saline attenuated PWT and inhibited the release of cytokines TNF-α,IL-1β,IL-6 in rats with PHN via activating autophagy.

[Hydrogen-rich saline attenuates hyperalgesia and reduces cytokines in rats with post-herpetic neuralgia via activating autophagy].

PubMed

Ma, Hongtao; Chen, Hongguang; Dong, Aili; Wang, Yanyan; Bian, Yingxue; Xie, Keliang

2017-02-01

Objective To investigate the role of autophagy in hydrogen-rich saline attenuating post-herpetic neuralgia (PHN) in rats. Methods A total of 100 male SD rats were randomly divided into the five groups (n=20): control group, PHN group, PHN group treated with hydrogen-rich saline (PHN-H 2 group), PHN group treated with hydrogen-rich saline and 3-MA (PHN-H 2 -3-MA group), PHN group treated with hydrogen-rich saline and rapamycin (PHN-H 2 -Rap group). PHN models were established by varicella-zoster virus (VZV) inoculation. After modeling, 15 mg/kg 3-MA or 10 mg/kg rapamycin were intraperitoneally injected in corresponding rats with PHN once two days for 3 times. Hydrogen-rich saline (10 mL/kg) was injected intraperitoneally twice a day for 7 consecutive days in PHN-H 2 group, PHN-H 2 -3-MA group and PHN-H 2 -Rap group after VZV injection. The paw withdrawal thresholds (PWT) of 50 rats were detected at 3, 7, 14 and 21 days after modeling. Spinal cord enlargements of the other 50 rats were collected to examine tumor necrosis factor α (TNF-α), interleukine 1β (IL-1β) and IL-6 by ELISA and autophagy protein microtubule-associated protein 1 light chain 3 (LC3), beclin 1 and P62 by Western blotting. Results Compared with the control group, the rats in the PHN group presented with decreased PWT, increased levels of TNF-α, IL-1β, IL-6, LC3II and beclin 1, and down-regulated P62 expression. Compared with PHN group, the rats in the PHN-H 2 group and PHN-H 2 -Rap group showed increased PWT, decreased levels of TNF-α, IL-1β and IL-6, further up-regulated expressions of LC3 and beclin 1 as well as P62 expression. Compared with PHN-H 2 group, the rats in the PHN-H 2 -3-MA group had reduced PWT, elevated expressions of TNF-α, IL-1β and IL-6, suppressed expressions of LC3 and beclin 1, and enhanced p62 expression. Conclusion Hydrogen-rich saline attenuated PWT and inhibited the release of cytokines TNF-α, IL-1β, IL-6 in rats with PHN via activating autophagy.

Administration of Intravenous Inf liximab for Prevention of Peritoneal Adhesions Formation in Rats.

PubMed

Nikeghbalian, Saman; Vafaei, Homeira; Moradian, Farid; Kazemi, Kourosh; Tanideh, Nader; Shayan, Leila; Nikeghbalian, Zahra

2015-07-01

To investigate the effects of intravenous infliximab in preventing the formation of peritoneal adhesions in an animal model of rat. This was an experimental study being performed in animal laboratory of Shiraz University of Medical Sciences during 2012. Sixty albino rats were randomly assigned in to three groups by Random Design Method. The first group received single infliximab injection (n=20), the second one received double infliximab injection (n=20) and the third received nothing (n=20), after receiving intra-peritoneal injection of talc for induction of peritoneal adhesions. All the animals were sacrificed after 6 weeks and the peritoneal adhesions were evaluated according to Nair classification. We observed that the mean adhesion grade was lower in those who received double dose of infliximib when compared to single dose and controls. However the difference did not reach a significant value (p=0.178). The grade of peritoneal adhesion was also comparable between the three study groups (p=0.103). The mean number of 1st WBC count was also comparable between three study groups (p=0.382). We observed that 2nd WBC count was also comparable between two study groups (p=0.317). Administration of intravenous infliximab after intraabdominal surgicalprocedures would not prevent the formation of peritoneal adhesions in animal model of albino rat.

Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats

PubMed Central

Kelly, Karen B.; Kennelly, John P.; Ordonez, Marta; Nelson, Randal; Leonard, Kelly; Stabler, Sally; Gomez-Muñoz, Antonio; Field, Catherine J.; Jacobs, René L.

2016-01-01

Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet. PMID:27669293

Hormone-induced rat model of polycystic ovary syndrome: A systematic review.

PubMed

Noroozzadeh, Mahsa; Behboudi-Gandevani, Samira; Zadeh-Vakili, Azita; Ramezani Tehrani, Fahimeh

2017-12-15

Despite polycystic ovary syndrome (PCOS) being one of the most common endocrine disorders affecting reproductive-aged women, the etiopathogenesis and mechanisms of this syndrome remain unclear. Considering the ethical limitations in human studies, animal models that reflect many features of PCOS are crucial resources to investigate this syndrome. We aimed to introduce the most suitable rat model of PCOS that closely mimics the endocrine, ovarian and metabolic disturbances of human PCOS phenotype, while maintaining normal reproductive system morphology in adulthood, in order to further more detailed investigations about PCOS. We searched Pubmed, Science direct, and Web of science between 1990 and 2016, for relevant English manuscripts, using keywords including the "Polycystic Ovary Syndrome AND Rat Model" to generate a subset of citations relevant to our research. Included were those articles that compared at least both ovarian histology or estrous cycle and reproductive hormonal profiles in hormone-induced rat model of PCOS and controls. Differences in the findings between hormone-induced PCOS rats appear to be a result of the degree of transplacental transfer of the steroid administered into the fetus, dose and type of hormone, route of administration and timing and duration of exposure. We conclude that prenatal hormone-induced rat model with a lower dose and shorter time of exposure during the critical period of fetal development that exhibits endocrine, ovarian and metabolic disturbances similar to PCOS in women, while maintaining normal reproductive system morphology in adulthood is more suitable than postnatal hormone-induced rat model to facilitate studies regarding PCOS. Copyright © 2017 Elsevier Inc. All rights reserved.

Coherence of neuronal firing of the entopeduncular nucleus with motor cortex oscillatory activity in the 6-OHDA rat model of Parkinson's disease with levodopa-induced dyskinesias.

PubMed

Jin, Xingxing; Schwabe, Kerstin; Krauss, Joachim K; Alam, Mesbah

2016-04-01

The pathophysiological mechanisms leading to dyskinesias in Parkinson's disease (PD) after long-term treatment with levodopa remain unclear. This study investigates the neuronal firing characteristics of the entopeduncular nucleus (EPN), the rat equivalent of the human globus pallidus internus and output nucleus of the basal ganglia, and its coherence with the motor cortex (MCx) field potentials in the unilateral 6-OHDA rat model of PD with and without levodopa-induced dyskinesias (LID). 6-hydroxydopamine-lesioned hemiparkinsonian (HP) rats, 6-OHDA-lesioned HP rats with LID (HP-LID) rats, and naïve controls were used for recording of single-unit activity under urethane (1.4 g/kg, i.p) anesthesia in the EPN "on" and "off" levodopa. Over the MCx, the electrocorticogram output was recorded. Analysis of single-unit activity in the EPN showed enhanced firing rates, burst activity, and irregularity compared to naïve controls, which did not differ between drug-naïve HP and HP-LID rats. Analysis of EPN spike coherence and phase-locked ratio with MCx field potentials showed a shift of low (12-19 Hz) and high (19-30 Hz) beta oscillatory activity between HP and HP-LID groups. EPN theta phase-locked ratio was only enhanced in HP-LID compared to HP rats. Overall, levodopa injection had no stronger effect in HP-LID rats than in HP rats. Altered coherence and changes in the phase lock ratio of spike and local field potentials in the beta range may play a role for the development of LID.

Effects of levothyroxine on learning and memory deficits in a rat model of Alzheimer's disease: the role of BDNF and oxidative stress.

PubMed

Bavarsad, Kowsar; Hadjzadeh, Mousa-Al-Reza; Hosseini, Mahmoud; Pakdel, Roghayeh; Beheshti, Farimah; Bafadam, Soleyman; Ashaari, Zeinab

2018-06-21

The effect of levothyroxine (L-T4) on the learning and memory impairment induced by streptozotocin (STZ) and brain tissue oxidative damage in rats was evaluated. An animal model of the Alzheimer's disease (AD) was established by intracerebroventricular injection of STZ (3 mg/kg) in male Wistar rats (250 ± 50 g). After that, the rats were treated for 3 weeks with L-T4 (10, 100 μg/kg) or normal saline. Passive avoidance (PA) learning and spatial memory were evaluated using shuttle box and Morris water maze (MWM), respectively. Finally, the rats were euthanized, their blood samples were collected for further thyroxine assessment and their brains were removed after decapitation in order to measure the oxidative stress parameters and brain-derived neurotrophic factor (BDNF). In the MWM, latency (s) increased in the AD rats compared with the normal control group while it decreased in the 10 μg/kg L-T4 injected AD rats compared with the AD group. In the PA, the latency for entering the dark compartment was lower in the AD group than in the normal control group and it decreased in the 10 μg/kg L-T4 injected AD rats. The low dose of L-T4 (10 μg/kg) reduced malondialdehyde concentration but increased thiols concentration, superoxide dismutase, catalase activities and BDNF level in hippocampal tissues of the AD rats. Injection of L-T4 (10 μg/kg) alleviated memory deficits and also improved factors of oxidative stress and BDNF level in the STZ-induced AD rats.

Aqueous extract of lavender (Lavandula angustifolia) improves the spatial performance of a rat model of Alzheimer's disease.

PubMed

Kashani, Masoud Soheili; Tavirani, Mostafa Rezaei; Talaei, Sayyed Alireza; Salami, Mahmoud

2011-04-01

Alzheimer's disease (AD) is one of the most important neurodegenerative disorders. It is characterized by dementia including deficits in learning and memory. The present study aimed to evaluate the effects of aqueous extract of lavender (Lavandula angustifolia) on spatial performance of AD rats. Male Wistar rats were first divided into control and AD groups. Rat model of AD was established by intracerebroventricular injection of 10 μg Aβ1-42 20 d prior to administration of the lavender extract. Rats in both groups were then introduced to 2 stages of task learning (with an interval of 20 d) in Morris water maze, each followed by one probe test. After the first stage of spatial learning, control and AD animals received different doses (50, 100 and 200 mg/kg) of the lavender extract. In the first stage of experiment, the latency to locate the hidden platform in AD group was significantly higher than that in control group. However, in the second stage of experiment, control and AD rats that received distilled water (vehicle) showed similar performance, indicating that the maze navigation itself could improve the spatial learning of AD animals. Besides, in the second stage of experiment, control and AD rats that received lavender extract administration at different doses (50, 100, and 200 mg/ kg) spent less time locating the platform (except for the AD rats with 50 mg/kg extract treatment), as compared with their counterparts with vehicle treatment, respectively. In addition, lavender extract significantly improved the performance of control and AD rats in the probe test, only at the dose of 200 mg/kg, as compared with their counterparts with vehicle treatment. The lavender extract can effectively reverse spatial learning deficits in AD rats.

Comparing models for perfluorooctanoic acid pharmacokinetics using Bayesian analysis.

PubMed

Wambaugh, John F; Barton, Hugh A; Setzer, R Woodrow

2008-12-01

Selecting the appropriate pharmacokinetic (PK) model given the available data is investigated for perfluorooctanoic acid (PFOA), which has been widely analyzed with an empirical, one-compartment model. This research examined the results of experiments [Kemper R. A., DuPont Haskell Laboratories, USEPA Administrative Record AR-226.1499 (2003)] that administered single oral or iv doses of PFOA to adult male and female rats. PFOA concentration was observed over time; in plasma for some animals and in fecal and urinary excretion for others. There were four rats per dose group, for a total of 36 males and 36 females. Assuming that the PK parameters for each individual within a gender were drawn from the same, biologically varying population, plasma and excretion data were jointly analyzed using a hierarchical framework to separate uncertainty due to measurement error from actual biological variability. Bayesian analysis using Markov Chain Monte Carlo (MCMC) provides tools to perform such an analysis as well as quantitative diagnostics to evaluate and discriminate between models. Starting from a one-compartment PK model with separate clearances to urine and feces, the model was incrementally expanded using Bayesian measures to assess if the expansion was supported by the data. PFOA excretion is sexually dimorphic in rats; male rats have bi-phasic elimination that is roughly 40 times slower than that of the females, which appear to have a single elimination phase. The male and female data were analyzed separately, keeping only the parameters describing the measurement process in common. For male rats, including excretion data initially decreased certainty in the one-compartment parameter estimates compared to an analysis using plasma data only. Allowing a third, unspecified clearance improved agreement and increased certainty when all the data was used, however a significant amount of eliminated PFOA was estimated to be missing from the excretion data. Adding an additional PK compartment reduced the unaccounted-for elimination to amounts comparable to the cage wash. For both sexes, an MCMC estimate of the appropriateness of a model for a given data type, the Deviance Information Criterion, indicated that this two-compartment model was better suited to describing PFOA PK. The median estimate was 142.1 +/- 37.6 ml/kg for the volume of the primary compartment and 1.24 +/- 1.1 ml/kg/h for the clearances of male rats and 166.4 +/- 46.8 ml/kg and 30.3 +/- 13.2 ml/kg/h, respectively for female rats. The estimates for the second compartment differed greatly with gender-volume 311.8 +/- 453.9 ml/kg with clearance 3.2 +/- 6.2 for males and 1400 +/- 2507.5 ml/kg and 4.3 +/- 2.2 ml/kg/h for females. The median estimated clearance was 12 +/- 6% to feces and 85 +/- 7% to urine for male rats and 8 +/- 6% and 77 +/- 9% for female rats. We conclude that the available data may support more models for PFOA PK beyond two-compartments and that the methods employed here will be generally useful for more complicated, including PBPK, models.

[Effect of ginsenoside Rb1 on cerebral infarction volume and IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion injury model rats].

PubMed

Liu, Jun-Wei; Ren, Ye-Long; Liu, Xu-Ling; Xia, Hong-Lian; Zhang, Hui-Ling; Jin, Shen-Hui; Dai, Qin-Xue; Wang, Jun-Lu

2013-12-01

To investigate the effect of ginsenoside Rb1 on cerebral infarction volume as well as IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion (I/R) injury model rats. The I/R rat model was established by using thread according to Zea-Longa. SD rats were randomly divided into five groups, i.e., the sham-operation group, the model group, the low dose ginsenoside Rb1 (20 mg/kg) group, the medium dose ginsenoside Rb1 group (40 mg/kg), and the high dose ginsenoside Rb1 group (80 mg/kg), 12 in each group. Rats in the sham-operation group only received middle cerebral artery occlusion (MCAO) but without thread insertion. The MCAO model was prepared in the rest 4 groups, followed by MCAO2 h later. Ginsenoside Rb1 at each dose was peritoneally administrated to rats in corresponding groups immediately after cerebral ischemia. Equal volume of normal saline was administered to rats in the sham-operation group. Rats' cerebral infarction volume, integrals of neurologic defect degree, expression of IL-1 beta content in the brain tissue and sera were observed 24 h after 2-h cerebral I/R. In the model group, integrals of neurologic defect degree were improved (P < 0.01), IL-1 beta positive cells in the brain tissue increased and serum IL-1 beta content elevated (P < 0.05), when compared with the sham-operation group. In comparison of the model group, integrals of neurologic defect degree were lowered in the medium dose and high dose ginsenoside Rb1 groups (P < 0.05, P < 0.01). The cerebral infarction volume was all shrunken in each ginsenoside Rb1 group, IL-1 beta positive cells in the brain tissue decreased, and IL-1 beta content in serum reduced (P < 0.01, P < 0.05). Compared with the low dose ginsenoside Rb1 group, integrals of neurologic defect degree decreased, the cerebral infarction volume shrunken, and IL-1 beta content in serum reduced in the high dose ginsenoside Rb1 group (P < 0.01, P < 0.05). Ginsenoside Rb1 (20, 40, 80 mg/kg) might effectively release local cerebral ischemia by down-regulating the IL-1 beta expression.

[Action mechanism of electroacupuncture at stomach meridian acupoints for oxidative damage in rats with gastric ulcer].

PubMed

Yang, Zongbao; Wang, Yadong; Liu, Qiong; Liu, Mi; Chen, Huijuan; Chang, Xiaorong

2016-06-12

To observe the effects of electroacupuncture (EA) at stomach meridian acupoints on expression of oxidation damage factors in serum and gastric mucosal cells in rats with gastric ulcer, and to explore the mechanism of EA at stomach meridian acupoints for oxidative damage in rats with gastric ulcer. Forty clean-grade SD rats were randomly divided into a normal group, a model group, a stomach meridian group and a gallbladder meridian group, ten rats in each one. Except the normal group, rats in the remaining groups were applied the restraint-cold stress method to establish the model of gastric ulcer. Rats in the normal group and model group received no treatment; rats in the stomach meridian group were treated with EA at "Liangmen" (ST 21) and "Zusanli" (ST 36); rats in the gallbladder meridian group were treated with EA at "Riyue" (GB 24) and "Yanglingquan" (GB 34). The EA was given for 30 min, once a day for 7 days totally. The change of gastric mucosal morphology was observed by routine light microscope; enzyme linked immunosorbent assay was used to detect the expressions of malondialdehyde (MDA), glutathione peroxidase (GSH-px) and tumor necrosis factor-α (TNF-α), interleukin-2(IL-2), interleukin-6(IL-6) in serum and gastric mucosal cells of rats. After treatment, compared with the model group, the gastric mucosal damage index was decreased in the stomach meridian group and gallbladder meridian group (both P <0.05), the expressions of MDA, TNF-α, IL-2 and IL-6 in serum and gastric mucosal cells were significantly decreased in the stomach meridian group (all P <0.01), but the contents of GSH-Px in serum and gastric mucosal cells were increased significantly (both P <0.01). Compared with the gallbladder meridian group, the gastric mucosal damage index as well as the expressions of MDA,TNF-α, IL-2 and IL-6 in serum and gastric mucosal cells were significantly decreased in the stomach meridian group rats ( P <0.05, P <0.01), and the contents of GSH-px in serum and gastric mucosal cells were increased significantly (both P <0.01). EA at stomach meridian acupoints is likely to inhibit the expressions of oxidative damage factors to promote the repair of gastric mucosal injury, which indicates the correlation between meridians and zang-fu .

Nootropic and antiamnestic effects of tenoten (pediatric formulation) in immature rat pups.

PubMed

Voronina, T A; Molodavkin, G M; Borodavkina, M V; Kheyfets, I A; Dugina, Yu L; Sergeeva, S A

2009-09-01

The antiamnestic effects of tenoten (pediatric formulation) was demonstrated on the model of scopolamine-induced amnesia of passive avoidance reflex and the nootropic effect of this preparation was demonstrated on the model of incomplete conditioning and in rat pups with experimental attention deficit syndrome. The efficiency of the preparation was comparable to that of piracetam and phenibut and even surpassed it by some parameters.

Study on perfume stimulating olfaction with volatile oil of Acorus gramineus for treatment of the Alzheimer's disease rat.

PubMed

Liu, Zhi-Bin; Niu, Wen-Min; Yang, Xiao-Hang; Wang, Yuan; Wang, Wei-Gang

2010-12-01

To probe into the therapeutic effect of perfume stimulating olfaction with volatile oil of Acorus Gramineus on the Alzheimer's disease (AD) rat. Totally 50 adult SD rats, male,weighing 300 +/- 10 g, were randomly divided into 5 groups, normal group (group A), olfactory nerve severing model group (group B), AD model group (group C), AD model plus perfume stimulation group (group D), AD model olfactory nerve severing plus perfume stimulation group (group E), 10 rats in each group. After perfume stimulation, Morris maze test was conducted for valuating the learning and memory ability; Malondaldehyde (MDA) content, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the brain, and the brain weight were detected. Compared with the AD model group, the average escape latency and swimming distance in 6 days were significantly shorter than those in the group A, B, D (P < 0.01), with no significant differences between the group C and the group E (P > 0.05); Compared with the group A, B and D, MDA content in the group C significantly increased (P < 0.01), and SOD and GSH-Px activities significantly decreased (P < 0.01), and brain weight/body weight decreased significantly in the group C (P < 0.01), with no significant differences between the group C and the group E (P > 0.05). Perfume stimultating olfaction with volatile oil of Acorus Gramineus can significantly increase the learning-memory ability, decrease MDA content and increase SOD and GSH-Px activities and weight of brain in AD rats.

Uncertainty exposure causes behavioural sensitization and increases risky decision-making in male rats: toward modelling gambling disorder.

PubMed

Zeeb, Fiona D; Li, Zhaoxia; Fisher, Daniel C; Zack, Martin H; Fletcher, Paul J

2017-11-01

An animal model of gambling disorder, previously known as pathological gambling, could advance our understanding of the disorder and help with treatment development. We hypothesized that repeated exposure to uncertainty during gambling induces behavioural and dopamine (DA) sensitization - similar to chronic exposure to drugs of abuse. Uncertainty exposure (UE) may also increase risky decision-making in an animal model of gambling disorder. Male Sprague Dawley rats received 56 UE sessions, during which animals responded for saccharin according to an unpredictable, variable ratio schedule of reinforcement (VR group). Control animals responded on a predictable, fixed ratio schedule (FR group). Rats yoked to receive unpredictable reward were also included (Y group). Animals were then tested on the Rat Gambling Task (rGT), an analogue of the Iowa Gambling Task, to measure decision-making. Compared with the FR group, the VR and Y groups experienced a greater locomotor response following administration of amphetamine. On the rGT, the FR and Y groups preferred the advantageous options over the risky, disadvantageous options throughout testing (40 sessions). However, rats in the VR group did not have a significant preference for the advantageous options during sessions 20-40. Amphetamine had a small, but significant, effect on decision-making only in the VR group. After rGT testing, only the VR group showed greater hyperactivity following administration of amphetamine compared with the FR group. Reward uncertainty was the only gambling feature modelled. Actively responding for uncertain reward likely sensitized the DA system and impaired the ability to make optimal decisions, modelling some aspects of gambling disorder.

Airflow and particle deposition simulations in health and emphysema: from in vivo to in silico animal experiments.

PubMed

Oakes, Jessica M; Marsden, Alison L; Grandmont, Celine; Shadden, Shawn C; Darquenne, Chantal; Vignon-Clementel, Irene E

2014-04-01

Image-based in silico modeling tools provide detailed velocity and particle deposition data. However, care must be taken when prescribing boundary conditions to model lung physiology in health or disease, such as in emphysema. In this study, the respiratory resistance and compliance were obtained by solving an inverse problem; a 0D global model based on healthy and emphysematous rat experimental data. Multi-scale CFD simulations were performed by solving the 3D Navier-Stokes equations in an MRI-derived rat geometry coupled to a 0D model. Particles with 0.95 μm diameter were tracked and their distribution in the lung was assessed. Seven 3D-0D simulations were performed: healthy, homogeneous, and five heterogeneous emphysema cases. Compliance (C) was significantly higher (p = 0.04) in the emphysematous rats (C = 0.37 ± 0.14 cm(3)/cmH2O) compared to the healthy rats (C = 0.25 ± 0.04 cm(3)/cmH2O), while the resistance remained unchanged (p = 0.83). There were increases in airflow, particle deposition in the 3D model, and particle delivery to the diseased regions for the heterogeneous cases compared to the homogeneous cases. The results highlight the importance of multi-scale numerical simulations to study airflow and particle distribution in healthy and diseased lungs. The effect of particle size and gravity were studied. Once available, these in silico predictions may be compared to experimental deposition data.

Ganglioside GM3 content in skeletal muscles is increased in type 2 but decreased in type 1 diabetes rat models: Implications of glycosphingolipid metabolism in pathophysiology of diabetes.

PubMed

Bozic, Josko; Markotic, Anita; Cikes-Culic, Vedrana; Novak, Anela; Borovac, Josip A; Vucemilovic, Hrvoje; Trgo, Gorana; Ticinovic Kurir, Tina

2018-02-01

Ganglioside GM3 is found in the plasma membrane, where its accumulation attenuates insulin receptor signaling. Considering the role of skeletal muscles in insulin-stimulated glucose uptake, the aim of the present study was to determine the expression of GM3 and its precursors in skeletal muscles of rat models of type 1 and type 2 diabetes mellitus (T1DM and T2DM, respectively). Diabetes was induced in male Sprague-Dawley rats by streptozotocin injection (55 mg/kg, i.p., for T1DM induction; 35 mg/kg, i.p., for T2DM induction), followed by feeding of rats with either a normal pellet diet (T1DM) or a high-fat diet (T2DM). Rats were killed 2 weeks after diabetes induction and samples of skeletal muscle were collected. Frozen quadriceps muscle sections were stained with a primary antibody against GM3 (Neu5Ac) and visualized using a secondary antibody coupled with Texas Red. The muscle content of ganglioside GM3 and its precursors was analyzed by high-performance thin-layer chromatography (HPTLC) followed by GM3 immunostaining. Muscle GM3 content was significantly higher in T2DM compared with control rats (P < 0.001). Furthermore, levels of the GM3 precursors ceramide, glucosylceramide, and lactosylceramide were significantly higher in T2DM compared with control rats (P < 0.05), whereas ceramide content was significantly lower in T1DM rats (P < 0.05). The intensity of the GM3 band on HPTLC was significantly higher in T2DM rats (P < 0.001) and significantly lower in T1DM rats (P < 0.05) compared with control. The expression patterns of GM3 ganglioside and its precursors in diabetic rats suggest that the role of glycosphingolipid metabolism may differ between T2DM and T1DM. © 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Surgical anatomy of the liver, hepatic vasculature and bile ducts in the rat.

PubMed

Martins, Paulo Ney Aguiar; Neuhaus, Peter

2007-04-01

The rat is the most used experimental model in surgical research. Virtually all procedures in clinical liver surgery can be performed in the rat. However, the use of the rat model in liver surgery is limited by its small size and limited knowledge of the liver anatomy. As in humans, the rat liver vasculature and biliary system have many anatomical variations. The development of surgical techniques, and the study of liver function and diseases require detailed knowledge of the regional anatomy. The objective of this study was to describe and illustrate systematically the surgical anatomy of the rat liver to facilitate the planning and performance of studies in this animal. Knowledge of the diameter and length of liver vessels is also important for the selection of catheters and perivascular devices. Twelve Wistar rat livers were dissected using a surgical microscope. Hepatic and extrahepatic anatomical structures were measured under magnification with a millimeter scale. In this study, we describe the rat liver topographical anatomy, compare it with the human liver and review the literature. Increased knowledge of the rat liver anatomy and microsurgical skills permit individualized dissection, parenchymal section, embolization and ligature of vascular and biliary branches.

Composition of Muscle Fiber Types in Rat Rotator Cuff Muscles.

PubMed

Rui, Yongjun; Pan, Feng; Mi, Jingyi

2016-10-01

The rat is a suitable model to study human rotator cuff pathology owing to the similarities in morphological anatomy structure. However, few studies have reported the composition muscle fiber types of rotator cuff muscles in the rat. In this study, the myosin heavy chain (MyHC) isoforms were stained by immunofluorescence to show the muscle fiber types composition and distribution in rotator cuff muscles of the rat. It was found that rotator cuff muscles in the rat were of mixed fiber type composition. The majority of rotator cuff fibers labeled positively for MyHCII. Moreover, the rat rotator cuff muscles contained hybrid fibers. So, compared with human rotator cuff muscles composed partly of slow-twitch fibers, the majority of fast-twitch fibers in rat rotator cuff muscles should be considered when the rat model study focus on the pathological process of rotator cuff muscles after injury. Gaining greater insight into muscle fiber types in rotator cuff muscles of the rat may contribute to elucidate the mechanism of pathological change in rotator cuff muscles-related diseases. Anat Rec, 299:1397-1401, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

BACHD rats expressing full-length mutant huntingtin exhibit differences in social behavior compared to wild-type littermates

PubMed Central

Manfré, Giuseppe; Novati, Arianna; Faccini, Ilaria; Rossetti, Andrea C.; Bosch, Kari; Molteni, Raffaella; Riva, Marco A.; Van der Harst, Johanneke E.; Homberg, Judith R.

2018-01-01

Background Huntington disease (HD) is a devastating inherited neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric symptoms without any cure to slow down or stop the progress of the disease. The BACHD rat model for HD carrying the human full-length mutant huntingtin protein (mHTT) with 97 polyQ repeats has been recently established as a promising model which reproduces several HD-like features. While motor and cognitive functions have been characterized in BACHD rats, little is known about their social phenotype. Objective This study focuses especially on social behavior since evidence for social disturbances exists in human patients. Our objective was to compare social behavior in BACHD and wild-type (WT) rats at different ages, using two different measures of sociability. Methods Animals were tested longitudinally at the age of 2, 4 and 8 months in the social interaction test to examine different parameters of sociability. A separate cohort of 7 month old rats was tested in the three chamber social test to measure both sociability and social novelty. Gene expression analyses in 8 months old animals were performed by real time qRT-PCR to evaluate a potential involvement of D1 and D2 dopaminergic receptors and the contribution of Brain-derived neurotrophic factor (BDNF) to the observed behavioral alterations. Results In the social interaction test, BACHD rats showed age-dependent changes in behaviour when they were-re introduced to their cagemate after a 24 hours-period of individual housing. The time spent on nape attacks increased with aging. Furthermore, a significant higher level of pinning at 2 months of age was shown in the BACHD rats compared to wild-types, followed by a reduction at 4 and 8 months. On the other hand, BACHD rats exhibited a decreased active social behaviour compared to wild-types, reflected by genotype-effects on approaching, following and social nose contact. In the three chamber social test, BACHD rats seemed to show a mild deficit in preference for social novelty, but no changes in social interest. Molecular analyses revealed that BACHD animals exposed to the social interaction test displayed decreased mRNA levels of the total form of BDNF in ventral striatum and unaltered striatal expression of D1 and D2 dopamine receptors. Conclusions Taken together, these results indicate deficits in several parameters representative of sociability. Altered BDNF expression in the ventral striatum may contribute to the deficits in sociability in 8 months old BACHD rats. These data support the validity of the BACHD rat model in mimicking features of certain social deficits that could be relevant to symptoms in patients. PMID:29415038

The effect of butylphthalide on the brain edema, blood-brain barrier of rats after focal cerebral infarction and the expression of Rho A.

PubMed

Hu, Jinyang; Wen, Qingping; Wu, Yue; Li, Baozhu; Gao, Peng

2014-06-01

The aim of this study was to explore the effect of butylphthalide on the brain edema, blood-brain barrier of rats of rats after focal cerebral infarction and the expression of Rho A. A total of 195 sprague-dawley male rats were randomly divided into control group, model group, and butylphthalide group (40 mg/kg, once a day, by gavage). The model was made by photochemical method. After surgery 3, 12, 24, 72, and 144 h, brain water content was done to see the effect of butylphthalide for the cerebral edema. Evans blue extravasation method was done to see the changes in blood-brain barrier immunohistochemistry, and Western blot was done to see the expression of Rho A around the infarction. Compared with the control group, the brain water content of model group and butylphthalide group rats was increased, the permeability of blood-brain barrier of model group and butylphthalide group rats was increased, and the Rho A protein of model group and butylphthalide group rats was increased. Compared with the model group, the brain water content of butylphthalide group rats was induced (73.67 ± 0.67 vs 74.14 ± 0.46; 74.89 ± 0.57 vs 75.61 ± 0.52; 77.49 ± 0.34 vs 79.33 ± 0.49; 76.31 ± 0.56 vs 78.01 ± 0.48; 72.36 ± 0.44 vs 73.12 ± 0.73; P < 0.05), the permeability of blood-brain barrier of butylphthalide group rats was induced (319.20 ± 8.11 vs 394.60 ± 6.19; 210.40 ± 9.56 vs 266.40 ± 7.99; 188.00 ± 9.22 vs 232.40 ± 7.89; 288.40 ± 7.86 vs 336.00 ± 6.71; 166.60 ± 6.23 vs 213.60 ± 13.79; P < 0.05), and the Rho A protein of butylphthalide group rats was decreased (western blot result: 1.2230 ± 0.0254 vs 1.3970 ± 0.0276; 1.5985 ± 0.0206 vs 2.0368 ± 0.0179; 1.4229 ± 0.0167 vs 1.7930 ± 0.0158;1.3126 ± 0.0236 vs 1.5471 ± 0.0158; P < 0.05). The butylphthalide could reduce the brain edema, protect the blood-brain barrier, and decrease the expression of Rho A around the infarction.

Meal patterns, satiety, and food choice in a rat model of Roux-en-Y gastric bypass surgery.

PubMed

Zheng, Huiyuan; Shin, Andrew C; Lenard, Natalie R; Townsend, R Leigh; Patterson, Laurel M; Sigalet, David L; Berthoud, Hans-Rudolf

2009-11-01

Gastric bypass surgery efficiently and lastingly reduces excess body weight and reverses type 2 diabetes in obese patients. Although increased energy expenditure may also play a role, decreased energy intake is thought to be the main reason for weight loss, but the mechanisms involved are poorly understood. Therefore, the aim of this study was to characterize the changes in ingestive behavior in a rat model of Roux-en-Y gastric bypass surgery (RYGB). Obese (24% body fat compared with 18% in chow-fed controls), male Sprague-Dawley rats maintained for 15 wk before and 4 mo after RYGB or sham-surgery on a two-choice low-fat/high-fat diet, were subjected to a series of tests assessing energy intake, meal patterning, and food choice. Although sham-operated rats gained an additional 100 g body wt during the postoperative period, RYGB rats lost approximately 100 g. Intake of a nutritionally complete and palatable liquid diet (Ensure) was significantly reduced by approximately 50% during the first 2 wk after RYGB compared with sham surgery. Decreased intake was the result of greatly reduced meal size with only partial compensation by meal frequency, and a corresponding increase in the satiety ratio. Similar results were obtained with solid food (regular or high-fat chow) 6 wk after surgery. In 12- to 24-h two-choice liquid or solid diet paradigms with nutritionally complete low- and high-fat diets, RYGB rats preferred the low-fat choice (solid) or showed decreased acceptance for the high-fat choice (liquid), whereas sham-operated rats preferred the high-fat choices. A separate group of rats offered chow only before surgery completely avoided the solid high-fat diet in a choice paradigm. The results confirm anecdotal reports of "nibbling" behavior and fat avoidance in RYGB patients and provide a basis for more mechanistic studies in this rat model.

Comparative pharmacokinetics of (S)-MP3950, a novel 5-HT4 receptor agonist, in normal and atropine-induced gastrointestinal motility disorders rats.

PubMed

Wang, Binjie; Sun, Xiaoyang; Wang, Shixiao; Guo, Ping; Li, Shujuan; Zhang, Meiyu; Zhao, Longshan; Chen, Xiaohui

2018-08-01

1. (S)-MP3950 is the (S)-enantiomer of active metabolite of mosapride, which exhibits higher 5-HT 4 receptor agonistic effect than mosapride. It shows promise to become a novel drug candidate for the treatment of gastrointestinal motility disorders (GMDs). However, the pharmacokinetic behavior of (S)-MP3950 in the pathological state of GMDs remains unclear. Herein, we investigated the comparative pharmacokinetics of (S)-MP3950 in normal and GMDs rats. 2. The comparative pharmacokinetics of (S)-MP3950 in normal and atropine-induced GMD rats were studied by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The validated UPLC-MS/MS method was successfully applied to investigate the pharmacokinetic profiles of (S)-MP3950 in normal and atropine-induced GMDs rats. Results showed that comparing to normal rats, C max reduced by 73.8%, AUC 0-t decreased by 57.6% and AUC 0-∞ declined by 56.8% in model rats. Additionally, the elimination half-life (t 1/2 ) and T max were prolonged slightly. 3. The pharmacokinetic results demonstrated that the atropine-induced GMDs reduced the absorption of (S)-MP3950. The pharmacokinetics research in the pathological state might provide more useful information for further study of novel gastric motility candidates.

Venous or arterial blood components trigger more brain swelling, tissue death after acute subdural hematoma compared to elderly atrophic brain with subdural effusion (SDE) model rats.

PubMed

Wajima, Daisuke; Sato, Fumiya; Kawamura, Kenya; Sugiura, Keisuke; Nakagawa, Ichiro; Motoyama, Yasushi; Park, Young-Soo; Nakase, Hiroyuki

2017-09-01

Acute subdural hematoma (ASDH) is a frequent complication of severe head injury, whose secondary ischemic lesions are often responsible for the severity of the disease. We focused on the differences of secondary ischemic lesions caused by the components, 0.4ml venous- or arterial-blood, or saline, infused in the subdural space, evaluating the differences in vivo model, using rats. The saline infused rats are made for elderly atrophic brain with subdural effusion (SDE) model. Our data showed that subdural blood, both venous- and arterial-blood, aggravate brain edema and lesion development more than SDE. This study is the first study, in which different fluids in rats' subdural space, ASDH or SDE are compared with the extension of early and delayed brain damage by measuring brain edema and histological lesion volume. Blood constituents started to affect the degree of ischemia underneath the subdural hemorrhage, leading to more pronounced breakdown of the blood-brain barrier and brain damage. This indicates that further strategies to treat blood-dependent effects more efficiently are in view for patients with ASDH. Copyright © 2017 Elsevier B.V. All rights reserved.

Male rats treated with subchronic PCP show intact olfaction and enhanced interest for a social odour in the olfactory habituation/dishabituation test.

PubMed

Tarland, Emilia; Brosda, Jan

2018-06-01

The olfactory system participates in many sensory processes, and olfactory endophenotypes appear in a variety of neurological disorders such as Alzheimer's and Parkinson's disease, depression and schizophrenia. Social withdrawal is a core negative symptom of schizophrenia and animal models have proven to be invaluable for studying the neurobiological mechanisms and cognitive processes behind the formation of social relationships. The subchronic phencyclidine (PCP) rat model is a validated model for negative symptoms of schizophrenia, such as impaired sociability. However, the complete range of social behaviour and deficits in the model are still not fully understood. Intact rodent olfaction is essential for a wide range of social behaviour and disrupted olfactory function could have severe effects on social communication and recognition. In order to examine the olfactory ability of male rats treated with subchronic PCP, we conducted an olfactory habituation/dishabituation test including both non-social and social odours. The subchronic PCP-treated rats successfully recognized and discriminated among the odours, indicative of intact olfaction. Interestingly, the subchronic PCP-treated rats showed greater interest for a novel social odour compared to the saline-treated rats and the rationale remains to be elucidated. Our data indicate that subchronic PCP treatment does not disrupt olfactory function in male rats. By ruling out impaired olfaction as cause for the poor social interaction performance in subchronic PCP-treated rats, our data supports the use of NMDA receptor antagonists to model the negative symptoms of schizophrenia. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

The effects of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 during myocardial ischemia/reperfusion in a model of rats with depression.

PubMed

Wang, Yiming; Zhang, Hongming; Chai, Fangxian; Liu, Xingde; Berk, Michael

2014-12-04

Major depressive disorder (MDD) is an independent risk factor for coronary heart disease (CHD), and influences the occurrence and prognosis of cardiovascular events. Although there is evidence that antidepressants may be cardioprotective after acute myocardial infarction (AMI) comorbid with MDD, the operative pathophysiological mechanisms remain unclear. Our aim was therefore to explore the molecular mechanisms of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 in a rat model of depression during myocardial ischemia/reperfusion (I/R). Rats were divided randomly into 3 groups (n = 8): D group (depression), DI/R group (depression with myocardial I/R) and escitalopram + DI/R group. The rats in all three groups underwent the same chronic mild stress and separation for 21 days, at the same time, in the escitalopram + DI/R group, rats were administered escitalopram by gavage (10 mg/kg/day). Ligation of the rat's left anterior descending branch was done in the myocardial I/R model. Following which behavioral tests were done. The size of the myocardial infarction was detected using 1.5% TTC dye. The Tunel method was used to detect apoptotic myocardial cells, and both the Rt-PCR method and immunohistochemical techniques were used to detect the expression of Bcl-2 and Bax. Compared with the D and DI/R groups, rats in Escitalopram + DI/R group showed significantly increased movements and sucrose consumption (P < .01). Compared with the DI/R group, the myocardial infarct size in the escitalopram + DI/R group was significantly decreased (P < .01). Compared with the D group, there were significantly increased apoptotic myocardial cells in the DI/R and escitalopram + DI/R groups (P < .01); however compared with the DI/R group, apoptotic myocardial cell numbers in the escitalopram + DI/R group were significantly decreased (P < .01). Compared with the DI/R group, there was a down-regulated Bax:Bcl-2 ratio in the escitalopram + DI/R group (P < .01). These results suggest that in patients with AMI comorbid with MDD, there is an increase in pro-apoptotic pathways that is reversed by escitalopram. This suggests that clinically escitalopram may have a direct cardioprotective after acute myocardial infarction.

[The toxic and protective effects of Polygonum multiflorum on normal and liver injured rats based on the symptom-based prescription theory].

PubMed

Pang, Jing-yao; Bai, Zhao-fang; Niu, Ming; Tu, Can; Ma, Zhi-jie; Zhao, Yan-ling; Zhao, Kui-jun; You, Yun; Wang, Jia-bo; Xiao, Xiao-he

2015-08-01

The dosage-efficacy/toxicity relationship of the 50% alcohol extracts of Polygonum multiflorum was comparatively investigated on either normal or CCl4-induced chronic liver injury rats, by determining the general condition, serum biochemical indices and liver histopathology, coupled with the factor analysis. The dosages were 10 and 20 g raw materials per kg body weight. Compared with the normal control group, the normal high dose group showed significant increases of the serum alanine transaminase (ALT), total bilirubin (TBIL), high mobility group box 1 (HMGB-1) and interleukin-1β (IL-1β) (P < 0.05 or P < 0.01), as well the frequent incidences of inflammatory cell infiltration, hepatic sinus enlargement and fiber stripes formation in histopathological sections. Compared with the model control group, the model low dose group showed significant declines of serum ALT, aspartate transaminase (AST) and total bile acid (TBA) (P < 0.05), as well the alleviation of vacuoles of hepatocytes, but no amelioration of the inflammatory cell infiltration and fibrous tissue hyperplasia; moreover, the model high dose group showed significant degeneration declines of serum HMGB-1, tumor necrosis factor-α (TNF-α) and IL-1β (P < 0.05, P < 0.01), as well the evident alleviation of vacuoles degeneration of hepatocytes, inflammatory cells infiltration and fibrosis degree. The factor analysis showed that the low dosage treatment had almost neither injuring effect on the normal rats nor protective effect on the model rats; while the high dosage treatment showed observable injuring effect on the normal rats, expressed by the significant increases of the factor-1 (HMGB-1, TNF-α and IL-1β as the main contributors) and factor-2 (TBIL, ALT and TBA as the main contributors) relative to the normal control group. The liver protective effect of the high dosage treatment could be observed with the significant reduction of the factor-1, indicating the effective alleviation of the expression of inflammatory cytokines. In conclusion, it could illustrated the phenomenon of symptom-based prescription theory of Polygonum multiflorum on rat livers: the high dosage of the herb had either an injuring effect on normal rats, or a therapeutic effect on the rats with chronic liver injury.

Dexmedetomidine alleviates anxiety-like behaviors and cognitive impairments in a rat model of post-traumatic stress disorder.

PubMed

Ji, Mu-Huo; Jia, Min; Zhang, Ming-Qiang; Liu, Wen-Xue; Xie, Zhong-Cong; Wang, Zhong-Yun; Yang, Jian-Jun

2014-10-03

Post-traumatic stress disorder (PTSD) is a psychiatric disease that has substantial health implications, including high rates of health morbidity and mortality, as well as increased health-related costs. Although many pharmacological agents have proven the effects on the development of PTSD, current pharmacotherapies typically only produce partial improvement of PTSD symptoms. Dexmedetomidine is a selective, short-acting α2-adrenoceptor agonist, which has anxiolytic, sedative, and analgesic effects. We therefore hypothesized that dexmedetomidine possesses the ability to prevent the development of PTSD and alleviate its symptoms. By using the rat model of PTSD induced by five electric foot shocks followed by three weekly exposures to situational reminders, we showed that the stressed rats displayed pronounced anxiety-like behaviors and cognitive impairments compared to the controls. Notably, repeated administration of 20μg/kg dexmedetomidine showed impaired fear conditioning memory, decreased anxiety-like behaviors, and improved spatial cognitive impairments compared to the vehicle-treated stressed rats. These data suggest that dexmedetomidine may exert preventive and protective effects against anxiety-like behaviors and cognitive impairments in the rats with PTSD after repeated administration. Copyright © 2014 Elsevier Inc. All rights reserved.

Alterations in hippocampal and cortical densities of functionally different interneurons in rat models of absence epilepsy.

PubMed

Papp, Péter; Kovács, Zsolt; Szocsics, Péter; Juhász, Gábor; Maglóczky, Zsófia

2018-05-31

Recent data from absence epileptic patients and animal models provide evidence for significant impairments of attention, memory, and psychosocial functioning. Here, we outline aspects of the electrophysiological and structural background of these dysfunctions by investigating changes in hippocampal and cortical GABAergic inhibitory interneurons in two genetically absence epileptic rat strains: the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and the Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. Using simultaneously recorded field potentials from the primary somatosensory cortex (S1 cortex, seizure focus) and the hippocampal hilus, we demonstrated that typical frequencies of spike-wave discharges (SWDs; 7-8 Hz, GAERS; 7-9 Hz, WAG/Rij) and their harmonics appeared and their EEG spectral power markedly increased on recordings not only from the S1 cortex, but also from the hilus in both GAERS and WAG/Rij rats during SWDs. Moreover, we observed an increased synchronization between S1 cortex and hilus at 7-8 Hz (GAERS) and 7-9 Hz (WAG/Rij) and at their harmonics when SWDs occurred in the S1 cortex in both rat strains. In addition, using immunohistochemistry we demonstrated changes in the densities of perisomatic (parvalbumin-immunopositive, PV+) and interneuron-selective (calretinin-immunopositive, CR+) GABAergic inhibitory interneuron somata. Specifically, GAERS and WAG/Rij rats displayed lower densities of PV-immunopositivity in the hippocampal hilus compared to non-epileptic control (NEC) and normal Wistar rats. GAERS and WAG/Rij rats also show a marked reduction in the density of CR + interneurons in the same region in comparison with NEC rats. Data from the S1 cortex reveals bidirectional differences in PV + density, with GAERS displaying a significant increase, whereas WAG/Rij a reduction compared to control rat strains. Our results suggest an enhanced synchronization and functional connections between the hippocampus and S1 cortex as well as thalamocortical activities during SWDs and a functional alteration of inhibitory mechanisms in the hippocampus and S1 cortex of two genetic models of absence epilepsy, presumably in relation with increased neuronal activity and seizure-induced neuronal injury. Copyright © 2018 Elsevier B.V. All rights reserved.

Downregulation of natriuretic peptide system and increased steroidogenesis in rat polycystic ovary.

PubMed

Pereira, Virginia M; Honorato-Sampaio, Kinulpe; Martins, Almir S; Reis, Fernando M; Reis, Adelina M

2014-10-01

Atrial natriuretic peptide (ANP) is known to regulate ovarian functions, such as follicular growth and steroid hormone production. The aim of the present study was to investigate the natriuretic peptide system in a rat model of chronic anovulation, the rat polycystic ovary. Adult female Wistar rats received a single subcutaneous injection of 2mg estradiol valerate to induce polycystic ovaries, while the control group received vehicle injection. Two months later, their ovaries were quickly removed and analyzed. Polycystic ovaries exhibited marked elevation of testosterone and estradiol levels compared to control ovaries. The levels of ANP and the expression of ANP mRNA were highly reduced in the polycystic ovaries compared to controls. By immunohistochemistry, polycystic ovaries showed weaker ANP staining in stroma, theca cells and oocytes compared to controls. Polycystic ovaries also had increased activity of neutral endopeptidase, the main proteolytic enzyme that degrades natriuretic peptides. ANP receptor C mRNA was reduced and ANP binding to this receptor was absent in polycystic ovaries. Collectively, these results indicate a downregulation of the natriuretic peptide system in rat polycystic ovary, an established experimental model of anovulation with high ovarian testosterone and estradiol levels. Together with previous evidence demonstrating that ANP inhibits ovarian steroidogenesis, these findings suggest that low ovarian ANP levels may contribute to the abnormal steroid hormone balance in polycystic ovaries. Copyright © 2014 Elsevier Inc. All rights reserved.

Self-organized huddles of rat pups modeled by simple rules of individual behavior.

PubMed

Schank, J C; Alberts, J R

1997-11-07

Starting at infancy and continuing throughout adult life, huddling is a major component of the behavioral repertoire of Norway rats (Rattus norvegicus). Huddling behavior maintains the cohesion of litters throughout early life, and in adulthood, it remains a consistent feature of social behavior of R. norvegicus. During infancy, rats have severely limited sensorimotor capabilities, and yet they are capable of aggregating and display a form of group regulatory behavior that conserves metabolic effort and augments body temperature regulation. The functions of huddling are generally understood as group adaptations, which are beyond the capabilities of the individual infant rat. We show, however, that huddling as aggregative or cohesive behavior can emerge as a self-organizing process from autonomous individuals following simple sensorimotor rules. In our model, two sets of sensorimotor parameters characterize the topotaxic responses and the dynamics of contact in 7-day-old rats. The first set of parameters are conditional probabilities of activity and inactivity given prior activity or inactivity and the second set are preferences for objects in the infant rat's environment. We found that the behavior of the model and of actual rat pups compare very favorably, demonstrating that the aggregative feature of huddling can emerge from the local sensorimotor interactions of individuals, and that complex group regulatory behaviors in infant rats may also emerge from self-organizing processes. We discuss the model and the underlying approach as a paradigm for investigating the dynamics of social interactions, group behavior, and developmental change.

Experimental non-alcoholic fatty liver disease results in decreased hepatic uptake transporter expression and function in rats

PubMed Central

Fisher, Craig D.; Lickteig, Andrew J.; Augustine, Lisa M.; Oude Elferink, Ronald P.J.; Besselsen, David G.; Erickson, Robert P.; Cherrington, Nathan J.

2009-01-01

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of diagnoses ranging from simple fatty liver (SFL), to non-alcoholic steatohepatitis (NASH). This study aimed to determine the effect of moderate and severe NAFLD on hepatic transporter expression and function in vivo. Rats were fed a high-fat diet (SFL model) or a methionine-choline-deficient diet (NASH model) for eight weeks. Hepatic uptake transporter function was determined by bromosulfophthalein (BSP) disposition. Transporter expression was determined by branched DNA signal amplification assay and western blotting; inflammation was identified by immunostaining of liver slices for interleukin 1 beta (IL-1β). MC- rats showed significant retention of BSP in the plasma when compared to control rats. Hepatic NTCP, OATP1a1, 1a4, 1b2 and 2b1; and OAT 2 and 3 mRNA levels were significantly decreased in high-fat and MC- diet rats when compared to control. Protein expression of OATP1a1 was significantly decreased in high-fat animals, while OATP1a1 and OATP1b2 expression was significantly lower in MC- rats when compared to control. Liver tissue from high-fat and MC- rats stained positive for IL-1β, a pro-inflammatory cytokine known to decrease expression of NTCP, OATP and OAT transporters, suggesting a plausible mechanism for the observed transporter alterations. These data suggest that different stages of NAFLD result in altered hepatic uptake transporter expression that can lead to a functional impairment of xenobiotic uptake from the blood. Furthermore, NAFLD may alter the plasma retention time of clinically relevant drugs that are reliant on these transporters and may increase the potential drug toxicity. PMID:19358839

Rat Models of Cardiovascular Disease Demonstrate Distinctive Pulmonary Gene Expressions for Vascular Response Genes: Impact of Ozone Exposure

EPA Science Inventory

Comparative gene expression profiling of multiple tissues from rat strains with genetic predisposition to diverse cardiovascular diseases (CVD) can help decode the transcriptional program that governs organ-specific functions. We examined expressions of CVD genes in the lungs of ...

Emodin plays an interventional role in epileptic rats via multidrug resistance gene 1 (MDR1).

PubMed

Yang, Tao; Kong, Bin; Kuang, Yongqin; Cheng, Lin; Gu, Jianwen; Zhang, Junhai; Shu, Haifeng; Yu, Sixun; Yang, Xiaokun; Cheng, Jingming; Huang, Haidong

2015-01-01

To observe the interventional effects of emodin in epileptic rats and elucidate its possible mechanism of action. Thirty-six female Wistar rats were randomly divided into normal control group, model group (intraperitoneal injection of kainic acid) and emodin group (intraperitoneal injection of kainic acid+emodin intervention). The rat epilepsy model was confirmed by behavioral tests and electroencephalography. The protein levels of P-glycoprotein and N-methyl-D-aspartate (NMDA) receptor in cerebral vascular tissue were analyzed by western blotting, and mRNA levels of multidrug resistance gene 1 (MDR1) and cyclooxygenase-2 (COX-2) were analyzed by real-time PCR. COX-2 and P-glycoprotein levels in the brains were detected by immunohistochemical assay. The seizures were relieved in emodin group. Laser scanning confocal microscopy showed P-glycoprotein fluorescence increased significantly after seizures, indicating that epilepsy can induce overexpression of P-glycoprotein. Compared with control group, protein levels of P-glycoprotein and NMDA receptor in cerebral vascular tissue were significantly higher in model group, and mRNA levels of MDR1 and COX-2 were also significantly increased. Compared with model group, P-glycoprotein and NMDA receptor levels in cerebral vascular tissue were significantly decreased in emodin group (P<0.05), and the levels of MDR1 and COX-2 were down-regulated (P<0.05). In the rat brain, seizures could significantly increase COX-2 and P-glycoprotein levels, while emodin intervention was able to significantly reduce the levels of both. These findings suggest that epileptic seizures are tightly associated with up-regulated MDR1 gene, and emodin shows good antagonistic effects on epileptic rats, possibly through inhibition of MDR1 gene and its associated genes.

Prenatal administration of neuropeptide bombesin promotes lung development in a rat model of nitrofen-induced congenital diaphragmatic hernia.

PubMed

Sakai, Kohei; Kimura, Osamu; Furukawa, Taizo; Fumino, Shigehisa; Higuchi, Koji; Wakao, Junko; Kimura, Koseki; Aoi, Shigeyoshi; Masumoto, Kouji; Tajiri, Tatsuro

2014-12-01

Fetal medical treatment to improve lung hypoplasia in congenital diaphragmatic hernia (CDH) has yet to be established. The neuropeptide bombesin (BBS) might play an important role in lung development. The present study aims to determine whether prenatally administered BBS could be useful to promote fetal lung development in a rat model of nitrofen-induced CDH. Pregnant rats were administered with nitrofen (100mg) on gestation day 9.5 (E9.5). BBS (50mg/kg/day) was then daily infused intraperitoneally from E14, and fetal lungs were harvested on E21. The expression of PCNA was assessed by both immunohistochemical staining and RT-PCR to determine the amount of cell proliferation. Lung maturity was assessed as the expression of TTF-1, a marker of alveolar epithelial cell type II. The lung-body-weight ratio was significantly increased in CDH/BBS(+) compared with CDH/BBS(-) (p<0.05). The number of cells stained positive for PCNA and TTF-1 was significantly decreased in CDH/BBS(+) compared with CDH/BBS(-) (p<0.01). The TTF-1 mRNA expression levels were significantly decreased in CDH/BBS(+) compared with CDH/BBS(-) (p<0.05). Prenatally administered BBS promotes lung development in a rat model of nitrofen-induced CDH. Neuropeptide BBS could help to rescue lung hypoplasia in fetal CDH. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of colchicine on polycystic ovary syndrome: an experimental study.

PubMed

Gozukara, Ilay Ozturk; Pınar, Neslihan; Ozcan, Oğuzhan; Ozgur, Tumay; Dokuyucu, Recep; Kurt, Raziye Keskin; Kucur, Suna Kabil; Aksoy, Ayşe Nur

2016-03-01

To investigate whether there is any therapeutic effect of colchicine on a rat model of polycystic ovary syndrome (PCOS). Twenty-two Wistar-Albino rats were randomly assigned into four with 8 rats in each group: control group; PCOS only group; PCOS-metformin group and PCOS-colchicine group. PCOS was induced by gavage with letrozole once daily at the concentration of 1 mg/kg orally with 21 consecutive days. After PCOS model assessment, PCOS-metformin group was received metformin orally with 500 mg/kg and PCOS-colchicine group was received colchicine orally with 1 mg/kg for the 35 day. Histopathology of ovaries, circulating estrone (E1), estradiol (E2), total testosterone, androstenedione and c-reactive protein (CRP) levels were evaluated. cystic and atretic follicle number was significantly decreased, but CRP and hormone parameters were not significantly changed with colchicine treatment. Colchicine has provided histopathological improvement compared with metformin in PCOS rat model.

Oxidative stress is not associated with vascular dysfunction in a model of alloxan-induced diabetic rats.

PubMed

Capellini, Verena Kise; Baldo, Caroline Floreoto; Celotto, Andréa Carla; Batalhão, Marcelo Eduardo; Cárnio, Evelin Capellari; Rodrigues, Alfredo José; Evora, Paulo Roberto Barbosa

2010-08-01

To verify if an experimental model of alloxan-diabetic rats promotes oxidative stress, reduces nitric oxide bioavailability and causes vascular dysfunction, and to evaluate the effect of N-acetylcysteine (NAC) on these parameters. Alloxan-diabetic rats were treated or not with NAC for four weeks. Plasmatic levels of malondialdehyde (MDA) and nitrite/nitrate (NOx), the endothelial and inducible nitric oxide synthase (eNOS and iNOS) immunostaining and the vascular reactivity of aorta were compared among diabetic (D), treated diabetic (TD) and control (C) rats. MDA levels increased in D and TD. NOx levels did not differ among groups. Endothelial eNOS immunostaining reduced and adventitial iNOS increased in D and TD. The responsiveness of rings to acetylcholine, sodium nitroprusside, and phenylephrine did not differ among groups. NAC had no effect on the evaluated parameters and this experimental model did not promote vascular dysfunction despite the development of oxidative stress.

[Bushen Huoxue Fang promotes the apoptosis of epithelial cells in the prostatic ductal system of rats with benign prostatic hyperplasia].

PubMed

Sun, Jie; Li, Qiu-Fen; Tian, Dai-Zhi; Jiang, Shao-Bo; Wu, Xian-De; Qiu, Shun-An; Ren, Xiao-Gang; Li, Yu-Bing

2014-09-01

To investigate the effects of Bushen Huoxue Fang (BSHX) on the apoptosis of epithelial cells in the prostatic ductal system of rats with benign prostatic hyperplasia (BPH) and its possible action mechanism. One hundred 3- month-old male Wistar rats were randomly divided into four groups of equal number (control, castrated, BPH model, and BSHX). BPH models were made by subcutaneous injection of testosterone following castration; the rats in the BSHX group were treated intragastrically with BSHX at 2.34 g/ml after modeling, while those in the other two groups with equal volume of saline, all for 37 days. On the 38th day, all the rats were sacrificed and their prostates harvested for detection of the distribution of TGF-beta1 and alpha-actin and the count of positive cells in the prostatic ductal system by immunohistochemical staining. The apoptosis rate of epithelial cells in the prostatic ductal system was determined by TUNEL assay. The expression of TGF-beta1 was significantly increased in the rats of the BSHX group as compared with the BPH models in both the proximal prostatic duct ([15.28 +/- 4.30]% vs [36.42 +/- 8.10]%, P < 0.01) and the distal prostatic duct ([4.42 +/- 2.07]% vs [8.71 +/- 2.28 ]%, P < 0.05), while the expression of alpha-actin in the proximal duct was remarkably higher in the BSHX-treated rats than in the models ([28.14 +/- 7.43]% vs [18.28 +/- 4.07]%, P < 0.01), but lower than in the control animals ([33.57 +/- 6.85]%, P < 0.05). Compared with the control group, the BPH models and BSHX-treated rats both exhibited markedly decreased apoptosis of epithelial cells in the proximal prostatic duct ([39.42 +/- 9.20]% vs [3.86 +/- 1.34]%, P < 0.01, and [31.14 +/- 5.64]%, P < 0.01) and distal prostatic duct ([17.60 +/- 4.86]% vs [3.07 +/- 1.14]%, P < 0.01, and [12.37 +/- 2.25]%, P < 0.05). The apoptosis rate of epithelial cells in the prostatic ductal system was significantly higher in the BSHX-treated rats than in the BPH models (P < 0.01). By upregulating the expression of TGF-beta, BSHX can suppress the reduction of smooth muscle cells in the proximal prostatic duct, promote the apoptosis of prostatic epithelial cells, and thus effectively inhibit benign prostatic hyperplasia.

A UPLC-TOF/MS-based metabolomics study of rattan stems of Schisandra chinensis effects on Alzheimer's disease rats model.

PubMed

Yang, Bing-You; Tan, Jin-Yan; Liu, Yan; Liu, Bo; Jin, Shuang; Guo, Hong-Wei; Kuang, Hai-Xue

2018-02-01

A UPLC-TOF/MS-based metabolomics method was established to explore the therapeutic mechanisms of rattan stems of S. chinensis (SCS) in Alzheimer's disease (AD). Experimental AD model was induced by intra-hippocampal Aβ 1-42 injection in rats. Cognitive function and oxidative stress condition in brain of AD rats were assessed using Morris water maze tests and antioxidant assays [malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)], respectively. UPLC-TOF/MS combined with multivariate statistical analysis were conducted to study the changes in metabolic networks in serum of rats. The results indicated that the AD model was established successfully and the inducement of Aβ 1-42 caused a decline in spatial learning and memory of rats. The injection of Aβ 1-42 in rat brains significantly elevated the level of MDA, and reduced SOD and GSH-Px activities. In addition, SCS showed significant anti-AD effects on model rats. A total of 30 metabolites were finally identified as potential biomarkers of AD and 14 of them had a significant recovery compared with the AD model after SCS administration. Changes in AD metabolite profiling were restored to different levels through the regulation of 13 pathways. This is first report on the use of the UPLC-TOF/MS-based serum metabolomics method to investigate therapeutic effects of SCS on AD, and enrich potential biomarkers and metabolic networks of AD. Copyright © 2017 John Wiley & Sons, Ltd.

Objective validation of central sensitization in the rat UVB and heat rekindling model

PubMed Central

Weerasinghe, NS; Lumb, BM; Apps, R; Koutsikou, S; Murrell, JC

2014-01-01

Background The UVB and heat rekindling (UVB/HR) model shows potential as a translatable inflammatory pain model. However, the occurrence of central sensitization in this model, a fundamental mechanism underlying chronic pain, has been debated. Face, construct and predictive validity are key requisites of animal models; electromyogram (EMG) recordings were utilized to objectively demonstrate validity of the rat UVB/HR model. Methods The UVB/HR model was induced on the heel of the hind paw under anaesthesia. Mechanical withdrawal thresholds (MWTs) were obtained from biceps femoris EMG responses to a gradually increasing pinch at the mid hind paw region under alfaxalone anaesthesia, 96 h after UVB irradiation. MWT was compared between UVB/HR and SHAM-treated rats (anaesthetic only). Underlying central mechanisms in the model were pharmacologically validated by MWT measurement following intrathecal N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801, or saline. Results Secondary hyperalgesia was confirmed by a significantly lower pre-drug MWT {mean [±standard error of the mean (SEM)]} in UVB/HR [56.3 (±2.1) g/mm2, n = 15] compared with SHAM-treated rats [69.3 (±2.9) g/mm2, n = 8], confirming face validity of the model. Predictive validity was demonstrated by the attenuation of secondary hyperalgesia by MK-801, where mean (±SEM) MWT was significantly higher [77.2 (±5.9) g/mm2 n = 7] in comparison with pre-drug [57.8 (±3.5) g/mm2 n = 7] and saline [57.0 (±3.2) g/mm2 n = 8] at peak drug effect. The occurrence of central sensitization confirmed construct validity of the UVB/HR model. Conclusions This study used objective outcome measures of secondary hyperalgesia to validate the rat UVB/HR model as a translational model of inflammatory pain. What's already known about this topic? Most current animal chronic pain models lack translatability to human subjects. Primary hyperalgesia is an established feature of the UVB/heat rekindling inflammatory pain model in rodents and humans, but the presence of secondary hyperalgesia, a hallmark feature of central sensitization and thus chronic pain, is contentious. What does this study add? Secondary hyperalgesia was demonstrated in the rat UVB/heat rekindling model using an objective outcome measure (electromyogram), overcoming the subjective limitations of previous behavioural studies. PMID:24590815

Differential Expression of microRNAs in the Ovaries from Letrozole-Induced Rat Model of Polycystic Ovary Syndrome.

PubMed

Li, Dandan; Li, Chunjin; Xu, Ying; Xu, Duo; Li, Hongjiao; Gao, Liwei; Chen, Shuxiong; Fu, Lulu; Xu, Xin; Liu, Yongzheng; Zhang, Xueying; Zhang, Jingshun; Ming, Hao; Zheng, Lianwen

2016-04-01

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disorder. To understand the pathogenesis of PCOS, we established rat models of PCOS induced by letrozole and employed deep sequencing to screen the differential expression of microRNAs (miRNAs) in PCOS rats and control rats. We observed vaginal smear and detected ovarian pathological alteration and hormone level changes in PCOS rats. Deep sequencing showed that a total of 129 miRNAs were differentially expressed in the ovaries from letrozole-induced rat model compared with the control, including 49 miRNAs upregulated and 80 miRNAs downregulated. Furthermore, the differential expression of miR-201-5p, miR-34b-5p, miR-141-3p, and miR-200a-3p were confirmed by real-time polymerase chain reaction. Bioinformatic analysis revealed that these four miRNAs were predicted to target a large set of genes with different functions. Pathway analysis supported that the miRNAs regulate oocyte meiosis, mitogen-activated protein kinase (MAPK) signaling, phosphoinositide 3-kinase/Akt (PI3K-Akt) signaling, Rap1 signaling, and Notch signaling. These data indicate that miRNAs are differentially expressed in rat PCOS model and the differentially expressed miRNA are involved in the etiology and pathophysiology of PCOS. Our findings will help identify miRNAs as novel diagnostic markers and therapeutic targets for PCOS.

Changes in erectile organ structure and function in a rat model of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Wang, X-J; Xia, L-L; Xu, T-Y; Zhang, X-H; Zhu, Z-W; Zhang, M-G; Liu, Y; Xu, C; Zhong, S; Shen, Z-J

2016-04-01

There is a growing recognition of the association between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED); however, most of the reports are based on questionnaires which cannot distinguish between organic and functional ED. The purpose of this study was to determine the exact relationship between CP/CPPS and ED, and to investigate the changes in erectile organ structure and function in a rat model of CP/CPPS. We established a rat model of experimental autoimmune prostatitis (EAP), which is a valid model for CP/CPPS. Erectile function in EAP and normal rats was comparable after cavernous nerve electrostimulation. The serum testosterone and oestradiol levels, ultrastructure of the corpus cavernosum and expression of endothelial nitric oxide synthase and neuronal nitric oxide synthase in the two groups were similar; however, there was a decrease in smooth muscle-to-collagen ratio and alpha-smooth muscle actin expression and an increase in transforming growth factor-beta 1 expression was observed in EAP rats. Thus, organic ED may not exist in EAP rats. We speculate that ED complained by patients with CP/CPPS may be psychological, which could be caused by impairment in the quality of life; however, further studies are needed to fully understand the potential mechanisms underlying the penile fibrosis in EAP rats. © 2015 Blackwell Verlag GmbH.

Additive effect of mesenchymal stem cells and defibrotide in an arterial rat thrombosis model.

PubMed

Dilli, Dilek; Kılıç, Emine; Yumuşak, Nihat; Beken, Serdar; Uçkan Çetinkaya, Duygu; Karabulut, Ramazan; Zenciroğlu, Ayşegu L

2017-06-01

In this study, we aimed to investigate the additive effect of mesenchymal stem cells (MSC) and defibrotide (DFT) in a rat model of femoral arterial thrombosis. Thirty Sprague Dawley rats were included. An arterial thrombosis model by ferric chloride (FeCl3) was developed in the left femoral artery. The rats were equally assigned to 5 groups: Group 1-Sham-operated (without arterial injury); Group 2-Phosphate buffered saline (PBS) injected; Group 3-MSC; Group 4-DFT; Group 5-MSC + DFT. All had two intraperitoneal injections of 0.5 ml: the 1st injection was 4 h after the procedure and the 2nd one 48 h after the 1st injection. The rats were sacrificed 7 days after the 2nd injection. Although the use of human bone marrow-derived (hBM) hBM-MSC or DFT alone enabled partial resolution of the thrombus, combining them resulted in near-complete resolution. Neovascularization was two-fold better in hBM-MSC + DFT treated rats (11.6 ± 2.4 channels) compared with the hBM-MSC (3.8 ± 2.7 channels) and DFT groups (5.5 ± 1.8 channels) (P < 0.0001 and P= 0.002, respectively). The combined use of hBM-MSC and DFT in a rat model of arterial thrombosis showed additive effect resulting in near-complete resolution of the thrombus.

Lack of Antidepressant Effects of (2R,6R)-Hydroxynorketamine in a Rat Learned Helplessness Model: Comparison with (R)-Ketamine

PubMed Central

Shirayama, Yukihiko

2018-01-01

Abstract Background (R)-Ketamine exhibits rapid and sustained antidepressant effects in animal models of depression. It is stereoselectively metabolized to (R)-norketamine and subsequently to (2R,6R)-hydroxynorketamine in the liver. The metabolism of ketamine to hydroxynorketamine was recently demonstrated to be essential for ketamine’s antidepressant actions. However, no study has compared the antidepressant effects of these 3 compounds in animal models of depression. Methods The effects of a single i.p. injection of (R)-ketamine, (R)-norketamine, and (2R,6R)-hydroxynorketamine in a rat learned helplessness model were examined. Results A single dose of (R)-ketamine (20 mg/kg) showed an antidepressant effect in the rat learned helplessness model. In contrast, neither (R)-norketamine (20 mg/kg) nor (2R,6R)-hydroxynorketamine (20 and 40 mg/kg) did so. Conclusions Unlike (R)-ketamine, its metabolite (2R,6R)-hydroxynorketamine did not show antidepressant actions in the rat learned helplessness model. Therefore, it is unlikely that the metabolism of ketamine to hydroxynorketamine is essential for ketamine’s antidepressant actions. PMID:29155993

Protective effect of co-administration of rosuvastatin and probucol on atherosclerosis in rats.

PubMed

Chen, Zuoyuan; Li, Shan; Zhao, Wenna; Chen, Xiuhua; Wang, Xiaxia

2014-10-01

This study aimed to study the combined effect of rosuvastatin and probucol on atherosclerosis (AS) in rats. In total, 95 male Wistar rats were divided into 5 groups: 25 in the control group (A), 25 in the model group (B), 15 in the rosuvastatin group (C), 15 in the probucol group (D), and 15 in the rosuvastatin combined probucol group (E). A high-lipid diet and vitamin D3 were administered to establish AS rat model. Groups C, D, and E received corresponding drugs. Blood lipids, oxidized low-density lipoprotein (OX-LDL), malonaldehyde (MDA), superoxide dismutase (SOD), adiponectin (APN), and vascular endothelial cadherin (VE-cadherin) were measured. Platelet endothelial cell adhesion molecule-1 (PECAM-1) was detected by immune histochemistry. In groups B-E, AS rat models were successfully constructed. In groups C-E, blood lipids, OX-LDL, VE-cadherin, MDA, PECAM-1, and intimal thickness were decreased (p < 0.01), while SOD and APN were increased (p < 0.05), compared with that in group B. Furthermore, group E had lower levels of OX-LDL, MDA, and PECAM-1 but higher levels of SOD and APN and attenuated intimal thickening compared with groups C or D (p < 0.05). Administering rosuvastatin and probucol could attenuate AS lesions through modulation of oxidative stress, PECAM-1, and APN. Both drugs might help slow the progression of AS.

Treatment of 9L gliosarcoma in rats by ferrociphenol-loaded lipid nanocapsules based on a passive targeting strategy via the EPR effect.

PubMed

Huynh, Ngoc Trinh; Morille, Marie; Bejaud, Jerome; Legras, Pierre; Vessieres, Anne; Jaouen, Gerard; Benoit, Jean-Pierre; Passirani, Catherine

2011-12-01

To study a passive targeting strategy, via the enhanced permeability and retention effect following systemic administration of lipid nanocapsules (LNCs) loaded with ferrociphenol, FcdiOH. Long chains of polyethylene glycol (DSPE-mPEG2000) were incorporated onto the surface of LNCs by post-insertion technique. Stealth properties of LNCs were investigated by in vitro complement consumption and macrophage uptake, and in vivo pharmacokinetics in healthy rats. Antitumour effect of FcdiOH-loaded LNCs was evaluated in subcutaneous and intracranial 9L gliosarcoma rat models. LNCs and DSPE-mPEG2000-LNCs presented low complement activation and weak macrophage uptake. DSPE-mPEG2000-LNCs exhibited prolonged half-life and extended area under the curve in healthy rats. In a subcutaneous gliosarcoma model, a single intravenous injection of FcdiOH-LNCs (400 μL, 2.4 mg/rat) considerably inhibited tumour growth when compared to the control. DSPE-mPEG2000-FcdiOH-LNCs exhibited a strong antitumour effect by nearly eradicating the tumour by the end of the study. In intracranial gliosarcoma model, treatment with DSPE-mPEG2000-FcdiOH-LNCs and FcdiOH-LNCs statistically improved median survival time (28 and 27.5 days, respectively) compared to the control (25 days). These results demonstrate the interesting perspectives for the systemic treatment of glioma thanks to bio-organometallic chemotherapy via lipid nanocapsules.

Validation and quantification of [18F]altanserin binding in the rat brain using blood input and reference tissue modeling

PubMed Central

Riss, Patrick J; Hong, Young T; Williamson, David; Caprioli, Daniele; Sitnikov, Sergey; Ferrari, Valentina; Sawiak, Steve J; Baron, Jean-Claude; Dalley, Jeffrey W; Fryer, Tim D; Aigbirhio, Franklin I

2011-01-01

The 5-hydroxytryptamine type 2a (5-HT2A) selective radiotracer [18F]altanserin has been subjected to a quantitative micro-positron emission tomography study in Lister Hooded rats. Metabolite-corrected plasma input modeling was compared with reference tissue modeling using the cerebellum as reference tissue. [18F]altanserin showed sufficient brain uptake in a distribution pattern consistent with the known distribution of 5-HT2A receptors. Full binding saturation and displacement was documented, and no significant uptake of radioactive metabolites was detected in the brain. Blood input as well as reference tissue models were equally appropriate to describe the radiotracer kinetics. [18F]altanserin is suitable for quantification of 5-HT2A receptor availability in rats. PMID:21750562

[Metabolic Characteristics of Lethal Bradycardia Induced by Myocardial Ischemia].

PubMed

Wu, J Y; Wang, D; Kong, J; Wang, X X; Yu, X J

2017-02-01

To explore the metabolic characteristics of lethal bradycardia induced by myocardial ischemia in rat's serum. A rat myocardial ischemia-bradycardia-sudden cardiac death （MI-B-SCD） model was established, which was compared with the sham-operation group. The metabolic profile of postmortem serum was analyzed by gas chromatography-mass spectrometry （GC-MS）, coupled with the analysis of serum metabolic characteristics using metabolomics strategies. The serum metabolic profiles were significantly different between the MI-B-SCD rats and the control rats. Compared to the control rats, the MI-B-SCD rats had significantly higher levels of lysine, ornithine, purine, serine, alanine, urea and lactic acid; and significantly lower levels of succinate, hexadecanoic acid, 2-ketoadipic acid, glyceraldehyde, hexendioic acid and octanedioic acid in the serum. There were some correlations among different metabolites. There is obvious metabolic alterations in the serum of MI-B-SCD rat. Both lysine and purine have a high value in diagnosing MI-B-SCD. The results are expected to provide references for forensic and clinical applications of prevention and control of sudden cardiac death. Copyright© by the Editorial Department of Journal of Forensic Medicine

A comparison of novel, selective fatty acid amide hydrolase (FAAH), monoacyglycerol lipase (MAGL) or dual FAAH/MAGL inhibitors to suppress acute and anticipatory nausea in rat models.

PubMed

Parker, Linda A; Limebeer, Cheryl L; Rock, Erin M; Sticht, Martin A; Ward, Jordan; Turvey, Greig; Benchama, Othman; Rajarshi, Girija; Wood, JodiAnne T; Alapafuja, Shakiru O; Makriyannis, Alexandros

2016-06-01

Drugs that block fatty acid amide hydrolase (FAAH, which elevates anandamide [AEA]) and drugs which block monoacylglycerol (MAGL, which elevates 2-arachidonyl glycerol [2-AG]) have promise in treating both acute and anticipatory nausea in human patients. This study aims to evaluate the relative effectiveness of dual MAGL/FAAH inhibition with either alone to reduce acute and anticipatory nausea in rat models. AM4302, a new dual MAGL/FAAH inhibitor, was compared with a new selective MAGL inhibitor, AM4301, and new selective FAAH inhibitor, AM4303, for their potential to reduce acute nausea (gaping in taste reactivity) and anticipatory nausea (contextually elicited conditioned gaping) in two rat models. Our in vitro studies indicate that AM4302 blocks human and rat FAAH: IC50 60 and 31 nM, respectively, with comparable potencies against human MAGL (IC50 41 nM) and rat MAGL (IC50 200 nM). AM4301 selectively blocks human and rat MAGL (IC50 8.9 and 36 nM, respectively), while AM4303 selectively inhibits human and rat FAAH (IC50 2 and 1.9 nM), respectively. Our in vivo studies show that the MAGL inhibitor, AM4301, suppressed acute nausea in a CB1-mediated manner, when delivered systemically or into the interoceptive insular cortex. Although the dual FAAH/MAGL inhibitor, AM4302, was equally effective as the FAAH inhibitor or MAGL inhibitor in reducing acute nausea, it was more effective than both in suppressing anticipatory nausea. Dual FAAH and MAGL inhibition with AM4302 may be an especially effective treatment for the very difficult to treat symptom of anticipatory nausea.

A comparison of novel, selective fatty acid amide hydrolase (FAAH), monoacyglycerol lipase (MAGL) or dual FAAH/MAGL inhibitors to suppress acute and anticipatory nausea in rat models

PubMed Central

Limebeer, Cheryl L.; Rock, Erin M.; Sticht, Martin A.; Ward, Jordan; Turvey, Greig; Benchama, Othman; Rajarshi, Girija; Wood, JodiAnne T.; Alapafuja, Shakiru O.; Makriyannis, Alexandros

2017-01-01

Rationale Drugs that block fatty acid amide hydrolase (FAAH, which elevates anandamide [AEA]) and drugs which block monoacylglycerol (MAGL, which elevates 2-arachidonyl glycerol [2-AG]) have promise in treating both acute and anticipatory nausea in human patients. Objective This study aims to evaluate the relative effectiveness of dual MAGL/FAAH inhibition with either alone to reduce acute and anticipatory nausea in rat models. Materials and methods AM4302, a new dual MAGL/FAAH inhibitor, was compared with a new selective MAGL inhibitor, AM4301, and new selective FAAH inhibitor, AM4303, for their potential to reduce acute nausea (gaping in taste reactivity) and anticipatory nausea (contextually elicited conditioned gaping) in two rat models. Results Our in vitro studies indicate that AM4302 blocks human and rat FAAH: IC50 60 and 31 nM, respectively, with comparable potencies against human MAGL (IC50 41 nM) and rat MAGL (IC50 200 nM). AM4301 selectively blocks human and rat MAGL (IC50 8.9 and 36 nM, respectively), while AM4303 selectively inhibits human and rat FAAH (IC50 2 and 1.9 nM), respectively. Our in vivo studies show that the MAGL inhibitor, AM4301, suppressed acute nausea in a CB1-mediated manner, when delivered systemically or into the interoceptive insular cortex. Although the dual FAAH/MAGL inhibitor, AM4302, was equally effective as the FAAH inhibitor or MAGL inhibitor in reducing acute nausea, it was more effective than both in suppressing anticipatory nausea. Conclusions Dual FAAH and MAGL inhibition with AM4302 may be an especially effective treatment for the very difficult to treat symptom of anticipatory nausea. PMID:27048155

Short Oxygenated Warm Perfusion With Prostaglandin E1 Administration Before Cold Preservation as a Novel Resuscitation Method for Liver Grafts From Donors After Cardiac Death in a Rat In Vivo Model.

PubMed

Maida, Kai; Akamatsu, Yorihiro; Hara, Yasuyuki; Tokodai, Kazuaki; Miyagi, Shigehito; Kashiwadate, Toshiaki; Miyazawa, Koji; Kawagishi, Naoki; Ohuchi, Noriaki

2016-05-01

We previously demonstrated that short oxygenated warm perfusion (SOWP) prevented warm ischemia-reperfusion injury in rat livers from donors after cardiac death (DCDs) in an ex vivo model. In the present study, we aimed to examine the in vivo effects of SOWP and SOWP with prostaglandin E1 (PGE1) in DCD rat liver transplants. We performed liver transplantation after 6-hour cold preservation using grafts retrieved from DCD rats, divided into nontreatment (NT), SOWP, and SOWP with PGE1 (SOWP + PG) treatment groups. The SOWP grafts were perfused with oxygenated buffer at 37°C for 30 minutes before cold preservation. Prostaglandin E1 was added to the SOWP + PG group perfusate. Eleven liver transplants from each group were performed to evaluate graft function and survival; 5 rats were used for data collection after 1-hour reperfusion, and 6 rats were used for the survival study. As a positive control, the same experiment was performed in a heart-beating donor group. In both the SOWP and SOWP + PG groups, serum liver enzymes, intercellular adhesion molecule 1 levels, and cellular damage were significantly decreased compared with the NT group. In the SOWP + PG group, bile production and energy status were significantly improved compared with the NT group. The 4-week survival was 0% (0/6), 67% (4/6), 83% (5/6), and 100% (6/6) in the NT, SOWP, SOWP + PG, and heart-beating donor group, respectively. Short oxygenated warm perfusion before cold preservation and the addition of PGE1 to SOWP were thus beneficial in an in vivo rat model.

[Nephro-protective effects of total triterpenoids from Psidium guajava leaves on type 2 diabetic rats].

PubMed

Kuang, Qiao-Ting; Zhao, Jing-Jing; Ye, Chun-Ling; Wang, Jing-Ru; Ye, Kai-He; Zhang, Xiao-Qi; Wang, Ying; Ye, Wen-Cai

2012-01-01

To investigate the nephro-protective effects of total triterpenoids from Psidium guajava leaves (TTPGL) on type 2 diabetic rats. Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 35 mg/kg) and a high-fat diet. Diabetic rats were divided into five groups: diabetic model control, low-dose TTPGL-treated (60 mg/kg, L-TTPGL), medium-dose TTPGL-treated (120 mg/kg, M-TTPGL), high-dose TTPGL-treated (240 mg/kg, H-TTPGL) and rosiglitazone-treated (3 mg/kg, RSG). The rats received daily treatment for six weeks. At the end of the period,the levels of fasting blood glucose (FPG), fasting insulin (FINS), creatinine (Cr) and blood urea nitrogen (BUN) in serum were measured. Kidneys for histopathological evaluation were stained with Hematoxylin and Eosin (HE). Compared with normal control group, the level of FPG was increased, the insulin and insulin sensitivity index were decreased in the model group; The levels of BUN and Cr were increased with histopathological changes related to diabetic nephropathy in the kidney, which were the glomerular endothelium and mesangial cell proliferation, capillary narrowed, the base-membrane incrassation, glomerular swelling, cysts narrowed and tubules edema. Compared with the model group, the levels of FPG were decreased, serum insulin and insulin sensitivity index were increased significantly in M-TTPGL and H-TTPGL groups (P<0.01 or P<0.05); The levels of BUN and Cr were decreased significantly (P<0.01 or P<0.05) and the renal structural damages were improved significantly. TTPGL could decrease the level of blood glucose of diabetic rat effectively, increase the insulin sensitivity index and protect renal lesions in diabetic rats.

Speech sound discrimination training improves auditory cortex responses in a rat model of autism

PubMed Central

Engineer, Crystal T.; Centanni, Tracy M.; Im, Kwok W.; Kilgard, Michael P.

2014-01-01

Children with autism often have language impairments and degraded cortical responses to speech. Extensive behavioral interventions can improve language outcomes and cortical responses. Prenatal exposure to the antiepileptic drug valproic acid (VPA) increases the risk for autism and language impairment. Prenatal exposure to VPA also causes weaker and delayed auditory cortex responses in rats. In this study, we document speech sound discrimination ability in VPA exposed rats and document the effect of extensive speech training on auditory cortex responses. VPA exposed rats were significantly impaired at consonant, but not vowel, discrimination. Extensive speech training resulted in both stronger and faster anterior auditory field (AAF) responses compared to untrained VPA exposed rats, and restored responses to control levels. This neural response improvement generalized to non-trained sounds. The rodent VPA model of autism may be used to improve the understanding of speech processing in autism and contribute to improving language outcomes. PMID:25140133

The Effects of Dietary Iron and Capsaicin on Hemoglobin, Blood Glucose, Insulin Tolerance, Cholesterol, and Triglycerides, in Healthy and Diabetic Wistar Rats.

PubMed

Márquez-Ibarra, Adriana; Huerta, Miguel; Villalpando-Hernández, Salvador; Ríos-Silva, Mónica; Díaz-Reval, María I; Cruzblanca, Humberto; Mancilla, Evelyn; Trujillo, Xóchitl

2016-01-01

Our aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance. Our animal model was the Wistar rat, fed a chow diet, with or without experimentally induced diabetes. Diabetic males were fed control, low, or high-iron diets, the latter, with or without capsaicin. Healthy rats were fed identical diets, but without the capsaicin supplement. We then measured the parameters listed above, using the Student t-test and ANOVA, to compare groups. Healthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable for the treatment of elevated hemoglobin, in patients.

[Expression of aquaporin-4 during brain edema in rats with thioacetamide-induced acute encephalopathy].

PubMed

Wang, Li-Qing; Zhu, Sheng-Mei; Zhou, Heng-Jun; Pan, Cai-Fei

2011-09-27

To investigate the expression of aquaporin-4 (AQP4) during brain edema in rats with thioacetamide-induced acute liver failure and encephalopathy. The rat model of acute hepatic failure and encephalopathy was induced by intraperitoneal injection of thioacetamide (TAA) at a 24-hour interval for 2 consecutive days. Thirty-two SD rats were randomly divided into the model group (n = 24) and the control group (normal saline, n = 8). And then the model group was further divided into 3 subgroups by the timepoint of decapitation: 24 h (n = 8), 48 h (n = 8) and 60 h (n = 8). Then we observed their clinical symptoms and stages of HE, indices of liver function and ammonia, liver histology and brain water content. The expression of AQP4 protein in brain tissues was measured with Western blot and the expression of AQP4mRNA with RT-PCR (reverse transcription-polymerase chain reaction). Typical clinical manifestations of hepatic encephalopathy occurred in all TAA-administrated rats. The model rats showed the higher indices of ALT (alanine aminotransferase), AST (aspartate aminotransferase), TBIL (total bilirubin) and ammonia than the control rats (P < 0.05). The brain water content was significantly elevated in TAA-administrated rats compared with the control (P < 0.05). The expressions of AQP4 protein and mRNA in brain tissues significantly increased in TAA-administrated rats (P < 0.05). In addition, the expressions of AQP4 protein and mRNA were positively correlated with brain water content (r = 0.536, P < 0.01; r = 0.566, P = 0.01). The high expression of AQP4 in rats with TAA-induced acute liver failure and encephalopathy plays a significant role during brain edema. AQP4 is one of the molecular mechanisms for the occurrence of brain edema in hepatic encephalopathy.

Exaggerated Acute Lung Injury and Impaired Antibacterial Defenses During Staphylococcus aureus Infection in Rats with the Metabolic Syndrome

PubMed Central

Feng, Xiaomei; Maze, Mervyn; Koch, Lauren G.; Britton, Steven L.; Hellman, Judith

2015-01-01

Rats with Metabolic Syndrome (MetaS) have a dysregulated immune response to the aseptic trauma of surgery. We hypothesized that rats with MetaS would have dysregulated inflammation, increased lung injury, and less effective antibacterial defenses during Staphylococcus (S.) aureus sepsis as compared to rats without MetaS. Low capacity runner (LCR; a model of MetaS) and high capacity runner (HCR) rats were challenged intravenously with S. aureus bacteria. After 48 h, inflammatory mediators and bacteria were quantified in the blood, bronchoalveolar lavage fluid (BALF), and lung homogenates. Lungs were analyzed histologically. BALF protein and lung wet-dry ratios were quantified to assess for vascular leak. Endpoints were compared in infected LCR vs HCR rats. LCR rats had higher blood and lung S. aureus counts, as well as higher levels of IL-6 in plasma, lungs and BALF, MIP-2 in plasma and lung, and IL-17A in lungs. Conversely, LCR rats had lower levels of IL-10 in plasma and lungs. Although lactate levels, and liver and renal function tests were similar between groups, LCR rats had higher BALF protein and lung wet-dry ratios, and more pronounced acute lung injury histologically. During S. aureus bacteremia, as compared with HCR rats, LCR (MetaS) rats have heightened pro-inflammatory responses, accompanied by increased acute lung injury and vascular leak. Notably, despite an augmented pro-inflammatory phenotype, LCR rats have higher bacterial levels in their blood and lungs. The MetaS state may exacerbate lung injury and vascular leak by attenuating the inflammation-resolving response, and by weakening antimicrobial defenses. PMID:25978669

Elabela/Toddler Is an Endogenous Agonist of the Apelin APJ Receptor in the Adult Cardiovascular System, and Exogenous Administration of the Peptide Compensates for the Downregulation of Its Expression in Pulmonary Arterial Hypertension

PubMed Central

Yang, Peiran; Read, Cai; Kuc, Rhoda E.; Buonincontri, Guido; Southwood, Mark; Torella, Rubben; Upton, Paul D.; Crosby, Alexi; Sawiak, Stephen J.; Carpenter, T. Adrian; Glen, Robert C.; Morrell, Nicholas W.; Maguire, Janet J.

2017-01-01

Background: Elabela/toddler (ELA) is a critical cardiac developmental peptide that acts through the G-protein–coupled apelin receptor, despite lack of sequence similarity to the established ligand apelin. Our aim was to investigate the receptor pharmacology, expression pattern, and in vivo function of ELA peptides in the adult cardiovascular system, to seek evidence for alteration in pulmonary arterial hypertension (PAH) in which apelin signaling is downregulated, and to demonstrate attenuation of PAH severity with exogenous administration of ELA in a rat model. Methods: In silico docking analysis, competition binding experiments, and downstream assays were used to characterize ELA receptor binding in human heart and signaling in cells expressing the apelin receptor. ELA expression in human cardiovascular tissues and plasma was determined using real-time quantitative polymerase chain reaction, dual-labeling immunofluorescent staining, and immunoassays. Acute cardiac effects of ELA-32 and [Pyr1]apelin-13 were assessed by MRI and cardiac catheterization in anesthetized rats. Cardiopulmonary human and rat tissues from PAH patients and monocrotaline- and Sugen/hypoxia-exposed rats were used to show changes in ELA expression in PAH. The effect of ELA treatment on cardiopulmonary remodeling in PAH was investigated in the monocrotaline rat model. Results: ELA competed for binding of apelin in human heart with overlap for the 2 peptides indicated by in silico modeling. ELA activated G-protein– and β-arrestin–dependent pathways. We detected ELA expression in human vascular endothelium and plasma. Comparable to apelin, ELA increased cardiac contractility, ejection fraction, and cardiac output and elicited vasodilatation in rat in vivo. ELA expression was reduced in cardiopulmonary tissues from PAH patients and PAH rat models, respectively. ELA treatment significantly attenuated elevation of right ventricular systolic pressure and right ventricular hypertrophy and pulmonary vascular remodeling in monocrotaline-exposed rats. Conclusions: These results show that ELA is an endogenous agonist of the human apelin receptor, exhibits a cardiovascular profile comparable to apelin, and is downregulated in human disease and rodent PAH models, and exogenous peptide can reduce the severity of cardiopulmonary remodeling and function in PAH in rats. This study provides additional proof of principle that an apelin receptor agonist may be of therapeutic use in PAH in humans. PMID:28137936

Elabela/Toddler Is an Endogenous Agonist of the Apelin APJ Receptor in the Adult Cardiovascular System, and Exogenous Administration of the Peptide Compensates for the Downregulation of Its Expression in Pulmonary Arterial Hypertension.

PubMed

Yang, Peiran; Read, Cai; Kuc, Rhoda E; Buonincontri, Guido; Southwood, Mark; Torella, Rubben; Upton, Paul D; Crosby, Alexi; Sawiak, Stephen J; Carpenter, T Adrian; Glen, Robert C; Morrell, Nicholas W; Maguire, Janet J; Davenport, Anthony P

2017-03-21

Elabela/toddler (ELA) is a critical cardiac developmental peptide that acts through the G-protein-coupled apelin receptor, despite lack of sequence similarity to the established ligand apelin. Our aim was to investigate the receptor pharmacology, expression pattern, and in vivo function of ELA peptides in the adult cardiovascular system, to seek evidence for alteration in pulmonary arterial hypertension (PAH) in which apelin signaling is downregulated, and to demonstrate attenuation of PAH severity with exogenous administration of ELA in a rat model. In silico docking analysis, competition binding experiments, and downstream assays were used to characterize ELA receptor binding in human heart and signaling in cells expressing the apelin receptor. ELA expression in human cardiovascular tissues and plasma was determined using real-time quantitative polymerase chain reaction, dual-labeling immunofluorescent staining, and immunoassays. Acute cardiac effects of ELA-32 and [Pyr 1 ]apelin-13 were assessed by MRI and cardiac catheterization in anesthetized rats. Cardiopulmonary human and rat tissues from PAH patients and monocrotaline- and Sugen/hypoxia-exposed rats were used to show changes in ELA expression in PAH. The effect of ELA treatment on cardiopulmonary remodeling in PAH was investigated in the monocrotaline rat model. ELA competed for binding of apelin in human heart with overlap for the 2 peptides indicated by in silico modeling. ELA activated G-protein- and β-arrestin-dependent pathways. We detected ELA expression in human vascular endothelium and plasma. Comparable to apelin, ELA increased cardiac contractility, ejection fraction, and cardiac output and elicited vasodilatation in rat in vivo. ELA expression was reduced in cardiopulmonary tissues from PAH patients and PAH rat models, respectively. ELA treatment significantly attenuated elevation of right ventricular systolic pressure and right ventricular hypertrophy and pulmonary vascular remodeling in monocrotaline-exposed rats. These results show that ELA is an endogenous agonist of the human apelin receptor, exhibits a cardiovascular profile comparable to apelin, and is downregulated in human disease and rodent PAH models, and exogenous peptide can reduce the severity of cardiopulmonary remodeling and function in PAH in rats. This study provides additional proof of principle that an apelin receptor agonist may be of therapeutic use in PAH in humans. © 2017 The Authors.

Characterization of enamel caries lesions in rat molars using synchrotron X-ray microtomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Free, R. D.; DeRocher, K.; Stock, S. R.

Dental caries is a ubiquitous infectious disease with a nearly 100% lifetime prevalence. Rodent caries models are widely used to investigate the etiology, progression and potential prevention or treatment of the disease. To explore the suitability of these models for deeper investigations of intact surface zones during enamel caries, the structures of early-stage carious lesions in rats were characterized and compared with previous reports on white spot enamel lesions in humans. Synchrotron X-ray microcomputed tomography non-destructively mapped demineralization in carious rat molar specimens across a range of caries severity, identifying 52 lesions across the 30 teeth imaged. Of these lesions,more » 13 were shown to have intact surface zones. Depth profiles of fractional mineral density were qualitatively similar to lesions in human teeth. However, the thickness of the surface zone in the rat model ranges from 10 to 58 µm, and is therefore significantly thinner than in human enamel. These results indicate that a fraction of lesions in rat caries possess an intact surface zone and are qualitatively similar to human lesions at the micrometer scale. This suggests that rat caries models may be a suitable analog through which to investigate the structure of surface zone enamel and its role during dental caries.« less

Usefulness of a New Gelatin Glue Sealant System for Dural Closure in a Rat Durotomy Model

PubMed Central

KAWAI, Hisashi; NAKAGAWA, Ichiro; NISHIMURA, Fumihiko; MOTOYAMA, Yasushi; PARK, Young-Su; NAKAMURA, Mitsutoshi; NAKASE, Hiroyuki; SUZUKI, Shuko; IKADA, Yoshito

2014-01-01

Watertight dural closure is imperative after neurosurgical procedures, because inadequately treated leakage of cerebrospinal fluid (CSF) can have serious consequences. We used a rat durotomy model to test the usefulness of a new gelatin glue as a dural sealant in a rat model of transdural CSF leakage. All rats were randomly divided into one of the following three treatment groups: no application (control group: N = 18), application of fibrin glue (fibrin glue group: N = 18), and application of the new gelatin glue (new gelatin glue group: N = 18). The craniotomy side was re-opened, and CSF leakage was checked and recorded at 1, 7, and 28 days postoperatively. The new gelatin glue was adequate for stopping CSF leakage; no leakage was observed at postoperative days 1 or 7, and leakage was observed in only one rat at postoperative day 28. This result was statistically significant when compared to the control group (P = 0.002, P = 0.015, P = 0.015, respectively). The pathologic score of the new gelatin group was not different from that of the control or fibrin glue groups. We conclude that our new gelatin glue provides effective watertight closure 1, 7, and 28 days after operation in the rat durotomy model. PMID:25070015

A comparative evaluation of models to predict human intestinal metabolism from nonclinical data

PubMed Central

Yau, Estelle; Petersson, Carl; Dolgos, Hugues

2017-01-01

Abstract Extensive gut metabolism is often associated with the risk of low and variable bioavailability. The prediction of the fraction of drug escaping gut wall metabolism as well as transporter‐mediated secretion (F g) has been challenged by the lack of appropriate preclinical models. The purpose of this study is to compare the performance of models that are widely employed in the pharmaceutical industry today to estimate F g and, based on the outcome, to provide recommendations for the prediction of human F g during drug discovery and early drug development. The use of in vitro intrinsic clearance from human liver microsomes (HLM) in three mechanistic models – the ADAM, Q gut and Competing Rates – was evaluated for drugs whose metabolism is dominated by CYP450s, assuming that the effect of transporters is negligible. The utility of rat as a model for human F g was also explored. The ADAM, Q gut and Competing Rates models had comparable prediction success (70%, 74%, 69%, respectively) and bias (AFE = 1.26, 0.74 and 0.81, respectively). However, the ADAM model showed better accuracy compared with the Q gut and Competing Rates models (RMSE =0.20 vs 0.30 and 0.25, respectively). Rat is not a good model (prediction success =32%, RMSE =0.48 and AFE = 0.44) as it seems systematically to under‐predict human F g. Hence, we would recommend the use of rat to identify the need for F g assessment, followed by the use of HLM in simple models to predict human F g. © 2017 Merck KGaA. Biopharmaceutics & Drug Disposition Published by John Wiley & Sons, Ltd. PMID:28152562

A comparative evaluation of models to predict human intestinal metabolism from nonclinical data.

PubMed

Yau, Estelle; Petersson, Carl; Dolgos, Hugues; Peters, Sheila Annie

2017-04-01

Extensive gut metabolism is often associated with the risk of low and variable bioavailability. The prediction of the fraction of drug escaping gut wall metabolism as well as transporter-mediated secretion (F g ) has been challenged by the lack of appropriate preclinical models. The purpose of this study is to compare the performance of models that are widely employed in the pharmaceutical industry today to estimate F g and, based on the outcome, to provide recommendations for the prediction of human F g during drug discovery and early drug development. The use of in vitro intrinsic clearance from human liver microsomes (HLM) in three mechanistic models - the ADAM, Q gut and Competing Rates - was evaluated for drugs whose metabolism is dominated by CYP450s, assuming that the effect of transporters is negligible. The utility of rat as a model for human F g was also explored. The ADAM, Q gut and Competing Rates models had comparable prediction success (70%, 74%, 69%, respectively) and bias (AFE = 1.26, 0.74 and 0.81, respectively). However, the ADAM model showed better accuracy compared with the Q gut and Competing Rates models (RMSE =0.20 vs 0.30 and 0.25, respectively). Rat is not a good model (prediction success =32%, RMSE =0.48 and AFE = 0.44) as it seems systematically to under-predict human F g . Hence, we would recommend the use of rat to identify the need for F g assessment, followed by the use of HLM in simple models to predict human F g . © 2017 Merck KGaA. Biopharmaceutics & Drug Disposition Published by John Wiley & Sons, Ltd. © 2017 Merck KGaA. Biopharmaceutics & Drug Disposition Published by John Wiley & Sons, Ltd.

Effect of alpha lipoic acid on intracerebroventricular streptozotocin model of cognitive impairment in rats.

PubMed

Sharma, Monisha; Gupta, Y K

2003-08-01

In the present study, the effect of alpha lipoic acid, a potent free radical scavenger, was investigated against the intracerebroventricular streptozotocin model of cognitive impairment in rats, which is characterized by a progressive deterioration of memory, cerebral glucose and energy metabolism, and oxidative stress. Wistar rats were injected with intracerebroventricular streptozotocin bilaterally. The rats were treated chronically with alpha lipoic acid (50, 100 and 200 mg/kg) orally for 21 days starting from day 1 of streptozotocin injection in separate groups. The learning and memory behavior was evaluated and the rats were sacrificed for estimation of oxidative stress. The intracerebroventricular streptozotocin rats treated with alpha lipoic acid (200 mg/kg, p.o.) showed significantly less cognitive impairment as compared to the vehicle treated rats. There was also an insignificant increase in oxidative stress in the alpha lipoic acid treated groups. The study demonstrated the effectiveness of alpha lipoic acid in preventing cognitive impairment and oxidative stress induced by intracerebroventricular streptozotocin and its potential in dementia associated with age and age related neurodegenerative disorders where oxidative stress is involved such as Alzheimer's disease.

Partial prevention of long-term femoral bone loss in aged ovariectomized rats supplemented with choline-stabilized orthosilicic acid.

PubMed

Calomme, M; Geusens, P; Demeester, N; Behets, G J; D'Haese, P; Sindambiwe, J B; Van Hoof, V; Vanden Berghe, D

2006-04-01

Silicon (Si) deficiency in animals results in bone defects. Choline-stabilized orthosilicic acid (ch-OSA) was found to have a high bioavailability compared to other Si supplements. The effect of ch-OSA supplementation was investigated on bone loss in aged ovariectomized (OVX) rats. Female Wistar rats (n = 58, age 9 months) were randomized in three groups. One group was sham-operated (sham, n = 21), and bilateral OVX was performed in the other two groups. OVX rats were supplemented orally with ch-OSA over 30 weeks (OVX1, n = 20; 1 mg Si/kg body weight daily) or used as controls (OVX0, n = 17). The serum Si concentration and the 24-hour urinary Si excretion of supplemented OVX rats was significantly higher compared to sham and OVX controls. Supplementation with ch-OSA significantly but partially reversed the decrease in Ca excretion, which was observed after OVX. The increase in bone turnover in OVX rats tended to be reduced by ch-OSA supplementation. ch-OSA supplementation increased significantly the femoral bone mineral content (BMC) in the distal region and total femoral BMC in OVX rats, whereas lumbar BMC was marginally increased. Femoral BMD was significantly increased at two sites in the distal region in OVX rats supplemented with ch-OSA compared to OVX controls. Total lumbar bone mineral density was marginally increased by ch-OSA supplementation. In conclusion, ch-OSA supplementation partially prevents femoral bone loss in the aged OVX rat model.

Paternal programming of breast cancer risk in daughters in a rat model: opposing effects of animal- and plant-based high-fat diets.

PubMed

Fontelles, Camile Castilho; Guido, Luiza Nicolosi; Rosim, Mariana Papaléo; Andrade, Fábia de Oliveira; Jin, Lu; Inchauspe, Jessica; Pires, Vanessa Cardoso; de Castro, Inar Alves; Hilakivi-Clarke, Leena; de Assis, Sonia; Ong, Thomas Prates

2016-07-26

Although males contribute half of the embryo's genome, only recently has interest begun to be directed toward the potential impact of paternal experiences on the health of offspring. While there is evidence that paternal malnutrition may increase offspring susceptibility to metabolic diseases, the influence of paternal factors on a daughter's breast cancer risk has been examined in few studies. Male Sprague-Dawley rats were fed, before and during puberty, either a lard-based (high in saturated fats) or a corn oil-based (high in n-6 polyunsaturated fats) high-fat diet (60 % of fat-derived energy). Control animals were fed an AIN-93G control diet (16 % of fat-derived energy). Their 50-day-old female offspring fed only a commercial diet were subjected to the classical model of mammary carcinogenesis based on 7,12-dimethylbenz[a]anthracene initiation, and mammary tumor development was evaluated. Sperm cells and mammary gland tissue were subjected to cellular and molecular analysis. Compared with female offspring of control diet-fed male rats, offspring of lard-fed male rats did not differ in tumor latency, growth, or multiplicity. However, female offspring of lard-fed male rats had increased elongation of the mammary epithelial tree, number of terminal end buds, and tumor incidence compared with both female offspring of control diet-fed and corn oil-fed male rats. Compared with female offspring of control diet-fed male rats, female offspring of corn oil-fed male rats showed decreased tumor growth but no difference regarding tumor incidence, latency, or multiplicity. Additionally, female offspring of corn oil-fed male rats had longer tumor latency as well as decreased tumor growth and multiplicity compared with female offspring of lard-fed male rats. Paternal consumption of animal- or plant-based high-fat diets elicited opposing effects, with lard rich in saturated fatty acids increasing breast cancer risk in offspring and corn oil rich in n-6 polyunsaturated fatty acids decreasing it. These effects could be linked to alterations in microRNA expression in fathers' sperm and their daughters' mammary glands, and to modifications in breast cancer-related protein expression in this tissue. Our findings highlight the importance of paternal nutrition in affecting future generations' risk of developing breast cancer.

Therapeutic mild hypothermia improves early outcomes in rats subjected to severe sepsis.

PubMed

Ding, Wu; Shen, Yuehong; Li, Qiang; Jiang, Shouyin; Shen, Huahao

2018-04-15

Therapeutic hypothermia has shown beneficial effects in sepsis. This study focused on its mechanism. Sixteen male Sprague-Dawley rats underwent cecal ligation and perforation and subsequently were treated with either hypothermia (HT; body temperature cooled and maintained at 34 °C by ice pad for 10 h; n = 8) or normothermia (NT; n = 8). Three additional rats underwent sham surgery. The body temperatures of the sham-operated and NT groups were maintained at 38 °C with a thermal pad. After the hypothermia treatment, the HT rats were rewarmed for 2 h. The groups were compared for circulating cytokines (IL-6, IL-10), lactate, high mobility group box-1 protein (HMGB1), and lung and intestinal lesions. Animals were observed for 24 h. Compared with the sham-operated group, the 2 sepsis group rats had significantly higher circulating IL-6, HMGB1, and lactate levels, and tissue injury. In the HT rats, the levels of IL-6, HMGB1, and lactate, the lung wet-to-dry ratio, and lung and intestinal damage were significantly lower than that of the NT group. Circulating IL-10 levels increased significantly after 12 h in the sepsis groups compared with sham animals, while that of the NT and HT groups were comparable. The survival rates of the NT and HT rats were also comparable. Therapeutic hypothermia in a rat model of sepsis was associated with lower levels of circulating IL-6 and HMGB1, and less capillary leakage and tissue edema. These results suggest that mild hypothermia has potential as a therapy in sepsis. Copyright © 2018 Elsevier Inc. All rights reserved.

Nephrotoxicity of ibandronate and zoledronate in Wistar rats with normal renal function and after unilateral nephrectomy.

PubMed

Bergner, R; Siegrist, B; Gretz, N; Pohlmeyer-Esch, G; Kränzlin, B

2015-09-01

A previous animal study compared the nephrotoxic effect of ibandronate (IBN) and zoledronate (ZOL), but interpretation of these study results was limited because of the model of minimal nephrotoxic dosage with a dosage ratio of 1:3. The present study investigated the nephrotoxicity of ibandronate and zoledronate in a 1.5:1 dose ratio, as used in clinical practice and compared the nephrotoxicity in rats with normal and with mildly to moderately impaired renal function. We compared rats with normal renal function (SHAM) and with impaired renal function after unilateral nephrectomy (UNX), treated either with ibandronate 1.5mg/kg, zoledronate 1mg/kg or placebo once (1×) or nine (9×) times. Renal function and markers of tubular toxicity were measured over a 27 week period. After last bisphosphonate treatment the rats were sacrificed and kidneys examined histologically. All bisphosphonate treated animals showed a significant tubular toxicity, which was temporary except in the ZOL-UNX-9×-group. Also the renal function was only transiently reduced except in the ZOL-UNX-9×-group. Histologically, bisphosphonate treatment led to cortical tubuloepithelial degeneration/necrosis and medullary tubuloepithelial swelling which were slightly more pronounced in ibandronate treated animals, when compared to zoledronate treated animals, especially with impaired renal function. In contrast to the previous study we found a similar nephrotoxicity of ibandronate and zoledronate in rats with normal renal function. In rats with impaired renal function the peak of toxicity had not even been fully reached until end of experiment in the zoledronate treated animals. The peak of toxicity seems to be more severe and delayed in rats with impaired renal function compared with rats with normal renal function. Copyright © 2015 Elsevier Ltd. All rights reserved.

Grammomys surdaster, the Natural Host for Plasmodium berghei Parasites, as a Model to Study Whole-Organism Vaccines Against Malaria.

PubMed

Conteh, Solomon; Anderson, Charles; Lambert, Lynn; Orr-Gonzalez, Sachy; Herrod, Jessica; Robbins, Yvette L; Carter, Dariyen; Karhemere, Stomy Bin Shamamba; Pyana, Pati; Büscher, Philippe; Duffy, Patrick E

2017-04-01

AbstractInbred mice are commonly used to test candidate malaria vaccines, but have been unreliable for predicting efficacy in humans. To establish a more rigorous animal model, we acquired African woodland thicket rats of the genus Grammomys , the natural hosts for Plasmodium berghei . Thicket rats were acquired and identified as Grammomys surdaster by skull and teeth measurements and mitochondrial DNA genotyping. Herein, we demonstrate that thicket rats are highly susceptible to infection by P. berghei , and moderately susceptible to Plasmodium yoelii and Plasmodium chabaudi : 1-2 infected mosquito bites or 25-100 sporozoites administered by intravenous injection consistently resulted in patent parasitemia with P. berghei , and resulted in patent parasitemia with P. yoelii and P. chabaudi strains for at least 50% of animals. We then assessed efficacy of whole-organism vaccines to induce sterile immunity, and compared the thicket rat model to conventional mouse models. Using P. berghei ANKA radiation-attenuated sporozoites, and P. berghei ANKA and P. yoelii chemoprophylaxis vaccination approaches, we found that standard doses of vaccine sufficient to protect laboratory mice for a long duration against malaria challenge, are insufficient to protect thicket rats, which require higher doses of vaccine to achieve even short-term sterile immunity. Thicket rats may offer a more stringent and pertinent model for evaluating whole-organism vaccines.

A two-hit model: behavioural investigation of the effect of combined neonatal MK-801 administration and isolation rearing in the rat.

PubMed

Lim, Ann Li; Taylor, David Alan; Malone, Daniel Thomas

2012-09-01

This study combined two neurodevelopmental manipulations, neonatal MK-801 treatment and isolation rearing, to produce a 'two-hit' model and determine whether two hits induce a more robust behavioural phenotype of an animal model of aspects of schizophrenia compared with individual manipulations alone. The effect of clozapine was also assessed. Male Sprague-Dawley rats received 0.2 mg/kg MK-801 or saline intraperitoneally (i.p.) once daily on postnatal days (PNDs) 7-10 and were assigned to group or isolation rearing at weaning (PND 21). From PND 77, they received a vehicle or 5 mg/kg clozapine (i.p.) treatment regimen and were subjected to three prepulse inhibition (PPI) tests, a locomotor activity assessment and a novel object recognition task. MK-801-treated rats reared in isolation displayed robust PPI disruptions which were consistently manifested in all three tests. PPI deficits were also detected in saline-treated rats reared in isolation but not in all tests. Only the two-hit rats demonstrated hyperlocomotion and impaired object recognition memory. Clozapine restored PPI anomalies in the two-hit rats. The two-hit model showed greater psychotic-like effects than either neonatal MK-801 or isolation rearing alone. The preliminary predictive validity shown with clozapine suggests this model may be useful for predicting the efficacy of putative antipsychotics.

[Effect of moxibustion on quantity of pinealocytes and pineal HSP 70 expression in subacute aging rats].

PubMed

Liang, Xin; Zhong, Yu

2011-08-01

To study the mechanism of moxibustion in postponing the process of aging. Thirty Wistar rats were equally randomized into control, model and moxibustion groups. The subacute aging model was established by hypodermic injection of 25% D-galactose (125 mg/kg). Moxibustion was applied to bilateral "Shenshu" (GV 23) and "Pishu" (GV 20) once everyday for 6 weeks. After slicing, the pineal gland tissue was stained with HE and insitu hybridization methods respectively for detecting the quantity of pinealocytes and the expression of heat shock protein (HSP 70). Compared with the control group, both the quantity of pinealocytes and the expression of HSP 70 in the pineal gland in the model group were downregulated significantly (P < 0.001, P < 0.01). Compared with model group, the quantity of pinealocytes and of HSP 70 mRNA in the pineal gland of moxibustion group were upregulated significantly (P < 0.01, P < 0.05). Moxibustion can suppress aging induced decrease of pinealocyte number and HSP 70 expression in subacute aging rats, which may contribute to its effect in postponing aging.

Effects of Handling and Vehicle Injections on Adrenocorticotropic and Corticosterone Concentrations in Sprague–Dawley Compared with Lewis Rats

PubMed Central

Deutsch-Feldman, Molly; Picetti, Roberto; Seip-Cammack, Katharine; Zhou, Yan; Kreek, Mary Jeanne

2015-01-01

The hypothalamic–pituitary–adrenal (HPA) axis is a key factor in the trajectory of the addiction-like cycle (a pattern of behavior characterized by escalating drug use, withdrawal, and relapse) in preclinical and clinical studies. Concentrations of HPA hormones change in laboratory animals in response to standard experimental procedures, including handling and vehicle injections. We compared HPA activity in adult male Lewis (inbred) and Sprague–Dawley (outbred) rats, 2 common strains in rodent models of addiction, after different schedules of handling and saline injections, to explore the extent to which HPA responses differ by strain and whether interindividual differences underlie addiction vulnerability. The 4 treatment conditions were no, short, or long handling and saline injections. In handled groups, rats were handled for 1 to 2 min for 3 times daily and were euthanized after 7 d (short handling) or 14 d (long handling). The injection schedule in the saline injection group mimicked that in a model of binge-like cocaine exposure. Across all treatment groups, concentrations of adrenocorticotropic hormone were higher in Sprague–Dawley than in Lewis rats. In Sprague–Dawley rats, corticosterone concentrations decreased after continued handling but remained constant in Lewis rats. Interindividual variability in hormone levels was greater in Sprague–Dawley than Lewis rats, although corticosterone variability decreased after continued handling. Prolactin did not differ between groups of either Sprague–Dawley and Lewis rats before or after handling. This study underscores the importance of prolonged handling before experimenter-provided drug-administration paradigms and of strain-associated differences that may affect study outcomes. PMID:25651089

Differences of bone healing in metaphyseal defect fractures between osteoporotic and physiological bone in rats.

PubMed

Thormann, Ulrich; El Khawassna, Thaqif; Ray, Seemun; Duerselen, Lutz; Kampschulte, Marian; Lips, Katrin; von Dewitz, Helena; Heinemann, Sascha; Heiss, Christian; Szalay, Gabor; Langheinrich, Alexander C; Ignatius, Anita; Schnettler, Reinhard; Alt, Volker

2014-03-01

Discrepancies in bone healing between osteoporotic and non-osteoporotic bone remain uncertain. The focus of the current work is to evaluate potential healing discrepancies in a metaphyseal defect model in rat femora. Female Sprague-Dawley rats were either ovariectomized (OVX, n=14) and combined with a calcium-, phosphorus- and vitamin D3-, soy- and phytoestrogen-free diet or received SHAM operation with standard diet rat (SHAM, n=14). Three months post-ovariectomy, DEXA measurement showed a reduction of bone mineral density reflecting an osteoporotic bone status in OVX rats. Rats then underwent a 3 mm wedge-shaped osteotomy at the distal metaphyseal area of the left femur stabilized with a T-shaped mini-plate and allowed to heal for 6 weeks. Biomechanical competence by means of a non-destructive three-point bending test showed significant lower flexural rigidity in the OVX rats at 3 mm lever span compared to SHAM animals (p=0.048) but no differences at 10 mm lever span. Microcomputer tomography (μCT) showed bridging cortices and consolidation of the defect in both groups, however, no measurable differences were found in either total ossified tissue or vascular volume fraction. Furthermore, histology showed healing discrepancies that were characterized by cartilaginous remnant and more unmineralized tissue presence in the OVX rats compared to more mature consolidation appearance in the SHAM group. In summary, bone defect healing in metaphyseal bone slightly differs between osteoporotic and non-osteoporotic bone in the current 3 mm defect model in both 3mm lever span biomechanical testing and histology. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of Artesunate on the Expressions of Insulin-Like Growth Factor-1, Osteopontin and C-Telopeptides of Type II Collagen in a Rat Model of Osteoarthritis.

PubMed

Bai, Zhe; Guo, Xiao-Hui; Tang, Chi; Yue, Si-Tong; Shi, Long; Qiang, Bo

2018-01-01

The study aims to explore the effects of artesunate on insulin-like growth factor-1 (IGF-1), Osteopontin (OPN), and C-telopeptides of type II collagen (CTX-II) in serum, synovial fluid (SF), and cartilage tissues of rats with osteoarthritis (OA). OA models were established. Normal model, artesunate, and Viatril-S groups (20 rats respectively) were set. Enzyme-linked immunosorbent assay, IHC staining, and quantitative real-time polymerase chain reaction were conducted to calculate IGF-1, OPN, and CTX-II levels in serum, SF, and cartilage tissues of rats. The pathological changes in cartilage tissues were evaluated with Mankin score and Hematoxylin-Eosin staining. Compared with the normal group, the model group showed increased IGF-1 level; decreased OPN, CTX-II levels in the serum and SF; and contrary results were seen in the cartilage tissues. A gradual ascending IGF-1 level and descending OPN and CTX-II levels existed in the serum and SF in the artesunate and Viatril-S groups after 2 weeks. The model group showed the most obvious pathological changes and highest Mankin score compared with the other groups. Higher IGF-1 level and lower OPN, CTX-II levels were exhibited in the cartilage tissue in the artesunate and Viatril-S groups but not in the model group. Artesunate and Viatril-S inhibit OA development by elevating IGF-1 level and reducing OPN and CTX-II levels. © 2017 S. Karger AG, Basel.

Contraction of Abdominal Wall Muscles Influences Incisional Hernia Occurrence and Size

PubMed Central

Lien, Samuel C.; Hu, Yaxi; Wollstein, Adi; Franz, Michael G.; Patel, Shaun P.; Kuzon, William M.; Urbanchek, Melanie G.

2015-01-01

Background Incisional hernias are a complication in 10% of all open abdominal operations and can result in significant morbidity. The purpose of this study is to determine if inhibiting abdominal muscle contraction influences incisional hernia formation during laparotomy healing. We hypothesize that reducing abdominal musculature deformation reduces incisional hernia occurrence and size. Study Design Using an established rat model for incisional hernia, a laparotomy through the linea alba was closed with one mid-incision, fast-absorbing suture. Three groups were compared: a SHAM group (SHAM; n = 6) received no laparotomies while the Saline Hernia (SH; n = 6) and Botox Hernia (BH; n = 6) groups were treated once with equal volume saline or Botulinum Toxin (Botox®, Allergan) before the incomplete laparotomy closure. On post-operative day 14, the abdominal wall was examined for herniation and adhesions and contractile forces were measured for abdominal wall muscles. Results No hernias developed in SHAM rats. Rostral hernias developed in all SH and BH rats. Caudal hernias developed in all SH rats, but in only 50% of the BH rats. Rostral hernias in the BH group were 35% shorter and 43% narrower compared to those in the SH group (p < 0.05). The BH group had weaker abdominal muscles compared to the SHAM and SH groups (p < 0.05). Conclusions In our rat model, partial paralysis of abdominal muscles reduces the number and size of incisional hernias. These results confirm abdominal wall muscle contractions play a significant role in the pathophysiology of incisional hernia formation. PMID:25817097

Establishment of rat model of silicotuberculosis and its pathological characteristic

PubMed Central

Dong, Hu; Jing, Wu; Yabo, Yang; Xiaokang, Yang; Wan, Wang; Min, Mu; Wenyang, Wang; Zhaoquan, Chen; Yingru, Xing; Rongbo, Zhang

2014-01-01

Objective: To establish different stages of silicosis rat model complicated with tuberculosis infection, and compare the pathological characteristics and analyze the impact of silicosis on tuberculosis infection. Methods: SD rats were subjected to intratracheal administration of silica with non-exposure method at the 1st, 30th, or 60th day. At the 50th day, the rats were injected with the suspension of H37Rv (a virulent standard strain of Mycobacterium tuberculosis) via tail-vein. After 40 days post-infection, rats were sacrificed, the lung tissues were isolated, and paraffin was embedded and sectioned. The sections were treated using HE staining for structure observation, acid fast stain of Ziehl–Neelsen for bacterial detection, and Warthin–Starry silver staining for displaying the distribution of dust particles. The bacterial load was quantified by colony counting. Results: Primary to tertiary silicosis could be discovered at the 30th, 60th, and 90th day of post-infection. The rats could be infected by injection of M. tuberculosis via tail vein, with tuberculosis load and the degree of lung tissue lesions positively correlated with silicosis. Conclusion: The rat model of silicotuberculosis was established successfully, which facilitated understanding the ‘cross-talk’ of silicosis and tuberculosis during the process they drive each other. PMID:25355545

Hypolipidemic and anti-inflammatory effects of aorta and heart tissues of cattle and pigs in the atherosclerosis rat model.

PubMed

Chernukha, Irina M; Fedulova, Liliya V; Kotenkova, Elena A; Takeda, Shiro; Sakata, Ryoichi

2018-05-01

The aim of this study was to investigate the effects of aorta and heart tissues obtained from cattle and pigs on atherosclerosis disorders. Atherosclerosis model rats were provided with the respective diets consisting of aorta and heart tissues. Administration of each tissue suppressed body weight gain as compared to that of the control. In particular, the aorta tissues of pigs and cattle demonstrated significant suppressions in body weight gain in the model rats. The aorta tissues of pigs and cattle showed a significant increase and decrease in the serum high-density lipoproteins and atherogenic index, respectively, which was correlated with the increase in apolipoprotein A1. Hematological analysis revealed that aorta tissues of pigs and cattle clearly reduced the ratio of granulocytes/lymphocytes in the atherosclerosis rats. Serum vascular cellular adhesion molecule-1 levels in the atherosclerosis rats, which were administered these aorta tissues, were also significantly reduced. Additionally, there was an increase in von Willebrand factor in the rat serum. Based on the results obtained, the aorta tissues of pigs and cattle, in particular, demonstrated positive effects in the atherosclerosis rats due to the alteration of lipid metabolism and reduction in inflammation related to atherosclerosis. © 2018 Japanese Society of Animal Science.

The influence of hepatic steatosis on the evaluation of fibrosis with non-alcoholic fatty liver disease by acoustic radiation force impulse.

PubMed

Yanrong Guo; Haoming Lin; Xinyu Zhang; Huiying Wen; Siping Chen; Xin Chen

2017-07-01

Acoustic radiation force impulse (ARFI) elastography is a non-invasive method for the assessment of liver by measuring liver stiffness. The aim of this study is to evaluate the accuracy of ARFI for the diagnosis of liver fibrosis and to assess impact of steatosis on liver fibrosis stiffness measurement, in rats model of non-alcoholic fatty liver disease (NAFLD). The rat models were conducted in 59 rats. The right liver lobe was processed and embedded in a fabricated gelatin solution. Liver mechanics were measured using shear wave velocity (SWV) induced by acoustic radiation force. In rats with NAFLD, the diagnostic performance of ARFI elastography in predicting severe fibrosis (F ≥ 3) and cirrhosis (F ≥ 4) had the areas under the receiver operating characteristic curves (AUROC) of 0.993 and 0.985. Among rats mean SWV values were significantly higher in rats with severe steatosis by histology compared to those mild or without steatosis for F0-F2 fibrosis stages (3.07 versus 2.51 m/s, P = 0.01). ARFI elastography is a promising method for staging hepatic fibrosis with NAFLD in rat models. The presence of severe steatosis is a significant factor for assessing the lower stage of fibrosis.

Serrapeptase and nattokinase intervention for relieving Alzheimer's disease pathophysiology in rat model.

PubMed

Fadl, N N; Ahmed, H H; Booles, H F; Sayed, A H

2013-07-01

Serrapeptase (SP) and nattokinase (NK) are proteolytic enzymes belonging to serine proteases. In this study, we hypothesized that SP and NK could modulate certain factors that are associated with Alzheimer's disease (AD) pathophysiology in the experimental model. Oral administration of aluminium chloride (AlCl3) in a dose of 17 mg/kg body weight (bw) daily for 45 days induced AD-like pathology in male rats with a significant increase in brain acetylcholinesterase (AchE) activity, transforming growth factor β (TGF-β), Fas and interleukin-6 (IL-6) levels. Meanwhile, AlCl3 supplementation produced significant decrease in brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) when compared with control values. Also, AlCl3 administration caused significant decline in the expression levels of disintegrin and metalloproteinase domain 9 (ADAM9) and a disintegrin and metalloproteinase domain 10 (ADAM10) genes in the brain. Histological investigation of brain tissue of rat model of AD showed neuronal degeneration in the hippocampus and focal hyalinosis with cellular as well as a cellular amyloid plaques formation. Oral administration of SP or NK in a rat model of AD daily for 45 days resulted in a significant decrease in brain AchE activity, TGF-β, Fas and IL-6 levels. Also, the treatment with these enzymes produced significant increase in BDNF and IGF-1 levels when compared with the untreated AD-induced rats. Moreover, both SP and NK could markedly increase the expression levels of ADAM9 and ADAM10 genes in the brain tissue of the treated rats. These findings were well confirmed by the histological examination of the brain tissue of the treated rats. The present results support our hypothesis that the oral administration of proteolytitc enzymes, SP and/or NK, would have an effective role in modulating certain factors characterizing AD. Thus, these enzymes may have a therapeutic application in the treatment of AD.

Anti-rheumatoid arthritis effects of traditional Chinese herb couple in adjuvant-induced arthritis in rats.

PubMed

Pan, Ting; Cheng, Tao-Fang; Jia, Yu-Ran; Li, Ping; Li, Fei

2017-06-09

Clematis chinensis Osbeck / Notopterygium incisum Ting ex H, T-Chang (CN) is a traditional Chinese herb couple with prominent efficacy. The herb couple has been commonly used for clinical treatment of arthralgia syndrome ("Bi Zheng" in Chinese) for centuries in China, including rheumatic arthritis, osteoarthritis and gout in modern medicine. To evaluate the anti-arthritic effect of CN herb couple in a rat model of rheumatoid arthritis (RA). Rats were divided randomly into six groups with eight each. Adjuvant-induced arthritis (AIA) model was established by intradermal injection of complete Freund's adjuvant (CFA). Rats were treated orally with different dosages of CN (0.7g/kg, 2.1g/kg, 6.3g/kg) from day 16 till day 40. Ibuprofen (50.4mg/kg) served as a positive control. Spontaneous activity, body weight, paw swelling, and arthritis index (AI) were monitored throughout drug treatment. Then serum levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) were determined by enzyme linked immunosorbent assay (ELISA) kits. In addition, histopathological examination and immunohistochemistry were used to assess the severity of arthritis. Three dosage of CN significantly ameliorated symptoms of RA via increasing body weight as well as reducing paw swelling (at dose of 6.3g/kg, p<0.01) in AIA rats. An extremely significant reduction of AI (p<0.001) was also observed with treatment of CN (6.3g/kg) compared with model group. In parallel, treatment of CN significantly down-regulated levels of TNF-α, IL-6, and VEGF both in serum (p<0.01) and in joint synovial compared with model rats. And histopathology revealed noticeable reduction in synovial hyperplasia, cartilage damage, and inflammatory infiltration by CN treatment, especially at dose of 6.3g/kg. To conclude, all results suggest that CN possesses evident anti-arthritic effects in AIA rats. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Of mice and rats: key species variations in the sexual differentiation of brain and behavior.

PubMed

Bonthuis, P J; Cox, K H; Searcy, B T; Kumar, P; Tobet, S; Rissman, E F

2010-07-01

Mice and rats are important mammalian models in biomedical research. In contrast to other biomedical fields, work on sexual differentiation of brain and behavior has traditionally utilized comparative animal models. As mice are gaining in popularity, it is essential to acknowledge the differences between these two rodents. Here we review neural and behavioral sexual dimorphisms in rats and mice, which highlight species differences and experimental gaps in the literature, that are needed for direct species comparisons. Moving forward, investigators must answer fundamental questions about their chosen organism, and attend to both species and strain differences as they select the optimal animal models for their research questions. Copyright 2010 Elsevier Inc. All rights reserved.

Parecoxib reduces renal injury in an ischemia/reperfusion model in rats.

PubMed

Calistro Neto, José Pedro; Torres, Rômulo da Costa; Gonçalves, Giovanna Maria; Silva, Leopoldo Muniz da; Domingues, Maria Aparecida Custódio; Módolo, Norma Sueli Pinheiro; Barros, Guilherme Antonio Moreira de

2015-04-01

To evaluate the effect of parecoxib (an NSAID) on renal function by measuring plasma NGAL (serum neutrophil gelatinase-associated lipocalin) levels in an induced-ischemia rat model. Forty male Wistar rats were randomly assigned to one of four groups: Ischemia (I), Ischemia/parecoxib (IP), No-ischemia (NI), and No-ischemia/parecoxib (NIP). Body weight, mean arterial pressure, heart rate, body temperature, NGAL levels, and renal histology were compared across groups. The Ischemia (I) group, which did not receive parecoxib, showed the highest NGAL levels (p=0.001), while the IP group, which received the medication, had NGAL levels similar to those of the non-ischemic (NI and NIP) groups. Parecoxib resulted in renal protection in this experimental model.

Different patterns of morphological changes in the hippocampus and dentate gyrus accompany the differential expression of disability following nerve injury.

PubMed

Kalman, Eszter; Keay, Kevin A

2014-12-01

Physical and psychological trauma which results in mood disorders and the disruption of complex behaviours is associated with reductions in hippocampal volume. Clinical evaluation of neuropathic pain reveals mood and behavioural change in a significant number of patients. A rat model of neuropathic injury results in complex behavioural changes in a subpopulation (~30%) of injured rats; these changes are co-morbid with a range of other 'disabilities'. The specific objective of this study was to determine in rats the morphology of the hippocampus and dentate gyrus in individuals with and without complex behavioural disruptions following a constriction injury of the sciatic nerve, and to determine whether rats that develop disabilities following nerve injury have a reduced hippocampal volume compared with injured rats with no disabilities. The social behaviours of nerve-injured rats were evaluated before and after nerve injury. The morphology of the hippocampus of rats with and without behavioural disruptions was compared in serial histological sections. Single-housing and repeated social-interaction testing had no effect on the morphology of either the hippocampus or the dentate gyrus. Rats with transient or ongoing disability identified by behavioural disruption following sciatic nerve injury, show bilateral reductions in hippocampal volume, and lateralised reduction in the dentate gyrus (left side). Disabled rats display a combination of behavioural and physiological changes, which resemble many of the criteria used clinically to diagnose mood disorders. They also show reductions in the volume of the hippocampus similar to people with clinically diagnosed mood disorders. The sciatic nerve injury model reveals a similarity to the human neuropathic pain presentation presenting an anatomically specific focus for the investigation of the neural mechanisms underpinning the co-morbidity of chronic pain and mood disorder. © 2014 Anatomical Society.

High dietary intake of sodium selenite does not affect gene mutation frequency in rat colon and liver.

PubMed

Zeng, Huawei; Uthus, Eric O; Ross, Sharon A; Davis, Cindy D

2009-10-01

Our previous studies have shown that selenium (Se) is protective against dimethylhydrazine (DMH)-induced preneoplastic colon cancer lesions, and protection against DNA damage has been hypothesized to be one mechanism for the anticancer effect of Se. The present study was designed to determine whether dietary selenite affects somatic mutation frequency in vivo. We used the Big Blue transgenic model to evaluate the in vivo mutation frequency of the cII gene in rats fed either a Se-deficient (0 microg Se/g diet) or Se-supplemented diet (0.2 or 2 microg Se/g diet; n = 3 rats/diet in experiment 1 and n = 5 rats/group in experiment 2) and injected with DMH (25 mg/kg body weight, i.p.). There were no significant differences in body weight between the Se-deficient and Se-supplemented (0.2 or 2 microg Se/g diet) rats, but the activities of liver glutathione peroxidase and thioredoxin reductase and concentration of liver Se were significantly lower (p < 0.0001) in Se-deficient rats compared to rats supplemented with Se. We found no effect of dietary Se on liver 8-hydroxy-2'-deoxyguanosine. Gene mutation frequency was significantly lower in liver (p < 0.001) than that of colon regardless of dietary Se. However, there were no differences in gene mutation frequency in DNA from colon mucosa or liver from rats fed the Se-deficient diet compared to those fed the Se-supplemented (0.2 or 2 microg Se/g diet) diet. Although gene mutations have been implicated in the etiology of cancer, our data suggest that decreasing gene mutation is not likely a key mechanism through which dietary selenite exerts its anticancer action against DMH-induced preneoplastic colon cancer lesions in a Big Blue transgenic rat model.

Age-related susceptibility to epileptogenesis and neuronal loss in male Fischer rats exposed to soman and treated with medical countermeasures.

PubMed

Marrero-Rosado, Brenda; Rossetti, Franco; Rice, Matthew W; Moffett, Mark C; Lee, Robyn; Stone, Michael F; Lumley, Lucille A

2018-03-27

Elderly individuals compose a large percentage of the world population; however, few studies have addressed the efficacy of current medical countermeasures (MCM) against the effects of chemical warfare nerve agent exposure in aged populations. We evaluated the efficacy of the anticonvulsant diazepam in an old adult rat model of soman (GD) poisoning and compared the toxic effects to those observed in young adult rats when anticonvulsant treatment is delayed. After determining their respective median lethal dose (LD50) of GD, we exposed young adult and old adult rats to an equitoxic 1.2 LD50 dose of GD followed by treatment with atropine sulfate and the oxime HI-6 at one minute after exposure, and diazepam at 30 minutes after seizure onset. Old adult rats that presented with status epilepticus were more susceptible to developing spontaneous recurrent seizures (SRS). Neuropathological analysis revealed that in rats of both age groups that developed SRS, there was a significant reduction in the density of mature neurons in the piriform cortex, thalamus, and amygdala, with more pronounced neuronal loss in the thalamus of old adult rats compared to young adult rats. Furthermore, old adult rats displayed a reduced density of cells expressing glutamic acid decarboxylase 67, a marker of GABAergic interneurons, in the basolateral amygdala and piriform cortex, and a reduction of astrocyte activation in the piriform cortex. Our observations demonstrate the reduced effectiveness of current MCM in an old adult animal model of GD exposure and strongly suggest the need for countermeasures that are more tailored to the vulnerabilities of an aging population.

A comparison of the ability of a 4:1 ketogenic diet and a 6.3:1 ketogenic diet to elevate seizure thresholds in adult and young rats.

PubMed

Nylen, Kirk; Likhodii, Sergei; Abdelmalik, Peter A; Clarke, Jasper; Burnham, W McIntyre

2005-08-01

The pentylenetetrazol (PTZ) infusion test was used to compare seizure thresholds in adult and young rats fed either a 4:1 ketogenic diet (KD) or a 6.3:1 KD. We hypothesized that both KDs would significantly elevate seizure thresholds and that the 4:1 KD would serve as a better model of the KD used clinically. Ninety adult rats and 75 young rats were placed on one of five experimental diets: (a) a 4:1 KD, (b) a control diet balanced to the 4:1 KD, (c) a 6.3:1 KD, (d) a standard control diet, or (e) an ad libitum standard control diet. All subjects were seizure tested by using the PTZ infusion test. Blood glucose and beta-hydroxybutyrate (beta-OHB) levels were measured. Neither KD elevated absolute "latencies to seizure" in young or adult rats. Similarly, neither KD elevated "threshold doses" in adult rats. In young rats, the 6.3:1 KD, but not the 4:1 KD, significantly elevated threshold doses. The 6.3:1 KD group showed poorer weight gain than the 4:1 KD group when compared with respective controls. The most dramatic discrepancies were seen in young rats. "Threshold doses" and "latency to seizure" data provided conflicting measures of seizure threshold. This was likely due to the inflation of threshold doses calculated by using the much smaller body weights found in the 6.3:1 KD group. Ultimately, the PTZ infusion test in rats may not be a good preparation to model the anticonvulsant effects of the KD seen clinically, especially when dietary treatments lead to significantly mismatched body weights between the groups.

Effects of dopamine agents on a schedule-induced polydipsia procedure in the spontaneously hypertensive rat and in Wistar control rats.

PubMed

Íbias, Javier; Miguéns, Miguel; Pellón, Ricardo

2016-09-01

The spontaneously hypertensive rat (SHR) has been proposed as an animal model for attention deficit hyperactivity disorder (ADHD), and typically develops excessive patterns of response under most behavioural protocols. Schedule-induced polydipsia (SIP) is the excessive water consumption that occurs as a schedule effect when food is intermittently delivered and animals are partially food- but not water-deprived. SIP has been used as a model of excessive behaviour, and considerable evidence has involved the dopaminergic system in its development and maintenance. The aim of this study was to evaluate the effects of the most common psychostimulants used in ADHD treatment on SIP, comparing their effects in SHRs with rats from control populations. SHR, Wistar Kyoto (WKY) and Wistar rats were submitted to a multiple fixed time (FT) food schedule with two components: 30 s and 90 s. The acute effects of different dopaminergic compounds were evaluated after 40 sessions of SIP acquisition. All animals showed higher adjunctive drinking under FT 30 s than FT 90 s, and SHRs displayed higher asymptotic SIP levels in FT 90 s compared to WKY and Wistar rats. SHRs were less sensitive to dopaminergic agents than control rats in terms of affecting rates of adjunctive drinking. These differences point to an altered dopaminergic system in the SHR and provide new insights into the neurobiological basis of ADHD pharmacological treatments. © The Author(s) 2016.

Active versus sedentary lifestyle from childhood to adult and ...

EPA Pesticide Factsheets

A pattern of sedentary lifestyle beginning in childhood is associated with obesity and related disorders such as type 2 diabetes. Obesity is associated with increased susceptibility to air pollutants and initiating regular exercise early in life should impact positively on respiratory symptoms of air pollutant exposure.An animal model of childhood-to-adult sedentary {SEO) vs. active {ACT) lifestyle was achieved by providing female Long-Evans rats with running wheels beginning at22d of age and then exposing to ozone {03) as adults. ACT rats ran 7.2 km/d over 74 days, had lower body fat, and improved glucose tolerance (GT) compared to SEO rats. Adult rats were exposed to 0, 0.25, 0.5, or 1.0 ppm 03 for 5 hr/d for 2 d. 03-induced impairment in GT was significantly improved in ACT animals.Bronchoalveolar lavage {BALF) protein markers of lung damage and neutrophilic inflammation were similarly affected in SEO and ACT animals. BALF eosinophils of SEO rats were markedly higher after exposure to 0.5 and 1.0 ppm 03 compared to ACT rats. Overall,this animal model suggests that regular exercise initiated early in life may afford protection in adulthood to the metabolic and pulmonary effects of 03. The attenuated 03-induced elevation in BALF eosinophils of ACT rats may suggest a protective mechanism of childhood exercise on asthma-related symptoms of air pollution. This is an abstract of a proposed presentation and does not reflect US EPA policy This abstract will be presen

The Establishment of Metabolic Syndrome Model by Induction of Fructose Drinking Water in Male Wistar Rats

PubMed Central

Thent, Zar Chi; Sapri, Shaiful Ridzwan; Sahruddin, Natasya Nadia; Mohd Yusof, Mohd Rafizul; Haji Suhaimi, Farihah

2014-01-01

Background. Metabolic syndrome can be caused by modification of diet by means of consumption of high carbohydrate and high fat diet such as fructose. Aims. To develop a metabolic syndrome rat model by induction of fructose drinking water (FDW) in male Wistar rats. Methods. Eighteen male Wistar rats were fed with FDW 20% and FDW 25% for a duration of eight weeks. The physiological changes with regard to food and fluid intake, as well as calorie intake, were measured. The metabolic changes such as obesity, dyslipidaemia, hypertension, and hyperglycaemia were determined. Data was presented in mean ± SEM subjected to one-way ANOVA. Results. Male Wistar rats fed with FDW 20% for eight weeks developed significant higher obesity parameters compared to those fed with FDW 25%. There was hypertrophy of adipocytes in F20 and F25. There were also systolic hypertension, hypertriglyceridemia, and hyperglycemia in both groups. Conclusion. We conclude that the metabolic syndrome rat model is best established with the induction of FDW 20% for eight weeks. This was evident in the form of higher obesity parameter which caused the development of the metabolic syndrome. PMID:25045660

Pathologic changes of wound tissue in rats with stage III pressure ulcers treated by transplantation of human amniotic epithelial cells.

PubMed

Zheng, Xilan; Jiang, Zhixia; Zhou, Aiting; Yu, Limei; Quan, Mingtao; Cheng, Huagang

2015-01-01

This study aims to determine the impact of orthotopic transplantation of human amniotic epithelial cells (hAECs) on the pathologic changes of wound tissues in a self-prepared rat stage III pressure ulcer model. Ninety-six SD rats were randomly divided into the model group (group M), hAEC transplantation group (group H), traditional treatment group (group T), and the control group (group C), with 24 rats in each group. The wound healing time was observed in 6 rats from each group, and 6 rats of each group were selected for post-modeling on day(s) (D) 1, 3, and 7 for HE staining to compare the pathological changes. The healing time of group H was significantly shorter than the other three groups. Moreover, pathological observations revealed that group H exhibited significant proliferation of fibrous tissues and vessels in the dermal layer, and the appearance time and degree of skin appendages were significantly greater than that observed in the other three groups. Pathological observations showed that hAEC transplantation could significantly speed up the healing of stage III pressure ulcer.

[Effects of extracts from ziziphi spinosae semen and schisandrae chinensis fructus on amino acid neurotransmitter in rats with insomnia induced by PCPA].

PubMed

Gao, Jia-Rong; Ji, Wen-Bo; Jiang, Hui; Chen, Jin-Feng

2013-10-01

To observe the effects of extract from Ziziphus Spinosa Semen and Schisandrae Chinensis Fructus on the content of amino acid neurotransmitter in the hypothalamus of insomnia rats induced by P-Chlorophenylalanine (PCPA) and its mechanism. The model of insomnia rats were established by PCPA intraperitoneal injection, after the modeling, all the therapeutic group were treated with corresponding drug for one week. The hypothalamus pathological changes of the rats were observed. The contents of GABA, Glu in the hypothalamus were detected by Elisa. The GABA, Glu protein expression were detected by immunohistochemical. GABA(A), R(alpha1) and GABA(A)R(gamma2) mRNA expressions were detected by RT-PCR. Compared with model group, the content of GABA in the hypothalamus of rats increased obviously in the alcohol-water group (P < 0.05 or P < 0.01), while the content of Glu decreased obviously (P < 0.05 or P < 0.01). The extract from Ziziphus Spinosae Semen and Schisandrae Chinensis Fructus has obviously Sedative-hypnotic effect. Its mechanism may be related to regulating the content of amino acid neurotransmitter in the hypothalamus of rats.

Beneficial effects of edaravone, a novel antioxidant, in rats with dilated cardiomyopathy

PubMed Central

Arumugam, Somasundaram; Thandavarayan, Rajarajan A; Veeraveedu, Punniyakoti T; Nakamura, Takashi; Arozal, Wawaimuli; Sari, Flori R; Giridharan, Vijayasree V; Soetikno, Vivian; Palaniyandi, Suresh S; Harima, Meilei; Suzuki, Kenji; Nagata, Masaki; Kodama, Makoto; Watanabe, Kenichi

2012-01-01

Edaravone, a novel antioxidant, acts by trapping hydroxyl radicals, quenching active oxygen and so on. Its cardioprotective activity against experimental autoimmune myocarditis (EAM) was reported. Nevertheless, it remains to be determined whether edaravone protects against cardiac remodelling in dilated cardiomyopathy (DCM). The present study was undertaken to assess whether edaravone attenuates myocardial fibrosis, and examine the effect of edaravone on cardiac function in rats with DCM after EAM. Rat model of EAM was prepared by injection with porcine cardiac myosin 28 days after immunization, we administered edaravone intraperitoneally at 3 and 10 mg/kg/day to rats for 28 days. The results were compared with vehicle-treated rats with DCM. Cardiac function, by haemodynamic and echocardiographic study and histopathology were performed. Left ventricular (LV) expression of NADPH oxidase subunits (p47phox, p67phox, gp91phox and Nox4), fibrosis markers (TGF-β1 and OPN), endoplasmic reticulum (ER) stress markers (GRP78 and GADD 153) and apoptosis markers (cytochrome C and caspase-3) were measured by Western blotting. Edaravone-treated DCM rats showed better cardiac function compared with those of the vehicle-treated rats. In addition, LV expressions of NADPH oxidase subunits levels were significantly down-regulated in edaravone-treated rats. Furthermore, the number of collagen-III positive cells in the myocardium of edaravone-treated rats was lower compared with those of the vehicle-treated rats. Our results suggest that edaravone ameliorated the progression of DCM by modulating oxidative and ER stress-mediated myocardial apoptosis and fibrosis. PMID:22268705

Effect of immune stress on body weight regulation is altered by ovariectomy in female rats.

PubMed

Iwasa, Takeshi; Matsuzaki, Toshiya; Kinouchi, Riyo; Gereltsetseg, Ganbat; Murakami, Masahiro; Nakazawa, Hiroshi; Fujisawa, Shinobu; Yamamoto, Satoshi; Kuwahara, Akira; Yasui, Toshiyuki; Irahara, Minoru

2011-09-01

It has been suggested that obesity and loss of ovarian function alter the inflammatory response to immune stress. Ovariectomized (OVX) rats, which are used as a model of human menopause, exhibit both hyperphagia-induced obesity and gonadal steroid deficiency. To evaluate the effects of ovariectomy on inflammatory responses, we compared the anorectic response to LPS in OVX rats and gonad intact female rats. As leptin and hypothalamic interleukin-1β (IL1β) play pivotal roles in the anorectic response to immune stress, these factors were also measured. It was found that the OVX rats exhibited an increased anorectic response to LPS compared with the sham-operated rats. The OVX rats showed higher serum leptin concentrations and a greater increase in hypothalamic IL1β mRNA expression after LPS injection. In addition, in order to determine whether gonadal steroid deficiency contributes to the changes in the inflammatory responses of OVX rats, we compared responses between OVX rats treated with gonadal steroids and untreated OVX rats. There were no differences in appetite, the serum leptin level, and hypothalamic IL1β mRNA expression between the two groups after LPS injection. These findings suggest that the loss of ovarian function increases the induction of leptin and hypothalamic IL1β synthesis and consequently increases the anorectic response under immune stress conditions. It is possible that these alterations are caused by OVX-induced obesity rather than the direct effects of gonadal steroid deficiency. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Cognitive impairment and spontaneous epilepsy in rats with malformations of cortical development.

PubMed

Ye-wei, Xiao; Rong, Wang; Xun-tai, Ma; Shan, Zhang; Qian, Chen; Shi-hua, Huang; Fu-qun, Mao; Xiao-ming, Xiong

2015-12-01

To examine the cognition, spontaneous epilepsy, and electroencephalography (EEG) characteristics of rats with malformations of cortical development (MCD) and their use as an animal model for investigating the pathogenesis of intractable epilepsy and screening novel antiepileptic drugs. An epileptic rat model of MCD was established with the F1 generation of pregnant rats after X-irradiation with 175 cGy (Group L), 195 cGy (Group M), or 215 cGy (Group H). Long-term video-EEG monitoring was used to record the seizures in the rats with MCD. Cognition was assessed with the Morris water maze. The EEGs were recorded and analyzed in the frontal and parietal lobes and hippocampi of adult rats. Finally, the brain tissues were processed for Nissl staining. The model groups exhibited markedly prolonged escape latencies and distinct decrements in the percent distance traveled in the target quadrant and platform-crossing frequency. These findings were dose-dependent. Frequent interictal epileptiform discharges were observed in the frontal and parietal lobes and hippocampi of adult rats, and their incidences were markedly higher in the model groups compared with that in the normal controls, with Group M having the highest incidence. Spontaneous seizures were observed in the model groups (mean incidence, 46.7%). The daily mean frequency of seizures and the incidence of spontaneous seizures were highest in Group M. Nissl staining revealed a dose-dependent pattern of hippocampal abnormalities, cortical and subcortical nodular heterotopia, and callosal agenesis in the model groups. The 195 cGy dose was most appropriate for establishing an epileptic model of MCD with X-irradiation. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Losartan suppresses the kainate-induced changes of angiotensin AT1 receptor expression in a model of comorbid hypertension and epilepsy.

PubMed

Atanasova, Dimitrinka; Tchekalarova, Jana; Ivanova, Natasha; Nenchovska, Zlatina; Pavlova, Ekaterina; Atanassova, Nina; Lazarov, Nikolai

2018-01-15

Experimental and clinical studies have demonstrated that components of renin-angiotensin system are elevated in the hippocampus in epileptogenic conditions. In the present work, we explored the changes in the expression of angiotensin II receptor, type 1 (AT 1 receptor) in limbic structures, as well as the effect of the AT1 receptor antagonist losartan in a model of comorbid hypertension and epilepsy. The expression of AT 1 receptors was compared between spontaneously hypertensive rats (SHRs) and Wistar rats by using immunohistochemistry in the kainate (KA) model of temporal lobe epilepsy (TLE). The effect of losartan was studied on AT 1 receptor expression in epileptic rats that were treated for a period of 4weeks after status epilepticus. The naive and epileptic SHRs were characterized by stronger protein expression of AT 1 receptor than normotensive Wistar rats in the CA1, CA3a, CA3b, CA3c field and the hilus of the dentate gyrus of the dorsal hippocampus but fewer cells were immunostained in the piriform cortex. Increased AT 1 immunostaining was observed in the basolateral amygdala of epileptic SHRs but not of epileptic Wistar rats. Losartan exerted stronger and structure-dependent suppression of AT 1 receptor expression in SHRs compared to Wistar rats. Our results confirm the important role of AT 1 receptor in epilepsy and suggest that the AT 1 receptor antagonists could be used as a therapeutic strategy for treatment of comorbid hypertension and epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

Sex differences in sleep pattern of rats in an experimental model of osteoarthritis.

PubMed

Silva, Andressa; Araujo, Paula; Zager, Adriano; Tufik, Sergio; Andersen, Monica Levy

2011-07-01

Osteoarthritis (OA) is a major healthcare burden with increasing incidence, and is characterised by the degeneration of articular cartilage. OA is associated with chronic pain and sleep disturbance. The current study examined and compared the long-term effects of chronic articular pain on sleep patterns between female and male rats in an experimental model of OA. Rats were implanted with electrodes for electrocorticography and electromyography and assigned to control, sham or OA groups. OA was induced by the intra-articular administration of (2 mg) monosodium iodoacetate into the left knee joint in male and female rats (at estrus and diestrus phases). Sleep was monitored at days 1, 10, 15, 20 and 28 after iodoacetate injection during light and dark periods. The results showed that the overall sleep architecture changed in both sexes. These alterations occurred during the light and dark periods, began on D1 and persisted until the end of the study. OA rats, regardless of sex, showed a fragmented sleep pattern with reduced sleep efficiency, slow-wave sleep and paradoxical sleep, and fewer paradoxical sleep bouts. However, the males showed lower sleep efficiency and reduced slow-wave sleep compared to females during the dark period. Additionally, OA affected the hormonal levels in male rats, as testosterone levels were reduced in comparison to the control and sham groups. In females, progesterone and estradiol remained unchanged throughout the study. Our results suggest that the chronic model of OA influenced the sleep patterns in both sexes. However, males appeared to be more affected. Copyright © 2010. Published by Elsevier Ltd.

Comparing the cardiovascular therapeutic indices of glycopyrronium and tiotropium in an integrated rat pharmacokinetic, pharmacodynamic and safety model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trifilieff, Alexandre; Ethell, Brian T.; Sykes, David A.

Long acting inhaled muscarinic receptor antagonists, such as tiotropium, are widely used as bronchodilator therapy for chronic obstructive pulmonary disease (COPD). Although this class of compounds is generally considered to be safe and well tolerated in COPD patients the cardiovascular safety of tiotropium has recently been questioned. We describe a rat in vivo model that allows the concurrent assessment of muscarinic antagonist potency, bronchodilator efficacy and a potential for side effects, and we use this model to compare tiotropium with NVA237 (glycopyrronium bromide), a recently approved inhaled muscarinic antagonist for COPD. Anaesthetized Brown Norway rats were dosed intratracheally at 1more » or 6 h prior to receiving increasing doses of intravenous methacholine. Changes in airway resistance and cardiovascular function were recorded and therapeutic indices were calculated against the ED{sub 50} values for the inhibition of methacholine-induced bronchoconstriction. At both time points studied, greater therapeutic indices for hypotension and bradycardia were observed with glycopyrronium (19.5 and 28.5 fold at 1 h; > 200 fold at 6 h) than with tiotropium (1.5 and 4.2 fold at 1 h; 4.6 and 5.5 fold at 6 h). Pharmacokinetic, protein plasma binding and rat muscarinic receptor binding properties for both compounds were determined and used to generate an integrated model of systemic M{sub 2} muscarinic receptor occupancy, which predicted significantly higher M{sub 2} receptor blockade at ED{sub 50} doses with tiotropium than with glycopyrronium. In our preclinical model there was an improved safety profile for glycopyrronium when compared with tiotropium. - Highlights: • We use an in vivo rat model to study CV safety of inhaled muscarinic antagonists. • We integrate protein and receptor binding and PK of tiotropium and glycopyrrolate. • At ED{sub 50} doses for bronchoprotection we model systemic M{sub 2} receptor occupancy. • Glycopyrrolate demonstrates lower M{sub 2} occupancy at bronchoprotective doses. • Glycopyrrolate demonstrates an improved CV safety profile, versus tiotropium.« less

Dysfunction of Inflammation-Resolving Pathways Is Associated with Exaggerated Postoperative Cognitive Decline in a Rat Model of the Metabolic Syndrome

PubMed Central

Su, Xiao; Feng, Xiaomei; Terrando, Niccolo; Yan, Yan; Chawla, Ajay; Koch, Lauren G; Britton, Steven L; Matthay, Michael A; Maze, Mervyn

2012-01-01

The cholinergic antiinflammatory pathway (CAP), which terminates in the spleen, attenuates postoperative cognitive decline (PCD) in rodents. Surgical patients with metabolic syndrome exhibit exaggerated and persistent PCD that is reproduced in postoperative rats selectively bred for easy fatigability and that contain all features of metabolic syndrome (low-capacity runners [LCRs]). We compared the CAP and lipoxin A4 (LXA4), another inflammation-resolving pathway in LCR, with its counterpart high-capacity runner (HCR) rats. Isoflurane-anesthetized LCR and HCR rats either underwent aseptic trauma involving tibial fracture (surgery) or not (sham). At postoperative d 3 (POD3), compared with HCR, LCR rats exhibited significantly exaggerated PCD (trace fear conditioning freezing time 43% versus 57%). Separate cohorts were killed at POD3 to collect plasma for LXA4 and to isolate splenic mononuclear cells (MNCs) to analyze CAP signaling, regulatory T cells (Tregs) and M2 macrophages (M2 Mφ). Under lipopolysaccharide (LPS) stimulation, tumor necrosis factor (TNF)-α produced by splenic MNCs was 117% higher in LCR sham and 52% higher in LCR surgery compared with HCR sham and surgery rats; LPS-stimulated TNF-α production could not be inhibited by an α7 nicotinic acetylcholine receptor agonist, whereas inhibition by the β2 adrenergic agonist, salmeterol, was significantly less (−35%) than that obtained in HCR rats. Compared to HCR, sham and surgery LCR rats had reduced β2 adrenergic receptor–expressing T lymphocytes (59%, 44%), Tregs (47%, 54%) and M2 Mφ (45%, 39%); surgical LCR rats’ hippocampal M2 Mφ was 66% reduced, and plasma LXA4 was decreased by 120%. Rats with the metabolic syndrome have ineffective inflammation-resolving mechanisms that represent plausible reasons for the exaggerated and persistent PCD. PMID:23296426

Intestinal absorption of hawthorn flavonoids--in vitro, in situ and in vivo correlations.

PubMed

Zuo, Zhong; Zhang, Li; Zhou, Limin; Chang, Qi; Chow, Moses

2006-11-25

Our previous studies identified hyperoside (HP), isoquercitrin (IQ) and epicatechin (EC) to be the major active flavonoid components of the hawthorn phenolic extract from hawthorn fruits demonstrating inhibitory effect on in vitro Cu(+2)-mediated low density lipoproteins oxidation. Among these three hawthorn flavonoids, EC was the only one detectable in plasma after the oral administration of hawthorn phenolic extract to rats. The present study aims to investigate the intestinal absorption mechanisms of these three hawthorn flavonoids by in vitro Caco-2 monolayer model, rat in situ intestinal perfusion model and in vivo pharmacokinetics studies in rats. In addition, in order to investigate the effect of the co-occurring components in hawthorn phenolic extract on the intestinal absorption of these three major hawthorn flavonoids, intestinal absorption transport profiles of HP, IQ and EC in forms of individual pure compound, mixture of pure compounds and hawthorn phenolic extract were studied and compared. The observations from in vitro Caco-2 monolayer model and in situ intestinal perfusion model indicated that all three studied hawthorn flavonoids have quite limited permeabilities. EC and IQ demonstrated more extensive metabolism in the rat in situ intestinal perfusion model and in vivo study than in Caco-2 monolayer model. Moreover, results from the Caco-2 monolayer model, rat in situ intestinal perfusion model as well as the in vivo pharmacokinetics studies in rats consistently showed that the co-occurring components in hawthorn phenolic extract might not have significant effect on the intestinal absorption of the three major hawthorn flavonoids studied.

Comparative antipyretic and analgesic activities of Cissampelos pareira Linn. and Cyclea peltata (Lam.) Hook. F. & Thomas.

PubMed

Singh, Suman G; Nishteswar, K; Patel, Bhupesh R; Nariya, Mukesh

2016-01-01

Cissampelos pareira Linn. is considered as an established source of Patha , whereas Cyclea peltata (Lam.) Hook. F. & Thomas is used as a source plant of Patha in the southern part of India. In classical texts, two different varieties of Patha , i.e. Rajpatha ( C. peltata ) and Laghupatha ( C. pareira ), are mentioned which possess almost similar properties. To compare antipyretic and analgesic activities of C. pareira and C. peltata in suitable experimental model. Powder (540 mg/kg) and ethanolic extract (200 mg/kg) of both the test drugs ( C. pareira and C. peltata ) were evaluated for antipyretic activity in Brewer's yeast-induced pyrexia model in rats. Analgesic activity was evaluated by radiant heat model in rats and acetic acid-induced writhing syndrome in mice. Result of the present study had shown that powder of C. pareira (540 mg/kg) has moderate antipyretic activity as compared to the powder of C. peltata and extract of both test drugs. C. pareira powder showed better analgesic effect than ethanolic extract (200 mg/kg) of both the test drugs in radiant heat model in rats, while in acetic acid-induced writhing syndrome, ethanolic extract (280 mg/kg) of both drugs showed pronounced effect as compared to powder form (780 mg/kg) in mice. Both C. pareira and C. peltata exhibited analgesic effects in experimental animals. The effect is more significant in C. peltata treated group compared to C. pareira . Antipyretic effect was observed with the pretreatment of C. pareira .

Protective effects of ginger root extract on Alzheimer disease-induced behavioral dysfunction in rats.

PubMed

Zeng, Gao-Feng; Zhang, Zhi-Yong; Lu, Li; Xiao, De-Qiang; Zong, Shao-Hui; He, Jian-Ming

2013-04-01

The aim of this study was to assess the ability of a traditional Chinese medicinal ginger root extract (GRE) to prevent behavioral dysfunction in the Alzheimer disease (AD) rat model. Rat AD models were established by an operation (OP) in which rats were treated with a one-time intra-cerebroventricuIar injection of amyloid β-protein (Aβ) and continuous gavage of aluminum chloride every day for 4 weeks. GRE was administered intra-gastrically to rats. After 35 days, learning and memory were assessed in all of the rats. Brain sections were processed for immunohistochemistry and Hematoxylin & Eosin (H&E) and Nissl staining. The latency to show significant memory deficits was shorter in the group that received OP with a high dose of GRE (HG)(OP+HG) than in the groups that received OP with a low or moderate dose of GRE (LG, MG)(OP+LG, OP+MG) (p<0.05). The expression of superoxide dismutase (SOD) and catalase (CAT) in the OP+MG and OP+LG groups was up-regulated compared to the OP+HG groups (p<0.05). The rats in the OP+HG groups had lower levels of nuclear factor-κB (NF-κB), interleukin-1β (IL-1β), and malondialdehyde (MDA) expression than the rats in the OP+MG and OP+LG groups (p<0.05). This experiment demonstrates that the administration of GRE reverses behavioral dysfunction and prevents AD-like symptoms in our rat model.

Characterization of SV-40 Tag rats as a model to study prostate cancer

PubMed Central

2009-01-01

Background Prostate cancer is the second most frequently diagnosed cancer in men. Animal models that closely mimic clinical disease in humans are invaluable tools in the fight against prostate cancer. Recently, a Simian Virus-40 T-antigen (SV-40 Tag) targeted probasin promoter rat model was developed. This model, however, has not been extensively characterized; hence we have investigated the ontogeny of prostate cancer and determined the role of sex steroid receptor and insulin-like growth factor-1 (IGF-1) signaling proteins in the novel SV-40 Tag rat. Methods The SV-40 Tag rat was histopathologically characterized for time to tumor development, incidence and multiplicity and in the ventral, dorsal, lateral and anterior lobes of the prostate. Immunoassay techniques were employed to measure cell proliferation, apoptosis, and sex steroid receptor and growth factor signaling-related proteins. Steroid hormone concentrations were measured via coated well enzyme linked immunosorbent assay (ELISA) kits. Results Prostatic intraepithelial neoplasia (PIN) and well-differentiated prostate cancer developed as early as 2 and 10 weeks of age, respectively in the ventral prostate (VP) followed by in the dorsolateral (DLP). At 8 weeks of age, testosterone and dihydrotestosterone (DHT) concentrations in SV-40 Tag rats were increased when compared to non-transgenic rats. High cell proliferation and apoptotic indices were found in VP and DLP of transgenic rats. Furthermore, we observed increased protein expression of androgen receptor, IGF-1, IGF-1 receptor, and extracellular signal-regulated kinases in the prostates of SV-40 Tag rats. Conclusion The rapid development of PIN and prostate cancer in conjunction with the large prostate size makes the SV-40 Tag rat a useful model for studying prostate cancer. This study provides evidence of the role of sex steroid and growth factor proteins in prostate cancer development and defines appropriate windows of opportunity for preclinical trials and aids in the rational design of chemoprevention, intervention, regression, and therapeutic studies using prostate cancer rodent models. PMID:19171036

Dyslipidemia is not associated with cardiovascular disease risk in an animal model of mild chronic suboptimal nutrition.

PubMed

Lifshitz, Fima; Pintos, Patricia M; Lezón, Christian E; Macri, Elisa V; Friedman, Silvia M; Boyer, Patricia M

2012-01-01

Previous studies performed in an experimental model of nutritional growth retardation (NGR) have observed metabolic adaptation. We hypothesized that changes in lipid-lipoprotein profile, glucose, and insulin levels occur, whereas overall body growth is reduced.The aim of this study was to assess serum lipid-lipoprotein profile, hepatogram, insulinemia and glycemia, and CVD risk markers in rats fed a suboptimal diet. Weanling male rats were assigned either to control (C) or NGR group. In this 4-week study, C rats were fed ad libitum a standard diet, and NGR rats received 80% of the amount of food consumed by C. Zoometric parameters, body fat content, serum lipid-lipoprotein profile, hepatogram, insulinemia, and glycemia were determined, and the cardiovascular disease (CVD) risk markers homeostasis model assessment-insulin resistance and homeostasis model assessment and β-cell function were calculated. Suboptimal food intake induced a significant decrease in body weight and length, which were accompanied by a reduction of 50% in body fat mass. Serum lipoproteins were significantly higher in NGR rats, with the exception of high-density lipoprotein cholesterol, which remained unchanged. Nutritional growth retardation rats had decreased triglycerides compared with C rats. No significant differences were detected in liver function parameters. The CVD risk markers homeostasis model assessment (HOMA)-insulin resistance and homeostasis model assessment and β-cell function were significantly lower in NGR rats. Mild chronic suboptimal nutrition in weanling male rats led to growth retardation and changes in the lipid-lipoprotein profile, glucose, and insulin levels while preserving the integrity of liver function. These data suggest a metabolic adaptation during suboptimal food intake, which ensures substrates flux to tissues that require constant energy-in detriment to body growth. The CVD risk markers suggested that mild chronic food restriction of approximately 20% could provide protection against this degenerative disease. Copyright © 2012 Elsevier Inc. All rights reserved.

[Improvement and the mechanism of cardiac function by knockdown of ADAM10 in adriamycin-induced cardiomyopathy rats].

PubMed

Li, Xiaoou; Xie, Lili; He, Bing; Huang, Wei

2018-01-01

Objective To study the role of a disintegrin and metalloproteinase10 (ADAM10) in shedding neural cadherin (N-cadherin) and develop an approach to interfere the process of ventricular remodeling in adriamycin-induced cardiomyopathy (ACM) rats. Methods In a rat model of ACM, the effects of intraperitoneal injection of the lentiviral RNAi vector of ADAM10 on the morphology of cardiomyocytes and contractile function were observed by HE staining and color Doppler echocardiography. The expressions of N-cadherin and C-terminal fragment 1 (CTF1) were detected by Western blotting and immunohistochemistry. Results In the in vivo experiment, a large amount of fluorescence was seen in the isolated primary cardiomyocytes, which indicated that the transfection in the rat model was successful. In the treatment group, the morphology of cardiomyocytes and function of the heart were evidently improved, N-cadherin protein expression was remarkably up-regulated and CTF1 protein was obviously down-regulated compared with the model group. Conclusion Knock-down of ADAM10 increases N-cadherin expression and decreases CTF1 expression, thus improves cardiac function in the rat model of ACM.

Point: From animal models to prevention of colon cancer. Systematic review of chemoprevention in min mice and choice of the model system.

PubMed

Corpet, Denis E; Pierre, Fabrice

2003-05-01

The Apc(Min/+) mouse model and the azoxymethane (AOM) rat model are the main animal models used to study the effect of dietary agents on colorectal cancer. We reviewed recently the potency of chemopreventive agents in the AOM rat model (D. E. Corpet and S. Tache, Nutr. Cancer, 43: 1-21, 2002). Here we add the results of a systematic review of the effect of dietary and chemopreventive agents on the tumor yield in Min mice. The review is based on the results of 179 studies from 71 articles and is displayed also on the internet http://corpet.net/min.(2) We compared the efficacy of agents in the Min mouse model and the AOM rat model, and found that they were correlated (r = 0.66; P < 0.001), although some agents that afford strong protection in the AOM rat and the Min mouse small bowel increase the tumor yield in the large bowel of mutant mice. The agents included piroxicam, sulindac, celecoxib, difluoromethylornithine, and polyethylene glycol. The reason for this discrepancy is not known. We also compare the results of rodent studies with those of clinical intervention studies of polyp recurrence. We found that the effect of most of the agents tested was consistent across the animal and clinical models. Our point is thus: rodent models can provide guidance in the selection of prevention approaches to human colon cancer, in particular they suggest that polyethylene glycol, hesperidin, protease inhibitor, sphingomyelin, physical exercise, epidermal growth factor receptor kinase inhibitor, (+)-catechin, resveratrol, fish oil, curcumin, caffeate, and thiosulfonate are likely important preventive agents.

Cyanidin-3-glucoside extracted from mulberry fruit can reduce N-methyl-N-nitrosourea-induced retinal degeneration in rats.

PubMed

Lee, Seung Hee; Jeong, Eojin; Paik, Sun-Sook; Jeon, Ji Hyun; Jung, Sung Won; Kim, Hyun-Bok; Kim, Muyan; Chun, Myung-Hoon; Kim, In-Beom

2014-01-01

To investigate the effect of cyanidin-3-O-glucoside (C3G) on a rat retinal degeneration (RD) model. Experimental RD was induced in rats by the intraperitoneal injection of N-methyl-N-nitrosourea (MNU) at 50 mg/kg. C3G extracted from mulberry (Morus alba L.) fruit (50 mg/kg) was orally administered, daily for 1, 2 and 4 weeks after MNU injection. The effects of C3G administration on MNU-induced RD retinas were histologically and functionally assessed by hematoxylin and eosin staining and electroretinography (ERG), respectively. The degree of retinal injury in C3G-administered RD rats was evaluated by immunohistochemistry with an antibody against glial fibrillary acidic protein (GFAP). The preferential protective effect of C3G on scotopic vision was examined by western blot analysis. Marked loss of photoreceptors in the outer nuclear layer (ONL) was observed in RD rats at 2 and 4 weeks after MNU injection, while the ONL in the MNU-induced RD rats given C3G was relatively well preserved. Immunohistochemistry with anti-GFAP showed that retinal injury was also reduced in the retinas of the rats given C3G. Functional assessment by using ERG recordings showed that scotopic ERG responses were significantly increased in RD rats given C3G for 4 weeks (p < 0.01) compared with that of untreated RD rats. In the RD rats given short-term C3G (for 1 and 2 weeks), the increase in ERG responses was not significant. In addition, western blot analysis showed that rhodopsin level in the C3G-administered RD retinas significantly increased compared to that in the non-administered RD retinas (p < 0.05), whereas red/green opsin level did not show any significant difference. Long-term administration of C3G extracted from mulberry fruit could structurally reduce photoreceptor damage and functionally improve scotopic visual functions in the RD rat model induced by MNU.

N-acetylcysteine ameliorates contrast‑induced kidney injury in rats with unilateral hydronephrosis.

PubMed

Xia, Qiang; Liu, Chunxiao; Zheng, Xia

2018-02-01

The aim of the present study was to investigate the protective effects of N‑acetylcysteine (NAC) on contrast‑induced acute kidney injury in rats with unilateral hyronephrosis. Eighty‑two male Sprague Dawley rats were randomized to undergo sham operation (n=14) or unilateral ureteral obstruction (UUO) (n=68). After 3 weeks, the UUO animals were randomized to three groups: NAC gastric perfusion, UUO+iohexol+NAC (n=24); normal saline perfusion, UUO+iohexol (n=24); and controls, UUO (n=20). After 3 days, UUO+iohexol+NAC and UUO+iohexol rats were injected with iohexol. One day after contrast, half of the rats were sacrificed to assess the pathological changes to the kidneys, serum creatinine, serum neutrophil gelatinase‑associated lipocalin (NGAL), renal cell apoptosis rate and expression of apoptosis regulators Bcl‑2/Bax. The remaining rats underwent obstruction relief and were analyzed 3 weeks later. Compared with the controls, serum NGAL levels were high in UUO+iohexol rats 1 day following injection and 3 weeks after obstruction relief, but UUO+iohexol+NAC rats exhibited lower serum NGAL levels compared with UUO+iohexol rats (all P<0.05). Following modeling, UUO+iohexol rats exhibited a significantly higher apoptosis rate of renal tubular cells, higher expression of Bax mRNA, and lower ratio of Bcl‑2/Bax (all P<0.05). Three weeks after obstruction relief, UUO+iohexol+NAC rats exhibited a lower apoptosis rate, lower Bax mRNA expression, higher expression of Bcl‑2 mRNA and higher ratio of Bcl‑2/Bax (all P<0.05) compared with day 1 following drug administration. The prophylactic use of NAC reduced the apoptotic rate of renal tubular cells following contrast exposition, which was accompanied by changes in the expression of Bcl‑2/Bax mRNA.

Efficacy of Polaprezinc for Acute Radiation Proctitis in a Rat Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doi, Hiroshi, E-mail: h-doi@hyo-med.ac.jp; Kamikonya, Norihiko; Takada, Yasuhiro

Purpose: The purpose of the present study was to standardize the experimental rat model of radiation proctitis and to examine the efficacy of polaprezinc on radiation proctitis. Methods and Materials: A total of 54 female Wistar rats (5 weeks old) were used. The rats were divided into three groups: those treated with polaprezinc (PZ+), those treated with base alone, exclusive of polaprezinc (PZ-), and those treated without any medication (control). All the rats were irradiated to the rectum. Polaprezinc was prepared as an ointment. The ointment was administered rectally each day after irradiation. All rats were killed on the 10thmore » day after irradiation. The mucosal changes were evaluated endoscopically and pathologically. The results were graded from 0 to 4 and compared according to milder or more severe status, as applicable. Results: According to the endoscopic findings, the proportion of mild changes in the PZ+, PZ-, and control group was 71.4%, 25.0%, and 14.3% respectively. On pathologic examination, the proportion of low-grade findings in the PZ+, PZ-, and control group was 80.0%, 58.3%, and 42.9% for mucosal damage, 85.0%, 41.7%, and 42.9% for a mild degree of inflammation, and 50.0%, 33.3%, and 4.8% for a shallow depth of inflammation, respectively. The PZ+ group tended to have milder mucosal damage than the other groups, according to all criteria used. In addition, significant differences were observed between the PZ+ and control groups regarding the endoscopic findings, degree of inflammation, and depth of inflammation. Conclusions: This model was confirmed to be a useful experimental rat model for radiation proctitis. The results of the present study have demonstrated the efficacy of polaprezinc against acute radiation-induced rectal disorders using the rat model.« less

The small-molecule fast skeletal troponin activator, CK-2127107, improves exercise tolerance in a rat model of heart failure.

PubMed

Hwee, Darren T; Kennedy, Adam R; Hartman, James J; Ryans, Julie; Durham, Nickie; Malik, Fady I; Jasper, Jeffrey R

2015-04-01

Heart failure-mediated skeletal myopathy, which is characterized by muscle atrophy and muscle metabolism dysfunction, often manifests as dyspnea and limb muscle fatigue. We have previously demonstrated that increasing Ca(2+) sensitivity of the sarcomere by a small-molecule fast skeletal troponin activator improves skeletal muscle force and exercise performance in healthy rats and models of neuromuscular disease. The objective of this study was to investigate the effect of a novel fast skeletal troponin activator, CK-2127107 (2-aminoalkyl-5-N-heteroarylpyrimidine), on skeletal muscle function and exercise performance in rats exhibiting heart failure-mediated skeletal myopathy. Rats underwent a left anterior descending coronary artery ligation, resulting in myocardial infarction and a progressive decline in cardiac function [left anterior descending coronary artery heart failure (LAD-HF)]. Compared with sham-operated control rats, LAD-HF rat hindlimb and diaphragm muscles exhibited significant muscle atrophy. Fatigability was increased during repeated in situ isokinetic plantar flexor muscle contractions. CK-2127107 produced a leftward shift in the force-Ca(2+) relationship of skinned, single diaphragm, and extensor digitorum longus fibers. Exercise performance, which was assessed by rotarod running, was lower in vehicle-treated LAD-HF rats than in sham controls (116 ± 22 versus 193 ± 31 seconds, respectively; mean ± S.E.M.; P = 0.04). In the LAD-HF rats, a single oral dose of CK-2127107 (10 mg/kg p.o.) increased running time compared with vehicle treatment (283 ± 47 versus 116 ± 22 seconds; P = 0.0004). In summary, CK-2127107 substantially increases exercise performance in this heart failure model, suggesting that modulation of skeletal muscle function by a fast skeletal troponin activator may be a useful therapeutic in heart failure-associated exercise intolerance. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Uraemic hyperparathyroidism causes a reversible inflammatory process of aortic valve calcification in rats

PubMed Central

Shuvy, Mony; Abedat, Suzan; Beeri, Ronen; Danenberg, Haim D.; Planer, David; Ben-Dov, Iddo Z.; Meir, Karen; Sosna, Jacob; Lotan, Chaim

2008-01-01

Aims Renal failure is associated with aortic valve calcification (AVC). Our aim was to develop an animal model for exploring the pathophysiology and reversibility of AVC, utilizing rats with diet-induced kidney disease. Methods and results Sprague–Dawley rats (n = 23) were fed a phosphate-enriched, uraemia-inducing diet for 7 weeks followed by a normal diet for 2 weeks (‘diet group’). These rats were compared with normal controls (n = 10) and with uraemic controls fed with phosphate-depleted diet (‘low-phosphate group’, n = 10). Clinical investigations included serum creatinine, phosphate and parathyroid hormone (PTH) levels, echocardiography, and multislice computed tomography. Pathological examinations of the valves included histological characterization, Von Kossa staining, and antigen and gene expression analyses. Eight diet group rats were further assessed for reversibility of valve calcification following normalization of their kidney function. At 4 weeks, all diet group rats developed renal failure and hyperparathyroidism. At week 9, renal failure resolved with improvement in the hyperparathyroid state. Echocardiography demonstrated valve calcifications only in diet group rats. Tomographic calcium scores were significantly higher in the diet group compared with controls. Von Kossa stain in diet group valves revealed calcium deposits, positive staining for osteopontin, and CD68. Gene expression analyses revealed overexpression of osteoblast genes and nuclear factor κB activation. Valve calcification resolved after diet cessation in parallel with normalization of PTH levels. Resolution was associated with down-regulation of inflammation and osteoblastic features. Low-phosphate group rats developed kidney dysfunction similar to that of the diet group but with normal levels of PTH. Calcium scores and histology showed only minimal valve calcification. Conclusion We developed an animal model for AVC. The process is related to disturbed mineral metabolism. It is associated with inflammation and osteoblastic features. Furthermore, the process is reversible upon normalization of the mineral homeostasis. Thus, our model constitutes a convenient platform for studying AVC and potential remedies. PMID:18390899

Uraemic hyperparathyroidism causes a reversible inflammatory process of aortic valve calcification in rats.

PubMed

Shuvy, Mony; Abedat, Suzan; Beeri, Ronen; Danenberg, Haim D; Planer, David; Ben-Dov, Iddo Z; Meir, Karen; Sosna, Jacob; Lotan, Chaim

2008-08-01

Renal failure is associated with aortic valve calcification (AVC). Our aim was to develop an animal model for exploring the pathophysiology and reversibility of AVC, utilizing rats with diet-induced kidney disease. Sprague-Dawley rats (n = 23) were fed a phosphate-enriched, uraemia-inducing diet for 7 weeks followed by a normal diet for 2 weeks ('diet group'). These rats were compared with normal controls (n = 10) and with uraemic controls fed with phosphate-depleted diet ('low-phosphate group', n = 10). Clinical investigations included serum creatinine, phosphate and parathyroid hormone (PTH) levels, echocardiography, and multislice computed tomography. Pathological examinations of the valves included histological characterization, Von Kossa staining, and antigen and gene expression analyses. Eight diet group rats were further assessed for reversibility of valve calcification following normalization of their kidney function. At 4 weeks, all diet group rats developed renal failure and hyperparathyroidism. At week 9, renal failure resolved with improvement in the hyperparathyroid state. Echocardiography demonstrated valve calcifications only in diet group rats. Tomographic calcium scores were significantly higher in the diet group compared with controls. Von Kossa stain in diet group valves revealed calcium deposits, positive staining for osteopontin, and CD68. Gene expression analyses revealed overexpression of osteoblast genes and nuclear factor kappaB activation. Valve calcification resolved after diet cessation in parallel with normalization of PTH levels. Resolution was associated with down-regulation of inflammation and osteoblastic features. Low-phosphate group rats developed kidney dysfunction similar to that of the diet group but with normal levels of PTH. Calcium scores and histology showed only minimal valve calcification. We developed an animal model for AVC. The process is related to disturbed mineral metabolism. It is associated with inflammation and osteoblastic features. Furthermore, the process is reversible upon normalization of the mineral homeostasis. Thus, our model constitutes a convenient platform for studying AVC and potential remedies.

The Effect of Phosphatidylcholine and Deoxycholate Compound Injections to the Localized Adipose Tissue: An Experimental Study with a Murine Model

PubMed Central

Noh, Yongjoon

2012-01-01

Background Phosphatidylcholine (PPC) and deoxycholate (DCA) compound has been recently used for the purpose of partial lipolysis and is valued for its efficacy and lower invasiveness compared to liposuction and dermolipectomy used previously. In this article, the authors discuss the efficacy of the PPC dissolved in DCA via an experimental rat study model, along with suggesting a useful animal experimental model for the study of adipose tissue and lipolysis. Methods Bilateral inguinal fat pads of an experimental rat were elevated with the deep inferior epigastric vessel as the sole vascular pedicle. Normal saline was injected on one side as a control group and a PPC and DCA compound was injected on the other side. After 4 days, the rats were euthanized for microscopic tissue examination. The pathology was scored by a semiquantitative system in 4 categories: normal fat amount, fat necrosis, inflammatory activity, and stage of fibrosis. A Wilcoxon signed-rank test powered by SPSS packet program was used for statistical analysis and to determine significance. Results Microscopic examination was performed on the obtained samples, and the experimental data of all four categories showed significant histologic differences compared to the control group. All of the data also showed statistical significance by the Wilcoxon signedrank test (P<0.01). Conclusions In the inguinal fat pad rat model, the control group and the experimental group had a differed significantly in the amount of normal fat tissue, inflammation, necrosis, and fibrosis. We recommend the rat inguinal fat pad model used in this study, as it is likely to be useful in related research. PMID:23094238

Voluntary Physical Exercise Improves Subsequent Motor and Cognitive Impairments in a Rat Model of Parkinson’s Disease

PubMed Central

Hsueh, Shih-Chang; Lai, Jing-Huei; Wu, Chung-Che; Yu, Yu-Wen; Luo, Yu; Hsieh, Tsung-Hsun; Chiang, Yung-Hsiao

2018-01-01

Background: Parkinson’s disease (PD) is typically characterized by impairment of motor function. Gait disturbances similar to those observed in patients with PD can be observed in animals after injection of neurotoxin 6-hydroxydopamine (6-OHDA) to induce unilateral nigrostriatal dopamine depletion. Exercise has been shown to be a promising non-pharmacological approach to reduce the risk of neurodegenerative disease. Methods: In this study, we investigated the long-term effects of voluntary running wheel exercise on gait phenotypes, depression, cognitive, rotational behaviors as well as histology in a 6-OHDA-lesioned rat model of PD. Results: We observed that, when compared with the non-exercise controls, five-week voluntary exercise alleviated and postponed the 6-OHDA-induced gait deficits, including a significantly improved walking speed, step/stride length, base of support and print length. In addition, we found that the non-motor functions, such as novel object recognition and forced swim test, were also ameliorated by voluntary exercise. However, the rotational behavior of the exercise group did not show significant differences when compared with the non-exercise group. Conclusions: We first analyzed the detailed spatiotemporal changes of gait pattern to investigate the potential benefits after long-term exercise in the rat model of PD, which could be useful for future objective assessment of locomotor function in PD or other neurological animal models. Furthermore, these results suggest that short-term voluntary exercise is sufficient to alleviate cognition deficits and depressive behavior in 6-OHDA lesioned rats and long-term treatment reduces the progression of motor symptoms and elevates tyrosine hydroxylase (TH), Brain-derived neurotrophic factor (BDNF), bone marrow tyrosine kinase in chromosome X (BMX) protein expression level without affecting dopaminergic (DA) neuron loss in this PD rat model. PMID:29419747

[Effects of acupuncture on bone metabolism and serum estradiol level in ovariectomy-induced osteoporosis rats].

PubMed

Ma, Jie; Yun-guang, Hu; Zhang, Da-hui

2008-08-01

To observe the effect of acupuncture (Acu) on bone metabolism and serum estradiol (E2) in ovariectomized (OVX) rats for studying its underlying mechanism in treating osteoporosis. Forty female SD rats of six months were randomized into sham operation (sham), model, Acu and Diethylstibestrol (DES) groups, with 10 cases in each. Postmenopausal osteoporosis model was established by removing ovaries under anesthesia. In Acu group, bilateral "Dazhu" (BL 11), "Shenshu" (BL 23) and "Pishu" (BL 20) were punctured and stimulated for 30 minutes, once daily for 60 days. Rats of DES group were drenched with saline+DES (22.5 microg/ml) 1 ml/100 g, once daily for 60 days. At the end of experiments, blood samples were collected from femoral artery for assaying serum alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) contents by using biochemistry, and serum bone gla protein (BGP) and E2 levels by immunoradioassay. Compared with sham group, uterus wet weight, serum E2 content in model group decreased significantly (P < 0.01) while body weight, serum ALP, BGP and TRAP levels in model group increased significantly (P < 0.01, 0.05). Compared with model group, uterus wet weight and serum Ez content in Acu and DES groups increased significantly (P < 0.01); while body weight, serum ALP, BGP and TRAP levels decreased considerably (P < 0.01). No significant differences were found between Acu and DES groups in serum E2, ALP, BGP and TRAP levels (P > 0.05). Acupuncture can suppress abnormal increase of body weight and decrease of serum E2 level, and significantly downregulate serum ALP, BGP and TRAP levels in OVX rats, which may contribute to its effect in relieving osteoporosis.

Establishment of a reversible model of prehepatic portal hypertension in rats

PubMed Central

Zhao, Xin; Dou, Jian; Gao, Qing-Jun

2016-01-01

The aim of the present study was to improve upon the traditional model of pre-hepatic portal hypertension in rats, and simulate the anhepatic phase of orthotopic liver transplantation without veno-venous bypass. A reversible model of portal hypertension was induced by portal vein ligation, with a label ring ligated along the portal vein. A total of 135 male Wistar rats were divided into three groups: i) Normal control (NC) group; ii) portal hypertensive control (PHTC) group; and iii) reperfusion (R) group. In the R group, rats with portal hypertension underwent simultaneous clamping of the portal triad and retrohepatic vena cava for 1 h, followed by removal of the clamps to enable blood reperfusion. Portal venography and portal vein pressure were recorded during the surgery. Arterial oxygen pressure (PaO2), and alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) levels were determined, and pathological changes of the liver were investigated by immunohistochemical staining. The results demonstrated that, 3 weeks after portal vein ligation, the vein area and the free portal pressures in the PHTC group were significantly increased compared with those in the NC group. The serum ALT and AST levels in the R group at different time points were significantly elevated compared with those in the PHTC group, and reached their maximal levels at 24 h after reperfusion. Furthermore, the PaO2 at 24 h after reperfusion was significantly decreased. In conclusion, the reversible model of pre-hepatic portal hypertension in rats was successfully established using the introduction of a label ring. This model may be useful for basic research focusing on the anhepatic phase of orthotopic liver transplantation without veno-venous bypass. PMID:27446299

Establishment of a reversible model of prehepatic portal hypertension in rats.

PubMed

Zhao, Xin; Dou, Jian; Gao, Qing-Jun

2016-08-01

The aim of the present study was to improve upon the traditional model of pre-hepatic portal hypertension in rats, and simulate the anhepatic phase of orthotopic liver transplantation without veno-venous bypass. A reversible model of portal hypertension was induced by portal vein ligation, with a label ring ligated along the portal vein. A total of 135 male Wistar rats were divided into three groups: i) Normal control (NC) group; ii) portal hypertensive control (PHTC) group; and iii) reperfusion (R) group. In the R group, rats with portal hypertension underwent simultaneous clamping of the portal triad and retrohepatic vena cava for 1 h, followed by removal of the clamps to enable blood reperfusion. Portal venography and portal vein pressure were recorded during the surgery. Arterial oxygen pressure (PaO 2 ), and alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) levels were determined, and pathological changes of the liver were investigated by immunohistochemical staining. The results demonstrated that, 3 weeks after portal vein ligation, the vein area and the free portal pressures in the PHTC group were significantly increased compared with those in the NC group. The serum ALT and AST levels in the R group at different time points were significantly elevated compared with those in the PHTC group, and reached their maximal levels at 24 h after reperfusion. Furthermore, the PaO 2 at 24 h after reperfusion was significantly decreased. In conclusion, the reversible model of pre-hepatic portal hypertension in rats was successfully established using the introduction of a label ring. This model may be useful for basic research focusing on the anhepatic phase of orthotopic liver transplantation without veno-venous bypass.

Effect of the herbal formulation Jianpijiedu on the TCRVβCDR3 repertoire in rats with hepatocellular carcinoma and subjected to food restriction combined with laxative.

PubMed

Sun, Baoguo; Meng, Jun; Xiang, Ting; Zhang, Lei; Deng, Liuxiang; Chen, Yan; Luo, Haoxuan; Yang, Zhangbin; Chen, Zexiong; Zhang, Shijun

2016-03-01

The aim of this study was to investigate the effects of the Chinese herbal formulation Jianpijiedu (JPJD) in a rat model of orthotopic hepatocellular carcinoma (OHC). The tumor-bearing rats underwent food restriction combined with laxative (FRL) treatment in order to model the nutritional and digestive symptoms of patients with hepatocellular carcinoma. In addition, the study aimed to elucidate the effect of JPJD on the T cell receptor Vβ-chain complementarity-determining region 3 (TCRVβCDR3) repertoire and the underlying mechanism. The FRL rat model was established by alternate-day food restriction and the oral administration of Glauber's salt (sodium sulfate), based on which the OHC model was then established. Subsequently, the FRL-OHC induced animals received JPJD or thymopentin-5 (TP5) for 17 days. Differences in the TCRVβCDR3 repertoire in the rat thymus, liver and hepatocellular carcinoma tissues were analyzed by polymerase chain reaction. Compared with the FRL-OHC model animals without any treatment, those treated with JPJD exhibited significantly inhibited hepatocellular carcinoma growth (P<0.05), reduced weight loss (P<0.01) and stable visceral indices (P<0.05). Furthermore, the JPJD treatment appeared to improve Simpsons diversity index (Ds) values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in the thymus, liver and hepatocellular carcinoma tissues. However, no anti-hepatoma effects were evident in the rats treated with TP5. In addition, TP5 increased the Ds values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in hepatocellular carcinoma tissues compared with those in the JPJD-treated group. The anti-hepatoma effects of JPJD in FRL-OHC-induced animals may be due to the promotion of the Ds values of the TCRVβCDR3 repertoire.

Effect of the herbal formulation Jianpijiedu on the TCRVβCDR3 repertoire in rats with hepatocellular carcinoma and subjected to food restriction combined with laxative

PubMed Central

SUN, BAOGUO; MENG, JUN; XIANG, TING; ZHANG, LEI; DENG, LIUXIANG; CHEN, YAN; LUO, HAOXUAN; YANG, ZHANGBIN; CHEN, ZEXIONG; ZHANG, SHIJUN

2016-01-01

The aim of this study was to investigate the effects of the Chinese herbal formulation Jianpijiedu (JPJD) in a rat model of orthotopic hepatocellular carcinoma (OHC). The tumor-bearing rats underwent food restriction combined with laxative (FRL) treatment in order to model the nutritional and digestive symptoms of patients with hepatocellular carcinoma. In addition, the study aimed to elucidate the effect of JPJD on the T cell receptor Vβ-chain complementarity-determining region 3 (TCRVβCDR3) repertoire and the underlying mechanism. The FRL rat model was established by alternate-day food restriction and the oral administration of Glauber's salt (sodium sulfate), based on which the OHC model was then established. Subsequently, the FRL-OHC induced animals received JPJD or thymopentin-5 (TP5) for 17 days. Differences in the TCRVβCDR3 repertoire in the rat thymus, liver and hepatocellular carcinoma tissues were analyzed by polymerase chain reaction. Compared with the FRL-OHC model animals without any treatment, those treated with JPJD exhibited significantly inhibited hepatocellular carcinoma growth (P<0.05), reduced weight loss (P<0.01) and stable visceral indices (P<0.05). Furthermore, the JPJD treatment appeared to improve Simpsons diversity index (Ds) values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in the thymus, liver and hepatocellular carcinoma tissues. However, no anti-hepatoma effects were evident in the rats treated with TP5. In addition, TP5 increased the Ds values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in hepatocellular carcinoma tissues compared with those in the JPJD-treated group. The anti-hepatoma effects of JPJD in FRL-OHC-induced animals may be due to the promotion of the Ds values of the TCRVβCDR3 repertoire. PMID:26997998

Extension of a PBPK model for ethylene glycol and glycolic acid to include the competitive formation and clearance of metabolites associated with kidney toxicity in rats and humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Corley, R.A., E-mail: rick.corley@pnl.gov; Saghir, S.A.; Bartels, M.J.

2011-02-01

A previously developed PBPK model for ethylene glycol and glycolic acid was extended to include glyoxylic acid, oxalic acid, and the precipitation of calcium oxalate that is associated with kidney toxicity in rats and humans. The development and evaluation of the PBPK model was based upon previously published pharmacokinetic studies coupled with measured blood and tissue partition coefficients and rates of in vitro metabolism of glyoxylic acid to oxalic acid, glycine and other metabolites using primary hepatocytes isolated from male Wistar rats and humans. Precipitation of oxalic acid with calcium in the kidneys was assumed to occur only at concentrationsmore » exceeding the thermodynamic solubility product for calcium oxalate. This solubility product can be affected by local concentrations of calcium and other ions that are expressed in the model using an ion activity product estimated from toxicity studies such that calcium oxalate precipitation would be minimal at dietary exposures below the NOAEL for kidney toxicity in the sensitive male Wistar rat. The resulting integrated PBPK predicts that bolus oral or dietary exposures to ethylene glycol would result in typically 1.4-1.6-fold higher peak oxalate levels and 1.6-2-fold higher AUC's for calcium oxalate in kidneys of humans as compared with comparably exposed male Wistar rats over a dose range of 1-1000 mg/kg. The converse (male Wistar rats predicted to have greater oxalate levels in the kidneys than humans) was found for inhalation exposures although no accumulation of calcium oxalate is predicted to occur until exposures are well in excess of the theoretical saturated vapor concentration of 200 mg/m{sup 3}. While the current model is capable of such cross-species, dose, and route-of-exposure comparisons, it also highlights several areas of potential research that will improve confidence in such predictions, especially at low doses relevant for most human exposures.« less

Temporary dietary iron restriction affects the process of thrombus resolution in a rat model of deep vein thrombosis.

PubMed

Oboshi, Makiko; Naito, Yoshiro; Sawada, Hisashi; Hirotani, Shinichi; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Morisawa, Daisuke; Eguchi, Akiyo; Nishimura, Koichi; Fujii, Kenichi; Mano, Toshiaki; Ishihara, Masaharu; Masuyama, Tohru

2015-01-01

Deep vein thrombosis (DVT) is a major cause of pulmonary thromboembolism and sudden death. Thus, it is important to consider the pathophysiology of DVT. Recently, iron has been reported to be associated with thrombotic diseases. Hence, in this study, we investigate the effects of dietary iron restriction on the process of thrombus resolution in a rat model of DVT. We induced DVT in 8-week-old male Sprague-Dawley rats by performing ligations of their inferior venae cavae. The rats were then given either a normal diet (DVT group) or an iron-restricted diet (DVT+IR group). Thrombosed inferior venae cavae were harvested at 5 days after ligation. The iron-restricted diet reduced venous thrombus size compared to the normal diet. Intrathrombotic collagen content was diminished in the DVT+IR group compared to the DVT group. In addition, intrathrombotic gene expression and the activity of matrix metalloproteinase-9 were increased in the DVT+IR group compared to the DVT group. Furthermore, the DVT+IR group had greater intrathrombotic neovascularization as well as higher gene expression levels of urokinase-type plasminogen activator and tissue-type plasminogen activator than the DVT group. The iron-restricted diet decreased intrathrombotic superoxide production compared to the normal diet. These results suggest that dietary iron restriction affects the process of thrombus resolution in DVT.

Temporary Dietary Iron Restriction Affects the Process of Thrombus Resolution in a Rat Model of Deep Vein Thrombosis

PubMed Central

Oboshi, Makiko; Naito, Yoshiro; Sawada, Hisashi; Hirotani, Shinichi; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Morisawa, Daisuke; Eguchi, Akiyo; Nishimura, Koichi; Fujii, Kenichi; Mano, Toshiaki; Ishihara, Masaharu; Masuyama, Tohru

2015-01-01

Background Deep vein thrombosis (DVT) is a major cause of pulmonary thromboembolism and sudden death. Thus, it is important to consider the pathophysiology of DVT. Recently, iron has been reported to be associated with thrombotic diseases. Hence, in this study, we investigate the effects of dietary iron restriction on the process of thrombus resolution in a rat model of DVT. Methods We induced DVT in 8-week-old male Sprague-Dawley rats by performing ligations of their inferior venae cavae. The rats were then given either a normal diet (DVT group) or an iron-restricted diet (DVT+IR group). Thrombosed inferior venae cavae were harvested at 5 days after ligation. Results The iron-restricted diet reduced venous thrombus size compared to the normal diet. Intrathrombotic collagen content was diminished in the DVT+IR group compared to the DVT group. In addition, intrathrombotic gene expression and the activity of matrix metalloproteinase-9 were increased in the DVT+IR group compared to the DVT group. Furthermore, the DVT+IR group had greater intrathrombotic neovascularization as well as higher gene expression levels of urokinase-type plasminogen activator and tissue-type plasminogen activator than the DVT group. The iron-restricted diet decreased intrathrombotic superoxide production compared to the normal diet. Conclusions These results suggest that dietary iron restriction affects the process of thrombus resolution in DVT. PMID:25962140

Effect of Ozone on Intestinal Epithelial Homeostasis in a Rat Model

PubMed Central

Sukhotnik, Igor; Starikov, Alona; Coran, Arnold G.; Pollak, Yulia; Sohotnik, Rima; Shaoul, Ron

2015-01-01

Background: The positive effects of ozone therapy have been described in many gastrointestinal disorders. The mechanisms of this positive effect of ozone therapy are poorly understood. The purpose of the present study was to investigate whether the use of ozone may potentiate the gut intestinal mucosal homeostasis in a rat model. Methods: Adult rats weighing 250–280 g were randomly assigned to one of three experimental groups of 8 rats each: 1) Control rats were given 2 mL of water by gavage and intraperitoneally (IP) for 5 days; 2) O3-PO rats were treated with 2 mL of ozone/oxygen mixture by gavage and 2 mL of water IP for 5 days; 3) O3-IP rats were treated with 2 mL of water by gavage and 2 mL of ozone/oxygen mixture IP for 5 days. Rats were sacrificed on day 6. Bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, and cell proliferation and apoptosis were evaluated following sacrifice. Results: The group of O3-IP rats demonstrated a greater jejunal and ileal villus height and crypt depth, a greater enterocyte proliferation index in jejunum, and lower enterocyte apoptosis in ileum compared to control animals. Oral administration of the ozone/oxygen mixture resulted in a less significant effect on cell turnover. Conclusions: Treatment with an ozone/oxygen mixture stimulates intestinal cell turnover in a rat model. Intraperitoneal administration of ozone resulted in a more significant intestinal trophic effect than oral administration. PMID:25717388

Craniotomy: true sham for traumatic brain injury, or a sham of a sham?

PubMed

Cole, Jeffrey T; Yarnell, Angela; Kean, William S; Gold, Eric; Lewis, Bobbi; Ren, Ming; McMullen, David C; Jacobowitz, David M; Pollard, Harvey B; O'Neill, J Timothy; Grunberg, Neil E; Dalgard, Clifton L; Frank, Joseph A; Watson, William D

2011-03-01

Abstract Neurological dysfunction after traumatic brain injury (TBI) is caused by both the primary injury and a secondary cascade of biochemical and metabolic events. Since TBI can be caused by a variety of mechanisms, numerous models have been developed to facilitate its study. The most prevalent models are controlled cortical impact and fluid percussion injury. Both typically use "sham" (craniotomy alone) animals as controls. However, the sham operation is objectively damaging, and we hypothesized that the craniotomy itself may cause a unique brain injury distinct from the impact injury. To test this hypothesis, 38 adult female rats were assigned to one of three groups: control (anesthesia only); craniotomy performed by manual trephine; or craniotomy performed by electric dental drill. The rats were then subjected to behavioral testing, imaging analysis, and quantification of cortical concentrations of cytokines. Both craniotomy methods generate visible MRI lesions that persist for 14 days. The initial lesion generated by the drill technique is significantly larger than that generated by the trephine. Behavioral data mirrored lesion volume. For example, drill rats have significantly impaired sensory and motor responses compared to trephine or naïve rats. Finally, of the seven tested cytokines, KC-GRO and IFN-γ showed significant increases in both craniotomy models compared to naïve rats. We conclude that the traditional sham operation as a control confers profound proinflammatory, morphological, and behavioral damage, which confounds interpretation of conventional experimental brain injury models. Any experimental design incorporating "sham" procedures should distinguish among sham, experimentally injured, and healthy/naïve animals, to help reduce confounding factors.

Fenoterol enantiomers do not possess beneficial therapeutic properties of their racemic mixture in the rat model of post myocardial infarction dilated cardiomyopathy.

PubMed

Ahmet, Ismayil; Turner, Tia; Lakatta, Edward G; Talan, Mark I

2012-04-01

A salutary effect of β(2) adrenergic receptor (AR) agonist, fenoterol has been demonstrated in a rat model of post-myocardial infarction (MI) dilated cardiomyopathy (DCM). Recent reports on single cardiomyocyte experiments suggested that out of two enantiomers, RR and SS, that constitute a racemic mixture of fenoterol, only RR-enantiomer is an active component that might be a promising new drug for treatment of chronic heart failure. The objective of this study was to compare the efficacy of the RR enantiomer of fenoterol with efficacy of racemic fenoterol, and SS, an inactive enantiomer, in whole animal experimental models of DCM. Two weeks after induction of MI by permanent ligation of the anterior descending coronary artery early cardiac remodeling and MI size were assessed via echocardiography and rats were divided into treatment groups. Treatment (placebo, racemic fenoterol, RR- or SS-enantiomers of fenoterol) continued for 6 months while progression of DCM was followed by serial echocardiography. Compared with untreated rats, rats treated with racemic fenoterol demonstrated previously described attenuation of LV remodeling, functional decline and the arrest of the MI expansion during the first 2 months of treatment. On the contrary, the treatment with either RR-, or with SS-enantiomers of fenoterol was completely ineffective. The conclusion drawn on the basis of previous experiments with single cardiomyocytes that RR-enantiomer of fenoterol represents an active component of racemic fenoterol and can be further investigated as a new drug for treatment of chronic heart failure was not confirmed in the whole animal model of DCM.

Comparison of 5 Different Rat Models to Establish a Standard Animal Model for Research Into Interstitial Cystitis.

PubMed

Song, Phil Hyun; Chun, So Young; Chung, Jae-Wook; Kim, Yeon Yong; Lee, Hyo Jung; Lee, Jun Nyung; Ha, Yun-Sok; Yoo, Eun Sang; Kwon, Tae Gyun; Kim, Jeongshik; Kim, Dae Hwan; Kim, Bum Soo

2017-09-01

We evaluated 5 different rat models using different agents in order to establish a standard animal model for interstitial cystitis (IC) in terms of the functional and pathologic characteristics of the bladder. Five IC models were generated in 8-week-old female Sprague-Dawley rats via transurethral instillation of 0.1M hydrogen chloride (HCl) or 3% acetic acid (AA), intraperitoneal injection of cyclophosphamide (CYP) or lipopolysaccharide (LPS), or subcutaneous injection of uroplakin II (UPK2). After generating the IC models, conscious cystometry was performed on days 3, 7, and 14. All rats were euthanized on day 14 and their bladders were obtained for histological and pro-inflammatory-related gene expression analysis. In the cystometric analysis, all experimental groups showed significantly decreased intercontraction intervals compared with the control group on day 3, but only the LPS and UPK groups maintained significantly shorter intercontraction intervals than the control group on day 14. The histological analysis revealed that areas with severe urothelial erosion (HCl, AA, and UPK) and hyperplasia (CYP and LPS), particularly in the UPK-treated bladders, showed a markedly increased infiltration of toluidine blue-stained mast cells and increased tissue fibrosis. In addition, significantly elevated expression of interleukin-1b, interleukin-6, myeloperoxidase, monocyte chemotactic protein 1, and Toll-like receptors 2 and 4 was observed in the UPK group compared to the other groups. Among the 5 different agents, the injection of UPK generated the most effective IC animal model, showing consequent urothelial barrier loss, inflammatory reaction, tissue fibrosis stimulation, and persistent hyperactive bladder.

[Effect of Electroacupuncture Intervention at Different Time-points on Levels of HSP 70, MDA, SOD and GSH-PX of Liver in Rats with Simulated Weightlessness].

PubMed

Song, Yan; Zhao, Guo-zhen; Zhao, Bai-xiao; Ji, Bo; Wang, De-sheng; Zhang, He; Mao, Ying-qiu; Zhang, Ping; Xu, Yong-si; Liu, Ya-li; Lu, Ya-wen; Dai, Jian; Li, Ying-hui

2015-10-01

To observe the effect of acupuncture intervention at different time-points on the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), the content of malonaldehyde (MDA) and expression of heat shock protein 70 (HSP 70) of liver tissue in rats with simulated weightlessness, so as to explore its mechanism underlying improvement of liver injury in rats with simulated weightlessness. Twenty male Wistar rats were randomly divided into control group, model group, pre-acupuncture group and EA group, 5 rats in each. The model of simulated weightlessness was established by tail suspension for 4 week. One week before the tail suspension, the rats in the pre-acupuncture group were treated with electroacupuncture (EA) at "Shenshu" (BL 23), "Pishu"(BL 20) and "Sanyinjiao" (SP 6) for 30 min before treatment, once a day for 7 days. The rats in the EA group received tail suspension and acupuncture intervention at the same time. EA was applied for 30 min per treatment, once every other day for 14 times. Immunohistochemical staining was used to assay the expression of HSP 70 in the liver tissue. The activities of SOD and GSH-PX and content of MDA in liver tissues were examined by means of colourimetric method. Results Compared with the control group,the expression of HSP 70 and the content of MDA in the liver tissue were increased significantly (P < 0.01), and the activity of SOD and GSH-PX was notably reduced (P < 0.05) in the model group. Compared with the model group, the content of HSP 70 was significantly reduced in the pre-acupuncture group (P < 0.01). There were no significant changes in the levels of SOD, GSH-PX, MDA and HSP 70 in the EA group (P > 0.05). In comparison with the pre-acupuncture group, the activity of GSH-PX was lower (P < 0.05) and the content of MDA was higher (P < 0.05) in the EA group. EA-pretreatment can suppress the increase of liver HSP 70 immunoactivity in rats with simulated weightlessness, being likely to improve the antioxidant ability of liver.

Spontaneously hypertensive rat (SHR) as an animal model for ADHD: a short overview.

PubMed

Meneses, Alfredo; Perez-Garcia, Georgina; Ponce-Lopez, Teresa; Tellez, Ruth; Gallegos-Cari, Andrea; Castillo, Carlos

2011-01-01

Diverse studies indicate that attention-deficit hyperactivity disorder (ADHD) is associated with alterations in encoding processes, including working or short-term memory. Some ADHD dysfunctional domains are reflected in the spontaneously hypertensive rat (SHR). Because ADHD, drugs and animal models are eliciting a growing interest, hence the aim of this work is to present a brief overview with a focus on the SHR as an animal model for ADHD and memory deficits. Thus, this paper reviews the concept of SHR as a model system for ADHD, comparing SHR, Wistar-Kyoto and Sprague-Dawley rats with a focus on the hypertension level and working, short-term memory and attention in different behavioral tasks, such as open field, five choice serial reaction time, water maze, passive avoidance, and autoshaping. In addition, drug treatments (d-amphetamine and methylphenidate) are evaluated.

A rat model of post-traumatic stress disorder reproduces the hippocampal deficits seen in the human syndrome.

PubMed

Goswami, Sonal; Samuel, Sherin; Sierra, Olga R; Cascardi, Michele; Paré, Denis

2012-01-01

Despite recent progress, the causes and pathophysiology of post-traumatic stress disorder (PTSD) remain poorly understood, partly because of ethical limitations inherent to human studies. One approach to circumvent this obstacle is to study PTSD in a valid animal model of the human syndrome. In one such model, extreme and long-lasting behavioral manifestations of anxiety develop in a subset of Lewis rats after exposure to an intense predatory threat that mimics the type of life-and-death situation known to precipitate PTSD in humans. This study aimed to assess whether the hippocampus-associated deficits observed in the human syndrome are reproduced in this rodent model. Prior to predatory threat, different groups of rats were each tested on one of three object recognition memory tasks that varied in the types of contextual clues (i.e., that require the hippocampus or not) the rats could use to identify novel items. After task completion, the rats were subjected to predatory threat and, one week later, tested on the elevated plus maze (EPM). Based on their exploratory behavior in the plus maze, rats were then classified as resilient or PTSD-like and their performance on the pre-threat object recognition tasks compared. The performance of PTSD-like rats was inferior to that of resilient rats but only when subjects relied on an allocentric frame of reference to identify novel items, a process thought to be critically dependent on the hippocampus. Therefore, these results suggest that even prior to trauma PTSD-like rats show a deficit in hippocampal-dependent functions, as reported in twin studies of human PTSD.

[Effect of Xiaozheng Rongmu powder for the treatment of liver cirrhosis in rats].

PubMed

Mu, Yong-Ping; Chen, Xiao-Rong; Lu, Yun-Fei

2010-10-01

To observe the therapeutic effect of Xiaozheng Rongmu Powder (XRP) for the treatment of progressive CCl4-induced liver cirrhosis in rats. Rat liver cirrhosis model was established by subcutaneous injection of 50% CCl4-olive oil 2 mL/kg twice a week for 12 weeks. Experimental rats were divided into the control group treated by saline and the two treatment groups, treated with XRP and Xiaochaihu Decoction, respectively, with the treatment starting from the 9th week of modeling. Rats were sacrificed at the terminal of experiment, the death rate, character of ascites, liver histological changes, liver function, mRNA expression of hepatocyte mitosis and the liver fibrosis associated markers in rats were observed. At the end of the 8th week of modeling, serum levels of ALT, AST and TBil were increased, and Alb decreased significantly in rats (P < 0.01), cirrhosis formation with ascites could be seen in all rats. Meantime, levels of vascular smooth muscle alpha-actin, transforming growth factor-beta1, collagen I A2, tumor necrosis factor-alpha, tissue inhibitor of melalloproteinase-1 mRNA increased, while matrix melalloproteinase-13 mRNA were decreased significantly (P < 0.01), with visible liver proliferation to some extents. Further changes of above-mentioned abnormalities and clear suppression of hepatocytes mitosis were found in the modeled rats at the end of the 12th week. As compared to those occurred in the control group, changes in the XRP treated group were significantly milder at the corresponding duration, and clearly active hepatocytes mitosis was shown. XRP, a Chinese drug with the effect of dissolving phlegm, removing stasis and supplementing qi, could reverse the progress of cirrhosis formation induced by CCl4, and it brings potential new hope for the treatment of advanced cirrhosis by Chinese medicine.

Diabetes-associated microbiota in fa/fa rats is modified by Roux-en-Y gastric bypass.

PubMed

Arora, Tulika; Seyfried, Florian; Docherty, Neil G; Tremaroli, Valentina; le Roux, Carel W; Perkins, Rosie; Bäckhed, Fredrik

2017-09-01

Roux-en-Y gastric bypass (RYGB) and duodenal jejunal bypass (DJB), two different forms of bariatric surgery, are associated with improved glucose tolerance, but it is not clear whether the gut microbiota contributes to this effect. Here we used fa/fa rats as a model of impaired glucose tolerance to investigate whether (i) the microbiota varies between fa/fa and nondiabetic fa/+ rats; (ii) the microbiota of fa/fa rats is affected by RYGB and/or DJB; and (iii) surgically induced microbiota alterations contribute to glucose metabolism. We observed a profound expansion of Firmicutes (specifically, Lactobacillus animalis and Lactobacillus reuteri) in the small intestine of diabetic fa/fa compared with nondiabetic fa/+ rats. RYGB-, but not DJB-, treated fa/fa rats exhibited greater microbiota diversity in the ileum and lower L. animalis and L. reuteri abundance compared with sham-operated fa/fa rats in all intestinal segments, and their microbiota composition resembled that of unoperated fa/+ rats. To investigate the functional role of RYGB-associated microbiota alterations, we transferred microbiota from sham- and RYGB-treated fa/fa rats to germ-free mice. The metabolic phenotype of RYGB-treated rats was not transferred by the transplant of ileal microbiota. In contrast, postprandial peak glucose levels were lower in mice that received cecal microbiota from RYGB- versus sham-operated rats. Thus, diabetes-associated microbiota alterations in fa/fa rats can be modified by RYGB, and modifications in the cecal microbiota may partially contribute to improved glucose tolerance after RYGB.

The effect of topiramate and lamotrigine on rat bone mass, structure and metabolism.

PubMed

Simko, Julius; Fekete, Sona; Gradosova, Iveta; Malakova, Jana; Zivna, Helena; Valis, Martin; Palicka, Vladimir; Zivny, Pavel

2014-05-15

There is only limited data concerning the effect of the newer antiepileptic drugs on bone. The objective of this study was to determine the effect of topiramate (TPM) and lamotrigine (LTG) monotherapy on bone mineral density (BMD), mineral content (BMC), bone markers, body composition and bone mechanical strength in the orchidectomized (ORX) rat model. 24 orchidectomized Wistar rats were divided into control and test groups, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed with SLD enriched with LTG or TPM for 12 weeks. Dual energy X-ray absorptiometry was used to measure bone mineral density. The concentrations of bone metabolism markers were assayed in bone homogenate. In addition, both femurs were measured and used for biomechanical testing. Compared to the control group, both test groups had significantly lower weight, fat mass, whole body and femur BMD, BMC and reduced mechanical strength of bone. All of these changes were more pronounced in rats exposed to LTG. In conclusion, both LTG and TPM significantly reduce BMD and body weight and impair mechanical strength of bone. A question arises as to the degree of dependence of the effect on the dose. Further studies are warranted to establish whether LTG and TPM may have a clinically significant effect on BMD exclusively in the model of gonadectomized rats, or whether the effect applies also in the model of gonadally intact animals, and in the respective human models. Copyright © 2014 Elsevier B.V. All rights reserved.

Elevated androstenedione in young adult but not early adolescent prenatally androgenized female rats.

PubMed

Shah, Ami B; Nivar, Isaac; Speelman, Diana L

2018-01-01

Elevated testosterone (T) is routinely reported as a marker of hyperandrogenemia in rodent models for polycystic ovary syndrome (PCOS). In women with PCOS, elevated serum androstenedione (A4) is associated with more severe phenotypes, including a positive correlation with serum T, DHEAS, free androgen index (FAI), LH, and LH/FSH ratio. Furthermore, A4, along with calculated free T and FAI, was identified as one of the best predictors of PCOS in adult women of all ages (18 to > 50 y). The objective of this study was to investigate serum A4 levels in early adolescent and young adult prenatally androgenized (PNA) female rats, a model for PCOS. Pregnant rats were injected with 5 mg T daily during gestational days 16-19 (PNA rats, experimental group) or an equal volume of vehicle (control group). Female offspring of both groups had tail vein blood drawn for serum analysis at 8 and 16 weeks of age. ELISAs were used to quantify serum A4 and T levels. Serum A4 and T were elevated in 16-week-old PNA rats compared to controls. There was no significant difference in either hormone at 8 weeks of age. The PNA rats demonstrated elevated serum A4 and T in young adulthood, as has been observed in women with PCOS, further validating this as a model for PCOS and underscoring the importance of serum A4 elevation as a parameter inherent to PCOS and a rodent model for the disorder. Significant A4 elevation develops between early adolescence and early adulthood in this PNA rat model.

[Age-related aspects of male rats sexual behavior with different senescence rates].

PubMed

Amstislavskaia, T G; Gladkikh, D V; Belousova, I I; Maslova, L N; Kolosova, N G

2010-01-01

Social and sexual behavior of males Wistar and senescence-accelerated OXYS rats was studied. The experimental model excluding direct interaction between partners showed that the exploratory activity decreased with aging in rats of both strains, but social motivation didn't change. No interstrain differences in intensity of sexual motivation in the presence of an inaccessible receptive female were observed in 4-month rats. The level of sexual motivation of 12-month Wistar rats didn't differ from that of 4-month animals. However, in 12-month OXYS males, sexual motivation was decreased as compared to both 4- and 12-month Wistar rats. The same regularities were found under conditions of direct interaction with a partner. Behavioral changes in 12-month OXYS rats were considered as genetically determinate abnormality at the initial stage of sexual behavior, i.e., sexual motivation. The results suggest the accelerated senescence of the reproductive system of OXYS rats.

[Effect of Warm Acupuncture on the Levels of Serum Immunoglobulin E, Interleukin-1 β and Tumor Necrosis Factor-α in Rats with Allergic Rhinitis].

PubMed

Zheng, Xian-Li; Tian, Yong-Ping; Luo, Hai-Yan; Zhao, Yao-Dong; Liu, Xiang-Yi; Jiang, Ying; Ma, Cheng-Xu; Wang, Ming-Juan; Liu, Min

2018-01-25

To observe the effect of warm acupuncture on behavior and contents of serum immunoglobulin E(IgE), interleukin-1 β(IL-1 β) and tumor necrosis factor-α(TNF-α) in allergic rhinitis(AR) rats, so as to explore its mechanism underlying improving AR. Forty Wistar rats were randomly divided into four groups: control group, model group, medication group and warm acupuncture group(10 rats/group). The AR model was established by intraperitoneal injection of sensitization and nasal drip. The rats in the medication group were given fluticasone propionate nasal spray, daily for 10 days. Warm acupuncture was applied to "Fengchi"(GB 20), "Yintang"(GV 29), "Yingxiang"(LI 20) for 60 seconds, once daily for 10 days. Behavioral scores were used to evaluate behavioral changes in rats. Enzyme linked immunosorbent assay (ELISA) was used to detect the expression levels of serum IgE, IL-1 β and TNF-α. Behavioral scores of the model group were significantly higher than those of the control group 0, 3, 7 and 10 days after modeling ( P <0.05). After treatment, the behavioral scores of medication group and the warm acupuncture group were lower than those of the model group ( P <0.05), and the score was more lower in the warm acupuncture group than in the medication group ( P <0.05). Compared with the control group, the levels of serum IgE, IL-1 β and TNF-α in the model group were all increased ( P <0.01), while the levels of serum IgE, IL-1 β and TNF-α were decreased in the medication and warm acupuncture groups after treatment in comparison with the model group ( P <0.05, P <0.01). Compared with the medication group, the levels of serum IgE, IL-1 β and TNF-α were significantly lower in the warm acupuncture group ( P <0.05, P <0.01). The expression levels of IgE, IL-1 β and TNF-α were elevated in serum after AR attack. Warm acupuncture can improve the symptoms of AR rats, which may be associated to its effect in inhibiting the expression of serum IgE, IL-1 β and TNF-α.

[Effects of Total Alkaloids of Harmaline on Learning and Memory in Vascular Dementia Rats].

PubMed

Zhang, Xiao-shuang; Sun, Jian-ning; Yu, Hui-ling

2015-11-01

To investigate the effects of total alkaloids of harmaline on learning and memory in vascular dementia rats, and its mechanism. The model rats of vascular dementia were established with bilateral carotid artery ligation. After 30 days, the model rats were randomly divided into six groups: sham group, model group, nicergoline tablets 7 mg/kg group, and 25, 12.5 and 6.25 mg/kg dose groups of total alkaloids of harmaline, the rats were given medicine for 30 days. Learning and memory abilities were tested by Morris water maze, histomorphology in hippocampal CA1 area were observed by HE staining, BAX and BCL-2 protein expression in hippocampal CA1 area were detected by immunohistochemistry. Compared with model group, 25 mg/kg group of total alkaloids of harmaline shortened the incubation period in the third and fourth day significantly, 12.5 mg/kg group of total alkaloids of harmaline shortened the incubation period in the fourth day. 25 and 12.5 mg/kg groups of total alkaloids of harmaline significantly increased the times crossing the target. Total alkaloids of harmaline improved the neurons pathological changes of rat in the hippocampus CA1 area, 25 and 12.5 mg/kg of total alkaloids of harmaline downregulated the expression of apoptosis proteins BAX, upregulated the protein expression of BCL-2. Total alkaloids of harmaline can improve the learning and memory abilities in vascular dementia rats, which probably is related to inhibiting apoptosis of hippocampus cell.

Early Activation of Ventral Hippocampus and Subiculum during Spontaneous Seizures in a Rat Model of Temporal Lobe Epilepsy

PubMed Central

Toyoda, Izumi; Bower, Mark R.; Leyva, Fernando

2013-01-01

Temporal lobe epilepsy is the most common form of epilepsy in adults. The pilocarpine-treated rat model is used frequently to investigate temporal lobe epilepsy. The validity of the pilocarpine model has been challenged based largely on concerns that seizures might initiate in different brain regions in rats than in patients. The present study used 32 recording electrodes per rat to evaluate spontaneous seizures in various brain regions including the septum, dorsomedial thalamus, amygdala, olfactory cortex, dorsal and ventral hippocampus, substantia nigra, entorhinal cortex, and ventral subiculum. Compared with published results from patients, seizures in rats tended to be shorter, spread faster and more extensively, generate behavioral manifestations more quickly, and produce generalized convulsions more frequently. Similarities to patients included electrographic waveform patterns at seizure onset, variability in sites of earliest seizure activity within individuals, and variability in patterns of seizure spread. Like patients, the earliest seizure activity in rats was recorded most frequently within the hippocampal formation. The ventral hippocampus and ventral subiculum displayed the earliest seizure activity. Amygdala, olfactory cortex, and septum occasionally displayed early seizure latencies, but not above chance levels. Substantia nigra and dorsomedial thalamus demonstrated consistently late seizure onsets, suggesting their unlikely involvement in seizure initiation. The results of the present study reveal similarities in onset sites of spontaneous seizures in patients with temporal lobe epilepsy and pilocarpine-treated rats that support the model's validity. PMID:23825415

Physical activity prevents augmented body fat accretion in moderately iron-deficient rats.

PubMed

McClung, James P; Andersen, Nancy E; Tarr, Tyson N; Stahl, Chad H; Young, Andrew J

2008-07-01

Recent studies describe an association between poor iron status and obesity in humans, although the mechanism explaining this relationship is unclear. The present study aimed to determine the effect of moderate iron deficiency and physical activity (PA) on body composition in an animal model. Male Sprague-Dawley rats consumed iron-adequate (IA; 40 mg/kg) or moderately iron-deficient (ID; 9 mg/kg) diets ad libitum for 12 wk. Rats were assigned to 4 treatment groups (n = 10 per group): IA, sedentary (IAS); IA, PA (IAPA); ID, sedentary (IDS); or ID, PA (IDPA). Activity involved running on motorized running wheels at 4 m/min for 1 h/d for 5 d/wk. After 12 wk, ID rats were not anemic, but body iron stores were reduced as indicated by diminished (P < 0.05) femur iron compared with IA rats. Treatment group did not affect body weight or feed consumption. However, fat mass was greater (P < 0.05) in IDS rats (38.6 +/- 6.7%) than IAS (31.8 +/- 2.9%), IAPA (31.8 +/- 2.0%), and IDPA (32.8 +/- 4.5%) rats. Furthermore, lean body mass was diminished in IDS rats (58.7 +/- 6.8%) compared with IAS (65.6 +/- 3.0%), IAPA (65.6 +/- 2.1%), and IDPA (64.7 +/- 4.5%) rats. Thus, moderate iron deficiency may cause increased body fat accretion in rats and PA attenuates that effect.

Salt-sparing diuretic action of a water-soluble urea analog inhibitor of urea transporters UT-A and UT-B in rats

PubMed Central

Cil, Onur; Esteva-Font, Cristina; Tas, Sadik Taskin; Su, Tao; Lee, Sujin; Anderson, Marc O.; Ertunc, Mert; Verkman, A. S.

2015-01-01

Inhibitors of kidney urea transporter (UT) proteins have potential use as salt-sparing diuretics (‘urearetics’) with a different mechanism of action than diuretics that target salt transporters. To study UT inhibition in rats, we screened about 10,000 drugs, natural products and urea analogs for inhibition of rat UT-A1. Drug and natural product screening found nicotine, sanguinarine and an indolcarbonylchromenone with IC50 of 10–20 μM. Urea analog screening found methylacetamide and dimethylthiourea (DMTU). DMTU fully and reversibly inhibited rat UT-A1 and UT-B by a noncompetitive mechanism with IC50 of 2–3 mM. Homology modeling and docking computations suggested DMTU binding sites on rat UT-A1. Following a single intraperitoneal injection of 500 mg/kg DMTU, peak plasma concentration was 9 mM with t1/2 of about 10 hours, and a urine concentration of 20–40 mM. Rats chronically treated with DMTU had a sustained, reversible reduction in urine osmolality from 1800 to 600 mOsm, a 3-fold increase in urine output, and mild hypokalemia. DMTU did not impair urinary concentrating function in rats on a low protein diet. Compared to furosemide-treated rats, the DMTU-treated rats had greater diuresis and reduced urinary salt loss. In a model of Syndrome of Inappropriate Antidiuretic Hormone secretion, DMTU treatment prevented hyponatremia and water retention produced by water-loading in dDAVP-treated rats. Thus, our results establish a rat model of UT inhibition and demonstrate the diuretic efficacy of UT inhibition. PMID:25993324

Salt-sparing diuretic action of a water-soluble urea analog inhibitor of urea transporters UT-A and UT-B in rats.

PubMed

Cil, Onur; Esteva-Font, Cristina; Tas, Sadik Taskin; Su, Tao; Lee, Sujin; Anderson, Marc O; Ertunc, Mert; Verkman, Alan S

2015-08-01

Inhibitors of kidney urea transporter (UT) proteins have potential use as salt-sparing diuretics ('urearetics') with a different mechanism of action than diuretics that target salt transporters. To study UT inhibition in rats, we screened about 10,000 drugs, natural products and urea analogs for inhibition of rat UT-A1. Drug and natural product screening found nicotine, sanguinarine and an indolcarbonylchromenone with IC50 of 10-20 μM. Urea analog screening found methylacetamide and dimethylthiourea (DMTU). DMTU fully and reversibly inhibited rat UT-A1 and UT-B by a noncompetitive mechanism with IC50 of 2-3 mM. Homology modeling and docking computations suggested DMTU binding sites on rat UT-A1. Following a single intraperitoneal injection of 500 mg/kg DMTU, peak plasma concentration was 9 mM with t1/2 of about 10 h, and a urine concentration of 20-40 mM. Rats chronically treated with DMTU had a sustained, reversible reduction in urine osmolality from 1800 to 600 mOsm, a 3-fold increase in urine output, and mild hypokalemia. DMTU did not impair urinary concentrating function in rats on a low protein diet. Compared to furosemide-treated rats, the DMTU-treated rats had greater diuresis and reduced urinary salt loss. In a model of syndrome of inappropriate antidiuretic hormone secretion, DMTU treatment prevented hyponatremia and water retention produced by water-loading in dDAVP-treated rats. Thus, our results establish a rat model of UT inhibition and demonstrate the diuretic efficacy of UT inhibition.

Beneficial effects of Acer okamotoanum sap on L-NAME-induced hypertension-like symptoms in a rat model.

PubMed

Yang, Hyun; Hwang, Inho; Koo, Tae-Hyoung; Ahn, Hyo-Jin; Kim, Sun; Park, Mi-Jin; Choi, Won-Sil; Kang, Ha-Young; Choi, In-Gyu; Choi, Kyung-Chul; Jeung, Eui-Bae

2012-02-01

The sap of Acer okamotoanum has been termed 'bone-benefit-water' in Korea owing to its mineral and sugar content. In particular, the calcium (Ca) and potassium (K) concentrations of the sap of Acer okamotoanum are 40- and 20-times higher, respectively, than commercial spring water. In the present study, we examined whether Acer okamotoanum sap improves or prevents hypertension-like symptoms in a rat model. Male Sprague-Dawley rats (8-weeks-old) were provided commercial spring water supplemented with 25, 50 or 100% Acer okamotoanum sap, 3% potassium ions (K+) or captopril, and treated daily for 2 weeks with NG-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg/day) by subcutaneous injection, in order to induce hypertensive symptoms. Rats were euthanized 6 h following the final injection. To assess the effect of the sap on hypertension-like symptoms, we examined the mean blood pressure (BP), protein levels and localization of endothelial nitric oxide synthase (eNOS) in the descending aorta of the rats. BP levels were significantly lower in hypertensive rats received 25, 50 and 100% sap compared with rats who were administered only commercial spring water. Protein levels of eNOS were repressed in L-NAME-only-treated rats, but were elevated in the descending aorta of rats administered captopril, K+ water and Acer okamotoanum sap (25, 50 and 100%) up to the level of the sham group provided commercial spring water, and then injected with dimethyl sulfoxide for the same period of time. Localized eNOS protein was abundantly expressed in the perivascular descending aorta adipose tissue of the rats. Taken together, these results demonstrated that the sap of Acer okamotoanum ameliorated high BP induced by L-NAME treatment in a rat model.

Effects of pinealectomy and melatonin supplementation on endometrial explants in a rat model.

PubMed

Koc, Onder; Gunduz, Bülent; Topcuoglu, Ata; Bugdayci, Güler; Yilmaz, Fahri; Duran, Bülent

2010-11-01

To determine the effects of pinealectomy on endometrial explants in rats and evaluate the activity of superoxide dismutase (SOD) and catalase (CAT) and the levels of malondialdehyde (MDA) in the rat endometriosis model. Rats with experimentally induced endometriosis were randomly divided into three groups after second-look laparotomies. Group 1 (pinealectomy, n = 8) and Group 2 (pinealectomy+melatonin, n = 8) underwent pinealectomies after the second-look laparotomies. Group 3 was presented as control group (vehicle solution+without pinealectomy (n = 6)). Melatonin was administered intraperitoneally for 4 weeks in Group 2, whereas an equal volume of vehicle solution was given to Groups 1 and 3. Evaluation of the volume of the endometrial explants, histopathological examination and preservation of explant epitheliums according to the scoring system were undertaken. There was a statistically significant increase in spherical explant volumes of Group 1 compared to Groups 2 and 3. In Group 1, the level of MDA was significantly higher and SOD and CAT activity was significantly lower compared to Groups 2 and 3. A statistically significant increase in the epithelial lining scores of explants was noted in Group 1 compared to Groups 2 and 3. The effects of pinealectomy on the progression of endometriosis explants were reversed by melatonin. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

A novel experimental model of erectile dysfunction in rats with heart failure using volume overload

PubMed Central

Silva, Fábio Henrique; Veiga, Frederico José Reis; Mora, Aline Gonçalves; Heck, Rodrigo Sader; De Oliveira, Caroline Candida; Gambero, Alessandra; Franco-Penteado, Carla Fernanda; Antunes, Edson; Gardner, Jason D.; Priviero, Fernanda Bruschi Marinho

2017-01-01

Background Patients with heart failure (HF) display erectile dysfunction (ED). However, the pathophysiology of ED during HF remains poorly investigated. Objective This study aimed to characterize the aortocaval fistula (ACF) rat model associated with HF as a novel experimental model of ED. We have undertaken molecular and functional studies to evaluate the alterations of the nitric oxide (NO) pathway, autonomic nervous system and oxidative stress in the penis. Methods Male rats were submitted to ACF for HF induction. Intracavernosal pressure in anesthetized rats was evaluated. Concentration-response curves to contractile (phenylephrine) and relaxant agents (sodium nitroprusside; SNP), as well as to electrical field stimulation (EFS), were obtained in the cavernosal smooth muscle (CSM) strips from sham and HF rats. Protein expression of endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) and phosphodiestarese-5 in CSM were evaluated, as well as NOX2 (gp91phox) and superoxide dismutase (SOD) mRNA expression. SOD activity and thiobarbituric acid reactive substances (TBARs) were also performed in plasma. Results HF rats display erectile dysfunction represented by decreased ICP responses compared to sham rats. The neurogenic contractile responses elicited by EFS were greater in CSM from the HF group. Likewise, phenylephrine-induced contractions were greater in CSM from HF rats. Nitrergic response induced by EFS were decreased in the cavernosal tissue, along with lower eNOS, nNOS and phosphodiestarese-5 protein expressions. An increase of NOX2 and SOD mRNA expression in CSM and plasma TBARs of HF group were detected. Plasma SOD activity was decreased in HF rats. Conclusion ED in HF rats is associated with decreased NO bioavailability in erectile tissue due to eNOS/nNOS dowregulation and NOX2 upregulation, as well as hypercontractility of the penis. This rat model of ACF could be a useful tool to evaluate the molecular alterations of ED associated with HF. PMID:29095897

A novel experimental model of erectile dysfunction in rats with heart failure using volume overload.

PubMed

Silva, Fábio Henrique; Veiga, Frederico José Reis; Mora, Aline Gonçalves; Heck, Rodrigo Sader; De Oliveira, Caroline Candida; Gambero, Alessandra; Franco-Penteado, Carla Fernanda; Antunes, Edson; Gardner, Jason D; Priviero, Fernanda Bruschi Marinho; Claudino, Mário Angelo

2017-01-01

Patients with heart failure (HF) display erectile dysfunction (ED). However, the pathophysiology of ED during HF remains poorly investigated. This study aimed to characterize the aortocaval fistula (ACF) rat model associated with HF as a novel experimental model of ED. We have undertaken molecular and functional studies to evaluate the alterations of the nitric oxide (NO) pathway, autonomic nervous system and oxidative stress in the penis. Male rats were submitted to ACF for HF induction. Intracavernosal pressure in anesthetized rats was evaluated. Concentration-response curves to contractile (phenylephrine) and relaxant agents (sodium nitroprusside; SNP), as well as to electrical field stimulation (EFS), were obtained in the cavernosal smooth muscle (CSM) strips from sham and HF rats. Protein expression of endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) and phosphodiestarese-5 in CSM were evaluated, as well as NOX2 (gp91phox) and superoxide dismutase (SOD) mRNA expression. SOD activity and thiobarbituric acid reactive substances (TBARs) were also performed in plasma. HF rats display erectile dysfunction represented by decreased ICP responses compared to sham rats. The neurogenic contractile responses elicited by EFS were greater in CSM from the HF group. Likewise, phenylephrine-induced contractions were greater in CSM from HF rats. Nitrergic response induced by EFS were decreased in the cavernosal tissue, along with lower eNOS, nNOS and phosphodiestarese-5 protein expressions. An increase of NOX2 and SOD mRNA expression in CSM and plasma TBARs of HF group were detected. Plasma SOD activity was decreased in HF rats. ED in HF rats is associated with decreased NO bioavailability in erectile tissue due to eNOS/nNOS dowregulation and NOX2 upregulation, as well as hypercontractility of the penis. This rat model of ACF could be a useful tool to evaluate the molecular alterations of ED associated with HF.

Generation of immunodeficient rats with Rag1 and Il2rg gene deletions and human tissue grafting models.

PubMed

Ménoret, Séverine; Ouisse, Laure-Hélène; Tesson, Laurent; Delbos, Frédéric; Garnier, Delphine; Remy, Séverine; Usal, Claire; Concordet, Jean-Paul; Giovannangeli, Carine; Chenouard, Vanessa; Brusselle, Lucas; Merieau, Emmanuel; Nerrière-Daguin, Véronique; Duteille, Franck; Bellier-Waast, Frédérique; Fraichard, Alexandre; Nguyen, Tuan H; Anegon, Ignacio

2018-04-24

Immunodeficient mice are invaluable tools to analyze the long-term effects of potentially immunogenic molecules in the absence of adaptive immune responses. Nevertheless, there are models and experimental situations that would beneficiate of larger immunodeficient recipients. Rats are ideally suited to perform experiments in which larger size is needed and are still a small animal model suitable for rodent facilities. Additionally, rats reproduce certain human diseases better than mice, such as ankylosing spondylitis and Duchenne disease and these disease models would greatly benefit of immunodeficient rats to test different immunogenic treatments. We describe the generation of Il2rg-deficient rats and their crossing with previously described Rag1-deficient rats to generate double-mutant RRG animals. As compared to Rag1-deficient rats, Il2rg-deficient rats were more immunodeficient since partially lacked not only T and B cells but also NK cells. RRG animals showed a more profound immunossuppressed phenotype since they displayed undetectable levels of T, B and NK cells. Similarly, all immunoglobulin isotypes in sera were decreased in Rag1 or Il2rg-deficient rats and undetectable in RRG animals. Rag1 or Il2rg-deficient rats rejected allogeneic skin transplants and human tumors whereas RRG animals not only accepted allogeneic rat skin but also xenogeneic human tumors, skin and hepatocytes. Immune humanization of RRG animals was unsuccessful. Thus, immunodeficient RRG animals are useful recipients for long term studies in which immune responses could be an obstacle, including tissue humanization of different tissues.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Hydroxyl Radical Modification of Collagen Type II Increases Its Arthritogenicity and Immunogenicity

PubMed Central

Shahab, Uzma; Ahmad, Saheem; Moinuddin; Dixit, Kiran; Habib, Safia; Alam, Khursheed; Ali, Asif

2012-01-01

Background The oxidation of proteins by endogenously generated free radicals causes structural modifications in the molecules that lead to generation of neo-antigenic epitopes that have implications in various autoimmune disorders, including rheumatoid arthritis (RA). Collagen induced arthritis (CIA) in rodents (rats and mice) is an accepted experimental model for RA. Methodology/Principal Findings Hydroxyl radicals were generated by the Fenton reaction. Collagen type II (CII) was modified by •OH radical (CII-OH) and analysed by ultraviolet-visible (UV-VIS), fluorescence and circular dichroism (CD) spectroscopy. The immunogenicity of native and modified CII was checked in female Lewis rats and specificity of the induced antibodies was ascertained by enzyme linked immunosorbent assay (ELISA). The extent of CIA was evaluated by visual inspection. We also estimated the oxidative and inflammatory markers in the sera of immunized rats. A slight change in the triple helical structure of CII as well as fragmentation was observed after hydroxyl radical modification. The modified CII was found to be highly arthritogenic and immunogenic as compared to the native form. The CII-OH immunized rats exhibited increased oxidative stress and inflammation as compared to the CII immunized rats in the control group. Conclusions/Significance Neo-antigenic epitopes were generated on •OH modified CII which rendered it highly immunogenic and arthritogenic as compared to the unmodified form. Since the rodent CIA model shares many features with human RA, these results illuminate the role of free radicals in human RA. PMID:22319617

Impulsive choice behavior in four strains of rats: Evaluation of possible models of Attention Deficit/Hyperactivity Disorder

PubMed Central

Garcia, Ana; Kirkpatrick, Kimberly

2012-01-01

Several studies have examined impulsive choice behavior in spontaneously hypertensive rats (SHRs) as a possible pre-clinical model for Attention-Deficit/Hyperactivity Disorder (ADHD). However, this strain was not specifically selected for the traits of ADHD and as a result their appropriateness as a model has been questioned. The present study investigated whether SHRs would exhibit impulsive behavior in comparison to their control strain, Wistar Kyoto (WKY) rats. In addition, we evaluated a strain that has previously shown high levels of impulsive choice, the Lewis (LEW) rats and compared them with their source strain, Wistar (WIS) rats. In the first phase, rats could choose between a Smaller-sooner (SS) reward of 1 pellet after 10 s and a Larger-later (LL) reward of 2 pellets after 30 s. Subsequently, the rats were exposed to increases in LL reward magnitude and SS delay. These manipulations were designed to assess sensitivity to magnitude and delay within the choice task to parse out possible differences in using the strains as models of specific deficits associated with ADHD. The SHR and WKY strains did not differ in their choice behavior under either delay or magnitude manipulations. In comparison to WIS, LEW showed deficits in choice behavior in the delay manipulation, and to a lesser extent in the magnitude manipulation. An examination of individual differences indicated that the SHR strain may not be sufficiently homogeneous in their impulsive choice behavior to be considered as a viable model for impulse control disorders such as ADHD. The LEW strain may be worthy of further consideration for their suitability as an animal model. PMID:23085479

Effect of exercise training and food restriction on endothelium-dependent relaxation in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous NIDDM.

PubMed

Sakamoto, S; Minami, K; Niwa, Y; Ohnaka, M; Nakaya, Y; Mizuno, A; Kuwajima, M; Shima, K

1998-01-01

We investigated whether endothelial function may be impaired in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous NIDDM. The effect of exercise training and food restriction on endothelial function was also studied. OLETF rats were divided into three groups at age 16 weeks: sedentary, exercise trained, and food restricted (70% of the food intake of sedentary rats). Otsuka Long-Evans Tokushima rats were used as the age-matched nondiabetic controls. Endothelium-dependent relaxation of the thoracic aorta induced by histamine was significantly attenuated in the sedentary or food-restricted rats, and exercise training improved endothelial function. Relaxation induced by sodium nitroprusside, a donor of nitric oxide, did not differ significantly among groups. Both exercise training and food restriction significantly suppressed plasma levels of glucose and insulin and serum levels of triacylglycerol and cholesterol and reduced the accumulation of abdominal fat. Insulin sensitivity, as measured by the hyperinsulinemic-euglycemic clamp technique, was significantly decreased in sedentary rats but was enhanced in exercise-trained and food-restricted rats. The urinary excretion of nitrite was significantly decreased in sedentary and food-restricted rats compared with nondiabetic rats and was significantly increased in exercise-trained rats. These results indicate that exercise training, but not food restriction, prevents endothelial dysfunction in NIDDM rats, presumably due to the exercise-induced increase in the production of nitric oxide.

Effect of Tripterygium Wilfordii Polyglycoside on Experimental Prostatitis Caused by Ureaplasma Urealyticum in Rats

PubMed Central

Shan, Pingnan; Lu, Zhiyong; Ye, Lihong; Fang, Yaqin; Tan, Suhong; Xuan, Guohong; Ru, Jincheng; Mao, Liming

2016-01-01

Background Prostatitis is a common and refractory urological disease with complicated etiology. Ureaplasma urealyticum (UU) has a close relationship with human urinary tract infection that can induce nonbacterial prostatitis. Tripterygium wilfordii polyglycoside (TWP) is a non-steroidal immune inhibitor that causes significant immune suppression and anti-inflammatory effects. Its role in prostatitis caused by UU has not yet been established. The aim of this study was to investigate the effect of TWP on UU-infected prostatitis in a rat model. Material/Methods UU-infected prostatitis SD model rats were randomly divided into 2 groups: the prostatitis group (model group) and the TWP treatment group (treatment group). At 7 days after treatment, prostate weight, leucocyte count, lecithin corpuscles, UU infection rate, and UU microbe count were compared between the 2 groups. Serum inflammatory cytokines TNF-α was determined by ELISA, and ICAM-1 and NF-κB expression were detected. Results UU infection rate was 80% after modeling. The rat prostate weight and leucocyte count in the model group increased significantly, while lecithin corpuscles decreased. Compared with controls, inflammatory factor TNF-α, ICAM-1, and NF-κB expression were obviously higher (P<0.05). TWP markedly reduced prostate weight and leucocyte count, increased lecithin corpuscles, and decreased UU microbe count and TNF-α, ICAM-1, and NF-κB expression (P<0.05). Conclusions TWP can inhibit expression of inflammatory factors and may be useful in treating UU-infected prostatitis through reducing UU infection rate. PMID:27743513

Effect of Tripterygium Wilfordii Polyglycoside on Experimental Prostatitis Caused by Ureaplasma Urealyticum in Rats.

PubMed

Shan, Pingnan; Lu, Zhiyong; Ye, Lihong; Fang, Yaqin; Tan, Suhong; Xuan, Guohong; Ru, Jincheng; Mao, Liming

2016-10-15

BACKGROUND Prostatitis is a common and refractory urological disease with complicated etiology. Ureaplasma urealyticum (UU) has a close relationship with human urinary tract infection that can induce nonbacterial prostatitis. Tripterygium wilfordii polyglycoside (TWP) is a non-steroidal immune inhibitor that causes significant immune suppression and anti-inflammatory effects. Its role in prostatitis caused by UU has not yet been established. The aim of this study was to investigate the effect of TWP on UU-infected prostatitis in a rat model. MATERIAL AND METHODS UU-infected prostatitis SD model rats were randomly divided into 2 groups: the prostatitis group (model group) and the TWP treatment group (treatment group). At 7 days after treatment, prostate weight, leucocyte count, lecithin corpuscles, UU infection rate, and UU microbe count were compared between the 2 groups. Serum inflammatory cytokines TNF-α was determined by ELISA, and ICAM-1 and NF-κB expression were detected. RESULTS UU infection rate was 80% after modeling. The rat prostate weight and leucocyte count in the model group increased significantly, while lecithin corpuscles decreased. Compared with controls, inflammatory factor TNF-α, ICAM-1, and NF-κB expression were obviously higher (P<0.05). TWP markedly reduced prostate weight and leucocyte count, increased lecithin corpuscles, and decreased UU microbe count and TNF-α, ICAM-1, and NF-κB expression (P<0.05). CONCLUSIONS TWP can inhibit expression of inflammatory factors and may be useful in treating UU-infected prostatitis through reducing UU infection rate.

Effects of compound Shenhua tablet on renal tubular Na+-K+-ATPase in rats with acute ischemic reperfusion injury.

PubMed

Yang, Yue; Wei, Ri-bao; Zheng, Xiao-yong; Qiu, Qiang; Cui, Shao-yuan; Yin, Zhong; Shi, Suo-zhu; Chen, Xiang-mei

2014-03-01

To observe the effect of Compound Shenhua Tablet (, SHT) on the sodium-potassium- exchanging adenosinetriphosphatase (Na(+)-K(+)-ATPase) in the renal tubular epithelial cells of rats with acute ischemic reperfusion and to investigate the mechanisms underlying the effects of SHT on renal ischemic reperfusion injury (RIRI). Fifty male Wistar rats were randomly divided into the sham surgery group, model group, astragaloside group [150 mg/(kg·d)], SHT low-dose group [1.5 g/(kg·d)] and SHT high-dose group [3.0 g/(kg·d)], with 10 rats in each group. After 1 week of continuous intragastric drug administration, surgery was performed to establish the model. At either 24 or 72 h after the surgery, 5 rats in each group were sacrificed, blood biochemistry, renal pathology, immunoblot and immunohistochemical examinations were performed, and double immunofluorescence staining was observed under a laser confocal microscope. Compared with the sham surgery group, the serum creatinine (SCr) and blood urea nitrogen (BUN) levels were significantly increased, Na(+)-K(+)-ATPase protein level was decreased, and kidney injury molecule-1 (KIM-1) protein level was increased in the model group after the surgery (P<0.01 or P<0.05). Compared with the model group, the SCr, BUN, pathological scores, Na(+)-K(+)-ATPase, and the KIM-1 protein level of the three treatment groups were significantly improved at 72 h after the surgery (P<0.05 or P<0.01). And the SCr, BUN of the SHT low- and high-dose groups, and the pathological scores of the SHT high-dose group were significantly lower than those of the astragaloside group (P<0.05). The localizations of Na(+)-K(+)-ATPase and megalin of the model group were disrupted, with the distribution areas overlapping with each other and alternately arranged. The severity of the disruption was slightly milder in three treatment groups compared with that of the model group. The results of immunofluorescence staining showed that the SHT high-dose group had a superior effect as compared with the astragaloside group and the SHT low-dose group. The SHT effectively alleviated RIRI caused by ischemic reperfusion, promoted the recovery of the polarity of renal tubular epithelial cells, and protected the renal tubules. The therapeutic effects of SHT were superior to those of astragaloside as a single agent.

Traditional Mongolian medicine Eerdun Wurile improves stroke recovery through regulation of gene expression in rat brain.

PubMed

Gaowa, Saren; Bao, Narisi; Da, Man; Qiburi, Qiburi; Ganbold, Tsogzolmaa; Chen, Lu; Altangerel, Altanzul; Temuqile, Temuqile; Baigude, Huricha

2018-05-16

Eerdun Wurile (EW) is one of the key Mongolian medicines for treatment of neurological and cardiological disorders. EW is ranked most regularly used Mongolian medicine in clinic. Components of EW which mainly originate from natural products are well defined and are unique to Mongolian medicine. Although the recipe of EW contains known neuroactive chemicals originated from plants, its mechanism of action has never been elucidated at molecular level. The objective of the present study is to explore the mechanism of neuroregenerative activity of EW by focusing on the regulation of gene expression in the brain of rat model of stroke. Rat middle cerebral artery occlusion (MCAO) models were treated with EW for 15 days. Then, total RNAs from the cerebral cortex of rat MCAO models treated with either EW or control (saline) were extracted and analyzed by transcriptome sequencing. Differentially expressed genes were analyzed for their functions during the recovery of ischemic stroke. The expression level of significantly differentially expressed genes such as growth factors, microglia markers and secretive enzymes in the lesion was further validated by RT-qPCR and immunohistochemistry. Previously identified neuroactive compounds, such as geniposide (Yu et al., 2009), myristicin (Shin et al., 1988), costunolide (Okugawa et al., 1996), toosendanin (Shi and Chen, 1999) were detected in EW formulation. Bederson scale indicated that the treatment of rat MCAO models with EW showed significantly lowered neurological deficits (p < 0.01). The regional cerebral blood circulation was also remarkably higher in rat MCAO models treated with EW compared to the control group. A total of 186 genes were upregulated in the lesion of rat MCAO models treated with EW compared to control group. Among them, growth factors such as Igf1 (p < 0.05), Igf2 (p < 0.01), Grn (p < 0.01) were significantly upregulated in brain after treatment of rat MCAO models with EW. Meanwhile, greatly enhanced expression of microglia markers, as well as complementary components and secretive proteases were also detected. Our data collectively indicated that EW enhances expression of growth factors including Igf1 and Igf2 in neurons and microglia, and may stimulate microglia polarization in the brain. The consequences of such activity include stimulation of neuron growth, hydrolysis and clearance of cell debris at the lesion, as well as the angiogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

Comparative toxicogenomic analysis of oral Cr(VI) exposure effects in rat and mouse small intestinal epithelia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kopec, Anna K.; Thompson, Chad M.; Kim, Suntae

2012-07-15

Continuous exposure to high concentrations of hexavalent chromium [Cr(VI)] in drinking water results in intestinal tumors in mice but not rats. Concentration-dependent gene expression effects were evaluated in female F344 rat duodenal and jejunal epithelia following 7 and 90 days of exposure to 0.3–520 mg/L (as sodium dichromate dihydrate, SDD) in drinking water. Whole-genome microarrays identified 3269 and 1815 duodenal, and 4557 and 1534 jejunal differentially expressed genes at 8 and 91 days, respectively, with significant overlaps between the intestinal segments. Functional annotation identified gene expression changes associated with oxidative stress, cell cycle, cell death, and immune response that weremore » consistent with reported changes in redox status and histopathology. Comparative analysis with B6C3F1 mouse data from a similarly designed study identified 2790 differentially expressed rat orthologs in the duodenum compared to 5013 mouse orthologs at day 8, and only 1504 rat and 3484 mouse orthologs at day 91. Automated dose–response modeling resulted in similar median EC{sub 50}s in the rodent duodenal and jejunal mucosae. Comparative examination of differentially expressed genes also identified divergently regulated orthologs. Comparable numbers of differentially expressed genes were observed at equivalent Cr concentrations (μg Cr/g duodenum). However, mice accumulated higher Cr levels than rats at ≥ 170 mg/L SDD, resulting in a ∼ 2-fold increase in the number of differentially expressed genes. These qualitative and quantitative differences in differential gene expression, which correlate with differences in tissue dose, likely contribute to the disparate intestinal tumor outcomes. -- Highlights: ► Cr(VI) elicits dose-dependent changes in gene expression in rat intestine. ► Cr(VI) elicits less differential gene expression in rats compared to mice. ► Cr(VI) gene expression can be phenotypically anchored to intestinal changes. ► Species-specific and divergent changes are consistent with species-specific tumors.« less

Neuroprotective effects of agmatine in experimental peripheral nerve injury in rats: a prospective randomized and placebo-controlled trial.

PubMed

Sezer, Aykut; Guclu, Bulent; Kazanci, Burak; Cakir, Murteza; Coban, Mustafa Kemal

2014-01-01

The purpose of this study was to demonstrate the activity of agmatine, an inducible nitric oxide synthase (iNOS) inhibitor and selective N-methyl-D-aspartate receptor (NMDAR) antagonist, on reducing tissue damage in distal part of traumatic nerve in an experimental rat peripheral nerve injury model. Sciatic nerves of 30 Sprague Dawley male rats were used. Rats were divided into 5 groups; group 1 (n=6), control group; group 2 (n=6), axonotmesis + placebo group; group 3 (n=6), axonotmesis + 50 mg/kg agmatine treatment group; group 4 (n=6), neurotmesis + placebo group; group 5 (n=6), neurotmesis + 50 mg/kg agmatine treatment group. Axonolysis, axon degeneration, edema, hemorrhage, and inflammation were evaluated in histopathologic examinations of all the groups. When group 2 was compared with group 3 in histopathologic sections, axonolysis was less in group 3 (p=0.007), as was axon degeneration (p=0.022) and edema (p=0.018). When group 4 was compared with group 5, axonolysis was less in group 5 (p=0.009), as was axon degeneration (p=0.006) and edema (p=0.021). This study demonstrated agmatine to have antioxidant and antineurotoxic effects in an experimental rat peripheral nerve injury model.

Protein and lipid oxidative damage in streptozotocin-induced diabetic rats submitted to forced swimming test: the insulin and clonazepam effect.

PubMed

Wayhs, Carlos Alberto Yasin; Manfredini, Vanusa; Sitta, Angela; Deon, Marion; Ribas, Graziela; Vanzin, Camila; Biancini, Giovana; Ferri, Marcelo; Nin, Maurício; Barros, Helena Maria Tannhauser; Vargas, Carmen Regla

2010-09-01

Diabetes may modify central nervous system functions and is associated with moderate cognitive deficits and changes in the brain, a condition that may be referred to as diabetic encephalopathy. The prevalence of depression in diabetic patients is higher than in the general population, and clonazepam is being used to treat this complication. Oxidative stress may play a role in the development of diabetes complications. We investigated oxidative stress parameters in streptozotocin-induced diabetic rats submitted to forced swimming test (STZ) and evaluated the effect of insulin (STZ-INS) and/or clonazepam (STZ-CNZ and STZ-INS-CNZ) acute treatment on these animal model. Oxidative damage to proteins measured as carbonyl content in plasma was significantly increased in STZ group compared to STZ treated groups. Malondialdehyde plasma levels were significantly reduced in STZ-INS and STZ-INS-CNZ groups when compared to STZ rats, being significantly reduced in STZ-INS-CNZ than STZ-INS rats. The activities of the antioxidant enzymes catalase, superoxide dismutase and glutathione peroxidase showed no significant differences among all groups of animals. These findings showed that protein and lipid damage occurs in this diabetes/depression animal model and that the associated treatment of insulin and clonazepam is capable to protect against oxidative damage in this experimental model.

[Expression of A-type atrial natriuretic peptide receptor in the kidneys of renovascular hypertension rats and its implication].

PubMed

Liu, Rong-Tao; Xiao, Jing; Guo, Hui-Ling; Qiu, Dun-Guo; Yin, Hua-Hu; Wang, Zheng-Rong

2005-11-01

To investigate the expression of A-type atrial natriuretic peptide receptor (ANPR-A) in the kidneys of renovascular hypertension rats and evaluate the significance of the expression. The rat model of renovascular hypertension was produced by constricting one lateral renal artery. After the renal artery being constricted for 4 weeks and 8 weeks, the systolic BP of rats was measured with a manometer using the tail-cuff method. Then, the expression of ANPR-A was respectively detected by immunohistochemical technique in the kidneys of the two-kidney, one-clip (2K1C) rats, and the expression level of ANPR-A was semi-quantitatively measured by Mias-2000 computer image analyzer. At 4 weeks after the artery-constricted operation,the expression of ANPR-A increased significantly in 2K1C hypertensive rat glomeruli and decreased significantly in renal tubules, compared with control (P<0.01), but there was no marked change in medullar collecting tubules. At 8 weeks after the artery-constricted operation, the expression of ANPR-A decreased significantly in 2K1C hypertensive rat renal tubules and medullar collecting tubules, compared with control (P<0.01); however, there was weak expression in glomeruli, and no statistically significant difference was seen when compared with control (P>0.05). The expression of ANPR-A decreased significantly in kidney tissues of renovascular

The Neuroprotective Effect of Erythropoietin in Rat Hippocampus in an Endotoxic Shock Model.

PubMed

Ramírez-Jirano, Luis Javier; Zenteno-Savín, Tania; Gaxiola-Robles, Ramón; Ramos-González, Elsy Janeth; Torres-Mendoza, Blanca Miriam; Bitzer-Quintero, Oscar Kurt

2016-01-01

Sepsis is characterized by an early systemic inflammation in response to infection. In the brain, inflammation is associated with expression of pro-inflammatory cytokines (e.g. tumor necrosis factor-α, interleukin-1β and interleukin-6, among others) that may induce an overproduction of reactive oxygen and nitrogen species. The constitutive expression of cytokines in the brain is low, but may be induced by various stimuli, including lipopolysaccharide, which causes neuronal damage. Erythropoietin, among other effects, acts as a multifunctional neurotrophic factor implicated in neurogenesis, angiogenesis, vascular permeability, and immune regulation in the central nervous system. In an experimental model of endotoxic shock, we studied the neuroprotective capacity of erythropoietin in the rat hippocampus and compared with melatonin, a neurohormone with an important antioxidant and immunomodulatory effect. In 21-day-old male Wistar rats divided into eight groups, we administered by intraperitoneal injection lipopolysaccharide, erythropoietin, melatonin, or combinations thereof. The hippocampus was dissected and morphological (histological analysis) and biochemical (cytokine levels) studies were conducted. The number of dead neuronal cells in histological sections in groups treated with lipopolysaccharide was higher compared to the erythropoietin group. There was a greater decrease (70%) in interleukin-1β concentrations in rats with endotoxic shock that received erythropoietin compared to the lipopolysaccharide group. The neuronal cell loss caused by endotoxic shock and interleukin-1β levels were reduced by the administration of the hematopoietic cytokine erythropoietin in this experimental model.

Impact of pneumoperitoneum on tumor growth.

PubMed

Lécuru, F; Agostini, A; Camatte, S; Robin, F; Aggerbeck, M; Jaïs, J P; Vilde, F; Taurelle, R

2002-08-01

To compare intraperitoneal tumor growth after CO2 laparoscopy (L), gasless laparoscopy (GL), midline laparotomy (ML), and general anesthesia (GA) as a control. A prospective randomized trial was carried out in nude rats. A carcinomatosis was obtained by intraperitoneal injection of either one of the two human ovarian cancer cell lines IGR-OV1 or NIH:OVCAR-3. Rats secondly underwent randomly different kind of procedures: CO2 L (8 mmHg, 60 min), GL (traction by a balloon for 60 min), ML (bowel removed and let on a mesh for 60 min), or GA. The rats were finally killed 10 or 35 days after surgery (respectively in IGR-OV1, or NIH:OVCAR-3 models). Tumor growth was assessed by the weight of the omental metastasis and MIB1 immunostaining. Peritoneal dissemination as well as abdominal wall metastases were assessed by pathological examination. Statistical analysis used the chi-square test (or Fisher exact test) and Bonferroni method for multiple comparison between groups. Fifteen rats were included in each group. Mean omental weight was significantly increased after surgery (3.1 to 5.6 g), when compared to control (2.4 g), but no significant difference was recorded between the three surgical accesses. MIB1 immunostaining was poor in the PNP group (37%), whereas it was higher after midline laparotomy (51%), but the difference was not significant (p = 0.07). Similarly, no significant variation was recorded in the NIH:OVCAR-3 model for omental weight or MIB1 staining. CO2 pneumoperitoneum significantly increased right diaphragmatic dome involvement in the NIH:OVCAR-3 model. Abdominal wall metastases were significantly more frequent after surgery when compared to the control group, but no significant difference could be demonstrated between surgical groups in each model. In these solid tumor models, CO2 pneumoperitoneum had no deleterious effect on tumor growth when compared to gasless laparoscopy or midline laparotomy.

Potent therapeutic effects of shouwu jiangqi decoction on polycystic ovary syndrome with insulin resistance in rats.

PubMed

Wang, Li-hong; Wang, Xu; Yu, Xi-zhong; Xu, Wen-ting

2016-02-01

To investigate the effect of Shouwu Jiangqi Decoction (SJD) on polycystic ovary syndrome (PCOS) with insulin resistance (IR) in rats and to explore the underlining molecular mechanisms. A total of 51 female Sprague-Dawley rats were randomly divided into 6 groups: control group (n=7), model group (n=8), SJD high-dose group (n=9), SJD medium-dose group (n=9), SJD low-dose group (n=9) and DMBG group (n=9). Radioimmunoassay was used to measure serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone concentrations and qRT-PCR and western blot were used to examine the expression levels of mRNA and protein respectively of insulin receptor substrate 1 (IRS-1) and phosphatidylinositide 3-kinases (PI3K) p85α in different groups. FSH level significantly decreased in the model group compared with the normal control (P<0.01), and high-dose SJD and DMBG can significantly increase FSH level (P<0.01). LH level showed a mild increase without statistic significance in the model group compared with the control and different dosages of SJD had no significance effect on LH level, while DMBG can significantly decrease LH level (P<0.01). Testosterone level significantly increased in the model group compared with the control group (P<0.01), and high-dose SJD and DMBG can significantly decrease testosterone level (P<0.01). The expression of IRS-1 as well as PI3Kp85α were significantly decreased in the model group compared with the normal control group at both mRNA (P<0.001) and protein (P<0.01) level, and both high-dose SJD and DMBG can enhance IRS-1 and PI3K expression (P<0.05). SJD has potent therapeutic effects on PCOS with IR in rats. The therapeutic effects of SJD on IR and ovulatory dysfunction are probably achieved through correcting the defective insulin signaling transduction.

[Effects of electroacupuncture at "Jiaji" (EX-B 2) on myocardial apoptosis and the expression of Bcl-2 and Bax in rats with ischemia-reperfusion injury].

PubMed

Kong, Su-Ping; Zhang, Xin; Tan, Qi-Wen

2013-06-01

To explore the protective mechanism of acupuncture on myocardial ischemia-reperfusion injury. Fifty Wistar rats were randomly divided into a sham-operation group, a model group, a Jiaji group , a Neiguan group and a Yanglingquan group, 10 rats in each group. The model of myocardial ischemia-reperfusion injury was duplicated by ligating the left anterior descending coronary artery (LADCA) in the later four groups, and the LADCA was not ligated in the sham-operation group. The rats in the treatment groups were treated with electroacupuncture at "Jiaji" (EX-B 2), "Neiguan" (PC 6) and "Yanglingquan" (GB 34) on both sides, respectively, once a day for 7 days. No interventions were produced in the sham-operation group and model group. Myocardial apoptosis were examined by the TUNEL method. The expressions of Bcl-2 and Bax proteins were measured by immunohistochemical method. Apoptosis index(AI) was significantly lower in the Jiaji group, Neiguan group and sham-operation group compared with model group (P < 0.01). Compared with the sham-operation group, AI were significantly increased in other groups (all P < 0.01). There was no significant difference in AI between Jiaji and Neiguan group (P > 0.05). Compared with the model group, the expression of Bcl-2 was significantly increased and Bax protein was significantly decreased in Jiaji group and Neiguan group (both P < 0.01). The expressions of Bcl-2 and Bax proteins were significantly increased in other groups compared with the sham-operation group (all P < 0.01). There was no significant difference in the expression of Bcl-2 and Bax proteins between Jiaji and Neiguan group (P > 0.05). Electroacupuncture at both Jiaji (EX-B 2) and Neiguan (PC 6) has protective effects on myocardial ischemia-reperfusion injury, and the mechanism is closely related to inhibiting myocardial apoptosis by adjusting the expression of Bcl-2 and Bax.

[Effect of Electroacupuncture at "Neiguan" (PC 6) and "Tianshu" (ST 25) for Colonic Motility and D 2 Receptor in Irritable Bowel Syndrome Rats].

PubMed

Wang, Shan; Guo, Meng-Wei; Gao, Yu-Shan; Ren, Xiao-Xuan; Lan, Ying; Ji, Mao-Xian; Wu, Yan-Ying; Li, Kai-Ge; Tan, Li-Hua; Sui, Ming-He

2018-01-25

To observe and compare the effects of electroacupuncture (EA) at "Tianshu" (ST 25) and "Neiguan" (PC 6) for colonic motility and the expression of colon dopamine D 2 in irritable bowel syndrome (IBS) rats, and to explore the specificity of different meridians and different acupoints. Forty Wistar newborn rats were randomly divided into blank, model, Tianshu and Neiguan groups. Separation of mother and child and acetic acid coloclyster combined with colorectal distension were used to establish IBS model in the model, Tianshu and Neiguan groups. At the age of 9 weeks, EA at bilateral ST 25 and PC 6 were applied in the corresponding groups 5 times, once every other day. After the intervention, the Bristol fecal score, the latent period of abdominal retraction reflex and the number of contraction waves were recorded. The expression of dopamine D 2 receptor was detected by immunohistochemistry. Compared with the blank group, the Bristol fecal score of the model group was higher ( P <0.01), the 1 st contraction wave latent period was shorter ( P <0.01), the number of contraction waves in 90 s increased ( P <0.01), the immunoreactive expression of D 2 receptor in colon decreased ( P <0.01). Compared with the model group, the Bristol fecal scores of the Tianshu and Neiguan groups decreased ( P <0.01), the 1 st contraction wave latent periods were longer ( P <0.01), the numbers of contraction waves in 90 s decreased ( P <0.01), the positive expressions of D 2 receptor in colon increased ( P <0.01, P <0.05). Compared with the Tianshu group, the immunoreactive expression of D 2 receptor in the Neiguan group decreased ( P <0.01). EA at ST 25 and PC 6 can improve the symptoms of colonic motility in IBS rats. The effect of EA at ST 25 is better, which indicates that different meridians and different acupoints play specific effects.

Sibutramine reduces feeding, body fat and improves insulin resistance in dietary-obese male Wistar rats independently of hypothalamic neuropeptide Y

PubMed Central

Brown, Michael; Bing, Chen; King, Peter; Pickavance, Lucy; Heal, David; Wilding, John

2001-01-01

We studied the effects of the novel noradrenaline and serotonin (5-HT) reuptake inhibitor sibutramine on feeding and body weight in a rat model of dietary obesity, and whether it interacts with hypothalamic neuropeptide Y (NPY) neurones.Chow-fed and dietary-obese (DIO) male Wistar rats were given sibutramine (3 mg kg−1 day−1 p.o.) or deionized water for 21 days.Sibutramine decreased food intake throughout the treatment period in both dietary-obese rats (P<0.0001) and lean rats (P<0.0001). Weight gain was reduced so that final body weight was 10% lower in dietary-obese (P<0.005) and 8% lower in lean (P<0.05) rats versus their untreated controls. Plasma leptin concentration was lower in sibutramine-treated dietary-obese rats (P<0.05), and in treated lean rats (P<0.05). Using the homeostasis model assessment (HOMA) as a measure of insulin resistance, untreated DIO rats were significantly more insulin resistant than controls (P<0.005), and this was corrected by sibutramine treatment (P<0.05). Neither hypothalamic NPY mRNA nor NPY peptide levels in a number of hypothalamic nuclei were significantly altered by sibutramine compared to untreated controls.The hypophagic and anti-obesity effects of sibutramine in dietary-obese Wistar rats appear not to be mediated by inhibition of ARC NPY neurones. PMID:11309262

[Effects of introduction of short peptides before carotid artery occlusion on behaviour and caspase-3 activity in the brain of old rats].

PubMed

Mendzheritskiĭ, A M; Karantysh, G V; Ivonina, K O

2011-01-01

The comparative research of effect of Pinealon and Cortexin on behavior and activity of caspase-3 in a brain of old rats in a model of carotid arteries occlusion was conducted. It is shown that introduction of short peptides promotes a survival rate of the animals that have modeled occlusion of carotid arteries. Under Pinealon before occlusion of carotid arteries, behavioral dream has been increased and a position-finding behavior, a motivational behavior and a motor performance have been reduced. The rats that were introduced Cortexin before carotid arteries occlusion demonstrated the raise of behavioral dream time. At introduction of Pinealon activity of caspase-3 moderately raises in false-operated animals and in a model of occlusion of carotid arteries.

8-Aminoquinolines from Walter Reed Army Institute for Research for treatment and prophylaxis of Pneumocystis pneumonia in rat models.

PubMed Central

Bartlett, M S; Queener, S F; Tidwell, R R; Milhous, W K; Berman, J D; Ellis, W Y; Smith, J W

1991-01-01

Three 8-aminoquinolines from the Walter Reed Army Institute for Research (WRAIR), WR6026, WR238605, and WR242511, strongly inhibited Pneumocystis carinii growth in vitro at 1 microgram/ml. This activity was similar to that of primaquine. In rat therapy models, the WRAIR compounds affected Pneumocystis pneumonia at doses as low as 0.25 mg/kg (WR242511) or 0.5 mg/kg (WR6026 and WR238605). At these doses, primaquine alone was ineffective as therapy. In a rat prophylaxis model, all three WRAIR 8-aminoquinolines were extremely effective at daily doses of 0.57 mg/kg, showing activity greater than that of primaquine at this dosage and comparable to that of trimethoprim-sulfamethoxazole at 50/250 mg/kg. PMID:2024961

[Effect of fermented cordyceps powder and prednisone on the Notch2/Hes-1 signaling activation in the kidney tubules of rats with acute aristolochic acid nephropathy].

PubMed

Huang, Ren-fa; Liang, Qun-qing; Cheng, Xin; Long, Yun; Wu, Jin-yu

2013-08-01

To investigate the effect of both fermented Cordyceps powder (CS) and prednisone on the Notch2/hes-1 signaling activation in the kidney tubules of rats with acute aristolochic acid nephropathy (AAAN). Totally 50 SD rats were randomly divided into 4 groups, i.e., the normal group, the model group, the CS group, the prednisone group, and the CS plus prednisone group, 10 in each group. The AAAN rat model was induced by intragastric administration of pure aristolochic acid A at the daily dose of 100 mg/kg for 3 days. Rats in the CS group were administered with CS at the daily dose of 5.0 g/kg by gastrogavage, while those in the prednisone group were administered with prednisone at the daily dose of 0.5 mg/kg. Rats in the CS plus prednisone group were treated by CS and prednisone. All treatment lasted for 3 successive weeks. Kidney functions [urea nitrogen (BUN) and serum creatinine (SCr)] were detected. The pathological changes of kidneys were observed by Hematoxylin-Eosin staining. The apoptosis of the renal tubular epithelial cells was detected by TUNEL. The protein expressions of Notch2 and Hes-1 in the renal tissue were detected by immunohistochemical assay and Western blot. Results of HE staining showed the structure in the nephridial tissue was regular in rats of the normal group. The renal tubular necrosis occurred in the rats of the model group. The pathological changes of kidneys were obviously improved in the CS group, the prednisone group, and the CS plus prednisone group. Compared with the normal group, levels of BUN and SCr, semi-quantitative score of the tubular interstitial tissue, ratio of apoptotic cells, and expressions of Notch2 and Hes-1 proteins significantly increased in the model group (P < 0.01). Compared with the model group, the aforesaid indices significantly decreased in the 3 treatment groups (P < 0.01). All indices decreased most obviously in the CS plus prednisone group (P < 0.05, P < 0. 01). Notch2/hes-1 signaling activation might be associated with apoptosis of renal tubular epithelial cells. Both CS and prednisone could play a nephroprotective role for AAAN. But CS plus prednisone could achieve the best effect. Inhabiting the Notch2/hes-1 signaling activation could be its nephroprotective mechanism.

Lack of Antidepressant Effects of (2R,6R)-Hydroxynorketamine in a Rat Learned Helplessness Model: Comparison with (R)-Ketamine.

PubMed

Shirayama, Yukihiko; Hashimoto, Kenji

2018-01-01

(R)-Ketamine exhibits rapid and sustained antidepressant effects in animal models of depression. It is stereoselectively metabolized to (R)-norketamine and subsequently to (2R,6R)-hydroxynorketamine in the liver. The metabolism of ketamine to hydroxynorketamine was recently demonstrated to be essential for ketamine's antidepressant actions. However, no study has compared the antidepressant effects of these 3 compounds in animal models of depression. The effects of a single i.p. injection of (R)-ketamine, (R)-norketamine, and (2R,6R)-hydroxynorketamine in a rat learned helplessness model were examined. A single dose of (R)-ketamine (20 mg/kg) showed an antidepressant effect in the rat learned helplessness model. In contrast, neither (R)-norketamine (20 mg/kg) nor (2R,6R)-hydroxynorketamine (20 and 40 mg/kg) did so. Unlike (R)-ketamine, its metabolite (2R,6R)-hydroxynorketamine did not show antidepressant actions in the rat learned helplessness model. Therefore, it is unlikely that the metabolism of ketamine to hydroxynorketamine is essential for ketamine's antidepressant actions. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Chronic sciatic neuropathy in rat reduces voluntary wheel running activity with concurrent chronic mechanical allodynia

PubMed Central

Whitehead, RA; Lam, NL; Sun, MS; Sanchez, JJ; Noor, S; Vanderwall, AG; Petersen, TR; Martin, HB

2016-01-01

BACKGROUND Animal models of peripheral neuropathy produced by a number of manipulations are assessed for the presence of pathological pain states such as allodynia. While stimulus-induced behavioral assays are frequently used and important to examine allodynia (i.e. sensitivity to light mechanical touch; von Frey fiber test) other measures of behavior that reflect overall function are not only complementary to stimulus-induced responsive measures, but are also critical to gain a complete understanding of the effects of the pain model on quality of life, a clinically relevant aspect of pain on general function. Voluntary wheel running activity in rodent models of inflammatory and muscle pain is emerging as a reliable index of general function that extends beyond stimulus-induced behavioral assays. Clinically, reports of increased pain intensity occur at night, a period typically characterized with reduced activity during the diurnal cycle. We therefore examined in rats whether alterations in wheel running activity were more robust during the inactive phase compared to the active phase of their diurnal cycle in a widely used rodent model of chronic peripheral neuropathic pain, the sciatic nerve chronic constriction injury (CCI) model. METHODS In adult male Sprague Dawley rats, baseline (BL) hindpaw threshold responses to light mechanical touch were assessed using the von Frey test prior to measuring BL activity levels using freely accessible running wheels (1 hr/day for 7 sequential days) to quantify distance traveled. Running wheel activity BL values are expressed as total distance traveled (m). The overall experimental design was: following BL measures, rats underwent either sham or CCI surgery followed by repeated behavioral re-assessment of hindpaw thresholds and wheel running activity levels for up to 18 days after surgery. Specifically, separate groups of rats were assessed for wheel running activity levels (1 hr total/trial) during the onset (within first 2 hrs) of either the (1) inactive (n=8/gp) or (2) active (n = 8/gp) phase of the diurnal cycle. An additional group of CCI-treated rats (n = 8/gp) were exposed to a locked running wheel to control for the potential effects of wheel running exercise on allodynia. The 1-hr running wheel trial period was further examined at discrete 20-min intervals to identify possible pattern differences in activity during the first, middle and last portion of the 1-hr trial. The effect of neuropathy on activity levels were assessed by measuring the change from their respective BLs to distance traveled in the running wheels. RESULTS While wheel running distances between groups were not different at BL from rats examined during either the inactive phase of the diurnal cycle or active phase of the diurnal cycle, sciatic nerve CCI reduced running wheel activity levels compared to sham-operated controls during the inactive phase. Additionally, compared to sham controls, bilateral low threshold mechanical allodynia was observed at all time-points after surgical induction of neuropathy in rats with free-wheel and locked-wheel access. Allodynia in CCI compared to shams was replicated in rats whose running wheel activity was examined during the active phase of the diurnal cycle. Conversely, no significant reduction in wheel running activity was observed in CCI-treated rats compared to sham controls at any timepoint when activity levels were examined during the active diurnal phase. Lastly, running wheel activity patterns within the 1 hr trial period during the inactive phase of the diurnal cycle were relatively consistent throughout each 20 min phase. CONCLUSIONS Compared to non-neuropathic sham controls, a profound and stable reduction of running wheel activity was observed in CCI rats during the inactive phase of the diurnal cycle. A concurrent robust allodynia persisted in all rats regardless of when wheel running activity was examined or whether they ran on wheels, suggesting that acute wheel running activity does not alter chronic low intensity mechanical allodynia as measured using the von Frey fiber test. Overall, these data support that acute wheel running exercise with limited repeated exposures does not itself alter allodynia and offers a behavioral assay complementary to stimulus-induced measures of neuropathic pain. PMID:27782944

Effects of microRNA-21 on Nerve Cell Regeneration and Neural Function Recovery in Diabetes Mellitus Combined with Cerebral Infarction Rats by Targeting PDCD4.

PubMed

Guo, Yun-Bao; Ji, Tie-Feng; Zhou, Hong-Wei; Yu, Jin-Lu

2018-03-01

We aimed to determine the effect and mechanism of microRNA-21 (miR-21) on nerve cell regeneration and nerve functional recovery in diabetes mellitus combined with cerebral infarction (DM + CI) rats by targeting PDCD4. A total of 125 male Wistar rats were selected for DM + CI rat model construction and assigned into the blank, miR-21 mimics, mimics control, miR-21 inhibitor, inhibitor control, miR-21 inhibitor + si-PDCD4 and si-PDCD4 groups. And, 20 healthy rats were selected for the normal group. Triphenylterazolium chloride (TTC) staining and HE staining were used for determination of the area of CI and pathological changes, respectively. Behaviors of rats in the eight groups were determined by forelimb placement test and balance beam walking test. Immunohistochemical staining, double immunofluorescence staining assay, Western blotting, and qRT-PCR were used to detect expressions of miR-21, PDCD4, HNA, Nestin, NeuN, β-III-Tub, PTEN, FasL, and GFAP. DNA laddering and TUNEL staining was used for cell apoptosis. TTC and HE staining confirmed that 87.5% rats were induced into CI + DM models successfully. Results of forelimb placement test and balance beam walking test showed that miR-21 mimics, and si-PCDC4 improved the nerve defect of model rats. Comparing with the blank group at the same time, rats in the miR-21 inhibitor group displayed significant decrease in the forelimb placement test score, significant increase in the balance beam walking test score, and exacerbation of nerve defect, while rats in the miR-21 mimics and si-PCDC4 groups displayed significant increase in forelimb placement test score and significant decrease in the balance beam walking test score and improvement of nerve defect situation. The HNA, Nestin, and PDCD4 expressions were decreased and the NeuN, β-III-Tub, and GFAP expressions were increased in the miR-21 mimics and si-PDCD4 groups comparing with the blank group. The results of miR-21 inhibitor group were on the contrary. In comparison to the blank group, the miR-21 mimics group and the si-PDCD4 had lower miR-21 expressions and higher expressions of PDCD4, PTEN, and FasL, while the miR-21 inhibitor group was in the opposite trend. The results of qRT-PCR were the same with Western blotting. The expressions of fluorescence in other groups were higher than the normal group; compared with the blank group, the miR-21 mimics group and the si-PDCD4 group had lower fluorescence expression and DNA ladder. However, the fluorescence expressions and DNA ladder of miR-21 inhibitor group increased markedly in contrast with the blank group. Comparing with the blank group, BrdU + /DEX + fluorescence intensity significantly enhanced in the miR-21 mimics and si-PDCD4 groups and significantly reduced in the miR-21 inhibitor group. And, comparing with the blank group, in the miR-21 mimics group, the signal strength of luciferase carrying the wild-type PDCD4 was reduced by 25%. The present studies demonstrated that miR-21 could promote the nerve cell regeneration, suppress apoptosis of nerve cells in DM + CI rats and improves the nerve defect situation of DM + CI rats by inhibiting PDCD4.

[Intramuscular injection of lentivirus-mediated EPAS1 gene improves hind limb ischemia and its mechanism in a rat model of peripheral artery vascular disease].

PubMed

Wang, Zhihong; Gu, Hongbin; Yang, Fan; Xie, Huajie; Sheng, Lei; Li, Mingfei

2017-11-01

Objective To investigate the effect of over-expressed endothelial Per-Arnt-Sim domain protein 1 (EPAS1) on peripheral arterial disease (PAD) in a rat model. Methods PAD rat model was established by external iliac artery ligation followed by lentivirus-mediated EPAS1 gene injection into rat right adductor magnus. The models were evaluated by quantitative analysis of gait disturbance. The changes of blood flow in the posterior extremity of the rats were detected using laser Doppler. The expressions of EPAS1, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) mRNAs were tested by real-time quantitative PCR. The expression of α-smooth muscle actin (αSMA) was detected by immunohistochemical staining. Results Compared with lenti-EGFP group, rat hind limb function and circulation got recovered obviously 7 days after lenti-EPAS1 injection. The mRNA expressions of EPAS1, HGF, bFGF, and VEGF were up-regulated in the lenti-EPAS1-treated sites.The expression of αSMA showed an obvious increase in the lenti-EPAS1-treated muscles. Conclusion Over-expressed lenti-EPAS1 can promote angiogenesis via the up-regulation of EPAS1-related angiogenic factors in the muscles of the affected hind limb and reduce gait disturbance.

Combined uridine and choline administration improves cognitive deficits in spontaneously hypertensive rats.

PubMed

De Bruin, N M W J; Kiliaan, A J; De Wilde, M C; Broersen, L M

2003-07-01

Rationale. Hypertension is considered a risk factor for the development of cognitive disorders, because of its negative effects on cerebral vasculature and blood flow. Genetically induced hypertension in rats has been associated with a range of cognitive impairments. Therefore, spontaneously hypertensive rats (SHR) can potentially be used as a model for cognitive deficits in human subjects. Consecutively, it can be determined whether certain food components can improve cognition in these rats. Objective. The present study aimed to determine whether SHR display specific deficits in attention, learning, and memory function. Additionally, effects of chronic uridine and choline administration were studied. Methods. 5-7 months old SHR were compared with normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats. (a) The operant delayed non-matching-to-position (DNMTP) test was used to study short-term memory function. (b) The five-choice serial reaction time (5-CSRT) task was used to assess selective visual attention processes. (c) Finally, the Morris water maze (MWM) acquisition was used as a measure for spatial learning and mnemonic capabilities. Results. (1) SHR exhibited significantly impaired performance in the 5-CSRT test in comparison with the two other rat strains. Both the SHR and WKY showed deficits in spatial learning when compared with the SD rats. (2) Uridine and choline supplementation normalized performance of SHR in the 5-CSRT test. (3) In addition, uridine and choline treatment improved MWM acquisition in both WKY and SHR rats. Conclusion. The present results show that the SHR have a deficiency in visual selective attention and spatial learning. Therefore, the SHR may provide an interesting model in the screening of substances with therapeutic potential for treatment of cognitive disorders. A combination of uridine and choline administration improved selective attention and spatial learning in SHR.

The soluble fiber complex PolyGlycopleX lowers serum triglycerides and reduces hepatic steatosis in high-sucrose-fed rats.

PubMed

Reimer, Raylene A; Grover, Gary J; Koetzner, Lee; Gahler, Roland J; Lyon, Michael R; Wood, Simon

2011-04-01

Viscous soluble fibers have been shown to reduce risk factors associated with type 2 diabetes and cardiovascular disease. The novel functional fiber, PolyGlycopleX (PGX) (InovoBiologic Inc, Calgary, Alberta, Canada) displays greater viscosity than other currently identified soluble fibers. The objective of this study was to determine if PGX lowers serum and hepatic triglycerides (TGs) in a high-sucrose-fed rat model. In this rodent model, feeding a high-sucrose diet consistently increases serum TGs. We hypothesized that consumption of PGX would attenuate hypertriglyceridemia and reduce hepatic steatosis compared with cellulose in rats fed a high-sucrose background diet. Male Sprague-Dawley rats were fed diets containing 65% sucrose and supplemented with either 5% cellulose (control) or 5% PGX (wt/wt) for 43 weeks. At study termination, serum insulin and TGs, hepatic steatosis, and hepatocellular injury were assessed. Body weight increased over time in both groups, but weight gain was attenuated in rats fed PGX vs cellulose in weeks 2 through 22 (P < .05). Serum TGs did not differ from baseline for the first half of the study but consistently increased in the cellulose group thereafter. PolyGlycopleX significantly reduced serum TG to near-baseline levels. At study termination, rats fed PGX had significantly lower hepatic steatosis scores (measured by Sudan black staining) compared with rats fed cellulose. Hepatocellular injury scores did not differ between the groups. In conclusion, PGX reduced serum TG and lipid accumulation in the liver of sucrose-fed rats. Further examination of its potential as a fiber supplement aimed at lessening the burden of hepatic steatosis is warranted. Copyright © 2011 Elsevier Inc. All rights reserved.

Impaired postprandial releases/syntheses of ghrelin and PYY(3-36) and blunted responses to exogenous ghrelin and PYY(3-36) in a rodent model of diet-induced obesity.

PubMed

Xu, Junying; McNearney, Terry A; Chen, J D Z

2011-04-01

This study investigated the effects of peripheral administration of ghrelin and PYY(3-36) on food intake and plasma and tissue fasting and postprandial ghrelin and PYY(3-36) levels in normal-weight (NW) and diet-induced-obese (DIO) rats. In experiment one, NW and DIO rats received a single intraperitoneal injection of saline, PYY(3-36) or ghrelin; food intake was measured for 4 h. In experiment two, total plasma ghrelin and PYY(3-36), gastric fundus ghrelin, and ascending colon PYY(3-36) were measured either after a 20-h fast or 2 h after refeeding in NW and DIO rats by radioimmunoassay. Compared to the NW rats, findings in the DIO rats revealed: (i) a reduced sensitivity to both the anorectic effect of exogenous PYY(3-36) and the orexigenic effect of exogenous ghrelin; (ii) the postprandial plasma ghrelin levels were significantly higher; and (iii) refeeding decreased endogenous plasma ghrelin levels by 53% in the NW rats and 39% in DIO rats. Refeeding increased the plasma PYY(3-36) level by 58% in the NW rats versus 9% in the DIO rats (P=0.003). Compared with regular rats, DIO rats exhibit blunted responses in food intake to exogenous ghrelin and PYY(3-36). Although endogenous ghrelin and PYY(3-36) in DIO rats are not altered in the fasting state, their responses to food ingestion are blunted in comparison with regular rats. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Effects of intracerebroventricular administration of beta-amyloid on the dynamics of learning in purebred and mongrel rats.

PubMed

Stepanov, I I; Kuznetsova, N N; Klement'ev, B I; Sapronov, N S

2007-07-01

The effects of intracerebroventricular administration of the beta-amyloid peptide fragment Abeta(25-35) on the dynamics of the acquisition of a conditioned reflex in a Y maze were studied in Wistar and mongrel rats. The dynamics of decreases in the number of errors were assessed using an exponential mathematical model describing the transfer function of a first-order system in response to stepped inputs using non-linear regression analysis. This mathematical model provided a good approximation to the learning dynamics in inbred and mongrel mice. In Wistar rats, beta-amyloid impaired learning, with reduced memory between the first and second training sessions, but without complete blockade of learning. As a result, learning dynamics were no longer approximated by the mathematical model. At the same time, comparison of the number of errors in each training sessions between the control group of Wistar rats and the group given beta-amyloid showed no significant differences (Student's t test). This result demonstrates the advantage of regression analysis based on a mathematical model over the traditionally used statistical methods. In mongrel rats, the effect of beta-amyloid was limited to an a slowing of the process of learning as compared with control mongrel rats, with retention of the approximation by the mathematical model. It is suggested that mongrel animals have some kind of innate, genetically determined protective mechanism against the harmful effects of beta-amyloid.

Tumorigenic action of beta, proton, alpha and electron radiation on the rat skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burns, F.J.

1980-01-01

Rat skin is utilized as a model system for studying dose and time related aspects of the oncogenic action of ionizing radiation, ultraviolet light and polycyclic aromatic hydrocarbons. Molecular lesions in the DNA of the epidermis, including strand breaks and thymine dimers, are measured and compared to the temporal and dose related aspects of tumor induction. The induction and repair kinetics of molecular lesions are compared to split dose recovery as modified by sensitizers and type of radition of oncogenic damage.

Thyroid organotypic rat and human cultures used to investigate drug effects on thyroid function, hormone synthesis and release pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vickers, Alison E.M., E-mail: vickers_alison@allergan.com; Heale, Jason; Sinclair, John R.

Drug induced thyroid effects were evaluated in organotypic models utilizing either a rat thyroid lobe or human thyroid slices to compare rodent and human response. An inhibition of thyroid peroxidase (TPO) function led to a perturbation in the expression of key genes in thyroid hormone synthesis and release pathways. The clinically used thiourea drugs, methimazole (MMI) and 6-n-propyl-2-thioruacil (PTU), were used to evaluate thyroid drug response in these models. Inhibition of TPO occurred early as shown in rat thyroid lobes (2 h) and was sustained in both rat (24–48 h) and human (24 h) with ≥ 10 μM MMI. Thyroidmore » from rats treated with single doses of MMI (30–1000 mg/kg) exhibited sustained TPO inhibition at 48 h. The MMI in vivo thyroid concentrations were comparable to the culture concentrations (∼ 15–84 μM), thus demonstrating a close correlation between in vivo and ex vivo thyroid effects. A compensatory response to TPO inhibition was demonstrated in the rat thyroid lobe with significant up-regulation of genes involved in the pathway of thyroid hormone synthesis (Tpo, Dio1, Slc5a5, Tg, Tshr) and the megalin release pathway (Lrp2) by 24 h with MMI (≥ 10 μM) and PTU (100 μM). Similarly, thyroid from the rat in vivo study exhibited an up-regulation of Dio1, Slc5a5, Lrp2, and Tshr. In human thyroid slices, there were few gene expression changes (Slc5a5, ∼ 2-fold) and only at higher MMI concentrations (≥ 1500 μM, 24 h). Extended exposure (48 h) resulted in up-regulation of Tpo, Dio1 and Lrp2, along with Slc5a5 and Tshr. In summary, TPO was inhibited by similar MMI concentrations in rat and human tissue, however an increased sensitivity to drug treatment in rat is indicated by the up-regulation of thyroid hormone synthesis and release gene pathways at concentrations found not to affect human tissue. -- Highlights: ► Novel model of rat thyroid or human thyroid slices to evaluate pathways of injury. ► TPO inhibition by MMI or PTU altered hormone synthesis and release genes. ► Rat thyroid was more sensitive to the drug effects than human tissue.« less

EFFECT OF SOIL PB INACTIVATION TREATMENTS ON BIOAVAILABILITY OF JOPLIN, MO, SMELTER CONTAMINATED SOIL PB TO RATS

EPA Science Inventory

The effects of treating contaminated soils with various soil amendments on the bioavailability of lead were assessed in the weanling rat model. The effect of treatment was assessed by comparing the adsorption of Pb of animals fed soil samples treated with (0.5%, 1% P and 2.5% Fe ...

Subchronic inhalation exposure of rats to Libby amphibole and amosite asbestos: Effects at 1 and 3 months post exposure#

EPA Science Inventory

Increased asbestosis, lung cancer, and mesothelioma rates are evident in humans after exposures to Libby amphibole (LA). To support dosimetry model development and compare potency, a subchronic nose-only inhalation study (6 hr/d, 5 d/wk, 13 wk) was conducted in male F344 rats. Ra...

THE TRANSCRIPTIONAL PROFILE OF THE KIDNEY IN TSC2 HETEROZYGOUS MUTANT LONG EVANS (EKER) RATS COMPARED TO WILD-TYPE

EPA Science Inventory

Hereditary renal cell carcinoma (RCC) in Eker rats results from an inherited insertional mutation in the Tsc2 tumor suppressor gene and provides a valuable experimental model to characterize the function of the Tsc2 gene product, tuberin in vivo. The Tsc2 mutation predisposes the...

Active vitamin D3, 1,25-(OH)2D3, protects against macrovasculopathy in a rat model of type 2 diabetes mellitus.

PubMed

Ma, R; Deng, X L; Du, G L; Li, C; Xiao, S; Aibibai, Y; Zhu, J

2016-06-03

To investigate the protective effect of the active form of vitamin D3, 1,25-(OH)2D3, on macrovasculopathy in rats with type 2 diabetes mellitus (T2DM), 8-week-old male Sprague-Dawley rats were randomly divided into control group, T2DM group, and treatment group. The T2DM model was established after 6 weeks by administering an intraperitoneal injection of streptozotocin (30 mg/kg). 1,25-(OH)2D3 was administered by gavage to rats in the treatment group, and an equal volume of peanut oil was administered to rats in the T2DM group. Fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterols were measured in all rats. The morphology of the thoracic aorta was examined, and the expression of tumor necrosis factor alpha (TNF-α), endothelin (ET), endothelial nitric oxide synthase (eNOS), CD54, and CD106 in the thoracic aorta was determined by immunohistochemistry. The expression of FPG, TG, TC, and LDL-C in rats from the T2DM and treatment groups was significantly elevated compared with rats from the control group (P < 0.05). Compared with that in control group, the expression of TNF-α, ET, eNOS, and CD106 was significantly upregulated in the T2DM group and the treatment group, while the expression of CD54 was increased only in the T2DM group (P < 0.05). Moreover, the levels of TNF-α, CD54, and CD106 in rats from the treatment group were lower than those in the T2DM group (P < 0.05). These data suggest that 1,25-(OH)2D3 may protect the macrovessels from injury in T2DM rats by inhibiting the expression of TNF-α, CD54, and CD106.

Dysfunction in Fatty Acid Amide Hydrolase Is Associated with Depressive-Like Behavior in Wistar Kyoto Rats

PubMed Central

Vinod, K. Yaragudri; Xie, Shan; Psychoyos, Delphine; Hungund, Basalingappa L.; Cooper, Thomas B.; Tejani-Butt, Shanaz M.

2012-01-01

Background While the etiology of depression is not clearly understood at the present time, this mental disorder is thought be a complex and multifactorial trait with important genetic and environmental contributing factors. Methodology/Principal Findings The role of the endocannabinoid (eCB) system in depressive behavior was examined in Wistar Kyoto (WKY) rat strain, a genetic model of depression. Our findings revealed selective abnormalities in the eCB system in the brains of WKY rats compared to Wistar (WIS) rats. Immunoblot analysis indicated significantly higher levels of fatty acid amide hydrolase (FAAH) in frontal cortex and hippocampus of WKY rats with no alteration in the level of N-arachidonyl phosphatidyl ethanolamine specific phospholipase-D (NAPE-PLD). Significantly higher levels of CB1 receptor-mediated G-protein coupling and lower levels of anandamide (AEA) were found in frontal cortex and hippocampus of WKY rats. While the levels of brain derived neurotropic factor (BDNF) were significantly lower in frontal cortex and hippocampus of WKY rats compared to WIS rats, pharmacological inhibition of FAAH elevated BDNF levels in WKY rats. Inhibition of FAAH enzyme also significantly increased sucrose consumption and decreased immobility in the forced swim test in WKY rats. Conclusions/Significance These findings suggest a critical role for the eCB system and BDNF in the genetic predisposition to depressive-like behavior in WKY rats and point to the potential therapeutic utility of eCB enhancing agents in depressive disorder. PMID:22606285

Dysfunction in fatty acid amide hydrolase is associated with depressive-like behavior in Wistar Kyoto rats.

PubMed

Vinod, K Yaragudri; Xie, Shan; Psychoyos, Delphine; Hungund, Basalingappa L; Cooper, Thomas B; Tejani-Butt, Shanaz M

2012-01-01

While the etiology of depression is not clearly understood at the present time, this mental disorder is thought be a complex and multifactorial trait with important genetic and environmental contributing factors. The role of the endocannabinoid (eCB) system in depressive behavior was examined in Wistar Kyoto (WKY) rat strain, a genetic model of depression. Our findings revealed selective abnormalities in the eCB system in the brains of WKY rats compared to Wistar (WIS) rats. Immunoblot analysis indicated significantly higher levels of fatty acid amide hydrolase (FAAH) in frontal cortex and hippocampus of WKY rats with no alteration in the level of N-arachidonyl phosphatidyl ethanolamine specific phospholipase-D (NAPE-PLD). Significantly higher levels of CB1 receptor-mediated G-protein coupling and lower levels of anandamide (AEA) were found in frontal cortex and hippocampus of WKY rats. While the levels of brain derived neurotropic factor (BDNF) were significantly lower in frontal cortex and hippocampus of WKY rats compared to WIS rats, pharmacological inhibition of FAAH elevated BDNF levels in WKY rats. Inhibition of FAAH enzyme also significantly increased sucrose consumption and decreased immobility in the forced swim test in WKY rats. These findings suggest a critical role for the eCB system and BDNF in the genetic predisposition to depressive-like behavior in WKY rats and point to the potential therapeutic utility of eCB enhancing agents in depressive disorder.

Comparing the Effects of Particulate Matter on the Ocular Surfaces of Normal Eyes and a Dry Eye Rat Model.

PubMed

Han, Ji Yun; Kang, Boram; Eom, Youngsub; Kim, Hyo Myung; Song, Jong Suk

2017-05-01

To compare the effect of exposure to particulate matter on the ocular surface of normal and experimental dry eye (EDE) rat models. Titanium dioxide (TiO2) nanoparticles were used as the particulate matter. Rats were divided into 4 groups: normal control group, TiO2 challenge group of the normal model, EDE control group, and TiO2 challenge group of the EDE model. After 24 hours, corneal clarity was compared and tear samples were collected for quantification of lactate dehydrogenase, MUC5AC, and tumor necrosis factor-α concentrations. The periorbital tissues were used to evaluate the inflammatory cell infiltration and detect apoptotic cells. The corneal clarity score was greater in the EDE model than in the normal model. The score increased after TiO2 challenge in each group compared with each control group (normal control vs. TiO2 challenge group, 0.0 ± 0.0 vs. 0.8 ± 0.6, P = 0.024; EDE control vs. TiO2 challenge group, 2.2 ± 0.6 vs. 3.8 ± 0.4, P = 0.026). The tear lactate dehydrogenase level and inflammatory cell infiltration on the ocular surface were higher in the EDE model than in the normal model. These measurements increased significantly in both normal and EDE models after TiO2 challenge. The tumor necrosis factor-α levels and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were also higher in the EDE model than in the normal model. TiO2 nanoparticle exposure on the ocular surface had a more prominent effect in the EDE model than it did in the normal model. The ocular surface of dry eyes seems to be more vulnerable to fine dust of air pollution than that of normal eyes.

A multi-site comparison of in vivo safety pharmacology studies conducted to support ICH S7A & B regulatory submissions.

PubMed

Ewart, Lorna; Milne, Aileen; Adkins, Debbie; Benjamin, Amanda; Bialecki, Russell; Chen, Yafei; Ericsson, Ann-Christin; Gardner, Stacey; Grant, Claire; Lengel, David; Lindgren, Silvana; Lowing, Sarah; Marks, Louise; Moors, Jackie; Oldman, Karen; Pietras, Mark; Prior, Helen; Punton, James; Redfern, Will S; Salmond, Ross; Skinner, Matt; Some, Margareta; Stanton, Andrea; Swedberg, Michael; Finch, John; Valentin, Jean-Pierre

2013-01-01

Parts A and B of the ICH S7 guidelines on safety pharmacology describe the in vivo studies that must be conducted prior to first time in man administration of any new pharmaceutical. ICH S7A requires a consideration of the sensitivity and reproducibility of the test systems used. This could encompass maintaining a dataset of historical pre-dose values, power analyses, as well as a demonstration of acceptable model sensitivity and robust pharmacological validation. During the process of outsourcing safety pharmacology studies to Charles River Laboratories, AstraZeneca set out to ensure that models were performed identically in each facility and saw this as an opportunity to review the inter-laboratory variability of these essential models. The five in vivo studies outsourced were the conscious dog telemetry model for cardiovascular assessment, the rat whole body plethysmography model for respiratory assessment, the rat modified Irwin screen for central nervous system assessment, the rat charcoal meal study for gastrointestinal assessment and the rat metabolic cage study for assessment of renal function. Each study was validated with known reference compounds and data were compared across facilities. Statistical power was also calculated for each model. The results obtained indicated that each of the studies could be performed with comparable statistical power and could achieve a similar outcome, independent of facility. The consistency of results obtained from these models across multiple facilities was high thus providing confidence that the models can be run in different facilities and maintain compliance with ICH S7A and B. Copyright © 2013 Elsevier Inc. All rights reserved.

[The effect of 18β-sodium glycyrrhetinic acid on the nasal mucosa epithelial cilia in rat models of allergic rhinitis].

PubMed

Yang, Jing; Xi, Kehu; Gui, Yan; Wang, Youhu; Zhang, Fuhong; Ma, Chunxia; Hong, Hao; Liu, Xiangyi; Meng, Nannan; Zhang, Xiaobing

2015-12-01

To investigate 18β-sodium glycyrrhetinic acid impact on nasal mucosa epithelial cilia in rat models of allergic rhinitis (AR). AR models were established by ovalbumin-induction. Wister rats were randomly divided into groups as normal group, model group, budesonide (0.2 mg/kg) group and sodium glycyrrhetinic acid (20 mg/kg and 40 mg/kg) group after the success of AR models. At 2 weeks and 4 weeks after treatment, the behavioral changes of rats were observed and recorded, and nasal septum mucosae were collected after 2 week and 4 week intervention, and the morphological changes of nasal mucosae were observed by electron microscope. Model group developed typical AR symptoms, the total score in all animals was > 5. With budesonide and sodium glycyrrhetinic acid treatment, the AR symptoms were relieved, and the total scores were reduced significantly (P < 0.01). Compared with the model group: after 2 weeks' intervention, thick mucous secretions on the top of columnar epithelium cilia in rat nasal mucosa was significantly reduced, and cilia adhesion, lodging, shedding were relieved in budesonide group and sodium glycyrrhetinic acid group, the relieve in budesonide group was slightly better than that in sodium glycyrrhetinic acid group; after 4 week intervention, Cilia adhesion, lodging, shedding were completely vanished, and the cilia were ranged in regular direction in budesonide group and sodium glycyrrhetinic acid group. Cilia in sodium glycyrrhetinic acid (20 mg/kg) group was more orderly, smooth than that in budesonide group and sodium glycyrrhetinic acid group (40 mg/kg), and the condition of cilia in sodium glycyrrhetinic acid group (20 mg/kg) was similar to the normal group. 18β-sodium glycyrrhetinic acid is effective to restrain the pathological changes of nasal mucosa cilia in rat models of AR.

Cannabinoid-induced conditioned place preference in the spontaneously hypertensive rat-an animal model of attention deficit hyperactivity disorder.

PubMed

Pandolfo, Pablo; Vendruscolo, Leandro F; Sordi, Regina; Takahashi, Reinaldo N

2009-08-01

Cannabis preparations are the most widely consumed illicit drugs, and their use typically begins in adolescence. The prevalence of cannabis abuse is higher in patients with attention deficit/hyperactivity disorder (ADHD) than in the general population, yet, knowledge about the motivational properties of cannabinoids in animal models of ADHD are lacking. To compare the motivational effects of the synthetic cannabinoid agonist WIN55,212-2 (WIN) in adolescent and adult spontaneously hypertensive rats (SHR), a validated animal model of ADHD, and Wistar rats, representing a "normal" genetically heterogeneous population. We also asked whether the effects of WIN depended (1) on the activation of the cerebral subtype of cannabinoid receptors, namely, the CB(1) cannabinoid receptor and (2) on putative changes by WIN in blood pressure. WIN was tested under an unbiased conditioned place preference (CPP) paradigm. Blood pressure after WIN administration was also monitored in additional groups of rats. In the Wistar rats, WIN produced place aversion only in the adult but not adolescent rats. In contrast, WIN produced CPP in both adolescent and adult SHR rats. The behavioral effects of WIN were CB(1)-mediated and not related to blood pressure. The contrasting effects of WIN in Wistar and SHR, and the higher resistance of adolescent rats to the aversive and rewarding effects of WIN in these two strains suggests that both adolescence and the ADHD-like profile exhibited by the SHR strain constitute factors that influence the motivational properties of cannabinoids.

Effects on Glycemic Control in Impaired Wound Healing in Spontaneously Diabetic Torii (SDT) Fatty Rats.

PubMed

Katsuhiro, Miyajima; Hui Teoh, Soon; Yamashiro, Hideaki; Shinohara, Masami; Fatchiyah, Fatchiyah; Ohta, Takeshi; Yamada, Takahisa

2018-02-01

Impaired diabetic wound healing is an important issue in diabetic complications. The present study aims to evaluate the protective effect on glycemic control against impaired diabetic wound healing using a diabetic rat model. We investigated the wound healing process and effect on the impaired wound repair by glycemic control in the Spontaneously Diabetic Torii (SDT) fatty rat, which is a new animal model of obese type 2 diabetes and may be a good model for study impaired wound healing. Male SDT fatty rats at 15 weeks of age were administered orally with sodium glucose co-transporter (SGLT) 2 inhibitor for 3 weeks. Wounds were induced at 2 weeks after SGLT 2 inhibitor treatment, and the wound areas were periodically examined in morphological and histological analyses. The SDT fatty rats showed a delayed wound healing as compared with the normal rats, but a glycemic control improved the impaired wound healing. In histological analysis in the skin of SDT fatty rats showed severe infiltration of inflammatory cell, hemorrhage and many bacterial masses in the remaining and slight fibrosis of crust on skin tissue . Thought that this results skin performance to be a delay of crust formation and regeneration of epithelium; however, these findings were ameliorated in the SGLT 2 inhibitor treated group. Glycemic control is effective for treatment in diabetic wounds and the SDT fatty rat may be useful to investigate pathophysiological changes in impaired diabetic wound healing.

Altered expression of intestinal duodenal cytochrome b and divalent metal transporter 1 might be associated with cardio-renal anemia syndrome.

PubMed

Naito, Yoshiro; Sawada, Hisashi; Oboshi, Makiko; Okuno, Keisuke; Yasumura, Seiki; Okuhara, Yoshitaka; Eguchi, Akiyo; Nishimura, Koichi; Soyama, Yuko; Asakura, Masanori; Ishihara, Masaharu; Tsujino, Takeshi; Masuyama, Tohru

2017-11-01

The interaction among heart failure (HF), chronic kidney disease (CKD), and anemia is called cardio-renal anemia syndrome. The mechanism of anemia in cardio-renal anemia syndrome is complex and remains completely unknown. We have previously reported that impaired intestinal iron transporters may contribute to the mechanism of anemia in HF using in vivo HF model rats. In this study, we assessed intestinal iron transporters in CKD model rats to investigate the association of intestinal iron transporters in the mechanism of cardio-renal anemia syndrome. CKD was induced by 5/6 nephrectomy in Sprague-Dawley rats. Sham-operated rats served as a control. After 24-week surgery, CKD rats exhibited normocytic normochromic anemia and normal serum erythropoietin levels despite of anemia. Serum iron levels were decreased in CKD rats compared with the controls. Of interest, intestinal expression of critical iron importers, such as duodenal cytochrome b (Dcyt-b) and divalent metal transporter 1 (DMT-1), was decreased in CKD rats compared with the controls. On the other hand, intestinal expression of ferroportin, an intestinal iron exporter, was not different in the control and CKD groups. Moreover, hepatic expression of hepcidin, a regulator of iron homeostasis, did not differ between the control and CKD groups. These results suggest that impaired intestinal expression of Dcyt-b and DMT-1 might be associated with the reduction of an iron uptake in CKD. Taken together, impaired these intestinal iron transporters may become a novel therapeutic target for cardio-renal anemia syndrome.

Effects of Mild Chronic Intermittent Cold Exposure on Rat Organs

PubMed Central

Wang, Xiaohui; Che, Honglei; Zhang, Wenbin; Wang, Jiye; Ke, Tao; Cao, Rui; Meng, Shanshan; Li, Dan; Weiming, Ouyang; Chen, Jingyuan; Luo, Wenjing

2015-01-01

Cold adaptation is a body's protective response to cold stress. Mild chronic intermittent cold (CIC) exposure has been used to generate animal models for cold adaptation studies. However, the effects of mild CIC exposure on vital organs are not completely characterized. In the present study, we exposed rats to mild CIC for two weeks, and then measured the body weights, the weights of brown adipose tissue (BAT), the levels of ATP and reactive oxygen species (ROS) in the brains, livers, hearts, muscles and BATs. Rats formed cold adaptation after exposure to CIC for two weeks. Compared to rats of the control group that were hosted under ambient temperature, rats exposed to mild CIC showed a lower average body weight, but a higher weight of brown adipose tissue (BAT). Rats exposed to CIC for two weeks also exhibited higher levels of ATP and ROS in all examined organs as compared to those of the control group. In addition, we determined the expression levels of cold-inducible RNA binding protein (Cirbp) and thioredoxin (TRX) in rat tissues after 2 weeks of CIC exposure. Both Cirbp and TRX were increased, suggesting a role of these two proteins for establishment of cold adaptation. Together, this study reveals the effects of mild CIC exposure on vital organs of rats during CIC exposure. PMID:26327811

Pneumonic plague pathogenesis and immunity in Brown Norway rats.

PubMed

Anderson, Deborah M; Ciletti, Nancy A; Lee-Lewis, Hanni; Elli, Derek; Segal, Joshua; DeBord, Kristin L; Overheim, Katie A; Tretiakova, Maria; Brubaker, Robert R; Schneewind, Olaf

2009-03-01

The Brown Norway rat was recently described as a bubonic plague model that closely mimics human disease. We therefore evaluated the Brown Norway rat as an alternative small animal model for pneumonic plague and characterized both the efficacy and potency of vaccine candidates. When infected by intranasal instillation, these rats rapidly developed fatal pneumonic plague within 2 to 4 days of infection. Plague disease was characterized by severe alveolar edema and vascular hemorrhage in the lung in addition to fulminant necrotizing pneumonia caused by massive bacterial replication and inflammation. Twenty-four hours before death, animals developed systemic disease with an apparent delayed inflammatory response. We evaluated the ability of the protective antigen, LcrV, and a mutant derivative, V10, to protect these rats from pneumonic plague. Both were highly effective vaccines because complete protection was observed at challenge doses of 7500 LD(50). Antibody analyses suggested stronger potency of V10 immune sera compared with LcrV in the passive transfer of immunity to bubonic plague, with multiple neutralizing epitopes in LcrV. Taken together, these data demonstrate the effectiveness of inhibiting type III secretion in the prevention of pneumonic plague in rats and reveal critical contributions from both the cellular and humoral immune systems. Thus, the Brown Norway rat is an appealing alternative small animal model for the study of pneumonic plague pathogenesis and immunity.

Impact of chronic unpredicted mild stress-induced depression on repaglinide fate via glucocorticoid signaling pathway.

PubMed

Wei, Hongyan; Zhou, Ting; Tan, Boyu; Zhang, Lei; Li, Mingming; Xiao, Zhijun; Xu, Feng

2017-07-04

Chronic unpredicted mild stress (CUMS)-induced depression could alter the pharmacokinetics of many drugs in rats, however, the underlying mechanism is not clear. In this work we studied the pharmacokinetics of repaglinide, and explored the role of glucocorticoid and adrenergic signaling pathway in regulating drug metabolizing enzymes (DMEs) in GK rats and BRL 3A cells. The plasma cortisol and epinephrine levels were increased, meanwhile the pharmacokinetics of repaglinide were altered significantly in depression model rats. Forty-nine genes in liver of model rats displayed significant difference comparing to control rats. The differentially expressed genes enriched in the drug metabolism and steroid hormone biosynthesis pathway significantly, and Nr1i3 matched 335 connectivity genes. CAR and Ugt1a1 protein expression were enhanced significantly in liver of model rats. The mRNA expression of Ugt1a1 and Nr1i2 were increased 2 and 4 times respectively with dexamethasone (DEX) and 8-Br-cAMP co-treatment in BRL 3A cells. The protein expression of PXR was up-regulated, too. However, RU486 reversed the up-regulated effect. The adrenergic receptor agonists had little impact on the DMEs in BRL 3A. Our data suggested that CUMS-induced depression might up-regulate DMEs expression via glucocorticoid signaling pathway, and accelerate the fate of the repaglinide in spontaneous diabetes rats.

Impact of chronic unpredicted mild stress-induced depression on repaglinide fate via glucocorticoid signaling pathway

PubMed Central

Tan, Boyu; Zhang, Lei; Li, Mingming; Xiao, Zhijun; Xu, Feng

2017-01-01

Chronic unpredicted mild stress (CUMS)-induced depression could alter the pharmacokinetics of many drugs in rats, however, the underlying mechanism is not clear. In this work we studied the pharmacokinetics of repaglinide, and explored the role of glucocorticoid and adrenergic signaling pathway in regulating drug metabolizing enzymes (DMEs) in GK rats and BRL 3A cells. The plasma cortisol and epinephrine levels were increased, meanwhile the pharmacokinetics of repaglinide were altered significantly in depression model rats. Forty-nine genes in liver of model rats displayed significant difference comparing to control rats. The differentially expressed genes enriched in the drug metabolism and steroid hormone biosynthesis pathway significantly, and Nr1i3 matched 335 connectivity genes. CAR and Ugt1a1 protein expression were enhanced significantly in liver of model rats. The mRNA expression of Ugt1a1 and Nr1i2 were increased 2 and 4 times respectively with dexamethasone (DEX) and 8-Br-cAMP co-treatment in BRL 3A cells. The protein expression of PXR was up-regulated, too. However, RU486 reversed the up-regulated effect. The adrenergic receptor agonists had little impact on the DMEs in BRL 3A. Our data suggested that CUMS-induced depression might up-regulate DMEs expression via glucocorticoid signaling pathway, and accelerate the fate of the repaglinide in spontaneous diabetes rats. PMID:28574832

A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

PubMed Central

Weckbach, Sebastian; Perl, Mario; Heiland, Tim; Braumüller, Sonja; Stahel, Philip F.; Flierl, Michael A.; Ignatius, Anita; Gebhard, Florian; Huber-Lang, Markus

2012-01-01

Background. The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response. Methods. Male Wistar rats (250 g, 6–10/group) were anesthetized and exposed to chest trauma (ChT), closed head injury (CHI), or Tib/Fib fracture including a soft tissue trauma (Fx + STT) or to the following combination of injuries: (1) ChT; (2) ChT + Fx + STT; (3) ChT + CHI; (4) CHI; (5) polytrauma (PT = ChT + CHI + Fx + STT). Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of “key” inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL) fluid samples. Results. Polytraumatized (PT) rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. Conclusion. This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma. PMID:22481866

Memory deficits with intact cognitive control in the methylazoxymethanol acetate (MAM) exposure model of neurodevelopmental insult.

PubMed

O'Reilly, Kally C; Perica, Maria I; Fenton, André A

2016-10-01

Cognitive impairments are amongst the most debilitating deficits of schizophrenia and the best predictor of functional outcome. Schizophrenia is hypothesized to have a neurodevelopmental origin, making animal models of neurodevelopmental insult important for testing predictions that early insults will impair cognitive function. Rats exposed to methylazoxymethanol acetate (MAM) at gestational day 17 display morphological, physiological and behavioral abnormalities relevant to schizophrenia. Here we investigate the cognitive abilities of adult MAM rats. We examined brain activity in MAM rats by histochemically assessing cytochrome oxidase enzyme activity, a metabolic marker of neuronal activity. To assess cognition, we used a hippocampus-dependent two-frame active place avoidance paradigm to examine learning and spatial memory, as well as cognitive control and flexibility using the same environment and evaluating the same set of behaviors. We confirmed that adult MAM rats have altered hippocampal morphology and brain function, and that they are hyperactive in an open field. The latter likely indicates MAM rats have a sensorimotor gating deficit that is common to many animal models used for schizophrenia research. On first inspection, cognitive control seems impaired in MAM rats, indicated by more errors during the two-frame active place avoidance task. Because MAM rats are hyperactive throughout place avoidance training, we considered the possibility that the hyperlocomotion may account for the apparent cognitive deficits. These deficits were reduced on the basis of measures of cognitive performance that account for motor activity differences. However, though other aspects of memory are intact, the ability of MAM rats to express trial-to-trial memory is delayed compared to control rats. These findings suggest that spatial learning and cognitive abilities are largely intact, that the most prominent cognitive deficit is specific to acquiring memory in the MAM neurodevelopmental model, and that hyperactivity can confound assessments of cognition in animal models of mental dysfunction. Copyright © 2016 Elsevier Inc. All rights reserved.

Inhibition of mirtazapine metabolism by Ecstasy (MDMA) in isolated perfused rat liver model.

PubMed

Jamshidfar, Sanaz; Ardakani, Yalda H; Lavasani, Hoda; Rouini, Mohammadreza

2017-06-28

Nowadays MDMA (3,4-methylendioxymethamphetamine), known as ecstasy, is widely abused among the youth because of euphoria induction in acute exposure. However, abusers are predisposed to depression in chronic consumption of this illicit compound. Mirtazapine (MRZ), an antidepressant agent, may be prescribed in MDMA-induced depression. MRZ is extensively metabolized in liver by CYP450 isoenzymes. 8-hydroxymirtazapine (8-OH) is mainly produced by CYP2D6. N-desmethylmirtazapine (NDES) is generated by CYP3A4. MDMA is also metabolized by the mentioned isoenzymes and demonstrates mechanism-based inhibition (MBI) in association with CYP2D6. Several studies revealed that MDMA showed inhibitory effects on CYP3A4. In the present study, our aim was to evaluate the impact of MDMA on the metabolism of MRZ in liver. Therefore, isolated perfused rat liver model was applied as our model of choice in this assessment. The subjects of the study were categorized into two experimental groups. Rats in the control group received MRZ-containing Krebs-Henselit buffer (1 μg/ml). Rats in the treatment group received aqueous solution of 1 mg/ml MDMA (3 mg/kg) intraperitoneally 1 hour before receiving MRZ. Perfusate samples were analyzed by HPLC. Analyses of perfusate samples showed 80% increase in the parent drug concentrations and 50% decrease in the concentrations of both metabolites in our treatment group compared to the control group. In the treatment group compared to the control group, AUC (0-120) of the parent drug demonstrated 50% increase and AUC (0-120) of 8-OH and NDES showed 70% and 60% decrease, respectively. Observed decrease in metabolic ratios were 83% and 79% for 8-OH and NDES in treatment group compared to control group, respectively. Hepatic clearance (CL h ) and intrinsic clearance (Cl int ) showed 20% and 60% decrease in treatment group compared to control group. All findings prove the inhibitory effects of ecstasy on both CYP2D6 and CYP3A4 hepatic isoenzymes. In conclusion, this study is the first investigation of MRZ metabolism in presence of MDMA in isolated perfused rat liver model.

A response-time approach to comparing generalized rational and take-the-best models of decision making.

PubMed

Bergert, F Bryan; Nosofsky, Robert M

2007-01-01

The authors develop and test generalized versions of take-the-best (TTB) and rational (RAT) models of multiattribute paired-comparison inference. The generalized models make allowances for subjective attribute weighting, probabilistic orders of attribute inspection, and noisy decision making. A key new test involves a response-time (RT) approach. TTB predicts that RT is determined solely by the expected time required to locate the 1st discriminating attribute, whereas RAT predicts that RT is determined by the difference in summed evidence between the 2 alternatives. Critical test pairs are used that partially decouple these 2 factors. Under conditions in which ideal observer TTB and RAT strategies yield equivalent decisions, both the RT results and the estimated attribute weights suggest that the vast majority of subjects adopted the generalized TTB strategy. The RT approach is also validated in an experimental condition in which use of a RAT strategy is essentially forced upon subjects. (c) 2007 APA, all rights reserved.

Cardiovascular and hormonal (aldosterone) responses in a rat model which mimics responses to weightlessness

NASA Technical Reports Server (NTRS)

Musacchia, X. J.; Steffen, J. M.

1984-01-01

Cardiovascular responses and fluid/electrolyte shifts seen during spaceflight have been attributed to cephalad redistribution of vascular fluid. The antiorthostatic (AO) rat (suspended, head-down tilt of 15-20 deg) is used to model these responses. This study documents that elevated blood pressures in AO rats are sustained for periods of up to seven days, compared with presuspension values. Increased blood pressures in AO rats suggests a specific response to AO positioning, potentially relatable to a cephalad fluid shift. To assess a role for hormonal regulation of sodium excretion, serum aldosterone levels were measured. Circulating aldosterone concentrations were seen to increase approximately 100 percent during seven days of AO suspension, concurrently with a pronounced natriuresis. These results suggest that aldosterone may not be involved in the long term regulation of increased Na(+) excretion in AO animals. These studies continue to show the usefulness of models for the development of animal protocols for space flight.

Rodent models in neuroscience research: is it a rat race?

PubMed Central

2016-01-01

ABSTRACT Rodents (especially Mus musculus and Rattus norvegicus) have been the most widely used models in biomedical research for many years. A notable shift has taken place over the last two decades, with mice taking a more and more prominent role in biomedical science compared to rats. This shift was primarily instigated by the availability of a much larger genetic toolbox for mice, particularly embryonic-stem-cell-based targeting technology for gene disruption. With the recent emergence of tools for altering the rat genome, notably genome-editing technologies, the technological gap between the two organisms is closing, and it is becoming more important to consider the physiological, anatomical, biochemical and pharmacological differences between rats and mice when choosing the right model system for a specific biological question. The aim of this short review and accompanying poster is to highlight some of the most important differences, and to discuss their impact on studies of human diseases, with a special focus on neuropsychiatric disorders. PMID:27736744

An animal model for the neuromodulation of neurogenic bladder dysfunction.

PubMed

Zvara, P; Sahi, S; Hassouna, M M

1998-08-01

To develop an animal model to examine the pathophysiology by which S3 sacral root electrostimulation alters the micturition reflex in patients with bladder hyper-reflexia. Chronic sacral nerve root electrostimulation was applied to spinally transected rats; 21 animals were divided into four groups. The spinal cord was completely transected at the T10-11 level and stainless-steel electrodes implanted into the sacral foramen in 17 animals; these animals were subsequently divided into two groups (1 and 2). Six rats in group 1 underwent sacral root elctrostimulation for 2 h/day and five in group 2 for 6 h/day, for 21 days. The sham group (group 3, six rats) received no stimulation and four rats were used as healthy controls (group 4). Voiding frequency was recorded and each animal was evaluated cystometrically at the end of the stimulation period. The results were compared with the sham and control groups. Spinal cord transection resulted in bladder areflexia and complete urinary retention; 7-9 days after the injury, the bladder recovered its activity. Twenty-one days after transection all animals had evidence of uninhibited bladder contractions. The mean (SD) hourly frequency of urination was 0.66 (0.18) in healthy controls, 0.83 (0.21) in group 1, 0.87 (0.34) in group 2 and 1.1 (0.31) in group 3. There was a significant decrease in eh cystometric signs of bladder hyper-reflexia in groups 1 and 2 when compared with group 3. This work reports and initial study showing that chronic electrostimulation of sacral nerve roots can reduce the signs of bladder hyper-reflexia in the spinally injured rat. To our knowledge, this is the first report describing the rat as an animal model to determine the effects of chronic electrostimulation on the micturition reflex.

The analgesic effect of tramadol in animal models of neuropathic pain and fibromyalgia.

PubMed

Kaneko, Kumi; Umehara, Masato; Homan, Takashi; Okamoto, Ken; Oka, Michiko; Oyama, Tatsuya

2014-03-06

(±)-Tramadol hydrochloride (tramadol) is a widely used analgesic for the treatment of cancer pain and chronic pain. Although many animal studies have shown antinociceptive effects of tramadol in both acute and chronic pain, little is known about the effect of tramadol in putative animal models of fibromyalgia. In this study, we compared the antiallodynic effects of oral administration of tramadol in two kinds of rat chronic pain models, neuropathic pain induced by partial sciatic nerve ligation (PSL) and reserpine-induced myalgia (RIM). In PSL rats, the threshold for responses induced by tactile stimulation with von Frey filaments was significantly decreased seven days after the operation, suggesting that the operation induced tactile allodynia. Orally administered tramadol showed a potent and dose-dependent antiallodynic effect on PSL-induced allodynia. In RIM rats, the threshold was significantly decreased five days after reserpine treatment. Orally administered tramadol also attenuated reserpine-induced tactile allodynia. To explore the mechanism of the antiallodynic effect of tramadol in RIM rats, we investigated the effect of the opioid antagonist naloxone on the tramadol-induced analgesic effect in these rats. The effect of tramadol was partially antagonized by naloxone, suggesting that the opioid receptor is involved at least in part in the antiallodynic effect of tramadol in RIM rats. These data indicate that orally administered tramadol produced improvement in both PSL rats and RIM rats at similar doses and provide evidence that the opioid system is partly involved in the analgesic effect of tramadol in RIM rats. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The use of motion analysis to measure pain-related behaviour in a rat model of degenerative tendon injuries.

PubMed

Fu, Sai-Chuen; Chan, Kai-Ming; Chan, Lai-Shan; Fong, Daniel Tik-Pui; Lui, Po-Yee Pauline

2009-05-15

Chronic tendinopathy is characterized with longstanding activity-related pain with degenerative tendon injuries. An objective tool to measure painful responses in animal models is essential for the development of effective treatment for tendinopathy. Gait analysis has been developed to monitor the inflammatory pain in small animals. We reported the use of motion analysis to monitor gait changes in a rat model of degenerative tendon injury. Intratendinous injection of collagenase into the left patellar tendon of Sprague Dawley rat was used to induce degenerative tendon injury, while an equal volume of saline was injected in the control groups. Motion analyses with a high speed video camera were performed on all rats at pre-injury, 2, 4, 8, 12 or 16 weeks post injection. In the end-point study, the rats were sacrificed to obtain tendon samples for histological examination after motion analyses. In the follow-up study, repeated motion analyses were performed on another group of collagenase-treated and saline-treated rats. The results showed that rats with injured patellar tendon exhibited altered walking gait as compared to the controls. The change in double stance duration in the collagenase-treated rats was reversible by administration of buprenorphrine (p=0.029), it suggested that the detected gait changes were associated with pain. Comparisons of end-point and follow-up studies revealed the confounding effects of training, which led to higher gait velocities and probably a different adaptive response to tendon pain in the trained rats. The results showed that motion analysis could be used to measure activity-related chronic tendon pain.

[Comparison of two rat models of IgA nephropathy].

PubMed

Peng, Wei; Liu, Zheng-rong

2008-10-01

To study the methods for rapid establishment of rat models of IgA nephropathy. Forty female SD rats weighing 160-200 g were randomized into 3 groups. In group A, the rats received intravenous injection of staphylococcal enterotoxin B (SEB) and oral bovine serum albumin (BSA), and in group B, CCl4 was injected subcutaneously in addition to the above treatments; the rats in group C received no treatments to serve as the normal control group. The rats were sacrificed 10 and 14 weeks after the treatment for biochemical testing of the arterial blood and histopathological and IgA immunofluorescence examination of the renal tissues. The twenty-four-hour urine was collected at 10, 12, and 14 weeks after the treatments for detecting the urine proteins. Compared with the control group, the rats in groups A and B showed significantly increased serum creatinine, urine nitrogen and protein levels. Pathological examination of the renal tissue showed mild to moderate mesangial expansion and mesangial cell proliferation in groups A and B, without obvious difference between the two groups; but hematuria and proteinuria occurred earlier in group B with stronger IgA immunofluorescence than in group A. Both of the methods used in group A and group B can successfully induce IgA nephropathy in rats, but in group B, hematuria and urineprotein occurs earlier and IgA immunofluorescence is more stronger. Therefore intravenous SEB injection combined with oral BSA and subcutaneous CCl4 administration is a better method for time-efficient establishment of rat models of IgA nephropathy.

Edaravone, a free radical scavenger, attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia.

PubMed

Okamura, Koichi; Tsubokawa, Tamiji; Johshita, Hiroo; Miyazaki, Hiroshi; Shiokawa, Yoshiaki

2014-01-01

Thrombolysis due to acute ischemic stroke is associated with the risk of hemorrhagic infarction, especially after reperfusion. Recent experimental studies suggest that the main mechanism contributing to hemorrhagic infarction is oxidative stress caused by disruption of the blood-brain barrier. Edaravone, a free radical scavenger, decreases oxidative stress, thereby preventing hemorrhagic infarction during ischemia and reperfusion. In this study, we investigated the effects of edaravone on hemorrhagic infarction in a rat model of hemorrhagic transformation. We used a previously established hemorrhagic transformation model of rats with hyperglycemia. Hyperglycemia was induced by intraperitoneal injection of glucose to all rats (n  =  20). The rats with hyperglycemia showed a high incidence of hemorrhagic infarction. Middle cerebral artery occlusion (MCAO) for 1.5 hours followed by reperfusion for 24 hours was performed in edaravone-treated rats (n  =  10) and control rats (n  =  10). Upon completion of reperfusion, both groups were evaluated for infarct size and hemorrhage volume and the results obtained were compared. Edaravone significantly decreased infarct volume, with the average infarct volume in the edaravone-treated rats (227.6 mm(3)) being significantly lower than that in the control rats (264.0 mm(3)). Edaravone treatment also decreased the postischemic hemorrhage volumes (53.4 mm(3) in edaravone-treated rats vs 176.4 mm(3) in controls). In addition, the ratio of hemorrhage volume to infarct volume was lower in the edaravone-treated rats (23.5%) than in the untreated rats (63.2%). Edaravone attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia.

Electrophysiological evidence for the antinociceptive effect of transcutaneous electrical stimulation on mechanically evoked responsiveness of dorsal horn neurons in neuropathic rats.

PubMed

Leem, J W; Park, E S; Paik, K S

1995-06-16

Using a rat model of peripheral neuropathy induced by a tight ligation of L5-6 spinal nerves, the effects of transcutaneous electrical stimulation on the mechanical responses of wide dynamic range (WDR) dorsal horn neurons were investigated. The responses of the WDR neurons to both the brush and pinch stimuli were found to be enhanced in the neuropathic rats compared to those in the normal rats. These enhanced responses were depressed by low-frequency and high-intensity transcutaneous electrical stimulation (2 Hz, 4-5 mA) applied to the somatic receptive field. The durations of the depressive effects on the brush responses ranged between 30 and 45 min and those on the pinch responses were 60-90 min. These results imply that the transcutaneous electrical stimulation used here produces an antinociceptive effect via a depressive action on the enhanced mechanical responsiveness of the spinal neurons in this rat model of peripheral neuropathy.

A new method to model electroconvulsive therapy in rats with increased construct validity and enhanced translational value.

PubMed

Theilmann, Wiebke; Löscher, Wolfgang; Socala, Katarzyna; Frieling, Helge; Bleich, Stefan; Brandt, Claudia

2014-06-01

Electroconvulsive therapy is the most effective therapy for major depressive disorder (MDD). The remission rate is above 50% in previously pharmacoresistant patients but the mechanisms of action are not fully understood. Electroconvulsive stimulation (ECS) in rodents mimics antidepressant electroconvulsive therapy (ECT) in humans and is widely used to investigate the underlying mechanisms of ECT. For the translational value of findings in animal models it is essential to establish models with the highest construct, face and predictive validity possible. The commonly used model for ECT in rodents does not meet the demand for high construct validity. For ECT, cortical surface electrodes are used to induce therapeutic seizures whereas ECS in rodents is exclusively performed by auricular or corneal electrodes. However, the stimulation site has a major impact on the type and spread of the induced seizure activity and its antidepressant effect. We propose a method in which ECS is performed by screw electrodes placed above the motor cortex of rats to closely simulate the clinical situation and thereby increase the construct validity of the model. Cortical ECS in rats induced reliably seizures comparable to human ECT. Cortical ECS was more effective than auricular ECS to reduce immobility in the forced swim test. Importantly, auricular stimulation had a negative influence on the general health condition of the rats with signs of fear during the stimulation sessions. These results suggest that auricular ECS in rats is not a suitable ECT model. Cortical ECS in rats promises to be a valid method to mimic ECT. Copyright © 2014 Elsevier Ltd. All rights reserved.

Morphology and Molecular Mechanisms of Hepatic Injury in Rats under Simulated Weightlessness and the Protective Effects of Resistance Training.

PubMed

Du, Fang; Ding, Ye; Zou, Jun; Li, Zhili; Tian, Jijing; She, Ruiping; Wang, Desheng; Wang, Huijuan; Lv, Dongqiang; Chang, Lingling

2015-01-01

This study investigated the effects of long-term simulated weightlessness on liver morphology, enzymes, glycogen, and apoptosis related proteins by using two-month rat-tail suspension model (TS), and liver injury improvement by rat-tail suspension with resistance training model (TS&RT). Microscopically the livers of TS rats showed massive granular degeneration, chronic inflammation, and portal fibrosis. Mitochondrial and endoplasmic reticulum swelling and loss of membrane integrity were observed by transmission electron microscopy (TEM). The similar, but milder, morphological changes were observed in the livers of TS&RT rats. Serum biochemistry analysis revealed that the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly higher (p<0.05) in TS rats than in controls. The levels of ALT and AST in TS&RT rats were slightly lower than in RT rats, but they were insignificantly higher than in controls. However, both TS and TS&RT rats had significantly lower levels (p<0.05) of serum glucose and hepatic glycogen than in controls. Immunohistochemistry demonstrated that the expressions of Bax, Bcl-2, and active caspase-3 were higher in TS rats than in TS&RT and control rats. Real-time polymerase chain reaction (real-time PCR) showed that TS rats had higher mRNA levels (P < 0.05) of glucose-regulated protein 78 (GRP78) and caspase-12 transcription than in control rats; whereas mRNA expressions of C/EBP homologous protein (CHOP) and c-Jun N-terminal kinase (JNK) were slightly higher in TS rats. TS&RT rats showed no significant differences of above 4 mRNAs compared with the control group. Our results demonstrated that long-term weightlessness caused hepatic injury, and may trigger hepatic apoptosis. Resistance training slightly improved hepatic damage.

Morphology and Molecular Mechanisms of Hepatic Injury in Rats under Simulated Weightlessness and the Protective Effects of Resistance Training

PubMed Central

Zou, Jun; Li, Zhili; Tian, Jijing; She, Ruiping; Wang, Desheng; Wang, Huijuan; Lv, Dongqiang; Chang, Lingling

2015-01-01

This study investigated the effects of long-term simulated weightlessness on liver morphology, enzymes, glycogen, and apoptosis related proteins by using two-month rat-tail suspension model (TS), and liver injury improvement by rat-tail suspension with resistance training model (TS&RT). Microscopically the livers of TS rats showed massive granular degeneration, chronic inflammation, and portal fibrosis. Mitochondrial and endoplasmic reticulum swelling and loss of membrane integrity were observed by transmission electron microscopy (TEM). The similar, but milder, morphological changes were observed in the livers of TS&RT rats. Serum biochemistry analysis revealed that the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly higher (p<0.05) in TS rats than in controls. The levels of ALT and AST in TS&RT rats were slightly lower than in RT rats, but they were insignificantly higher than in controls. However, both TS and TS&RT rats had significantly lower levels (p<0.05) of serum glucose and hepatic glycogen than in controls. Immunohistochemistry demonstrated that the expressions of Bax, Bcl-2, and active caspase-3 were higher in TS rats than in TS&RT and control rats. Real-time polymerase chain reaction (real-time PCR) showed that TS rats had higher mRNA levels (P < 0.05) of glucose-regulated protein 78 (GRP78) and caspase-12 transcription than in control rats; whereas mRNA expressions of C/EBP homologous protein (CHOP) and c-Jun N-terminal kinase (JNK) were slightly higher in TS rats. TS&RT rats showed no significant differences of above 4 mRNAs compared with the control group. Our results demonstrated that long-term weightlessness caused hepatic injury, and may trigger hepatic apoptosis. Resistance training slightly improved hepatic damage. PMID:26000905

A Strategy Using Photodynamic Therapy and Clofibric Acid to Treat Peritoneal Dissemination of Ovarian Cancer.

PubMed

Yokoyama, Yoshihito; Shigeto, Tatsuhiko; Miura, Rie; Kobayashi, Asami; Mizunuma, Makito; Yamauchi, Aisa; Futagami, Masayuki; Mizunuma, Hideki

2016-01-01

The current study examined the effectiveness of concurrent therapy using photodynamic therapy (PDT) and clofibric acid (CA) to treat peritoneal carcinomatosis resulting from ovarian cancer. Nude rats were used to create a model of peritoneal carcinomatosis resulting from ovarian cancer and the effectiveness of PDT with 5-aminolevulinic acid methyl ester hydrochloride (methyl-ALA-PDT) was determined. The survival time of rats receiving that therapy was compared to the survival time of a control group. Rats with peritoneal carcinomatosis resulting from ovarian cancer were divided into 3 groups: a group that received debulking surgery (DS) alone, a group that received DS+methyl-ALA-PDT, and a group that received DS+methyl-ALA-PDT+CA. The survival time of the 3 groups was compared. Protoporphyrin, a metabolite of methyl-ALA, produces a photochemical action when activated by light. The level of protoporphyrin (the concentration) that reached organs in the abdomen was measured with HPLC. Rats receiving methyl- ALA-PDT had a significantly longer survival time compared to the controls. Rats with peritoneal carcinomatosis that received DS+methyl-ALA-PDT+CA had a significantly longer survival time compared to the rats that received DS alone. Some of the rats that received concurrent therapy survived for a prolonged period. Protoporphyrin was highly concentrated in peritoneal metastases, but only small amounts reached major organs in the abdomen. PDT was not found to result in necrosis in the intestines. The results indicated that concurrent therapy consisting of PDT with methyl-ALA and CA is effective at treating peritoneal carcinomatosis resulting from ovarian cancer without damaging organs.

Pharmacokinetic evaluation of avicularin using a model-based development approach.

PubMed

Buqui, Gabriela Amaral; Gouvea, Dayana Rubio; Sy, Sherwin K B; Voelkner, Alexander; Singh, Ravi S P; da Silva, Denise Brentan; Kimura, Elza; Derendorf, Hartmut; Lopes, Norberto Peporine; Diniz, Andrea

2015-03-01

The aim of this study was to use the pharmacokinetic information of avicularin in rats to project a dose for humans using allometric scaling. A highly sensitive and specific bioanalytical assay to determine avicularin concentrations in the plasma was developed and validated for UPLC-MS/MS. The plasma protein binding of avicularin in rat plasma determined by the ultrafiltration method was 64%. The pharmacokinetics of avicularin in nine rats was studied following an intravenous bolus administration of 1 mg/kg and was found to be best described by a two-compartment model using a nonlinear mixed effects modeling approach. The pharmacokinetic parameters were allometrically scaled by body weight and centered to the median rat weight of 0.23 kg, with the power coefficient fixed at 0.75 for clearance and 1 for volume parameters. Avicularin was rapidly eliminated from the systemic circulation within 1 h post-dose, and the avicularin pharmacokinetic was linear up to 5 mg/kg based on exposure comparison to literature data for a 5-mg/kg single dose in rats. Using allometric scaling and Monte Carlo simulation approaches, the rat doses of 1 and 5 mg/kg correspond to the human equivalent doses of 30 and 150 mg, respectively, to achieve comparable plasma avicularin concentrations in humans. Georg Thieme Verlag KG Stuttgart · New York.

Hepatoprotective and antioxidant effects of lycopene on non-alcoholic fatty liver disease in rat.

PubMed

Jiang, Wei; Guo, Mei-Hua; Hai, Xin

2016-12-14

To evaluate the hepatoprotective effect of lycopene (Ly) on non-alcoholic fatty liver disease (NAFLD) in rat. A rat model of NAFLD was first established by feeding a high-fat diet for 14 wk. Sixty-five rats were randomly divided into normal group, model group and Ly treatment groups. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total cholesterol (TC) in serum and low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), free fatty acid (FFA), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) in liver tissue were evaluated, respectively. While the hepatoprotective effect was also confirmed by histopathological analysis, the expression levels of TNF-α and cytochrome P 450 (CYP) 2E1 in rat liver were determined by immunohistochemistry analysis. A significant decrease was observed in the levels of serum AST (2.07-fold), ALT (2.95-fold), and the blood lipid TG (2.34-fold) and TC (1.66-fold) in the dose of 20 mg/kg Ly-treated rats ( P < 0.01), compared to the model group. Pretreatment with 5, 10 and 20 mg/kg of Ly significantly raised the levels of antioxidant enzyme SOD in a dose-dependent manner, to 90.95 ± 9.56, 109.52 ± 11.34 and 121.25 ± 10.68 ( P < 0.05, P < 0.01), as compared with the model group. Similarly, the levels of GSH were significantly increased ( P < 0.05, P < 0.01) after the Ly treatment. Meanwhile, pretreatment with 5, 10 and 20 mg/kg of Ly significantly reduced MDA amount by 30.87, 45.51 and 54.49% in the liver homogenates, respectively ( P < 0.01). The Ly treatment group showed significantly decreased levels of lipid products LDL-C ( P < 0.05, P < 0.01), improved HDL-C level and significantly decreased content of FFA, compared to the model group ( P < 0.05, P < 0.01). Furthermore, the Ly-treated group also exhibited a down-regulated TNF-α and CYP2E1 expression, decreased infiltration of liver fats and reversed histopathological changes, all in a dose-dependent manner ( P < 0.05, P < 0.01). This study suggests that Ly has a protective effect on NAFLD, down-regulates expression of TNF-α, and that CYP2E1 may be one of the action mechanisms for Ly.

AGN-2979, an inhibitor of tryptophan hydroxylase activation, does not affect serotonin synthesis in Flinders Sensitive Line rats, a rat model of depression, but produces a significant effect in Flinders Resistant Line rats

PubMed Central

Kanemaru, Kazuya; Nishi, Kyoko; Diksic, Mirko

2009-01-01

The neurotransmitter, serotonin, is involved in several brain functions, including both normal, physiological functions, and pathophysiological functions. Alterations in any of the normal parameters of serotonergic neurotransmission can produce several different psychiatric disorders, including major depression. In many instances, brain neurochemical variables are not able to be studied properly in humans, thus making the use of good animal models extremely valuable. One of these animal models is the Flinders Sensitive Line (FSL) of rats, which has face, predictive and constructive validities in relation to human depression. The objective of this study was to quantify the effect of the tryptophan hydroxylase (TPH) activation inhibitor, AGN-2979, on the FSL rats (rats with depression-like behaviour), and compare it to the effect on the Flinders Resistant Line (FRL) of rats used as the control rats. The effect was evaluated by measuring changes in regional serotonin synthesis in the vehicle treated rats (FSL-VEH and FRL-VEH) relative to those measured in the AGN-2979 treated rats (FSL-AGN and FRL-AGN). Regional serotonin synthesis was measured autoradiographically in more than thirty brain regions. The measurements were performed using α-[14C]methyl-L-tryptophan as the tracer. The results indicate that AGN-2979 did not produce a significant reduction of TPH activity in the AGN-2979 group relative to the vehicle group (a reduction would have been observed if there had been an activation of TPH by the experimental set up) in the FSL rats. On the other hand, there was a highly significant reduction of synthesis in the FRL rats treated by AGN-2979, relative to the vehicle group. Together, the results demonstrate that in the FSL rats, AGN-2979 does not affect serotonin synthesis. This suggests that there was no activation of TPH in the FSL rats during the experimental procedure, but such activation did occur in the FRL rats. Because of this finding, it could be hypothesised that TPH in the FSL rats cannot be easily activated. This may contribute to the development of depressive-like symptoms in the FSL rats (“depressed” rats), as they cannot easily modulate their need for elevated amounts of this neurotransmitter, and possibly other neurotransmitters. Further, because these rats represent a very good model of human depression, one can hypothesize that humans who do not have readily activated TPH may be more prone to develop depression. PMID:19463878

A Surgical Model in Male Obese Rats Uncovers Protective Effects of Bile Acids Post-Bariatric Surgery

PubMed Central

Setchell, Kenneth DR; Kirby, Michelle; Myronovych, Andriy; Ryan, Karen K.; Ibrahim, Samar H.; Berger, Jose; Smith, Kathi; Toure, Mouhamadoul; Woods, Stephen C.; Seeley, Randy J.

2013-01-01

Bariatric surgery elevates serum bile acids. Conjugated bile acid administration, such as tauroursodeoxycholic acid (TUDCA), improves insulin sensitivity, whereas short-circuiting bile acid circulation through ileal interposition surgery in rats raises TUDCA levels. We hypothesized that bariatric surgery outcomes could be recapitulated by short circuiting the normal enterohepatic bile circulation. We established a model wherein male obese rats underwent either bile diversion (BD) or Sham (SH) surgery. The BD group had a catheter inserted into the common bile duct and its distal end anchored into the middistal jejunum for 4–5 weeks. Glucose tolerance, insulin and glucagon-like peptide-1 (GLP-1) response, hepatic steatosis, and endoplasmic reticulum (ER) stress were measured. Rats post-BD lost significantly more weight than the SH rats. BD rats gained less fat mass after surgery. BD rats had improved glucose tolerance, increased higher postprandial glucagon-like peptide-1 response and serum bile acids but less liver steatosis. Serum bile acid levels including TUDCA concentrations were higher in BD compared to SH pair-fed rats. Fecal bile acid levels were not different. Liver ER stress (C/EBP homologous protein mRNA and pJNK protein) was decreased in BD rats. Bile acid gavage (TUDCA/ursodeoxycholic acid [UDCA]) in diet-induced obese rats, elevated serum TUDCA and concomitantly reduced hepatic steatosis and ER stress (C/EBP homologous protein mRNA). These data demonstrate the ability of alterations in bile acids to recapitulate important metabolic improvements seen after bariatric surgery. Further, our work establishes a model for focused study of bile acids in the context of bariatric surgery that may lead to the identification of therapeutics for metabolic disease. PMID:23592746

Adolescent peer-rejection persistently alters pain perception and CB1 receptor expression in female rats.

PubMed

Schneider, Peggy; Hannusch, Christin; Schmahl, Christian; Bohus, Martin; Spanagel, Rainer; Schneider, Miriam

2014-02-01

Peer-interactions are particularly important during adolescence and teenagers display enhanced sensitivity toward rejection by peers. Social rejection has been shown to induce alterations in pain perception in humans. However, the neurobiological consequences of adolescent social rejection have yet to be extensively characterized, and no appropriate animal model is available. Here, we propose inadequate playful interactions in adolescent rats as a novel animal model for social peer-rejection and examine potential long-term consequences into adulthood. Acute social pairing of female adolescent Wistar rats with an age-matched rat from the less playful Fischer344 strain was found to alter social play and decrease pain reactivity, indicating Fischer rats as inadequate social partners for Wistar animals. Therefore, in a second experiment, adolescent female Wistar rats were either reared with another Wistar rat (adequate social rearing; control) or with a Fischer rat (inadequate social rearing; play-deprived). Beginning on day 50, all Wistar rats were group housed with same-strain partners and tested for behavioral, neurobiological and endocrine differences in adulthood. Playful peer-interactions were decreased during adolescence in play-deprived animals, without affecting social contact behavior. Consequently, adult play-deprived rats showed decreased pain sensitivity and increased startle reactivity compared to controls, but did not differ in activity, anxiety-related behavior or social interaction. Both groups also differed in their endocrine stress-response, and expression levels of the cannabinoid CB1 receptor were increased in the thalamus, whereas FAAH levels were decreased in the amygdala. The present animal model therefore represents a novel approach to assess the long-term consequences of peer-rejection during adolescence. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Impact of Perinatal Systemic Hypoxic–Ischemic Injury on the Brain of Male Offspring Rats: An Improved Model of Neonatal Hypoxic–Ischemic Encephalopathy in Early Preterm Newborns

PubMed Central

Xu, Hongwu; Wu, Weizhao; Lai, Xiulan; Ho, Guyu; Ma, Lian; Chen, Yunbin

2013-01-01

In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE) in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND) 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions. PMID:24324800

Effects of tretinoin on wound healing in aged skin.

PubMed

de Campos Peseto, Danielle; Carmona, Erica Vilaça; Silva, Kellyn Cristina da; Guedes, Flavia Roberta Valente; Hummel Filho, Fernando; Martinez, Natalia Peres; Pereira, José Aires; Rocha, Thalita; Priolli, Denise Gonçalves

2016-03-01

Aged and adult populations have differences in the structural, biological, and healing properties of skin. Comparative studies of healing under the influence of retinoids in both these populations are very important and, to the best of our knowledge, have not been performed to date. The purpose of this study was to compare the activities of topical tretinoin in aged and adult animal models of wound healing by secondary intention. Male aged rats (24 months old, n = 7) and adult rats (6 months old, n = 8) were used. The rats were assigned to the following groups according to the dates on which wound samples were excised (day 14 or 21 after model creation): treated group, control group, and naive group. Topical application of tretinoin cream was used only on the proximal wound and was applied daily for 7 days. Wound healing areas were measured using metal calipers, and morphological analysis was performed. Slides were stained with Hematoxylin and Eosin, Masson's trichrome, and periodic acid-Schiff stains. Statistical analysis adopted a 5% coefficient for rejection of the null hypothesis. Although aged animals showed skin repair, complete reepithelialization was found on day 21 in some animals of both groups (treated and control). In aged rats, the wound area was significantly smaller in treated wounds than in untreated wounds, resulting in a larger scar area compared with the adult group. When treated wounds were compared, no differences were found between the wound areas in adult and aged rats. As expected, the collagen concentration was higher in normal skin from adult rats than in normal skin from aged animals, but there was no difference when aged skin was treated with tretinoin. These results indicate that tretinoin increases collagen synthesis in aged skin and returns the healing process to a normal state of skin healing. © 2016 by the Wound Healing Society.

[Effect of high frequency electrotherapy on caspase-3 and ultra microstructure of hippocampus in rats following cerebral ischemia/reperfusion].

PubMed

Fan, Yongmei; Wang, Rumi; Zhang, Changjie; Peng, Wenna; Yin, Jing; Hu, Zhiping

2017-01-28

To investigate the effect of high frequency electrotherapy (HFE) on rat hippocampus after cerebral ischemia/reperfusion (I/R).
 Methods: A rat model of cerebral I/R injury was established. The rats were randomly divided into a sham group, an I/R group and an HFE group. The HFE group received thearapy daily for different sessions for 1, 3, 7 d. Neuronal deficit score,neuron ultra microstructure in the hippocampus and caspase-3 protein expression were measured on 1 st, 3 th and 7th d.
 Results: Compared with the I/R group, the HFE group showed the decreased neurological deficit scores, with significant differences between the 2 groups (P<0.05). The injury in HFE group was reduced compared with that in the I/R group based on the electron microscope test, with significant difference. Caspase-3 protein in brain tissue in the HFE group also downregulated compared with that in the I/R group (P<0.05).
 Conclusion: High frequency electrotherapy can improve neural function, suppress caspase-3 expression and apoptosis in nerve cells and improve the ultra microstructure of neurons, displaying a protective effect on cerebral I/R injury in rats.

Pharmacokinetic and Pharmacodynamic Interaction of Boswellic Acids and Andrographolide with Glyburide in Diabetic Rats: Including Its PK/PD Modeling.

PubMed

Samala, Sujatha; Veeresham, Ciddi

2016-03-01

The effect of boswellic acids (BA) and andrographolide (AD) on the pharmacokinetics and pharmacodynamics of glyburide in normal as well as in streptozotocin-induced diabetic rats was studied. In normal and diabetic rats, the combination of glyburide with BA or AD increased significantly (p < 0.01) all the pharmacokinetic parameters, such as Cmax, AUC0-n, AUCtotal, t1/2, and mean residence time, and decreased the clearance, Vd, markedly as compared with the control group. In rat liver, microsomes BA and AD have shown CYP3A4 inhibitory activity significantly (p < 0.01), compared with the vehicle group. The increase in hypoglycemic action by concomitant administration of glyburide with BA or AD was more in diabetic rats than when the drugs were used singly and with the control group, which suggests the enhancement of glucose reduction capacity of glyburide in diabetic rats along with BA or AD. In PK/PD modeling of BA and AD with glyburide, the predicted PK and PD parameters are in line with the observed PK and PD parameters. The results revealed that BA and AD led to the PK/PD changes because of glyburide-increased bioavailability and because of the inhibition of CYP3A4 enzyme. In conclusion, add-on preparations containing BA or AD may increase the bioavailability of glyburide, and hence the dose should be monitored. Copyright © 2016 John Wiley & Sons, Ltd.

Modulation of fatty acid metabolism is involved in the alleviation of isoproterenol-induced rat heart failure by fenofibrate

PubMed Central

LI, PING; LUO, SHIKE; PAN, CHUNJI; CHENG, XIAOSHU

2015-01-01

Heart failure is a disease predominantly caused by an energy metabolic disorder in cardiomyocytes. The present study investigated the inhibitory effects of fenofibrate (FF) on isoproterenol (ISO)-induced hear failure in rats, and examined the underlying mechanisms. The rats were divided into CON, ISO (HF model), FF and FF+ISO (HF animals pretreated with FF) groups. The cardiac structure and function of the rats were assessed, and contents of free fatty acids and glucose metabolic products were determined. In addition, myocardial cells were isolated from neonatal rats and used in vitro to investigate the mechanisms by which FF relieves heart failure. Western blot analysis was performed to quantify the expression levels of peroxisome proliferator-activated receptor (PPAR)α and uncoupling protein 2 (UCP2). FF effectively alleviated the ISO-induced cardiac structural damage, functional decline, and fatty acid and carbohydrate metabolic abnormalities. Compared with the ISO group, the serum levels of brain natriuretic peptide (BNP), free fatty acids, lactic acid and pyruvic acid were decreased in the FF animals. In the cultured myocardial cells, lactic acid and pyruvic acid contents were lower in the supernatants obtained from the FF animals, with lower levels of mitochondrial ROS production and cell necrosis, compared with the ISO group, whereas PPARα upregulation and UCP2 downregulation occurred in the FF+ISO group. The results demonstrated that FF efficiently alleviated heart failure in the ISO-induced rat model, possibly via promoting fatty acid oxidation. PMID:26497978

Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function.

PubMed

Hamann, Christine; Goettsch, Claudia; Mettelsiefen, Jan; Henkenjohann, Veit; Rauner, Martina; Hempel, Ute; Bernhardt, Ricardo; Fratzl-Zelman, Nadja; Roschger, Paul; Rammelt, Stefan; Günther, Klaus-Peter; Hofbauer, Lorenz C

2011-12-01

Patients with diabetes mellitus have an impaired bone metabolism; however, the underlying mechanisms are poorly understood. Here, we analyzed the impact of type 2 diabetes mellitus on bone physiology and regeneration using Zucker diabetic fatty (ZDF) rats, an established rat model of insulin-resistant type 2 diabetes mellitus. ZDF rats develop diabetes with vascular complications when fed a Western diet. In 21-wk-old diabetic rats, bone mineral density (BMD) was 22.5% (total) and 54.6% (trabecular) lower at the distal femur and 17.2% (total) and 20.4% (trabecular) lower at the lumbar spine, respectively, compared with nondiabetic animals. BMD distribution measured by backscattered electron imaging postmortem was not different between diabetic and nondiabetic rats, but evaluation of histomorphometric indexes revealed lower mineralized bone volume/tissue volume, trabecular thickness, and trabecular number. Osteoblast differentiation of diabetic rats was impaired based on lower alkaline phosphatase activity (-20%) and mineralized matrix formation (-55%). In addition, the expression of the osteoblast-specific genes bone morphogenetic protein-2, RUNX2, osteocalcin, and osteopontin was reduced by 40-80%. Osteoclast biology was not affected based on tartrate-resistant acidic phosphatase staining, pit formation assay, and gene profiling. To validate the implications of these molecular and cellular findings in a clinically relevant model, a subcritical bone defect of 3 mm was created at the left femur after stabilization with a four-hole plate, and bone regeneration was monitored by X-ray and microcomputed tomography analyses over 12 wk. While nondiabetic rats filled the defects by 57%, diabetic rats showed delayed bone regeneration with only 21% defect filling. In conclusion, we identified suppressed osteoblastogenesis as a cause and mechanism for low bone mass and impaired bone regeneration in a rat model of type 2 diabetes mellitus.