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Sample records for hyperlipidemic rat model

  1. 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.

  2. Effects of an Enriched Extract of Paeoniflorin, a Monoterpene Glycoside used in Chinese Herbal Medicine, on Cholesterol Metabolism in a Hyperlipidemic Rat Model.

    PubMed

    Hu, Huiming; Zhu, Qiaoqiao; Su, Jie; Wu, Yajun; Zhu, Yanchen; Wang, Yin; Fang, Hui; Pang, Minxia; Li, Bo; Chen, Suhong; Lv, Guiyuan

    2017-07-14

    BACKGROUND Paeoniflorin is a monoterpene glycoside extracted from the roots of Paeonia lactiflora and is used in Chinese herbal medicine to treat hyperlipidemia. The aim of this study was to evaluate the effects of an enriched extract of paeoniflorin on cholesterol levels, hemodynamics, and oxidative stress in a hyperlipidemic rat model. MATERIAL AND METHODS Male Sprague-Dawley rats were fed high-cholesterol diets and treated with three different doses of paeoniflorin for 12 weeks. The effects of paeoniflorin treatment were assessed on cholesterol levels, cholesterol metabolism, red blood cell vascular flow using hemorheology, antioxidant enzymes, and expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR). Rat liver histology and immunohistochemical analysis were performed to evaluate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), cytochrome P450 7A1 (CYP7A1), and peroxisome proliferator-activated receptors (PPAR)-α. Protein expression HMG-CoAR, low-density lipoprotein receptor (LDLR), PPAR-α and CYP7A1 was measured by Western blotting. Antioxidant activity in rat liver was determined by measuring superoxide dismutase (SOD) and malondialdehyde (MDA). RESULTS Serum and hepatic cholesterol, hepatic steatosis and the products of cholesterol metabolism were reduced by paeoniflorin treatment, which also reduced the activity of HMG-CoAR and upregulated the expression of LDLR, PPAR-α, and CYP7A1 expression, increased SOD, decreased MDA, and upregulated Nrf2 expression. CONCLUSIONS The findings of this study in a rat model of hyperlipidemia have shown that paeoniflorin regulates hepatic cholesterol synthesis and metabolism and may also protect the liver from oxidative stress.

  3. Hypolipidemic activity of Eclipta prostrata (L.) L. leaf extract in atherogenic diet induced hyperlipidemic rats.

    PubMed

    Dhandapani, R

    2007-07-01

    In atherogenic diet induced hyperlipidemic model, the rats receiving treatment with the aqueous extract of the leaves of E. prostrata showed significant reduction in total cholesterol, triglyceride, total protein and elevation in high density lipoprotein cholesterol. The aqueous extract of E. prostrata was found to possess significant hypolipidemic activity. The results also suggest that E. prostrata leaf extract at 100 and 200 mg/kg b.wt. concentrations is an excellent lipid-lowering agent.

  4. Neuroprotective effects of pretreatment with quercetin as assessed by acetylcholinesterase assay and behavioral testing in poloxamer-407 induced hyperlipidemic rats.

    PubMed

    Braun, Josiane B S; Ruchel, Jader B; Adefegha, Stephen A; Coelho, Ana Paula V; Trelles, Kelly B; Signor, Cristiane; Rubin, Maribel A; Oliveira, Juliana S; Dornelles, Guilherme L; de Andrade, Cinthia M; Castilhos, Lívia G; Leal, Daniela B R

    2017-04-01

    Hyperlipidemia is a group of disorders characterized by excessive lipids in the bloodstream. It is associated with the incidence of cardiovascular diseases and recognized as the most important factor underlying the occurrence of atherosclerosis. This study was conducted to investigate whether pretreatment with quercetin can protect against possible memory impairment and deterioration of the cholinergic system in hyperlipidemic rats. Animals were divided into ten groups (n=7): saline/control, saline/quercetin 5mg/kg, saline/quercetin 25mg/kg, saline/quercetin 50mg/kg, saline/simvastatin (0.04mg/kg), hyperlipidemia, hyperlipidemia/quercetin 5mg/kg, hyperlipidemia/quercetin 25mg/kg, hyperlipidemia/quercetin 50mg/kg and hyperlipidemia/simvastatin. The animals were pretreated with quercetin by oral gavage for a period of 30days and hyperlipidemia was subsequently induced by intraperitoneal administration of a single dose of 500mg/kg of poloxamer-407. Simvastatin was administered after the induction of hyperlipidemia. The results demonstrated that hyperlipidemic rats had memory impairment compared with the saline control group (P<0.001). However, pretreatment with quercetin and simvastatin treatment attenuated the damage caused by hyperlipidemia compared with the hyperlipidemic group (P<0.05). Acetylcholinesterase (AChE) activity in the cerebral hippocampus was significantly (P<0.001) reduced in the hyperlipidemic group compared with the control saline group. Pretreatment with quercetin and simvastatin treatment in the hyperlipidemic groups significantly (P<0.05) increased AChE activity compared with the hyperlipidemic group. Our results thus suggest that quercetin may prevent memory impairment, alter lipid metabolism, and modulate AChE activity in an experimental model of hyperlipidemia. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Hypolipidemic effect of aqueous extract of Carum carvi (black Zeera) seeds in diet induced hyperlipidemic rats.

    PubMed

    Saghir, Muhammad Rashad; Sadiq, Soban; Nayak, Salma; Tahir, Muhammad Usman

    2012-04-01

    Medicinal plants play a key role in preventing various diseases. Hyperlipidemia is a major contributor to the pathogenesis of cardiovascular diseases. The purpose of the present study was to assess the effect of aqueous extract of Carum carvi seeds in diet induced hyperlipidemia in rats. 2% cholesterol diet were given to rats for six weeks and rats showed high lipid levels were included in the study. Then all rats were divided into, normal control group (A), hyperlipidemia positive control group (B), and the remaining two groups (C and D) served as experimental groups. Group C hyperlipidemic experimental rats received aqueous dried extract of Carum carvi seeds at 60 mg/kg of body weight for eight weeks on daily basis. On the other hand group D rats received simvastatin at 1.0 mg/kg body weight for eight weeks. Blood samples were collected after eight weeks. The hyperlipidemic positive control group rats showed variable increase in serum triglycerides, LDL and total cholesterol levels. Serum HDL levels decreased in hyperlipidemic positive control groups. Carum carvi and simvastatin significantly decreased the levels of these parameters in rats. On comparison Carum carvi reduced lipid levels more, effectively than the simvastatin. Carum carvi constituents, especially flavonoids and carvone have strong anti-oxidant activity which might be involved in hypolipidemia. In conclusion, Carum carvi aqueous seeds extract decrease lipid levels in diet induced hyperlipidemic rats.

  6. GCG-rich tea catechins are effective in lowering cholesterol and triglyceride concentrations in hyperlipidemic rats.

    PubMed

    Lee, Sang Min; Kim, Chae Wook; Kim, Jung Kee; Shin, Hyun Jung; Baik, Joo Hyun

    2008-05-01

    The (-)-gallocatechin gallate (GCG) concentration in some tea beverages can account for as much as 50% of the total catechins, as a result of sterilization. The present study aims to examine the effects of GCG-rich tea catechins on hyperlipidemic rats and the mechanisms associated with regulating cholesterol metabolism in the liver. By performing heat epimerization of (-)-epigallocatechin gallate (EGCG), we manufactured a mixture of catechins that had a GCG content of approximately 50% (w/w). In sucrose-rich diet-induced hyperlipidemic rats, the GCG-rich tea catechins exhibited strong activity in reducing plasma cholesterol and triglyceride concentrations. Furthermore, the hepatic cholesterol and triglyceride concentrations that had increased as a result of the sucrose-rich diet were reduced due to GCG-rich tea catechins consumption. In order to investigate the hyperlipidemic mechanism of GCG-rich tea catechins, we examined the hepatic expressions of LDL receptor and HMG-CoA reductase in hyperlipidemic rats. We further evaluated the action of purified GCG on LDL receptor activity, which is a key contributor to the regulation of cholesterol concentrations. We found that purified GCG increased LDL receptor protein level and activity to a greater extent than EGCG. In conclusion, our study indicates that GCG-rich tea catechins in tea beverages may be effective in preventing hyperlipidemia by lowering plasma and hepatic cholesterol concentrations.

  7. Hyperlipidemic chicken as a model of non-alcoholic steatohepatitis.

    PubMed

    Ayala, Ignacio; Castillo, Antonia Martín; Adánez, Gracia; Fernández-Rufete, Ana; Pérez, Bartolomé García; Castells, Maria T

    2009-01-01

    Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease (NAFLD), currently the most common cause of abnormal liver tests. Given the difficulty of studying all the factors involved in it in human populations, studies in animal models might provide crucial insights in the pathogenesis of steatohepatitis. Several physiological features predispose birds to fat deposition in the liver. The present study was conceived to explore the possibilities of the chicken fed a cholesterol and fat enriched diet as a model for steatohepatitis. We used two different diets: a standard growing mash (control group) and a standard growing mash enriched with 2% cholesterol and 20% palm oil (hyperlipidemic group). We investigated the effect of feeding a cholesterol and fat enriched diet, on plasma lipid levels, liver enzymes and hepatic histopathology. Semiquantitative and quantitative assessment by image analysis was performed to determine changes in lipid deposits and inflammatory infiltration. Statistically significant increases were observed in all plasma lipid parameters, liver macroscopic features, fat deposits and cell-ballooning of hepatocytes between control and hyperlipidemic animals. Significant differences were also observed in the inflammatory infiltration parameters (number of foci, density, area and maximal diameter). Results show that diet-induced hypercholesterolemia and hypertriglyceridemia are associated with severe impairment of liver histology (fat accumulation, inflammation and cell-ballooning), reproducing histological features of human NAFLD. This model, which is easy and reproducible, offers economic and technical advantages. Furthermore, the reversibility of the pathologic changes makes it suitable for drug intervention studies of steatohepatitis.

  8. Effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart.

    PubMed

    Kansal, Sunil Kumar; Jyoti, Uma; Sharma, Samridhi; Kaura, Arun; Deshmukh, Rahul; Goyal, Sandeep

    2015-06-01

    Hyperlipidemia is regarded as independent risk factor in the development of ischemic heart disease, and it can increase the myocardial susceptibility to ischemia-/reperfusion (I/R)-induced injury. Hyperlipidemia attenuates the cardioprotective response of ischemic preconditioning (IPC). The present study investigated the effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat hearts. Hyperlipidemia was induced in rat by feeding high-fat diet (HFD) for 6 weeks then the serum lipid profile was observed. In experiment, the isolated Langendorff rat heart preparation was subjected to 4 cycles of ischemic preconditioning (IPC), then 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size was elaborated morphologically by triphenyltetrazolium chloride (TTC) staining and biochemically by lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) release from coronary effluent and left ventricular collagen content. However, the effect of zinc supplement, i.e., zinc pyrithione (10 μM) perfused during reperfusion for 120 min, significantly abrogated the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart whereas administration of chelator of this zinc ionophore, i.e., N,N,N',N'-tetrakis(2-pyridylmethyl)ethylene diamine (TPEN; 10 μM), perfused during reperfusion 2 min before the perfusion of zinc pyrithione abrogated the cardioprotective effect of zinc supplement during experiment in hyperlipidemic rat heart. Thus, the administration of zinc supplements limits the infarct size, LDH, and CK-MB and enhanced the collagen level which suggests that the attenuated cardioprotective effect of IPC in hyperlipidemic rat is due to zinc loss during reperfusion caused by ischemia/reperfusion.

  9. Hypolipidemic and Antioxidant Effects of Malus toringoides (Rehd.) Hughes Leaves in High-Fat-Diet-Induced Hyperlipidemic Rats.

    PubMed

    Huang, Shan; Liu, Haifeng; Meng, Ning; Li, Bin; Wang, Jule

    2017-03-01

    Malus toringoides (Rehd.) Hughes (MT) leaves are traditionally used as a medicine for treating or preventing cardiovascular disease in Tibet. In addition to the effect of this medicinal plant on thrombosis, we tested its effect on dyslipidemia in a hypolipidemic rat model. A total of 60 healthy Sprague-Dawley rats were randomly divided into six groups, as follows: normal control, model control, simvastatin groups, and MT low-, medium-, and high-dose groups. The normal controls were fed with a normal diet, whereas all other groups were fed with a high-fat diet. After 6 weeks, the high-fat diet had induced hyperlipidemia in the rats, which were then orally administered with different doses of MT leaf extract (50, 100, and 200 mg/kg) for an additional 6 weeks. Serum levels of total cholesterol (TC), triglycerides (TG), low- and high-density lipoprotein cholesterol (LDL-c and HDL-c, respectively), as well as the antioxidant capacity of glutathione peroxidase (GSHP-x), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured at the end of the study. MT significantly reduced serum TC, TG, and LDL-c and increased the HDL-c content in MT-treated rats compared with the model group. These changes were dose dependent. MT treatment also significantly elevated the activity of SOD and GSHP-x, and decreased the serum levels of MDA compared with untreated hyperlipidemic rats, thereby increasing serum antioxidant capacity. In addition, MT reduced liver steatosis in hyperlipidemic rats. Overall, MT exerts considerable hypolipidemic and antioxidant properties.

  10. Policosanol as a new inhibitor candidate for vascular calcification in diabetic hyperlipidemic rats

    PubMed Central

    Zein, Nabila; Aldhamy, Samih E; Elsawy, Marwa M; Saeid, Saeid A

    2016-01-01

    This work mainly aimed to investigate the probable changes of aortic calcification by policosanol, omega-3 fatty acids in comparison with atorvastatin and subsequent progression of atherosclerosis in diabetic hyperlipemic rat model. Adult male albino rats of wistar strain (30) were divided into five groups (n = 6/group); one was fed normal diet and was used as a normal group, the other groups received alloxan, atherogenic diet (CCT – rat chow diet supplemented with 4% cholesterol, 1% cholic acid, and 0.5% thiouracil) and categorized as follows: the second group received no treatment and kept as control (diabetic hyperlipidemic control group (DHC)). The other groups received daily oral doses of atorvastatin, policosanol (10 mg/kg body weight) and ω-3 (50 mg/kg body weight), respectively, for eight weeks. Different biomarkers were used for the evaluation that included inflammatory (C reactive protein (CRP), tumor necrosis factor α (TNF-α)), oxidative stress (glutathione (GSH), malondialdehyde (MDA)) bone calcification markers (alkaline phosphatase (ALP), Vitamin D, parathyroid hormone (PTH)), lipogram pattern in addition to histochemical demonstration of calcium in the aorta. Diabetic hyperlipemic group demonstrated significant hyperglycemia, hyperlipidemia, and increased inflammation, oxidative stress, calcification, and finally atherogenesis progression. Treatment of diabetic hyperlipemic rats with, policosanol, omega-3 fatty acids (natural products) and atorvastatin for eight weeks significantly increased high-density lipoprotein cholesterol (HDL-C), Vitamin D, decreased aortic vacuoles number, and inhibited calcification process. Policosanol induced more remarkable reduction in the density and number of foam cells and improved the intimal lesions of the aorta as compared to atorvastatin. Drugs under study exerted hypoglycemic effect along with an inhibition of inflammation, oxidative stress, and calcium deposition with certain variations but

  11. Policosanol as a new inhibitor candidate for vascular calcification in diabetic hyperlipidemic rats.

    PubMed

    Elseweidy, Mohamed M; Zein, Nabila; Aldhamy, Samih E; Elsawy, Marwa M; Saeid, Saeid A

    2016-11-01

    This work mainly aimed to investigate the probable changes of aortic calcification by policosanol, omega-3 fatty acids in comparison with atorvastatin and subsequent progression of atherosclerosis in diabetic hyperlipemic rat model. Adult male albino rats of wistar strain (30) were divided into five groups (n = 6/group); one was fed normal diet and was used as a normal group, the other groups received alloxan, atherogenic diet (CCT - rat chow diet supplemented with 4% cholesterol, 1% cholic acid, and 0.5% thiouracil) and categorized as follows: the second group received no treatment and kept as control (diabetic hyperlipidemic control group (DHC)). The other groups received daily oral doses of atorvastatin, policosanol (10 mg/kg body weight) and ω-3 (50 mg/kg body weight), respectively, for eight weeks. Different biomarkers were used for the evaluation that included inflammatory (C reactive protein (CRP), tumor necrosis factor α (TNF-α)), oxidative stress (glutathione (GSH), malondialdehyde (MDA)) bone calcification markers (alkaline phosphatase (ALP), Vitamin D, parathyroid hormone (PTH)), lipogram pattern in addition to histochemical demonstration of calcium in the aorta. Diabetic hyperlipemic group demonstrated significant hyperglycemia, hyperlipidemia, and increased inflammation, oxidative stress, calcification, and finally atherogenesis progression. Treatment of diabetic hyperlipemic rats with, policosanol, omega-3 fatty acids (natural products) and atorvastatin for eight weeks significantly increased high-density lipoprotein cholesterol (HDL-C), Vitamin D, decreased aortic vacuoles number, and inhibited calcification process. Policosanol induced more remarkable reduction in the density and number of foam cells and improved the intimal lesions of the aorta as compared to atorvastatin. Drugs under study exerted hypoglycemic effect along with an inhibition of inflammation, oxidative stress, and calcium deposition with certain variations but

  12. Effects of astaxanthin on blood coagulation, fibrinolysis and platelet aggregation in hyperlipidemic rats.

    PubMed

    Deng, Zu-Yue; Shan, Wei-Guang; Wang, Shen-Feng; Hu, Meng-Mei; Chen, Yan

    2017-12-01

    Astaxanthin (ASTX) is a xanthophyll carotenoid that reduces hemostasis in hyperlipidemic organisms. Its antihemostatic mechanisms remain unclear. The effects of ASTX on coagulation, the fibrinolytic system and platelet aggregation were investigated in hyperlipidemic rats. Different doses of ASTX (5, 10 and 30 mg/kg/day, p.o.) were administered for four weeks to high-fat diet-induced hyperlipidemic rats. Serum lipid and lipoprotein levels were measured with an automatic biochemical analyzer. The prothrombin time (PT), activated partial thromboplastin time (APTT) and maximum platelet aggregation rate (MAR) were determined by a coagulation analyzer. The activities of the tissue-type plasminogen activator (t-PA), type-1 plasminogen activator inhibitor (PAI-1) and endothelial nitric oxide synthase (eNOS), as well as the levels of thromboxane B(2) [TXB(2)], 6-keto prostaglandin F(1α) [6-keto-PGF(1α)] and platelet granule membrane protein (GMP-140), were measured with enzyme-linked immunosorbent assay kits. Gene and protein expression levels were analyzed by reverse transcriptase polymerase chain reaction and Western blot, respectively. ASTX (30 mg/kg) treatment in hyperlipidemic rats reduced serum TG (0.58 ± 0.14 versus 1.12 ± 0.24 mmol/L), serum TC (1.77 ± 0.22 versus 2.24 ± 0.21 mmol/L), serum LDL-C (1.13 ± 0.32 versus 2.04 ± 0.48 mmol/L), serum MDA (69%), plasma MAR (55%), serum TXB2/6-keto-PGF1α (34%) and serum GMP-140 levels (25%), plasma PAI-1 activity (48%) and downregulated the mRNA (33%) and protein (23%) expression of aorta eNOS, the mRNA (79%) and protein (72%) expression levels of aorta PAI-1. However, ASTX (30 mg/kg/d) treatment increased serum SOD activity (2.1 fold), serum GPx activity (1.8 fold), plasma PT (1.3 fold), plasma APTT (1.7 fold), serum NO (1.4-fold), serum 6-keto-PGF1α (1.3 fold). ASTX reduced blood coagulation and platelet aggregation and promoted fibrinolytic activity in hyperlipidemic rats

  13. Probing the anti-hyperlipidemic efficacy of the allspice (Pimenta officinalis Lindl.) in rats fed with high fat diet.

    PubMed

    Shyamala, M P; Paramundayil, Julie J; Venukumar, M R; Latha, M S

    2005-01-01

    In this study, the anti-hyperlipidemic effect of aqueous extract of Pimenta officinalis (APO) was investigated in experimental rats fed with high fat diet (HFD). Hyperlipidemia in experimental rats was evidenced by a significant enhancement in the level of glycerol, triglycerides and phopholipids in serum, and also in liver and kidney tissues. HFD caused oxidative stress in these animals as shown by marked increment in the levels of thiobarbituric acid reactive substances (TBARS) and diene conjugates (CD), and a distinct diminution in reduced glutathione (GSH) content in liver and kidneys. Antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) showed reduced activity in hyperlipidemic rats. All these biochemical parameters showed reliable signs of retrieving towards near-normalcy in APO-administered HFD fed rats. This study unveiled the anti-hyperlipidemic as well as antioxidant activity of APO.

  14. Hypolipidemic effect of β-caryophyllene to treat hyperlipidemic rats.

    PubMed

    Baldissera, Matheus D; Souza, Carine F; Grando, Thirssa H; Doleski, Pedro H; Boligon, Aline A; Stefani, Lenita M; Monteiro, Silvia G

    2017-02-01

    The aim of this study was to evaluate the effect of β-caryophyllene on hypercholesterolemia using a model of hyperlipidemia induced by Triton WR-1339 in rats, as well as its possible effect on hepatic antioxidant enzymes. Thus, total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were measured in serum, while reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), hepatic 3-hydroxy-3-methylglutayl coenzyme A (HMG-CoA) reductase, superoxide dismutase (SOD), and catalase (CAT) activities were measured in the hepatic tissue. In addition, seric concentrations of β-caryophyllene were measured to perform correlation studies. Serum samples from hypercholesterolemic rats show higher (p < 0.05) levels of total cholesterol, triglycerides, and LDL cholesterol, and lower (p < 0.05) levels of HDL cholesterol compared to non-hypercholesterolemic rats. β-Caryophyllene treatment reduced (p < 0.05) the levels of total cholesterol, triglycerides and LDL cholesterol, similar to the reference drug simvastatin. However, HDL cholesterol levels did not increase with the treatment. β-Caryophyllene treatment was able to inhibit the HMG-CoA reductase activity, as well as to prevent the increase on ROS and TBARS levels, and ameliorate the antioxidant system. In summary, our findings demonstrated that β-caryophyllene has hypolipidemic effect via inhibition of the hepatic HMG-CoA reductase, like the standard drug simvastatin, and this inhibition suggests a possible mechanism of hypolipidemic action. Thus, our results indicate that β-caryophyllene can be used to treat dyslipidemic diseases because it exerts a similar effect as the reference drug, protecting the liver against lipid damage and improving the hepatic antioxidant defense system.

  15. Anti-hyperlipidemic activity of Cucumis melo fruit peel extracts in high cholesterol diet induced hyperlipidemia in rats.

    PubMed

    Bidkar, Jayant S; Ghanwat, Dhanaji Dadaso; Bhujbal, Madhuri D; Dama, Ganesh Y

    2012-09-24

    Abstract Cucumis melo Linn. (Cucurbitaceae) fruits have been used, traditionally in Indian traditional system of medicine, for the treatment of various disorders such as liver tonic, cardioprotective, antidiabetic, antiobesity, etc. The aim of the present study was to investigate the possible anti-hyperlipidemic activity of Cucumis melo fruit peel (CMFP) methanolic and aqueous extract in high cholesterol diet induced hyperlipidemia in rats. Treatment with CMFP methanolic and aqueous extract showed significant (P<0.01) reduction in gain in body weight, serum lipid profile like total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) level, atherogenic index and increased the serum high density lipoprotein cholesterol (HDL-C) levels in 28 days treatment when compared to the hyperlipidemic control group. The fecal excretion of bile acids and sterols was further increased upon treatment with CMFP methanolic and aqueous extract and standard drug. Administration of methanolic extract of CMFP at a dose of 500 mg/kg showed higher antihyperlipidemic activity as compared to other extract treated groups. The results concluded that CMFP methanolic extract (500 mg/kg) have potent antihyperlipidemic activity in high cholesterol diet induced hyperlipidemia model and which is equipotent activity when compared with atorvastatin treated group.

  16. Anti-inflammatory and anti-hyperlipidemic effect of Semecarpus anacardium in a high fat diet: STZ-induced type 2 diabetic rat model.

    PubMed

    Khan, Haseena Banu Hedayathullah; Vinayagam, Kaladevi Siddhi; Moorthy, Balaji T; Palanivelu, Shanthi; Panchanatham, Sachdanandam

    2013-02-01

    Semecarpus anacardium, known as marking nut, has been used in indigenous system of medicine against various ailments. To evaluate the antilipidemic and anti-inflammatory effect of S. anacardium Linn. nut milk extract (SA) in Type 2 diabetic rats. Diabetes was induced in rats by feeding them with a high fat diet followed by i.p. of 35 mg/kg body weight of streptozotocin. Diabetic rats were treated with the drugs, SA (200 mg/kg body weight) and metformin (500 mg/kg body weight) for 30 days. Antilipidemic effect of the drug was established by studying the lipoprotein alterations and also the alterations in the lipid profile and lipid metabolizing enzymes in the experimental group of rats. The effect of the drug on the expression of PPAR γ was also studied. To determine the anti-inflammatory effect of the drug, the levels of inflammatory cytokines, TNF-α and IL-6 and also C-reactive protein were determined. Semecarpus anacardium nut milk extract at a dosage of 200 mg/kg orally significantly (p < 0.05) reduced and normalized the alterations in the lipid metabolism in diabetic rats effectively than metformin. SA treatment significantly (p < 0.05) increased the mRNA expression of PPAR γ, thereby establishing the antilipidemic effect of the drug. The increase in the levels of inflammatory cytokines were significantly (p < 0.05) brought down to near normal levels on treatment with the drug SA. The present study thereby establishes the antilipidemic and anti-inflammatory effect of the drug. Thus, by decreasing the alterations in the lipid metabolism and inflammatory status, the drug can effectively improve the insulin sensitivity in rats and can serve as an excellent drug in the treatment of Type 2 diabetes mellitus.

  17. N-Acetylneuraminic acid attenuates hypercoagulation on high fat diet-induced hyperlipidemic rats

    PubMed Central

    Yida, Zhang; Imam, Mustapha Umar; Ismail, Maznah; Wong, WaiTeng; Abdullah, Maizaton Atmadini; Ideris, Aini; Ismail, Norsharina

    2015-01-01

    Background and objective N-Acetylneuraminic acid (Neu5Ac), a type of sialic acid, has close links with cholesterol metabolism and is often used as a biomarker in evaluating the risk of cardiovascular diseases. However, most studies on the health implications of Neu5Ac have focused on its effects on the nervous system, while its effects on cardiovascular risk factors have largely been unreported. Thus, the effects of Neu5Ac on coagulation status in high fat diet (HFD)-induced hyperlipidemic rats were evaluated in this study. Methods Sprague Dawley male rats were divided into five different groups and fed with HFD alone, HFD low-dose Neu5Ac, HFD high-dose Neu5Ac, HFD simvastatin (10 mg/kg day), and normal pellet alone. Food was given ad libitum while body weight of rats was measured weekly. After 12 weeks of intervention, rats were sacrificed and serum and tissue samples were collected for biochemistry and gene expression analysis, respectively. Results The results showed that Neu5Ac could improve lipid metabolism and hyperlipidemia-associated coagulation. Neu5Ac exerted comparable or sometimes better physiological effects than simvastatin, at biochemical and gene expression levels. Conclusions The data indicated that Neu5Ac prevented HFD-induced hyperlipidemia and associated hypercoagulation in rats through regulation of lipid-related and coagulation-related genes and, by extension, induced metabolite and protein changes. The implications of the present findings are that Neu5Ac may be used to prevent coagulation-related cardiovascular events in hyperlipidemic conditions. These findings are worth studying further. PMID:26642300

  18. DIVERSITY OF VASCULAR REACTIVITY AND THE TREATMENT RESPONSE IN DIABETIC, HYPERTENSIVE, HYPERLIPIDEMIC, AND HEALTHY RATS SUBJECTED TO HEMORRHAGIC SHOCK.

    PubMed

    Wu, Yue; Zhu, Yu; Chen, Xiang-Yun; Liu, Liang-Ming; Li, Tao

    2016-02-01

    The current diagnosis and treatment guidelines for severe trauma and shock are all for healthy population. Few studies focused on the pathophysiological features and treatments in metabolic diseases after severe trauma and shock. Vascular reactivity is significantly decreased after severe trauma and shock. Improving the vascular reactivity with arginine vasopressin (AVP) and phorbol-12 myristate-13-acetate (PMA) is beneficial to trauma and shock. Whether the cardiovascular function and treatment responses have the own features in hypertensive, diabetic, and hyperlipidemic patients after traumatic hemorrhagic shock is not known. Using hypertensive, diabetic, and hyperlipidemic and healthy rats, we compared the change patterns in cardiovascular function including vascular reactivity, tissue perfusion, and the hemodynamics after hemorrhagic shock and their responses to AVP, PMA, and common antishock agents including dopamine and norepinephrine. A same degree of hemorrhagic shock (40% hemorrhage or mean arterial pressure maintained at 40 mm Hg for 2 h) resulted in a more obvious decrease in vascular reactivity, hemodynamics, tissue perfusion, and mitochondrial function of liver and kidney in hypertensive, diabetic, and hyperlipidemic rats, and a more rapidly natural death than in healthy rats. The effectiveness of AVP and PMA in these diseased rats was lower than in healthy rats. The effective dosage of common antishock agents including norepinephrine, dopamine, and AVP in healthy rats was wider than that in these diseased rats. Among the antishock agents used in the current study, AVP had the best effect in improving animal survival and vascular reactivity both in healthy and in diseased rats. These findings suggest that hypertensive, diabetic, and hyperlipidemic rats have a worse vascular reactivity and organ function than the healthy rats after traumatic hemorrhagic shock, which result in the worse treatment responses and effects to vasoactive agents. Lower dose

  19. Antihyperlipidemic activity of Cassia auriculata flowers in triton WR 1339 induced hyperlipidemic rats.

    PubMed

    Vijayaraj, Panneerselvam; Muthukumar, Kannan; Sabarirajan, Jayaraja; Nachiappan, Vasanthi

    2013-01-01

    The flower extract of Cassia auriculata, herb has been used traditionally in India for medicinal purposes. The plant has been reported to treat hyperglycemia and associated hyperlipidemia. Hyperlipidemia and oxidative stress are known to accelerate coronary artery disease and progression of atherosclerotic lesions. The present work was undertaken to investigate the possible antihyperlipidemic and antioxidative effect of C. auriculata flower on hyperlipidemic rats. Hyperlipidemia was induced in rats by a single intravenous (iv) injection of Triton WR 1339 (300 mg/kg b.w.) and it showed sustained elevated levels of serum cholesterol and triglyceride. Ethanolic extract of C. auriculata flowers (Et-CAF) (150, 300, 450 mg/kg b.w./day) was administered to normal and hyperlipidemic rats for 14 days. Serum and liver tissue were analysed at three different time intervals for lipid profile, lipid peroxidation products, antioxidants enzymes and the activity were compared to the cholesterol-lowering drug, lovastatin (10 mg/kg/b.w.). Parameters were altered during hyperlipidemia and reverted back to near normal values after Et-CAF treatment or standard drug lovastatin. Lipid peroxidation decreased whereas the activities of superoxide dismutase, glutathione peroxidase and catalase increased in Et-CAF treated rats. Pronounced changes were observed at 450 mg/kg b.w. of Et-CAF for 2 weeks and it was comparable to the standard drug lovastatin. The current study provides a strong evidence that Et-CAF has a beneficial effect in treating hyperlipidemia and ROS without any side effects at the dosage and duration studied. Copyright © 2011 Elsevier GmbH. All rights reserved.

  20. The Regulation of Alfalfa Saponin Extract on Key Genes Involved in Hepatic Cholesterol Metabolism in Hyperlipidemic Rats

    PubMed Central

    Shi, Yinghua; Guo, Rui; Wang, Xianke; Yuan, Dedi; Zhang, Senhao; Wang, Jie; Yan, Xuebing; Wang, Chengzhang

    2014-01-01

    To investigate the cholesterol-lowering effects of alfalfa saponin extract (ASE) and its regulation mechanism on some key genes involved in cholesterol metabolism, 40 healthy 7 weeks old male Sprague Dawley (SD) rats were randomly divided into four groups with 10 rats in each group: control group, hyperlipidemic group, ASE treatment group, ASE prevention group. The body weight gain, relative liver weight and serum lipid 1evels of rats were determined. Total cholesterol (TC) and total bile acids (TBA) levels in liver and feces were also measured. Furthermore, the activity and mRNA expressions of Hmgcr, Acat2, Cyp7a1 and Ldlr were investigated. The results showed the following: (1) The abnormal serum lipid levels in hyperlipidemic rats were ameliorated by ASE administration (both ASE prevention group and treatment group) (P<0.05). (2) Both ASE administration to hyperlipidemic rats significantly reduced liver TC and increased liver TBA level (P<0.05). TC and TBA levels in feces of hyperlipidemic rats were remarkably elevated by both ASE administration (P<0.05). (3) mRNA expressions of Hmgcr and Acat2 in the liver of hyperlipidemic rats were remarkably down-regulated (P<0.05), as well as mRNA expressions of Cyp7a1 and Ldlr were dramatically up-regulated by both ASE administration (P<0.05). The activities of these enzymes also paralleled the observed changes in mRNA levels. (4) There was no significant difference between ASE treatment and ASE prevention group for most parameters evaluated. Our present study indicated that ASE had cholesterol-lowering effects. The possible mechanism could be attributed to (1) the down-regulation of Hmgcr and Acat2, as well as up-regulation of Cyp7a1 and Ldlr in the liver of hyperlipidemic rats, which was involved in cholesterol biosynthesis, uptake, and efflux pathway; (2) the increase in excretion of cholesterol. The findings in our study suggested ASE had great potential usefulness as a natural agent for treating hyperlipidemia. PMID

  1. Hypolipidemic and antioxidant effects of buckwheat leaf and flower mixture in hyperlipidemic rats.

    PubMed

    Ðurendić-Brenesel, Maja; Popović, Tamara; Pilija, Vladimir; Arsić, Aleksandra; Milić, Miljan; Kojić, Danijela; Jojić, Nikola; Milić, Nataša

    2013-05-01

    As a source of biologically active compounds, buckwheat has beneficial effects in nutrition due to its high content of flavonoids, particularly rutin. Aim of our study was to examine effects of buckwheat on plasma lipid status and phospholipids fatty acids composition, histological and parameters of oxidative stress in Wistar rats fed a high-fat diet. This study showed that buckwheat leaf and flower (BLF) mixture supplementation significantly reduce weight gain, plasma lipid concentrations and atherogenic index in rats fed a high-fat diet. Treatment of the high-fat group of animals with buckwheat significantly increased percentage of n-6 fatty acids as well as eicosapentaenoic acid (EPA) and decreased percentage of saturated fatty acids (SFA) and oleic acid. Buckwheat antioxidant effects diminished negative influence of high-fat diet in hyperlipidemic rats, while pathohistological analysis of liver confirmed changes after high-fat consumption. Our results showed hypolipidemic, antiatherogenic and antioxidative features of buckwheat leaf and flower mixture, and these parts of the plant with the highest rutin content could be beneficial in prevention and curing of hyperlipidemia. © 2013 Association of Basic Medical Sciences of FB&H. All rights reserved.

  2. Hypolipidemic and antioxidant effects of buckwheat leaf and flower mixture in hyperlipidemic rats

    PubMed Central

    Đurendić - Brenesel, Maja; Popović, Tamara; Pilija, Vladimir; Arsić, Aleksandra; Milić, Miljan; Kojić, Danijela; Jojić, Nikola; Milić, Nataša

    2013-01-01

    As a source of biologically active compounds, buckwheat has beneficial effects in nutrition due to its high content of flavonoids, particularly rutin. Aim of our study was to examine effects of buckwheat on plasma lipid status and phospholipids fatty acids composition, histological and parameters of oxidative stress in Wistar rats fed a high-fat diet. This study showed that buckwheat leaf and flower (BLF) mixture supplementation significantly reduce weight gain, plasma lipid concentrations and atherogenic index in rats fed a high-fat diet. Treatment of the high-fat group of animals with buckwheat significantly increased percentage of n-6 fatty acids as well as eicosapentaenoic acid (EPA) and decreased percentage of saturated fatty acids (SFA) and oleic acid. Buckwheat antioxidant effects diminished negative influence of high-fat diet in hyperlipidemic rats, while pathohistological analysis of liver confirmed changes after high-fat consumption. Our results showed hypolipidemic, antiatherogenic and antioxidative features of buckwheat leaf and flower mixture, and these parts of the plant with the highest rutin content could be beneficial in prevention and curing of hyperlipidemia. PMID:23725506

  3. Antioxidant Effects of Spinach (Spinacia oleracea L.) Supplementation in Hyperlipidemic Rats

    PubMed Central

    Ko, Sang-Heui; Park, Jae-Hee; Kim, So-Yun; Lee, Seon Woo; Chun, Soon-Sil; Park, Eunju

    2014-01-01

    Increased consumption of fresh vegetables that are high in polyphenols has been associated with a reduced risk of oxidative stress-induced disease. The present study aimed to evaluate the antioxidant effects of spinach in vitro and in vivo in hyperlipidemic rats. For measurement of in vitro antioxidant activity, spinach was subjected to hot water extraction (WE) or ethanol extraction (EE) and examined for total polyphenol content (TPC), oxygen radical absorbance capacity (ORAC), cellular antioxidant activity (CAA), and antigenotoxic activity. The in vivo antioxidant activity of spinach was assessed using blood and liver lipid profiles and antioxidant status in rats fed a high fat-cholesterol diet (HFCD) for 6 weeks. The TPC of WE and EE were shown as 1.5±0.0 and 0.5±0.0 mg GAE/g, respectively. Increasing the concentration of the extracts resulted in increased ORAC value, CAA, and antigenotoxic activity for all extracts tested. HFCD-fed rats displayed hyperlipidemia and increased oxidative stress, as indicated by a significant rise in blood and liver lipid profiles, an increase in plasma conjugated diene concentration, an increase in liver thiobarbituric acid reactive substances (TBARS) level, and a significant decrease in manganese superoxide dismutase (Mn-SOD) activity compared with rats fed normal diet. However, administration of 5% spinach showed a beneficial effect in HFCD rats, as indicated by decreased liver TBARS level and DNA damage in leukocyte and increased plasma conjugated dienes and Mn-SOD activity. Thus, the antioxidant activity of spinach may be an effective way to ameliorate high fat and cholesterol diet-induced oxidative stress. PMID:24772405

  4. Antioxidant Effects of Spinach (Spinacia oleracea L.) Supplementation in Hyperlipidemic Rats.

    PubMed

    Ko, Sang-Heui; Park, Jae-Hee; Kim, So-Yun; Lee, Seon Woo; Chun, Soon-Sil; Park, Eunju

    2014-01-01

    Increased consumption of fresh vegetables that are high in polyphenols has been associated with a reduced risk of oxidative stress-induced disease. The present study aimed to evaluate the antioxidant effects of spinach in vitro and in vivo in hyperlipidemic rats. For measurement of in vitro antioxidant activity, spinach was subjected to hot water extraction (WE) or ethanol extraction (EE) and examined for total polyphenol content (TPC), oxygen radical absorbance capacity (ORAC), cellular antioxidant activity (CAA), and antigenotoxic activity. The in vivo antioxidant activity of spinach was assessed using blood and liver lipid profiles and antioxidant status in rats fed a high fat-cholesterol diet (HFCD) for 6 weeks. The TPC of WE and EE were shown as 1.5±0.0 and 0.5±0.0 mg GAE/g, respectively. Increasing the concentration of the extracts resulted in increased ORAC value, CAA, and antigenotoxic activity for all extracts tested. HFCD-fed rats displayed hyperlipidemia and increased oxidative stress, as indicated by a significant rise in blood and liver lipid profiles, an increase in plasma conjugated diene concentration, an increase in liver thiobarbituric acid reactive substances (TBARS) level, and a significant decrease in manganese superoxide dismutase (Mn-SOD) activity compared with rats fed normal diet. However, administration of 5% spinach showed a beneficial effect in HFCD rats, as indicated by decreased liver TBARS level and DNA damage in leukocyte and increased plasma conjugated dienes and Mn-SOD activity. Thus, the antioxidant activity of spinach may be an effective way to ameliorate high fat and cholesterol diet-induced oxidative stress.

  5. Hypolipidemic effects of chitosan and its derivatives in hyperlipidemic rats induced by a high-fat diet

    PubMed Central

    Pan, Haitao; Yang, Qingyun; Huang, Guidong; Ding, Chen; Cao, Peiqiu; Huang, Lanlan; Xiao, Tiancun; Guo, Jiao; Su, Zhengquan

    2016-01-01

    Background Hyperlipidemia (HLP) is the primary risk factor of cardiovascular disease (CVD). Various factors, including genetics, physical inactivity, and daily nutritional habits, affect the prevalence of HLP. Recently, it was revealed that dietary fibers, such as pectin, psyllium, and especially chitosan (CTS), may play important roles in hypolipidemic management. Thus, this study aims to determine the hypolipidemic effect and mechanism of CTS and its water-soluble derivatives, chitosan oligosaccharides (MN≤1,000 Da (COSI) and MN≤3,000 Da (COSIII)), in male hyperlipidemic rats induced by a high-fat diet (HFD). Design After the model creation, 120 Sprague-Dawley (SD) rats were equally assigned to 12 groups fed various diets as follows: the normal group with basic diet, an HFD group, an HFD group supplemented with three doses of CTS, COSI and COSIII groups, and an HFD group treated with simvastatin (7 mg/kg·d). After 6 weeks, body weight, fat/body ratio, and the relevant biomarkers of serum, liver, and feces were measured. Additionally, the histological analysis of liver and adipose tissue was performed, and the mRNA expressions of liver peroxisome proliferator-activated receptor-α (PPARα) and hepatic lipase (HL) were examined. Results Compared with HFD group, rats fed CTS, COSI, and COSIII showed a better ability to regulate their body weight, liver and cardiac indices, fat/body ratio, as well as serum, liver, and fecal lipids, and simultaneously to maintain the appropriate activity of liver and serum superoxide dismutase (SOD), alanine aminotransferase (ALT), aspartate aminotransferase (AST), as well as liver and fecal total bile acids (TBA). Simultaneously, there had been a higher mRNA expression of PPARα and HL in the treatment groups. Conclusion The obtained results suggested that these three function foods can effectively improve liver lipid metabolism by normalizing the expressions of PPARα and HL, and protect liver from the oxidized trauma by

  6. Beneficial effects of natural Jeju groundwaters on lipid metabolism in high-fat diet-induced hyperlipidemic rats

    PubMed Central

    Wang, Yan-chao; Lu, Jin-miao; Jin, Hui-zi; Ma, Ai-niu; Zhang, Jin-yang; Gong, Nian; Xiao, Qi; Zhu, Bin; Lv, Ying-fang; Yu, Na; Zhang, Wei-dong

    2014-01-01

    BACKGROUND Groundwater is believed to possess many beneficial effects due to its natural source of various minerals. In this study, we examined the effects of natural Jeju groundwater S1 (Samdasoo™), S2 and S3 pumped up from different locations of Jeju Island, Korea, along with local tap water, on body weight gain, serum lipids and lipoproteins, and liver histopathology in high-fat diet-induced hyperlipidemic rats. MATERIALS/METHODS Rats were randomly and equally divided into 6 groups. Different water samples were supplied to the hyperlipidemic rats as their daily drinking water and the widely-used anti-hyperlipidemic drug simvastatin was used as a positive control. Body weight, serum lipids and lipoproteins were measured weekly. Liver weight, liver index and liver histopathology were examined after the execution of the rats. RESULTS After drinking Jeju groundwaters for two months, S2 but not S3 significantly reduced weight growth and serum triglycerides levels and increased high density lipoprotein-C (HDL-C) without affecting total cholesterol or LDL-C. S1 and particularly S2 significantly reduced the severity of liver hypertrophy and steatosis. All Groundwaters had much higher contents of vanadium (S3>S2>S1>>tap water) whereas S1 and S2 but not S3 markedly blocked autoxidation of ferrous ions. CONCLUSION Jeju Groundwater S1 and particularly S2 exhibit protective effects against hyperlipidemia and fatty liver and hypothesize that the beneficial effect of Jeju Groundwaters may be contributed from blockade of autoxidation of ferrous ions rather than their high contents of vanadium. PMID:24741400

  7. Effects of Tanshinone IIA on the modulation of miR-33a and the SREBP-2/Pcsk9 signaling pathway in hyperlipidemic rats

    PubMed Central

    JIA, LIANQUN; SONG, NAN; YANG, GUANLIN; MA, YIXIN; LI, XUETAO; LU, REN; CAO, HUIMIN; ZHANG, NI; ZHU, MEILIN; WANG, JUNYAN; LENG, XUE; CAO, YUAN; DU, YING; XU, YUE

    2016-01-01

    Tanshinone IIA is the active compound isolated from Salvia miltiorrhiza bunge, which is a traditional Chinese medicine known as Danshen. The aim of the present study was to assess the effect of Tanshinone IIA on the regulation of lipid metabolism in the livers of hyperlipidemic rats and the underlying molecular events. An in vivo model of hyperlipidemia was established in rats, with the animals receiving a daily dose of Tanshinone IIA. The serum lipid profiles were analyzed using an automatic biochemical analyzer, and the histopathological alterations and lipid deposition in liver tissue were assessed using hematoxylin and eosin staining, and oil red O staining, respectively. The mRNA expression levels of microRNA (miR)-33a, ATP-binding cassette transporter (ABC)A1, ABCG1, sterol regulatory element-binding protein 2 (SREBP-2), proprotein convertase subtilisin/kexin type 9 (Pcsk9) and low-density lipoprotein receptor (LDL-R) in liver tissues were measured using reverse transcription-quantitative polymerase chain reaction, and the protein expression levels of ABCA1, ABCG1, SREBP-2, Pcsk9, and LDL-R were analyzed using western blotting. Tanshinone IIA reduced lipid deposition and improved histopathology in the rat liver tissue, however, did not alter the lipid profile in rat serum. In addition, Tanshinone IIA treatment suppressed the expression of miR-33a, whereas the protein expression levels of ABCA1, SREBP-2, Pcsk9 in addition to LDL-R mRNA and protein were upregulated. In conclusion, the present study indicated that Tanshinone IIA attenuated lipid deposition in the livers of hyperlipidemic rats and modulated the expression of miR-33a and SREBP-2/Pcsk9 signaling pathway proteins. PMID:27082100

  8. The effects of the decaffeination of coffee samples on platelet aggregation in hyperlipidemic rats.

    PubMed

    Silvério, Alessandra dos Santos Danziger; Pereira, Rosemary Gualberto Fonseca Alvarenga; Lima, Adriene Ribeiro; Paula, Fernanda Borges de Araújo; Rodrigues, Maria Rita; Baldissera, Lineu; Duarte, Stella Maris da Silveira

    2013-09-01

    The effect of coffee on cardiovascular diseases is still controversial. It is known that the process of decaffeination may influence the chemical constitution and, therefore, the biological effects of coffee. This study thus evaluated the effects of decaffeination on the levels of total phenols and chlorogenic acids in Coffea arabica L. samples, as well as the effects of ingesting both integral and decaffeinated coffee on the lipid profile and hemostatic and hematological parameters in normal and hyperlipidemic rats. Samples of integral and decaffeinated lyophilized coffee (Coffea arabica L., planted in Brazil) were used for chemical analysis (total phenols, chlorogenic acid and caffeine contents). For the bioassays, coffee beverages were prepared with non-lyophilized samples (10% w/v) and were filtered and administered to animals by gavage (7.2 mL/kg/day) over 30 days. On the 31st day after beginning the treatment with coffee beverages, hyperlipidemia was induced to the animals by administering Triton WR-1339 (300 mg/kg body weight). On day 32, blood was taken to determine the lipid profile, platelet aggregation, prothrombin time, partially activated thromboplastin time and hemogram. The contents of both phenolic compounds and chlorogenic acid in the integral coffee beverage were significantly lower than those in the decaffeinated coffee beverage. The animals treated with Triton WR-1339 presented a mixed hyperlipidemia. Although the decaffeination process caused a relative increase in total phenols and chlorogenic acids, the coffee drinks were unable to change the lipid profile or the hemostatic and hematological parameters in the studied animals.

  9. Analysis of lipid profile and atherogenic index in hyperlipidemic rat (Rattus norvegicus Berkenhout, 1769) that given the methanolic extract of Parijoto (Medinilla speciosa)

    NASA Astrophysics Data System (ADS)

    Sa'adah, Noor Nailis; Purwani, Kristanti Indah; Nurhayati, Awik Puji Dyah; Ashuri, Nova Maulidina

    2017-06-01

    Diet of high lipids cause hyperlipidemia, which marked by an increase of total cholesterols, triglycerides, LDL-C, and decreasing of HDL-C. Hyperlipidemia lead the occurrence of atherosclerosis, one of factors that trigger cardiovascular disease, as hypertention; coronary heart and stroke. Parijoto (M. speciosa) is endemic plants in Asia with a distribution center in Malaysia, Indonesia and Philippines. Parijoto contain phytochemical components such as flavonoids, saponins and kardenolin. Flavonoid potensial as an antioxidants and can improve the hyperlipidemia condition. This study was aimed to determine lipid profiles and atherogenic index of hyperlipidemic Wistar rats (R. norvegicus Berkenhout, 1769) which given the methanolic extract of Parijoto (M. speciosa). The research was done with pre and post test randomized control group design. Rats were given a mixture of duck yolk and reused cooking oil (1:1) orally as much as 1% of body weight (BW) for 30 days. After hyperlipidemia achieved, rats were divided into 5 group: normal rats, hyperlipidemic rats, hyperlipidemic rats were given the methanolic extract of Parijoto (M. speciosa) 500 mg/kg, 1000 mg/kg, and 1500 mg/kg BW. Blood samples were collected when rats in hyperlipidemia conditions and after treatment with the methanolic extract of Parijoto (M. speciosa) for 30 days. The data of total cholesterol, HDL-Cholesterol, LDL-Cholesterol level, and atherogenic index were analyzed using ANOVA followed by Tukey test at 5% significance level. The result showed that giving of methanolic extract of Parijoto (M. speciosa) in hyperlipidemic rats reduced the total cholesterol, LDL-Cholesterol levels, and increased of HDL-cholesterol levels significantly (p<0.01), so atherogenic index reduced significantly too (p<0.01). Total cholesterol and LDL-Cholesterol levels were positively correlated with the atherogenic index, whereas HDL-cholesterol levels were negatively correlated with the atherogenic index.

  10. Hypocholesterolemia of Rhizoma Coptidis alkaloids is related to the bile acid by up-regulated CYP7A1 in hyperlipidemic rats.

    PubMed

    Cao, Yang; Bei, Weijian; Hu, Yinming; Cao, Le; Huang, Lihua; Wang, Laiyou; Luo, Duosheng; Chen, Yuanyuan; Yao, Xi; He, Wei; Liu, Xiaobo; Guo, Jiao

    2012-06-15

    This study is to investigate the cholesterol-lowering effect and the new mode of action of coptis alkaloids on high lipid diet-induced hyperlipidemic rats. Coptis alkaloids extract (CAE) was prepared by alcohol extraction from Rhizoma Coptidis that have been quality-controlled according to the protocol. The cholesterol-lowering effect of CAE was evaluated on SD rats fed with high-lipid diet. Serum level of lipid, Bile acid and cholesterol in the liver and feces of the rats were measured using colorimetric assay kit. RT-PCR and Western blot were used to analyze the mRNA and protein expression of cholesterol metabolism-related genes including cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptor-alpha (PPARα) and farnesoid X receptor (FXR) in the livers of the rats. A HPLC analysis was used to assess the activity of CYP7A1. The results showed that CAE reduced the levels of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C). CYP7A1 gene expression and its activity was up-regulated dose-dependently accompanying with the increased level of bile acid and the reduced cholesterol level in the livers of the CAE treated hyperlipidemic rats. Meanwhile, the mRNA expression of PPARα was also up-regulated in dose-dependent way accompanying the down-modulation of the FXR mRNA expression in the livers of the CAE treated hyperlipidemic rats. The results indicate that the cholesterol-lowering effect of coptis alkaloid extract is at least partly attributed to its promoting the cholesterol conversion into bile acids by up-regulating the gene expression of CYP7A1 and thus increasing its activity in the liver of the hyperlipidemic rats, which might related to the positive regulation of PPARα and the negative modulation of FXR.

  11. Anti-hyperlipidemic and cardioprotective effects of Ocimum sanctum L. fixed oil in rats fed a high fat diet.

    PubMed

    Suanarunsawat, Thamolwan; Boonnak, Theewara; Na Ayutthaya, Watcharaporn Devakul; Thirawarapan, Suwan

    2010-01-01

    Ocimum sanctum (OS) has a lipid-lowering action in both normal and diabetic animals. Because OS leaves are rich in oil, the present study was conducted to explain the anti-hyperlipidemic and organ-protective effect of OS fixed oil in rats fed with a high fat (HF) diet. OS fixed oil was extracted by hexane and the fatty acids composition identified by GC-MS. Four groups of male Wistar rats included a normal control group, a high fat fed-diet (HF) group, a HF group treated with OS fixed oil, and a HF group treated with a reference drug simvastatin. The results show that OS fixed oil contains five kinds of fatty acids, of which alpha-linolenic acid was the major fatty acid. OS fixed oil depressed high serum levels of total cholesterol, triglyceride, LDL-C, and AI, whereas no significant effect on HDL-C was observed. OS fixed oil also suppressed high levels of liver cholesterol and triglyceride with no significant effect on both lipids in feces. In addition, OS fixed oil normalized the high serum levels of LDH and CK-MB but no significant effect on high serum levels of ALT, AST, and ALP was obtained. We conclude that treatment with OS fixed oil during the last three weeks of HF diet feeding decreased the high serum lipid profile and expressed antiartherogenic and cardioprotective actions against hyperlipidemia. The anti-hyperlipidemic action of OS fixed oil was mainly resulted from the suppression of liver lipid synthesis. Linolenic acid and linoleic acid contained in OS fixed oil were possibly responsible for both lipid-lowering and cardiac protective action against hyperlipidemia.

  12. Chronic effects of berberine on blood, liver glucolipid metabolism and liver PPARs expression in diabetic hyperlipidemic rats.

    PubMed

    Zhou, Ji Yin; Zhou, Shi Wen; Zhang, Ke Bin; Tang, Jian Lin; Guang, Li Xia; Ying, Yi; Xu, Ying; Zhang, Le; Li, Dan Dan

    2008-06-01

    Berberine is one of the main alkaloids of Rhizoma coptidis which has been used as a folk medicine to treat diabetes mellitus for more than 1400 years in China. To investigate the chronic effect of berberine on diabetic hyperlipidemic rats, fasted rats were intraperitoneally injected 35 mg/kg streptozotocin. Diabetic rats were admitted after 2 weeks and given a high-carbohydrate/high-fat diet to induce hyperlipidemia. The rats were divided into 7 groups at the end of week 16: normal and diabetic rats received no drug, 5 treatment groups were administered with either 75, 150, 300 mg/kg berberine, 100 mg/kg fenofibrate or 4 mg/kg rosiglitazone per day for 16 weeks, respectively. The blood glucose, hemoglobin A1c, lipid metabolic parameters and hepatic glycogen and triglyceride were measured, and histopathology and peroxisome proliferator-activated receptors (PPARs) alpha/delta/gamma expression of liver were determined by hematoxylin eosin and immunohistochemical staining. Berberine reduced diabetic rats' body weight, liver weight and liver to body weight ratio. Berberine restored the increased blood glucose, hemoglobin A1c, total cholesterol, triglyceride, low density lipoprotein-cholesterol, apolipoprotein B and the decreased high density lipoprotein-cholesterol, apolipoprotein AI levels in diabetic rats to near the control ones. Berberine alleviated the pathological progression of liver and reverted the increased hepatic glycogen and triglyceride to near the control levels. Berberine increased PPARalpha/delta expression and reduced PPARgamma expression in liver of diabetic rat to near the control ones. Berberine improved glucolipid metabolism both in blood and liver in diabetic rats possibly through modulating the metabolic related PPARalpha/delta/gamma protein expression in liver.

  13. The hypolipidemic activity of Ayurvedic medicine, Arogyavardhini vati in Triton WR-1339-induced hyperlipidemic rats: A comparison with fenofibrate

    PubMed Central

    Kumar, Gajendra; Srivastava, Amita; Sharma, Surinder Kumar; Gupta, Yogendra Kumar

    2013-01-01

    Background: Hyperlipidemia is a major risk factor of coronary heart disease. Currently available hypolipidemic drugs have been associated with number of side effects. Arogyavardhini vati, an Ayurvedic polyherbal formulation has been used for liver disorders. Therefore, present study was designed to evaluate the effect of Arogyavardhini vati in Triton WR-1339-induced hyperlipidemia in rats. Objectives: Anti-hyperlipidemic activity evaluation of Arogyavardhini vati against Triton WR-1339-induced hyperlipidemia in rats. Materials and Methods: Overnight fasted male Wistar rats (150-200 g) were randomly divided into normal control group [4% Dimethyl Sulfoxide (DMSO), i.p.], positive control group (Triton WR-1339 in 4% DMSO, 400 mg/kg, i.p.), standard drug treated (fenofibrate 65 mg/kg, p.o. for 7 days after inducing hyperlipidemia) and Arogyavardhini vati treated (50, 100, 200 mg/kg, p.o. for 7 days after inducing hyperlipidemia). Rat doses were calculated by extrapolating the equivalent human dose (therapeutic dose, sub-maximum, and maximum dose). Serum total cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein HDL, liver malondialdehyde (MDA), and glutathione (GSH) levels were estimated at end of experiments. Results: Arogyavardhini vati significantly decreased serum cholesterol, triglyceride, LDL, and C-reactive protein (CRP) and significantly increased serum HDL in a dose-dependent manner. Decreased MDA and increased GSH levels in liver were observed at all doses of Arogyavardhini vati (50, 100, 200 mg/kg) and fenofibrate-treated groups when compared with Triton-treated group. Atherogenic Index (AI) level was significantly decreased in fenofibrate and Arogyavardhini vati (200 mg/kg) treated rats when compared with normal control. Conclusion: Arogyavardhini vati, a traditionally used Ayurvedic medicine may be a useful therapy for hypercholesterolemia through reducing oxidative stress (decreasing MDA and increasing GSH) and lipid levels

  14. Comparative effects of piperine and simvastatin in fat accumulation and antioxidative status in high fat-induced hyperlipidemic rats.

    PubMed

    Tunsophon, Sakara; Chootip, Krongkarn

    2016-12-01

    The present study investigated the comparative effects of piperine (PIP) - the active ingredient of black and long peppers - and simvastatin (SIM) on hepatic steatosis in hyperlipidemic rats. Male Wistar rats were fed a cholesterol mixture daily by intragastric gavage for 8 weeks. Piperine was given by oral gavage 8 h after cholesterol feeding. The animals were divided into 4 groups: control, high fat (HF), high fat plus 40 mg PIP/kg, and high fat plus 2 mg SIM/kg. At the end of the treatment, liver cholesterol, triglyceride, thiobaribituric reacting substances, superoxide dismutase (SOD), serum aminotransferase (AST), and alanine transferase (ALT) were measured. The result demonstrated that PIP and SIM significantly reduced the accumulation of cholesterol, triglyceride, and lipid peroxidation in the liver, while elevation of SOD was observed. The activities of AST and ALT significantly decreased in PIP when compared with the HF group. Our in vitro study of pancreatic lipase also showed the inhibitory effect of PIP higher than 30% at 5 mmol/L. These results demonstrate that PIP has beneficial effects in the treatment and (or) prevention of fat accumulation in the liver and that this mechanism is due to the inhibition of pancreatic lipase and the improvement of oxidative status.

  15. Rosiglitazone attenuates the severity of hyperlipidemic severe acute pancreatitis in rats

    PubMed Central

    NIYAZ, BATUR; ZHAO, KAI-LIANG; LIU, LI-MIN; CHEN, CHEN; DENG, WEN-HONG; ZUO, TENG; SHI, QIAO; WANG, WEI-XING

    2013-01-01

    Peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand regulates adipocyte differentiation and insulin sensitivity, and exerts antihyperlipidemic and anti-inflammatory effects. However, the mechanisms by which PPAR-γ ligands affect hyperlipidemia with severe acute pancreatitis (SAP) have not been fully elucidated. The present study investigated the effects of rosiglitazone, a PPAR-γ ligand, on hyperlipidemia with SAP in a rat model. The hyperlipidemia was induced with a high-fat diet and SAP was induced by the administration of sodium taurocholate (TCA). The hyperlipidemia was shown to aggravate the severity of the sodium taurocholate-induced SAP. However, rosiglitazone demonstrated significant antihyperlipidemic and anti-inflammatory effects in the rats with high-lipid diet-induced hyperlipidemia and SAP. PMID:24137303

  16. Potential Lipid-Lowering Effects of Eleusine indica (L) Gaertn. Extract on High-Fat-Diet-Induced Hyperlipidemic Rats.

    PubMed

    Ong, Siew Ling; Nalamolu, Koteswara Rao; Lai, How Yee

    2017-01-01

    To date, anti-obesity agents based on natural products are tested for their potential using lipase inhibition assay through the interference of hydrolysis of fat by lipase resulting in reduced fat absorption without altering the central mechanisms. Previous screening study had indicated strong anti-obesity potential in Eleusine indica (E. indica), but to date, no pharmacologic studies have been reported so far. This study was performed to investigate the lipid-lowering effects of E. indica using both in vitro and in vivo models. The crude methanolic extract of E. indica was fractionated using hexane (H-Ei), dichloromethane (DCM-Ei), ethyl acetate (EA-Ei), butanol (B-Ei), and water (W-Ei). All the extracts were tested for antilipase activity using porcine pancreatic lipase. Because H-Ei showed the highest inhibition, it was further subjected to chemical profiling using high-performance liquid chromatography. Subsequently, oral toxicity analysis of H-Ei was performed [Organization for Economic Cooperation and Development guidelines using fixed dose procedure (No. 420)]; efficacy analysis was performed using high-fat diet (HFD)-induced hyperlipidemic female Sprague-Dawley rats. According to the toxicity and efficacy analyses, H-Ei did not demonstrate any noticeable biochemical toxicity or physiologic abnormalities and did not cause any tissue damage as per histologic analysis. Furthermore, H-Ei significantly reduced body weight and improved serum profile and did not show hepatotoxicity and nephrotoxicity based on the serum profile. Moreover, H-Ei alleviated HFD-induced hepatosteatosis and ameliorated induced adiposity in both visceral and subcutaneous adipose tissue. Our results demonstrate that H-Ei effectively improved hyperlipidemia. Further studies to explore its possibility as an alternative pharmacologic agent to treat obesity are warranted. Hexane extract of Eleusine indica (H-Ei) showed strong potential in the inhibition of porcine pancreatic lipase (27.01

  17. Red yeast rice and coenzyme Q10 as safe alternatives to surmount atorvastatin-induced myopathy in hyperlipidemic rats.

    PubMed

    Abdelbaset, Marwan; Safar, Marwa M; Mahmoud, Sawsan S; Negm, Seham A; Agha, Azza M

    2014-06-01

    Statins are the first line treatment for the management of hyperlipidemia. However, the primary adverse effect limiting their use is myopathy. This study examines the efficacy and safety of red yeast rice (RYR), a source of natural statins, as compared with atorvastatin, which is the most widely used synthetic statin. Statin interference with the endogenous synthesis of coenzyme Q10 (CoQ10) prompted the hypothesis that its deficiency may be implicated in the pathogenesis of statin-associated myopathy. Hence, the effects of combination of CoQ10 with either statin have been evaluated. Rats were rendered hyperlipidemic through feeding them a high-fat diet for 90 days, during the last 30 days of the diet they were treated daily with either atorvastatin, RYR, CoQ10, or combined regimens. Lipid profile, liver function tests, and creatine kinase were monitored after 15 and 30 days of drug treatments. Heart contents of CoQ9 and CoQ10 were assessed and histopathological examination of the liver and aortic wall was performed. RYR and CoQ10 had the advantage over atorvastatin in that they lower cholesterol without elevating creatine kinase, a hallmark of myopathy. RYR maintained normal levels of heart ubiquinones, which are essential components for energy production in muscles. In conclusion, RYR and CoQ10 may offer alternatives to overcome atorvastatin-associated myopathy.

  18. Effects of Tribuli saponins on ventricular remodeling after myocardial infarction in hyperlipidemic rats.

    PubMed

    Guo, Yan; Shi, Da-Zhuo; Yin, Hui-Jun; Chen, Ke-Ji

    2007-01-01

    This experiment was designed to determine whether Tribuli saponins (TS) relieve left ventricular remodeling (VR) after myocardial infarction (MI) in a murine hyperlipemia (HL) model. MI and HL models were induced and high and low doses of TS and simvastatin were administrated to the rats. Four weeks later, echocardiographic observation was performed and the left and right ventricular weight index (LVWI, RVWI) was calculated. Echocardiographic results showed that both high dose of TS and simvastatin had a beneficial effect on increasing fractional shortening (FS) and ejection fraction (EF), reducing left ventricular end diastolic volume (LVEDV), systolic volume (LVESV), left ventricular dimension end diastole (LVDd) and systole (LVDs), and decreasing LVWI, as compared to those in the HL-MI model group (p < 0.05, 0.01). Both medicines had little impact on thickness of the anterior and posterior wall. No significant difference was observed between each treatment group (p > 0.05). In conclusion, TS not only lowered serum lipidemia, but also relieved left ventricular remodeling, and improved cardiac function in the early stage after MI.

  19. Activation of transsulfuration pathway by salvianolic acid a treatment: a homocysteine-lowering approach with beneficial effects on redox homeostasis in high-fat diet-induced hyperlipidemic rats

    PubMed Central

    2013-01-01

    Background Elevated homocysteine is a cardiovascular risk factor in hyperlipidemia. Transsulfuration pathway provides an endogenous pathway for homocysteine conversion to antioxidant glutathione (GSH). Salvianolic acid A (Sal A) contains two molecules of caffeic acid and one molecule of danshensu that is capable of enhancing homocysteine transsulfuration, which led to the hypothesis that Sal A has activatory effect on transsulfuration pathway and this effect may have beneficial effects on both homocysteine and redox status in hyperlipidemia. Methods and results To test this hypothesis, we developed a rat model of hyperlipidemia induced by high-fat diet for 16 weeks, during which rats were treated with 1 mg/kg salvianolic acid A (Sal A) for the final 4 weeks. Activities of key enzymes and metabolite profiling in the transsulfuration pathway revealed that hyperlipidemia led to elevated plasma homocysteine levels after 16-week dietary treatment, which was associated with reduced activities of homocysteine transsulfuration enzymes, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). The impaired transsulfuration pathway prevented homocysteine transsulfuration to cysteine, resulting in cysteine deficiency and subsequent reduction in GSH pool size. The redox status was altered in the setting of hyperlipidemia as indicated by GSH/GSSG ratio. Sal A treatment increased hepatic CBS and CSE activities, which was associated with reduced accumulation in circulating homocysteine levels and attenuated decline in hepatic cysteine content in hyperlipidemic rats. Sal A also led to an increase in GSH pool size, which subsequently caused a restored GSH/GSSG ratio. The activatory effect of Sal A on CBS was also observed in normal rats and in in vitro experiment. Conclusion Our results suggest that activation of transsulfuration pathway by Sal A is a promising homocysteine-lowering approach that has beneficial effects on redox homeostasis in hyperlipidemic settings

  20. Effect of garlic on liver phosphatidate phosphohydrolase and plasma lipid levels in hyperlipidemic rats.

    PubMed

    Heidarian, Esfandiar; Jafari-Dehkordi, Effat; Seidkhani-Nahal, Ali

    2011-05-01

    Studies on the effects of garlic (Allium sativum) on hyperlipidemia have demonstrated somewhat controversial results and there have been few studies on its enzymatic mechanism. The purpose of this study was to assess the effect of garlic on the liver phosphatidate phosphohydrolase (PAP) activity, plasma lipid levels, malondialdehyde (MDA) and plasma antioxidant in rats fed either by normal or high-lipogenic diet with or without garlic. Male Wistar rats were fed by standard pellet diet (group I), standard diet supplemented with 4% garlic (group II), lipogenic diet (containing sunflower oil, cholesterol and ethanol) plus 4% garlic (group III) and only lipogenic diet (group IV). Results showed that garlic significantly reduced total cholesterol (TC), plasma triglyceride (TG), LDL-C, VLDL-C, liver triglyceride, plasma malondialdehyde (MDA) and elevated plasma antioxidant in garlic treated rats (groups II and III) compared to group IV (lipogenic diet group). Also, liver PAP activity was decreased in group II than group I whereas, the decrease in its activity in groups III and IV was due to the accumulation of triglyceride in liver. Therefore, the results are clearly indicative of the beneficial effects of garlic in reducing lateral side effects of hyperlipidemia. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Effect of ambrex (a herbal formulation) on oxidative stress in hyperlipidemic rats and differentiation of 3T3-L1 preadipocytes

    PubMed Central

    Devi, A. Jamuna; Ravindran, Rekha; Sankar, M.; Rajkumar, Johanna

    2014-01-01

    Background: Ambrex is a polyherbal formulation which consists of Withania somnifera, Orchis mascula, Cycas circirnalis, Shorea robusta with amber. Objective: The present study was designed to explore the potential effects of ambrex on the antioxidant status in high fat diet fed rats and to investigate the possible mechanisms focusing on the gene expression involved in adipogenesis and inflammation in 3T3-L1 cell line. Materials and Methods: Male Wistar rats were divided into four groups (n = 6); Group A received normal diet, Group B received high fat diet for 30 days, Group C and D received high fat diet for 30 days and treated with ambrex (40 mg/kg b.w) and atorvastatin (10 mg/kg b.w) for successive 15 days respectively. This study also assesses the effect of ambrex on adipogenesis in 3T3-L1 adipocytes. Results: The serum total cholesterol and triglycerides were significantly decreased in ambrex treated hyperlipidemic animals when compared to untreated animals. The activities of catalase, superoxide dismutase and reduced glutathione were significantly augmented in the serum, liver, and heart of hyperlipidemic rats treated with ambrex when compared to control. Ambrex treated rats had significant reductions in malondiadehyde levels in the serum, liver and heart compared to untreated rats. In addition, we observed that treatment with ambrex resulted in a major inhibition of pre-adipocyte differentiation of 3T3-L1 cells in vitro by suppression of peroxisome proliferator activated receptor gamma, sterol regulatory binding proteins, tumor necrosis factor-α, inducible nitricoxide synthase, leptin, and upregulation of thioredoxin 1 (TRX1) and TRX2 mRNA expression. Conclusion: Therefore, ambrex may be a potential drug for treatment of hyperlipidemia and related disorders. PMID:24914283

  2. Camphene, a plant-derived monoterpene, reduces plasma cholesterol and triglycerides in hyperlipidemic rats independently of HMG-CoA reductase activity.

    PubMed

    Vallianou, Ioanna; Peroulis, Nikolaos; Pantazis, Panayotis; Hadzopoulou-Cladaras, Margarita

    2011-01-01

    Central to the pathology of coronary heart disease is the accumulation of lipids, cholesterol and triglycerides, within the intima of arterial blood vessels. The search for drugs to treat dislipidemia, remains a major pharmaceutical focus. In this study, we evaluated the hypolipidemic properties of the essential oil from Chios mastic gum (MGO). The hypolipidemic effect of MGO was investigated in naïve as well as in rats susceptible to detergent-induced hyperlipidemia. Serum cholesterol and triglycerides were determined using commercial kits. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase activity was measured in HepG2 cell extracts using a radioactive assay; cellular cholesterol and cholesterol esters were assessed using gas chromatography. MGO administration into naïve rats resulted in a dose-dependent reduction in the constitutive synthesis of serum cholesterol and triglycerides. In hyperlipidemic rats, MGO treatment had also a strong hypolipidemic effect. By testing various components of MGO, we show for the first time that the hypolipidemic action is associated with camphene. Administration of camphene at a dose of 30 µg/gr of body weight in hyperlipidemic rats resulted in a 54.5% reduction of total cholesterol (p<0.001), 54% of Low Density Lipoprotein (LDL)-cholesterol (p<0.001) and 34.5% of triglycerides (p<0.001). Treatment of HepG2 cells with camphene led to a decrease in cellular cholesterol content to the same extend as mevinolin, a known HMG-CoA reductase inhibitor. The hypolipidemic action of camphene is independent of HMG-CoA reductase activity, suggesting that its hypocholesterolemic and hypotriglyceridemic effects are associated with a mechanism of action different than that of statins. Given the critical role that the control of hyperlipidemia plays in cardiovascular disease, the results of our study provide insights into the use of camphene as an alternative lipid lowering agent and merits further evaluation.

  3. Camphene, a Plant-Derived Monoterpene, Reduces Plasma Cholesterol and Triglycerides in Hyperlipidemic Rats Independently of HMG-CoA Reductase Activity

    PubMed Central

    Vallianou, Ioanna; Peroulis, Nikolaos; Pantazis, Panayotis; Hadzopoulou-Cladaras, Margarita

    2011-01-01

    Background Central to the pathology of coronary heart disease is the accumulation of lipids, cholesterol and triglycerides, within the intima of arterial blood vessels. The search for drugs to treat dislipidemia, remains a major pharmaceutical focus. In this study, we evaluated the hypolipidemic properties of the essential oil from Chios mastic gum (MGO). Methodology/Principal Findings The hypolipidemic effect of MGO was investigated in naïve as well as in rats susceptible to detergent-induced hyperlipidemia. Serum cholesterol and triglycerides were determined using commercial kits. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase activity was measured in HepG2 cell extracts using a radioactive assay; cellular cholesterol and cholesterol esters were assessed using gas chromatography. MGO administration into naïve rats resulted in a dose-dependent reduction in the constitutive synthesis of serum cholesterol and triglycerides. In hyperlipidemic rats, MGO treatment had also a strong hypolipidemic effect. By testing various components of MGO, we show for the first time that the hypolipidemic action is associated with camphene. Administration of camphene at a dose of 30 µg/gr of body weight in hyperlipidemic rats resulted in a 54.5% reduction of total cholesterol (p<0.001), 54% of Low Density Lipoprotein (LDL)-cholesterol (p<0.001) and 34.5% of triglycerides (p<0.001). Treatment of HepG2 cells with camphene led to a decrease in cellular cholesterol content to the same extend as mevinolin, a known HMG-CoA reductase inhibitor. The hypolipidemic action of camphene is independent of HMG-CoA reductase activity, suggesting that its hypocholesterolemic and hypotriglyceridemic effects are associated with a mechanism of action different than that of statins. Conclusions Given the critical role that the control of hyperlipidemia plays in cardiovascular disease, the results of our study provide insights into the use of camphene as an alternative lipid lowering agent

  4. Myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits with mesenteric fat accumulation are a novel animal model for metabolic syndrome.

    PubMed

    Shiomi, Masashi; Kobayashi, Tsutomu; Kuniyoshi, Nobue; Yamada, Satoshi; Ito, Takashi

    2012-01-01

    To examine whether the myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbit with visceral fat accumulation is a new animal model for human metabolic syndrome, we examined the relationship between mesenteric fat accumulation and insulin resistance, hyperlipidemia and atherosclerosis. Glucose tolerance tests were performed using adult (11- to 15-month-old) and middle-aged (17- to 21-month-old) WHHLMI rabbits fed standard chow restrictedly. In addition, lipoprotein lipid levels, serum C-reactive protein (CRP) levels, mesenteric fat weight and physical and physiological parameters were measured. Mesenteric fat was stained immunohistochemically. The mesenteric adipose tissue was positive for monoclonal antibodies against macrophages, C-reactive protein and monocyte chemoattractant protein. In adult rabbits, mesenteric fat correlated to aortic lesion area, insulin resistance, fasting immunoreactive insulin, serum CRP, abdominal circumference and body weight. In middle-aged rabbits, mesenteric fat correlated to lipoprotein lipid levels in addition to the parameters showing a significant correlation in adult rabbits, excluding aortic lesion area. The WHHLMI rabbit with visceral fat accumulation is a new animal model for metabolic syndrome. Copyright © 2012 S. Karger AG, Basel.

  5. Antihyperlipidemic potential of Albizia amara (Roxb) Boiv. bark against Triton X-100 induced hyperlipidemic condition in rats

    PubMed Central

    Gundamaraju, Rohit; Hwi, Kim Kah; Singla, Rajeev K.; Vemuri, Ravi Chandra; Mulapalli, Sartaj Banu

    2014-01-01

    Background: The plant Albizia amara (Roxb.) Boiv. bark was used in traditional medical practices of India to treat cardiovascular diseases. Hyperlipidemia is the greatest risk factor of coronary heart disease. Objective: The objective of this study was to screen the potential of A. amara against the condition of hyperlipidemia in rats. Materials and Methods: The antihyperlipidemic activity of A. amara ethanolic extract (AAEE) was studied on Triton X-100 induced model of hyperlipidemia in rats. Hyperlipidemia in experimental rats was evidenced by an enhancement in the levels of serum cholesterol, triglycerides (TGs), low density lipoprotein (LDL), very LDL (VLDL) and decrease in high density lipoprotein (HDL). Results: AAEE showed significant antihyperlipidemic effect by lowering the serum levels of biochemical parameters such as a significant reduction in the level of serum cholesterol, TG (104.1 ± 3.39), LDL (48.2 ± 2.19), VLDL (20.81 ± 0.67) and increase in HDL (47.25 ± 2.05) level with an increase in a dose of AAEE (41.39 ± 1.24) < (47.25 ± 2.05), which was similar to the standard drug atorvastatin. The results of serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase also revealed that the plant extract was found to be safe on liver. Histopathological evaluation also revealed the positive effect of the plant extract. Preliminary phytochemical analysis revealed the presence of phytoconstituents such as saponins, glycosides and tannins. The preliminary chemical constituents stood as a strong evidence for the study. Conclusion: Summing up the evidences of the pragmatic study, we can conclude that the extract of A. amara (Roxb.) Boiv. Bark aids in declining the condition of hyperlipidemia in rats. PMID:25276061

  6. Red mold rice promotes neuroprotective sAPPalpha secretion instead of Alzheimer's risk factors and amyloid beta expression in hyperlipidemic Abeta40-infused rats.

    PubMed

    Lee, Chun-Lin; Kuo, Tzong-Fu; Wu, Cheng-Lun; Wang, Jyh-Jye; Pan, Tzu-Ming

    2010-02-24

    Amyloid beta (Abeta) peptide is closely related to the onset of Alzheimer's disease (AD). A high-cholesterol or high-energy diet was demonstrated to stimulate Abeta formation and deposition in the amyloid precursor protein (APP) pathway and, oppositely, downregulate the secretion of the neuroprotective soluble APP alpha-fragment (sAPPalpha). Monascus-fermented red mold rice (RMR) including multiple cholesterol-lowering agents, antioxidants, and anti-inflammatory agents has been proven to ameliorate Abeta40 infusion-induced memory deficit in our previous study. In this study, the ethanol extract of RMR (RE) and natural RMR were respectively tested for their effect on the mediation of the proteolytic process of APP in cholesterol-treated human neuroblastoma IMR32 cell, as well as their effect on memory and learning ability and the expression of AD risk factors in intracerebroventricular Abeta40-infused hyperlipidemic rats. In the results, RE suppressed cholesterol-raised beta-secretase activity and further resulted in the increase of sAPPalpha secretion in the IMR32 cell. In the animal test, RMR potently reversed the memory deficit in the water maze and passive avoidance tasks. RMR administration could prevent against Abeta40 infusion plus the great damage caused by a high energy diet in hippocampus and cortex involved in the raise of thiobarbituric acid reactive substances and reactive oxygen species. The neuroprotection provided by RMR downregulates Abeta40 formation and deposition by suppressing the cholesterol-raised beta-secretase activity and apolipoprotein E expression, as well as mediates the proteolytic process of APP toward neuroprotective sAPPalpha secretion in hippocampus.

  7. Effect of Centella asiatica on Oxidative Stress and Lipid Metabolism in Hyperlipidemic Animal Models

    PubMed Central

    Zhao, Yun; Shu, Ping; Zhang, Youzhi; Lin, Limin; Zhou, Haihong; Xu, Zhentian; Suo, Daqin; Xie, Anzhi; Jin, Xin

    2014-01-01

    Hyperlipidemia and many other metabolic diseases are related to oxidative stress. Centella asiatica is a traditional Chinese medicine whose antioxidant effect in vitro has been reported. We are interested in whether it possesses this effect in vivo and hence modulates lipid metabolism. Therefore, experiments were carried out on mice and golden hamsters regarding its antioxidant and hypolipidemic effect. We observed that a fraction (CAF3) of the ethanol extract (CAE) of Centella asiatica had a cholesterol decrease of 79% and a triglyceride decrease of 95% in acute mice model, so CAF3 was further investigated in high-fat-fed hamster model. It was shown that CAF3 increased SOD and GSH-Px activities and decreased MDA level, and it also improved TC, TG, LDL-C, HDL-C, AST, and ALT levels. L-CAT and SR-BI gene expression in hamsters were increased. Taken together, our data suggest that the CAF3 fraction of Centella asiatica has antioxidant and hypolipidemic properties. PMID:24829618

  8. Effect of Centella asiatica on oxidative stress and lipid metabolism in hyperlipidemic animal models.

    PubMed

    Zhao, Yun; Shu, Ping; Zhang, Youzhi; Lin, Limin; Zhou, Haihong; Xu, Zhentian; Suo, Daqin; Xie, Anzhi; Jin, Xin

    2014-01-01

    Hyperlipidemia and many other metabolic diseases are related to oxidative stress. Centella asiatica is a traditional Chinese medicine whose antioxidant effect in vitro has been reported. We are interested in whether it possesses this effect in vivo and hence modulates lipid metabolism. Therefore, experiments were carried out on mice and golden hamsters regarding its antioxidant and hypolipidemic effect. We observed that a fraction (CAF3) of the ethanol extract (CAE) of Centella asiatica had a cholesterol decrease of 79% and a triglyceride decrease of 95% in acute mice model, so CAF3 was further investigated in high-fat-fed hamster model. It was shown that CAF3 increased SOD and GSH-Px activities and decreased MDA level, and it also improved TC, TG, LDL-C, HDL-C, AST, and ALT levels. L-CAT and SR-BI gene expression in hamsters were increased. Taken together, our data suggest that the CAF3 fraction of Centella asiatica has antioxidant and hypolipidemic properties.

  9. Anti-oxidant and anti-hyperlipidemic activity of Hemidesmus indicus in rats fed with high-fat diet

    PubMed Central

    Venkateshan, Suganya; Subramaniyan, Vetriselvan; Chinnasamy, Velmurugan; Chandiran, Sarath

    2016-01-01

    Objective: Dietary changes play major risk roles in oxidative stress and cardiovascular disease and modulate normal metabolic function. The present study was designed to investigate the ameliorative potential of different extracts of Hemidesmus indicus to experimental high-fat diet in wistar rats, and their possible mechanism of action. Materials and Methods: Male wistar rats were divided into 6 groups (n=6/group) and fed with a standard diet (control), high-fat diet (HFD), high-fat diet supplemented with different extracts and positive control for 9 weeks. High-fat diet induced changes in average body weight and oxidative stress and elevated levels of plasma lipid profile in rats. Results: Oral administration of methanolic extract of H. indicus (200 mg/kg) offered a significant dose-dependent protection against HFD-induced oxidative stress, as reflected in the levels of catalase (p<0.001 in the aorta, heart and liver), superoxide dismutase (p<0.001 in the aorta, heart and liver), and glutathione peroxidase (p<0.001 in the aorta, heart and liver). Hyperlipidemia condition assessed in terms of body weight, total cholesterol, free cholesterol, ester cholesterol, phospholipids, triglycerides, and atherogenic index and the results showed significant differences between HFD and non-HFD fed rats (p<0.001). High-fat diet treated rats showed changes in hepatic tissue architecture such as micro and macrovascular steatosis, increased fatty infiltration, and inflammation. Conclusion: The present study revealed that the methanolic extract of H. indicus protects against oxidative stress, hyperlipidemia and liver damage. PMID:27761421

  10. Simultaneous determination of five free and total flavonoids in rat plasma by ultra HPLC-MS/MS and its application to a comparative pharmacokinetic study in normal and hyperlipidemic rats.

    PubMed

    Wang, Xiaofan; Zhao, Xu; Gu, Liqiang; Lv, Chunxiao; He, Bosai; Liu, Zhenzhen; Hou, Pengyi; Bi, Kaishun; Chen, Xiaohui

    2014-03-15

    A simple and rapid ultra-high performance liquid chromatography-tandem mass spectrometry (uHPLC-MS/MS) method has been developed for the simultaneous determination of five free flavonoids (amentoflavone, isorhamnetin, naringenin, kaempferol and quercetin) and their total (free and conjugated) forms, and to compare the pharmacokinetics of these active ingredients in normal and hyperlipidemic rats. The free and total forms of these flavonoids were extracted by liquid-liquid extraction with ethyl acetate. The conjugated flavonoids were deconjugated by the enzyme β-Glucuronidase and Sulfatase. Chromatographic separation was accomplished on a ZORBAX Eclipse XDB-C8 USP L7 column using gradient elution. Detection was performed on a 4000Q uHPLC-MS/MS system from AB Sciex using negative ion mode in the multiple reaction monitoring (MRM) mode. The lower limits of quantification were 2.0-5.0ng/mL for all the analytes. Intra-day and inter-day precision were less than 15% and accuracy ranged from -9.3% to 11.0%, and the mean extraction recoveries of analytes and internal standard (IS) from rat plasma were all more than 81.7%. The validated method was successfully applied to a comparative pharmacokinetic study of five free and total analytes in rat plasma. The results indicated that the absorption of five total flavonoids in hyperlipidemia group were significantly higher than those in normal group with similar concentration-time curves.

  11. Influence of Sorghum Kafirin on Serum Lipid Profile and Antioxidant Activity in Hyperlipidemic Rats (In Vitro and In Vivo Studies)

    PubMed Central

    Ortíz Cruz, Raquel A.; Cárdenas López, José L.; González Aguilar, Gustavo A.; Astiazarán García, Humberto; Gorinstein, Shela; Canett Romero, Rafael; Robles Sánchez, Maribel

    2015-01-01

    The aim of this study was to compare in vitro the antioxidant potential of sorghum kafirin and sorghum flour and their influence on lipids and antioxidant capacity in rats. The antioxidant activity in sorghum kafirin extract measured by the DPPH and TEAC methods was increased 30 and 65 times, respectively, compared to that of its counterpart, sorghum flour. According to electrophoresis assay, the kafirins tert-butanol extract showed a high proportion of α-kafirin monomers, and its amino acid composition revealed higher hydrophobic amino acid content such as alanine, isoleucine, leucine, tyrosine and phenylalanine than sorghum flour extract. Diets supplemented with sorghum kafirin extract have improved lipid metabolism and increased the serum antioxidant potential (67%) especially in rats fed with added cholesterol. The bioactive peptides generated from kafirin in vivo hydrolysis appear to be associated with the positive effect on serum lipids and antioxidant activity. According to these results, sorghum kafirin extract at the levels used in this study apparently could be used for prevention of atherosclerosis and other chronic diseases. PMID:26634202

  12. Influence of Sorghum Kafirin on Serum Lipid Profile and Antioxidant Activity in Hyperlipidemic Rats (In Vitro and In Vivo Studies).

    PubMed

    Ortíz Cruz, Raquel A; Cárdenas López, José L; González Aguilar, Gustavo A; Astiazarán García, Humberto; Gorinstein, Shela; Canett Romero, Rafael; Robles Sánchez, Maribel

    2015-01-01

    The aim of this study was to compare in vitro the antioxidant potential of sorghum kafirin and sorghum flour and their influence on lipids and antioxidant capacity in rats. The antioxidant activity in sorghum kafirin extract measured by the DPPH and TEAC methods was increased 30 and 65 times, respectively, compared to that of its counterpart, sorghum flour. According to electrophoresis assay, the kafirins tert-butanol extract showed a high proportion of α-kafirin monomers, and its amino acid composition revealed higher hydrophobic amino acid content such as alanine, isoleucine, leucine, tyrosine and phenylalanine than sorghum flour extract. Diets supplemented with sorghum kafirin extract have improved lipid metabolism and increased the serum antioxidant potential (67%) especially in rats fed with added cholesterol. The bioactive peptides generated from kafirin in vivo hydrolysis appear to be associated with the positive effect on serum lipids and antioxidant activity. According to these results, sorghum kafirin extract at the levels used in this study apparently could be used for prevention of atherosclerosis and other chronic diseases.

  13. Aorta Atherosclerosis Lesion Analysis in Hyperlipidemic Mice

    PubMed Central

    Mohanta, Sarajo; Yin, Changjun; Weber, Christian; Hu, Desheng; Habenicht, Andreas JR

    2016-01-01

    Atherosclerosis is a chronic inflammatory disease of large and medium-sized arteries. Apolipoprotein E-deficient (ApoE-/-) mice are used as experimental models to study human atherosclerosis. ApoE-/- mice are constitutively hyperlipidemic and develop intima plaques that resemble human plaques. Various issues including experimental design for lesion analysis, dietary conditions, isolation of the aorta, staining methods, morphometry, group size, age, the location within the arterial tree, and statistical analyses are important parameters that need to be addressed to obtain robust data. Here, we provide detailed methods to quantify aorta atherosclerosis. PMID:27366759

  14. Protective effects of two Lactobacillus plantarum strains in hyperlipidemic mice

    PubMed Central

    Wang, Li-Xin; Liu, Kai; Gao, Da-Wei; Hao, Ji-Kui

    2013-01-01

    AIM: To investigate the effects of Lactobacillus plantarum (L. plantarum) CAI6 and L. plantarum SC4 on hyperlipidemic mice. METHODS: Male Kunming mice were fed a high-cholesterol diet for 28 d to construct hyperlipidemic models. Hyperlipidemic mice and normal mice were assigned to 3 groups which were separately treated with L. plantarum CAI6, L. plantarum SC4, and physiological saline through oral gavage for 28 d. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured by commercially available enzyme kits. FACS Calibur flow cytometry was used to examine hepatic and renal nuclear factor-erythroid 2-related factor 2 (Nrf2) expression. The morphology of livers was checked by hematoxylin and eosin staining and optical microscope observation. RESULTS: Compared with normal mice, hyperlipidemic mice possessed significantly higher TC (3.50 ± 0.43 vs 2.89 ± 0.36, P < 0.01), TG (1.76 ± 0.07 vs 1.10 ± 0.16, P < 0.01), and LDL-C (1.72 ± 0.20 vs 0.82 ± 0.10, P< 0.01) levels, resulting in an increase of atherogenic index (AI) (2.34 ± 1.60 vs 0.93 ± 0.55, P < 0.05) and LDL-C/HDL-C ratio (1.43 ± 0.12 vs 0.51 ± 0.16, P < 0.05). After treatment with L. plantarum CAI6/L. plantarum SC4, TG (1.43 ± 0.27/1.54 ± 0.10 vs 1.76 ± 0.07, P < 0.01/P < 0.05) and LDL-C (1.42 ± 0.07/1.47 ± 0.12 vs 1.72 ± 0.20, P < 0.01/P < 0.01) in hyperlipidemic mice significantly decreased. In addition, TC, HDL-C, AI, and LDL-C/HDL-C ratio were all positively changed. Meanwhile, the treatment markedly alleviated hepatic steatosis and significantly stimulated Nrf2 expression (73.79 ± 0.80/72.96 ± 1.22 vs 54.94 ± 1.84, P < 0.01/P < 0.01) in hepatocytes of hyperlipidemic mice. CONCLUSION: L. plantarum CAI6 and L. plantarum SC4 may protect against cardiovascular disease by lipid metabolism regulation and Nrf2-induced antioxidative defense in hyperlipidemic mice. PMID:23716997

  15. Attenuated atherosclerotic lesions in apoE-Fcγ chain-deficient hyperlipidemic mouse model is associated with inhibition of Th17 cells and promotion of Tregs1

    PubMed Central

    Pong Ng, Hang; Burris, Ramona L.; Nagarajan, Shanmugam

    2011-01-01

    Though the presence of anti-oxLDL IgG is well documented in clinical and animal studies, the role for FcγRs to the progression of atherosclerosis has not been studied in detail. In the present study, we investigated the role for activating FcγR in the progression of atherosclerosis using apoE-Fcγ chain double knockout (DKO) mice. Relative to apoE KO mice, arterial lesion formation was significantly decreased in apoE-Fcγ chain DKO mice. Bone marrow chimera studies showed reduced lesions in apoE KO mice receiving the bone marrow of apoE-Fcγ chain DKO mice. Compared to apoE KO mice, anti-oxLDL IgG1 (Th2) and IgG2a (Th1), IL-10, and IFN-γ secretion by activated T cells were increased in apoE-Fc γ chain DKO mice. These findings suggest that reduced atherosclerotic lesion in apoE-Fcγ chain DKO mice is not due to Th1/Th2 imbalance. Interestingly, number of Th17 cells and the secretion of IL-17 by activated CD4+ cells were decreased in apoE-Fcγ chain DKO mice. Notably, the number of T-regulatory cells, expression of mRNA, and secretion of TGF-β and IL-10 were increased in apoE-Fcγ chain DKO mice. Furthermore, secretions of IL-6 and STAT-3 phosphorylation essential for Th17 cell genesis were reduced in apoE-Fcγ chain DKO mice. Importantly, decrease in Th17 cells in apoE-Fcγ chain DKO mice was due to reduced IL-6 release by antigen presenting cells of apoE-Fcγ chain DKO mice. Collectively, our data suggest that activating FcγR promotes atherosclerosis by inducing Th17 response in the hyperlipidemic apoE KO mouse model. PMID:22043015

  16. Prestroke Proteomic Changes in Cerebral Microvessels in Stroke-Prone, Transgenic[hCETP]-Hyperlipidemic, Dahl Salt-Sensitive Hypertensive Rats

    PubMed Central

    Bergerat, Agnes; Decano, Julius; Wu, Chang-Jiun; Choi, Hyungwon; Nesvizhskii, Alexey I; Moran, Ann Marie; Ruiz-Opazo, Nelson; Steffen, Martin; Herrera, Victoria LM

    2011-01-01

    Stroke is the third leading cause of death in the United States with high rates of morbidity among survivors. The search to fill the unequivocal need for new therapeutic approaches would benefit from unbiased proteomic analyses of animal models of spontaneous stroke in the prestroke stage. Since brain microvessels play key roles in neurovascular coupling, we investigated prestroke microvascular proteome changes. Proteomic analysis of cerebral cortical microvessels (cMVs) was done by tandem mass spectrometry comparing two prestroke time points. Metaprotein-pathway analyses of proteomic spectral count data were done to identify risk factor–induced changes, followed by QSPEC-analyses of individual protein changes associated with increased stroke susceptibility. We report 26 cMV proteome profiles from male and female stroke-prone and non–stroke-prone rats at 2 months and 4.5 months of age prior to overt stroke events. We identified 1,934 proteins by two or more peptides. Metaprotein pathway analysis detected age-associated changes in energy metabolism and cell-to-microenvironment interactions, as well as sex-specific changes in energy metabolism and endothelial leukocyte transmigration pathways. Stroke susceptibility was associated independently with multiple protein changes associated with ischemia, angiogenesis or involved in blood brain barrier (BBB) integrity. Immunohistochemical analysis confirmed aquaporin-4 and laminin-α1 induction in cMVs, representative of proteomic changes with >65 Bayes factor (BF), associated with stroke susceptibility. Altogether, proteomic analysis demonstrates significant molecular changes in ischemic cerebral microvasculature in the prestroke stage, which could contribute to the observed model phenotype of microhemorrhages and postischemic hemorrhagic transformation. These pathways comprise putative targets for translational research of much needed novel diagnostic and therapeutic approaches for stroke. PMID:21519634

  17. Polysorbates as novel lipid-modulating candidates for reducing serum total cholesterol and low-density lipoprotein levels in hyperlipidemic C57BL/6J mice and rats.

    PubMed

    Li, Xiaorong; Wang, Lijuan; Li, Yuhang; Ho, Yeung; Yang, Dongxu; Chen, Yi; Hu, Xiaomin; Xue, Ming

    2011-06-25

    Polysorbates are amphiphilic, non-ionic surfactants composed of fatty acid esters of polyoxyethylene sorbitan which are widely used in the cosmetic, food and pharmaceutical industries owing to these special characteristics and their low toxicity profiles. In the present study, polysorbates were investigated for their hypolipidemic activity. C57BL/6J mice and Sprague-Dawley rats were fed a high-fat diet for four weeks, then were divided into several groups, normal saline, polysorbates and positive control drugs such as lovastatin and colestyramine were administered orally to the animals for another four weeks. Complete lipid profiles of the experimental animals were determined by assessing the serum levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. The results indicate that polysorbates significantly lowered the lipid components. Polysorbates are potential candidates for preventing intestinal absorption of redundant lipid from daily intake and subsequently for preventing hyperlipidemia as well as atherosclerosis. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Effects of F-1394, an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, on ACAT activity in HepG2 cells and on hepatic secretion of lipids in Triton WR-1339-induced hyperlipidemic rats: possible role of hepatic ACAT in very low density lipoprotein secretion.

    PubMed

    Aragane, K; Kusunoki, J; Kitamine, T; Yamaura, T; Ohnishi, H

    1998-03-01

    We examined the inhibitory potency of F-1394 ((1S,2S)-2-[3-(2,2-dimethylpropyl)-3-nonylureido]cyclohexane -1-yl 3-[(4R)-N-(2,2,5,5-tetramethyl-1,3-dioxane-4-carbonyl)amino]propionate), an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, on ACAT activity and its hypolipidemic effect. F-1394 inhibited whole-cell ACAT activity in HepG2 cells with an IC50 value of 42 nM. The potency of F-1394 was greater than that of the five other ACAT inhibitors tested (YM-17E, CI-976, 57-118, CL-277,082 and DL-melinamide). In rats made hyperlipidemic by Triton WR-1339, F-1394 caused a reduction in the hepatic secretion rate of cholesterol. These data suggest that inhibition of hepatic ACAT activity helps to reduce very low density lipoprotein secretion from the liver into the circulation.

  19. Regulation of lipid metabolism by obeticholic acid in hyperlipidemic hamsters.

    PubMed

    Dong, Bin; Young, Mark; Liu, Xueqing; Singh, Amar Bahadur; Liu, Jingwen

    2017-02-01

    The farnesoid X receptor (FXR) plays critical roles in plasma cholesterol metabolism, in particular HDL-cholesterol (HDL-C) homeostasis. Obeticholic acid (OCA) is a FXR agonist being developed for treating various chronic liver diseases. Previous studies reported inconsistent effects of OCA on regulating plasma cholesterol levels in different animal models and in different patient populations. The mechanisms underlying its divergent effects have not yet been thoroughly investigated. The scavenger receptor class B type I (SR-BI) is a FXR-modulated gene and the major receptor for HDL-C. We investigated the effects of OCA on hepatic SR-BI expression and correlated such effects with plasma HDL-C levels and hepatic cholesterol efflux in hyperlipidemic hamsters. We demonstrated that OCA induced a time-dependent reduction in serum HDL-C levels after 14 days of treatment, which was accompanied by a significant reduction of liver cholesterol content and increases in fecal cholesterol in OCA-treated hamsters. Importantly, hepatic SR-BI mRNA and protein levels in hamsters were increased to 1.9- and 1.8-fold of control by OCA treatment. Further investigations in normolipidemic hamsters did not reveal OCA-induced changes in serum HDL-C levels or hepatic SR-BI expression. We conclude that OCA reduces plasma HDL-C levels and promotes transhepatic cholesterol efflux in hyperlipidemic hamsters via a mechanism involving upregulation of hepatic SR-BI.

  20. Increased hair selenium concentration in hyperlipidemic patients

    PubMed Central

    Fülöp, Péter; Seres, Ildikó; Jenei, Zoltán; Juhász, Imre; Paragh, György

    2013-01-01

    Selenium is an essential trace element with potential anti-atherogenic and antioxidant effects. Experimental data suggest that selenium might be beneficial in the prevention of atherosclerosis and its complications, whereas human epidemiological studies have yielded conflicting results. Data on hair selenium status in hyperlipidemic patients are still lacking. Therefore, we analysed selenium concentrations by X-ray fluorescence in the hair of 81 statin-naïve patients with newly diagnosed Fredrickson-type IIa and IIb hyperlipoproteinemia and compared their data with 43 healthy volunteers. We also assessed the frequency of other classical risk factors of atherosclerosis. Hair selenium levels were found to be significantly higher in hyperlipidemic patients compared with volunteers with normal lipid levels. Also, a significantly increased number of traditional atherosclerosis risk factors were observed in hyperlipidemic patients with hair selenium concentrations above the median in contrast to those with below. Our results suggest that high hair selenium status might be associated with adverse blood lipid profile together with an increased number of traditional risk factors in a selenium-deplete population. These findings warrant further investigations to study the impact of selenium supplementation on the incidence of cardiovascular events. PMID:23402643

  1. Hyperlipidemic myeloma: review of 53 cases.

    PubMed

    Misselwitz, Benjamin; Goede, Jeroen S; Pestalozzi, Bernhard C; Schanz, Urs; Seebach, Jörg D

    2010-06-01

    Hyperlipidemic myeloma is a rare and poorly understood variant of multiple myeloma. We report the case of a 53-year-old woman with hyperlipidemic myeloma, skin xanthomas and hyperviscosity syndrome who underwent allogeneic bone marrow transplantation. A comprehensive literature search identified 52 additional cases with plasma cell disease and hyperlipidemia. A detailed analysis revealed several characteristics of these patients as compared to multiple myeloma with normal lipid status: (1) IgA paraprotein was present in the majority (53% vs. 21% in classical multiple myeloma). (2) Skin xanthomas, especially in the palmar creases, elbows, and knees were common (70%). (3) Hyperviscosity syndrome occurred more often (26% vs. 2-6%). While conventional lipid-lowering therapy had only marginal effects, successful anti-myeloma therapy also reduced hyperlipidemia. Analyses of the mechanisms leading to hyperlipidemia documented complexes of paraprotein and lipoprotein in 75% of the 32 cases tested, suggesting an inhibitory role of the paraprotein on lipid degradation. In conclusion, the clinical characteristics, the therapeutic options, and the pathophysiologic mechanisms of hyperlipidemic myeloma are comprehensively reported using the available data from all 53 published cases in the literature.

  2. In vitro and In vivo Antioxidant, Anti-hyperlipidemic Properties and Chemical Characterization of Centella asiatica (L.) Extract

    PubMed Central

    Kumari, Sima; Deori, Meetali; Elancheran, R.; Kotoky, Jibon; Devi, Rajlakshmi

    2016-01-01

    The study aimed to identify the phenolic compounds present in Centella asiatica (L.) (C. asiatica) extract and evaluate the respective antioxidant potential as well as its cholesterol-lowering effects in the experimental animal model. Herein, the antioxidant potential of extracts was assessed by its free radical scavenging activity such as 2, 2-diphenyl -1- picrylhydrazyl as well as reducing capability. The anti-hyperlipidemic effects of C. asiatica extract (CAE) were evaluated in high cholesterol-fed (HCF) rats for 4 weeks, where different concentrations of extracts (0.25, 0.5, and 1 g/kg/day) were orally administrated daily. Lipid and antioxidant profiles, including total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and superoxide dismutase (SOD), together with the indices of hepatic functions were also examined. C. asiatica revealed excellent free radical scavenging activity as revealed by 2-2- diphenyl-1-picryl-hydrazyl (DPPH) assay, with the IC50 values (9.62 ± 0.88 μg/mL). Furthermore, C. asiatica extracts and fenofibrate remarkably lowered the level of TC, TG, LDL-C, and showed elevated levels of HDL-C, SOD. The histopathological observations further demonstrated clear differentiation and structural changes in liver of HCF and CAE treated group. Furthermore, gulonic acid, ferulic acid, kaempferol, chlorogenic acid, and asiatic acid were identified to be the major components which might be responsible for the antioxidant activity of the C. asiatica extract as evidenced from an ultra-high performance liquid chromatography–mass spectrometer. Taken together, these results signifies the excellent antioxidant and anti-hyperlipidemic properties of C. asiatica leaf extracts, which might be useful for the treatment of oxidative-stress related diseases such as hyperlipidemia. PMID:27840607

  3. In vitro and In vivo Antioxidant, Anti-hyperlipidemic Properties and Chemical Characterization of Centella asiatica (L.) Extract.

    PubMed

    Kumari, Sima; Deori, Meetali; Elancheran, R; Kotoky, Jibon; Devi, Rajlakshmi

    2016-01-01

    The study aimed to identify the phenolic compounds present in Centella asiatica (L.) (C. asiatica) extract and evaluate the respective antioxidant potential as well as its cholesterol-lowering effects in the experimental animal model. Herein, the antioxidant potential of extracts was assessed by its free radical scavenging activity such as 2, 2-diphenyl -1- picrylhydrazyl as well as reducing capability. The anti-hyperlipidemic effects of C. asiatica extract (CAE) were evaluated in high cholesterol-fed (HCF) rats for 4 weeks, where different concentrations of extracts (0.25, 0.5, and 1 g/kg/day) were orally administrated daily. Lipid and antioxidant profiles, including total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and superoxide dismutase (SOD), together with the indices of hepatic functions were also examined. C. asiatica revealed excellent free radical scavenging activity as revealed by 2-2- diphenyl-1-picryl-hydrazyl (DPPH) assay, with the IC50 values (9.62 ± 0.88 μg/mL). Furthermore, C. asiatica extracts and fenofibrate remarkably lowered the level of TC, TG, LDL-C, and showed elevated levels of HDL-C, SOD. The histopathological observations further demonstrated clear differentiation and structural changes in liver of HCF and CAE treated group. Furthermore, gulonic acid, ferulic acid, kaempferol, chlorogenic acid, and asiatic acid were identified to be the major components which might be responsible for the antioxidant activity of the C. asiatica extract as evidenced from an ultra-high performance liquid chromatography-mass spectrometer. Taken together, these results signifies the excellent antioxidant and anti-hyperlipidemic properties of C. asiatica leaf extracts, which might be useful for the treatment of oxidative-stress related diseases such as hyperlipidemia.

  4. Rat Endovascular Perforation Model

    PubMed Central

    Sehba, Fatima A.

    2014-01-01

    Experimental animal models of aneurysmal subarachnoid hemorrhage (SAH) have provided a wealth of information on the mechanisms of brain injury. The Rat endovascular perforation model (EVP) replicates the early pathophysiology of SAH and hence is frequently used to study early brain injury following SAH. This paper presents a brief review of historical development of the EVP model, details the technique used to create SAH and considerations necessary to overcome technical challenges. PMID:25213427

  5. Aloe barbadensis Mill. formulation restores lipid profile to normal in a letrozole-induced polycystic ovarian syndrome rat model

    PubMed Central

    Desai, Bhavna N.; Maharjan, Radha H.; Nampoothiri, Laxmipriya P.

    2012-01-01

    Background: Polycystic ovarian syndrome (PCOS), characterized by ovulatory infertility and hyperandrogenism, is associated with metabolic complications such as dyslipidemia, insulin resistance and endothelial dysfunction. Almost 70% PCOS women have abnormal serum lipid levels (dyslipidemia) and 50% of these women are obese. Several classes of pharmacological agents have been used to manage dyslipidemia. However, studies have shown adverse effects associated with these drugs. In the light of alternate therapy, many medicinal herbs have been reported to show hypoglycemic, anti-hyperlipidemic potential. Aloe barbadensis Mill. or Aloe vera is reported as one such herb. This study was to evaluate the lipid correcting effect of Aloe vera gel (AVG) in a PCOS rat model. Materials and Methods: PCOS was induced in Charles Foster female rats by oral administration of non-steroidal aromatase inhibitor letrozole (0.5 mg/kg body weight, 21 days). All rats were hyperglycemic and 90% rats also showed elevated plasma triglycerides, elevated LDL cholesterol levels, and lowered plasma HDL cholesterol levels indicative of a dyslipidemic profile. PCOS positive rats with an aberrant lipid profile were selected for treatment. An AVG formulation (1 ml (10 mg)/day, 30 days) was administered orally. Results and Conclusion: AVG treated PCOS rats exhibited significant reduction in plasma triglyceride and LDL cholesterol levels, with an increase in HDL cholesterol. The gel treatment also caused reversion of abnormal estrous cyclicity, glucose intolerance, and lipid metabolizing enzyme activities, bringing them to normal. In conclusion, AVG has phyto components with anti-hyperlipidemic effects and it has shown efficacy in management of not only PCOS but also the associated metabolic complication : dyslipidemia. PMID:22518083

  6. Antihyperlipidemic activity of adenosine triphosphate in rabbits fed a high-fat diet and hyperlipidemic patients.

    PubMed

    Zhang, Lianshan; Liang, Libin; Tong, Tong; Qin, Yuguo; Xu, Yanping; Tong, Xinglong

    2016-10-01

    Context Recently, adenosine triphosphate (ATP) was occasionally found to decrease the triglyceride (TG) levels in several hyperlipidemic patients in our clinical practice. Objective The study investigates the anti-hyperlipidemic effects of ATP in a high-fat fed rabbit model and hyperlipidemic patients. Materials and methods Twenty-four rabbits were randomly divided into three groups of eight animals each as follows: normal diet, high-fat diet and high-fat diet + ATP group. ATP supplementation (40 mg/day) was started at the 20th day and lasted for 10 days. Serum concentrations of total cholesterol (TC), TG, LDL-C, HDL-C were measured on the 20th day and 30th day. Heart, liver and aorta were subjected histopathological examination. Twenty outpatients diagnosed primary hyperlipidemia took ATP at a dose of 60 mg twice a day for 1 week. Results Feeding rabbits with a high-fat diet resulted in a significant elevation of lipid parameters including TC, TG, LDL-C, VLDL-C compared to the normal diet group (p < 0.01). ATP treatment significantly decreased serum TG level (p < 0.01), whilst other parameters remained statistically unaltered. Meanwhile, ATP significantly reduced the thickness of fat layer in cardiac epicardium (p < 0.05) and pathological gradation of ballooning degeneration in hepatocytes (p < 0.05). After taking ATP for 1 week, hyperlipidemia patients exhibited a significant decrease of TG (p < 0.01), but other lipid parameters had no significant change. Discussion and conclusion The study indicates that ATP selectively decreases serum TG levels in high-fat diet rabbits and hyperlipidemic patients. Therefore, ATP supplementation may provide an effective approach to control TG level.

  7. Rat Genome and Model Resources.

    PubMed

    Shimoyama, Mary; Smith, Jennifer R; Bryda, Elizabeth; Kuramoto, Takashi; Saba, Laura; Dwinell, Melinda

    2017-07-01

    Rats remain a major model for studying disease mechanisms and discovery, validation, and testing of new compounds to improve human health. The rat's value continues to grow as indicated by the more than 1.4 million publications (second to human) at PubMed documenting important discoveries using this model. Advanced sequencing technologies, genome modification techniques, and the development of embryonic stem cell protocols ensure the rat remains an important mammalian model for disease studies. The 2004 release of the reference genome has been followed by the production of complete genomes for more than two dozen individual strains utilizing NextGen sequencing technologies; their analyses have identified over 80 million variants. This explosion in genomic data has been accompanied by the ability to selectively edit the rat genome, leading to hundreds of new strains through multiple technologies. A number of resources have been developed to provide investigators with access to precision rat models, comprehensive datasets, and sophisticated software tools necessary for their research. Those profiled here include the Rat Genome Database, PhenoGen, Gene Editing Rat Resource Center, Rat Resource and Research Center, and the National BioResource Project for the Rat in Japan. © The Author 2017. Published by Oxford University Press.

  8. Hypocholesterolemic effects of Kluyveromyces marxianus M3 isolated from Tibetan mushrooms on diet-induced hypercholesterolemia in rat

    PubMed Central

    Xie, Yuanhong; Zhang, Hongxing; Liu, Hui; Xiong, Lixia; Gao, Xiuzhi; Jia, Hui; Lian, Zhengxing; Tong, Nengsheng; Han, Tao

    2015-01-01

    To investigate the effects of Kluyveromyces marxianus M3 isolated from Tibetan mushrooms on diet-induced hypercholesterolemia in rats, female Wistar rats were fed a high-cholesterol diet (HCD) for 28 d to generate hyperlipidemic models. Hyperlipidemic rats were assigned to four groups, which were individually treated with three different dosages of K. marxianus M3+HCD or physiological saline+HCD via oral gavage for 28 d. The total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels in the serum and liver of the rats were measured using commercially available enzyme kits. In addition, the liver morphology was also examined using hematoxylin and eosin staining and optical microscopy. According to our results, the serum and liver TC, TG, LDL-C levels and atherogenic index (AI) were significantly decreased in rats orally administered K. marxianus M3 (p <0.01), and the HDL-C levels and anti atherogenic index (AAI) were significantly increased (p <0.01) compared to the control group. Moreover, K. marxianus M3 treatment also reduced the build-up of lipid droplets in the liver and exhibited normal hepatocytes, suggesting a protective effect of K. marxianus M3 in hyperlipidemic rats. PMID:26273253

  9. Cardiometabolic Risk in Hyperlipidemic Men and Women

    PubMed Central

    Leutner, Michael; Wielandner, Alice; Howorka, Eleonora; Prünner, Marlies; Bozkurt, Latife; Harreiter, Jürgen; Prosch, Helmut; Schlager, Oliver; Charwat-Resl, Silvia

    2016-01-01

    Objective. The aim of this study was to evaluate sex specific differences of metabolic and clinical characteristics of treated hyperlipidemic men and women (HL-men and HL-women). Methods. In this study vascular and metabolic characteristics of 35 HL-women and 64 HL-men were assessed. In addition a sex specific analysis of metabolic and nutritional habits of HL-patients with prediabetes (HL-IGR) was done. Results. HL-women were older and had favourable concentrations of high density lipoprotein cholesterol (HDL-cholesterol), triglycerides (TG), and triglyceride/HDL-cholesterol ratio (TG/HDL-ratio) but were also shown to have higher concentrations of lipoprotein-a compared to HL-men. HL-men were characterized as having higher levels of liver-specific parameters and body weight as well as being more physically active compared to HL-women. Brain natriuretic peptide (pro-BNP) was higher in HL-women than HL-men, while no differences in metabolic syndrome and glycemic parameters were shown. HL-IGR-women were also older and still had a better profile of sex specific lipid parameters, as well as a lower body weight compared to HL-IGR-men. No differences were seen in vascular parameters such as the intima media thickness (IMT). Conclusion. HL-women were older and had overall more favourable concentrations of lipid parameters and liver enzymes but did not differ regarding vascular morphology and insulin sensitivity compared to HL-men of comparable body mass index (BMI). PMID:27895666

  10. Iron overload alters glucose homeostasis, causes liver steatosis, and increases serum triacylglycerols in rats.

    PubMed

    Silva, Maísa; Silva, Marcelo E; de Paula, Heberth; Carneiro, Cláudia Martins; Pedrosa, Maria Lucia

    2008-06-01

    The objective of this study was to investigate the effect of iron overload with a hyperlipidemic diet on the histologic feature of hepatic tissue, the lipid and glycemic serum profiles, and the markers of oxidative damage and stress in a rat model. Twenty-four male Fischer rats, purchased from Experimental Nutrition Laboratory, Federal University of Ouro Preto, were assigned to 4 equal groups, 2 were fed a standard cholesterol-free diet (group C or control and CI or control with iron) containing 8.0% soybean oil and 2 were fed a hyperlipidemic diet (group H or hyperlipidemic and HI or hyperlipidemic with iron) containing 1.0% cholesterol and 25.0% soybean oil. A total of 50 mg of iron was administered to rats in groups CI and HI in 5 equal doses (1 every 3 weeks for a 16-week period) by intraperitoneal injections of 0.1 mL of iron dextran solution (100 g Fe(2+)/L; Sigma, St Louis, Mo). The other rats in groups C and H were treated in a similar manner but with sterile saline (0.1 mL). Irrespective of the diet, iron excess enhanced serum triacylglycerols (P < .05) and reduced serum glucose and glycated hemoglobin levels (P < .05) but did not affect serum cholesterol concentration. Histologic analysis showed steatosis in groups H and to a lesser extent in HI. No significant differences (P > .05) were observed in paraoxonase activities or in serum levels of free or total sulfhydryl radicals, malondialdehyde, or total antioxidants. The findings suggest that iron excess in the rat probably modifies lipid metabolism and, as a consequence, alters glucose homeostasis and increases the level of serum triacylglycerols but not of cholesterol.

  11. Animal Model of Gestational Diabetes Mellitus with Pathophysiological Resemblance to the Human Condition Induced by Multiple Factors (Nutritional, Pharmacological, and Stress) in Rats

    PubMed Central

    Abdul Aziz, Siti Hajar; Nordin, Massita; Ramasamy, Rajesh; Adam, Aishah

    2016-01-01

    This study attempts to develop an experimental gestational diabetes mellitus (GDM) animal model in female Sprague-Dawley rats. Rats were fed with high fat sucrose diet, impregnated, and induced with Streptozotocin and Nicotinamide on gestational day 0 (D0). Sleeping patterns of the rats were also manipulated to induce stress, a lifestyle factor that contributes to GDM. Rats were tested for glycemic parameters (glucose, C-peptide, and insulin), lipid profiles (total cholesterol, triglycerides, HDL, and LDL), genes affecting insulin signaling (IRS-2, AKT-1, and PCK-1), glucose transporters (GLUT-2 and GLUT-4), proinflammatory cytokines (IL-6, TNF-α), and antioxidants (SOD, CAT, and GPX) on D6 and D21. GDM rats showed possible insulin resistance as evidenced by high expression of proinflammatory cytokines, PCK-1 and CRP. Furthermore, low levels of IRS-2 and AKT-1 genes and downregulation of GLUT-4 from the initial to final phases indicate possible defect of insulin signaling. GDM rats also showed an impairment of antioxidant status and a hyperlipidemic state. Additionally, GDM rats exhibited significantly higher body weight and blood glucose and lower plasma insulin level and C-peptide than control. Based on the findings outlined, the current GDM animal model closely replicates the disease state in human and can serve as a reference for future investigations. PMID:27379252

  12. Anti-hyperlipidemic and anti-oxidative effects of gelsemine in high-fat-diet-fed rabbits.

    PubMed

    Wu, Tao; Chen, Guoping; Chen, Xiaolong; Wang, Qiqi; Wang, Gang

    2015-01-01

    The present study investigated the anti-hyperlipidemic proprieties of a natural alkaloid, gelsemine, in a high-fat-fed rabbit model. Animals were randomly divided into five groups and fed normal diet, hypercholesterolemic diet (1% cholesterol), or hypercholesterolemic diet (1% cholesterol) supplemented with gelsemine (1, 5, or 25 mg/kg). After 60 days, serum concentrations of total cholesterol (TC), LDL-C, HDL-C, triglycerides, apolipoproteins A and B, SGOT, SGPT, glucose, and insulin were measured in all experimental groups. Hypercholesterolemic diet resulted in significantly elevated levels of TC, TG, LDL-C, SGOT, and SGPT, and reduced HDL-C compared to the normocholesterolemic diet group. Gelsemine treatment significantly improved lipid profile parameters, affected by hyperlipidemia, while having no effect on the levels of apolipoproteins, glucose, and insulin. Furthermore, gelsemine treatment decreased hyperlipidemia-induced oxidative stress in a dose-dependent manner, as indicated by the increased activity of superoxide dismutase and catalase, and reduction in serum nitric oxide, and malondialdehyde concentrations in hyperlipidemic animals that received gelsemine supplementation. Dietary supplementation with gelsemine may, therefore, reverse the effect of the lipogenic diet on lipid profile and hepatic enzymes in hyperlipidemic rabbits, and protect tissues from oxidative stress, caused by high-fat diet.

  13. Transgenic Rat Models of Huntington's Disease.

    PubMed

    Carreira, João Casaca; Jahanshahi, Ali; Zeef, Dagmar; Kocabicak, Ersoy; Vlamings, Rinske; von Hörsten, Stephan; Temel, Yasin

    2015-01-01

    Several animal models for Huntington's disease (HD) have been created in order to investigate mechanisms of disease, and to evaluate the potency of novel therapies. Here, we describe the characteristics of the two transgenic rat models: transgenic rat model of HD (fragment model) and the Bacterial Artificial Chromosome HD model (full-length model). We discuss their genetic, behavioural, neuropathological and neurophysiological features.

  14. Experimental mammary carcinogenesis - Rat models.

    PubMed

    Alvarado, Antonieta; Faustino-Rocha, Ana I; Colaço, Bruno; Oliveira, Paula A

    2017-03-15

    Mammary cancer is one of the most common cancers, victimizing more than half a million of women worldwide every year. Despite all the studies in this field, the current therapeutic approaches are not effective and have several devastating effects for patients. In this way, the need to better understand the mammary cancer biopathology and find effective therapies led to the development of several rodent models over years. With this review, the authors intended to provide the readers with an overview of the rat models used to study mammary carcinogenesis, with a special emphasis on chemically-induced models.

  15. Advances on genetic rat models of epilepsy.

    PubMed

    Serikawa, Tadao; Mashimo, Tomoji; Kuramoro, Takashi; Voigt, Birger; Ohno, Yukihiro; Sasa, Masashi

    2015-01-01

    Considering the suitability of laboratory rats in epilepsy research, we and other groups have been developing genetic models of epilepsy in this species. After epileptic rats or seizure-susceptible rats were sporadically found in outbred stocks, the epileptic traits were usually genetically-fixed by selective breeding. So far, the absence seizure models GAERS and WAG/Rij, audiogenic seizure models GEPR-3 and GEPR-9, generalized tonic-clonic seizure models IER, NER and WER, and Canavan-disease related epileptic models TRM and SER have been established. Dissection of the genetic bases including causative genes in these epileptic rat models would be a significant step toward understanding epileptogenesis. N-ethyl-N-nitrosourea (ENU) mutagenesis provides a systematic approach which allowed us to develop two novel epileptic rat models: heat-induced seizure susceptible (Hiss) rats with an Scn1a missense mutation and autosomal dominant lateral temporal epilepsy (ADLTE) model rats with an Lgi1 missense mutation. In addition, we have established episodic ataxia type 1 (EA1) model rats with a Kcna1 missense mutation derived from the ENU-induced rat mutant stock, and identified a Cacna1a missense mutation in a N-Methyl-N-nitrosourea (MNU)-induced mutant rat strain GRY, resulting in the discovery of episodic ataxia type 2 (EA2) model rats. Thus, epileptic rat models have been established on the two paths: 'phenotype to gene' and 'gene to phenotype'. In the near future, development of novel epileptic rat models will be extensively promoted by the use of sophisticated genome editing technologies.

  16. Advances on genetic rat models of epilepsy

    PubMed Central

    Serikawa, Tadao; Mashimo, Tomoji; Kuramoto, Takashi; Voigt, Birger; Ohno, Yukihiro; Sasa, Masashi

    2014-01-01

    Considering the suitability of laboratory rats in epilepsy research, we and other groups have been developing genetic models of epilepsy in this species. After epileptic rats or seizure-susceptible rats were sporadically found in outbred stocks, the epileptic traits were usually genetically-fixed by selective breeding. So far, the absence seizure models GAERS and WAG/Rij, audiogenic seizure models GEPR-3 and GEPR-9, generalized tonic-clonic seizure models IER, NER and WER, and Canavan-disease related epileptic models TRM and SER have been established. Dissection of the genetic bases including causative genes in these epileptic rat models would be a significant step toward understanding epileptogenesis. N-ethyl-N-nitrosourea (ENU) mutagenesis provides a systematic approach which allowed us to develop two novel epileptic rat models: heat-induced seizure susceptible (Hiss) rats with an Scn1a missense mutation and autosomal dominant lateral temporal epilepsy (ADLTE) model rats with an Lgi1 missense mutation. In addition, we have established episodic ataxia type 1 (EA1) model rats with a Kcna1 missense mutation derived from the ENU-induced rat mutant stock, and identified a Cacna1a missense mutation in a N-Methyl-N-nitrosourea (MNU)-induced mutant rat strain GRY, resulting in the discovery of episodic ataxia type 2 (EA2) model rats. Thus, epileptic rat models have been established on the two paths: ‘phenotype to gene’ and ‘gene to phenotype’. In the near future, development of novel epileptic rat models will be extensively promoted by the use of sophisticated genome editing technologies. PMID:25312505

  17. Effect of Eclipta prostrata on lipid metabolism in hyperlipidemic animals.

    PubMed

    Zhao, Yun; Peng, Lu; Lu, Wei; Wang, Yiqing; Huang, Xuefeng; Gong, Chen; He, Lin; Hong, Junhao; Wu, Songsong; Jin, Xin

    2015-02-01

    Eclipta prostrata (Linn.) Linn. is a traditional Chinese medicine and has previously been reported to have hypolipidemic effects. However, its mechanism of action is not well understood. This study was conducted to identify the active fraction of Eclipta, its toxicity, its effect on hyperlipidemia, and its mechanism of action. The ethanol extract (EP) of Eclipta and fractions EPF1-EPF4, obtained by eluting with different concentrations of ethanol from a HPD-450 macroporous resin column chromatography of the EP, were screened in hyperlipidemic mice for lipid-lowering activity, and EPF3 was the most active fraction. The LD50 of EPF3 was undetectable because no mice died with administration of EPF3 at 10.4 g/kg. Then, 48 male hamsters were used and randomly assigned to normal chow diet, high-fat diet, high-fat diet with Xuezhikang (positive control) or EPF3 (75, 150 and 250 mg/kg) groups. We evaluated the effects of EPF3 on body weight gain, liver weight gain, serum lipid concentration, antioxidant enzyme activity, and the expression of genes involved in lipid metabolism in hyperlipidemic hamsters. The results showed that EPF3 significantly decreased body-weight gain and liver-weight gain and reduced the serum lipid levels in hyperlipidemic hamsters. EPF3 also increased the activities of antioxidant enzymes; up-regulated the mRNA expression of peroxisome proliferator-activated receptor α (PPARα), low density lipoprotein receptor (LDLR), lecithin-cholesterol transferase (LCAT) and scavenger receptor class B type Ι receptor (SR-BI); and down-regulated the mRNA expression of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) in the liver. These results indicate that EPF3 ameliorates hyperlipidemia, in part, by reducing oxidative stress and modulating the transcription of genes involved in lipid metabolism. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Isolation of bioactive phytoconstituent from Alpinia galanga L. with anti-hyperlipidemic activity.

    PubMed

    Iyer, Deepa; Sharma, Brajesh K; Patil, U K

    2013-12-01

    The present study was undertaken to explore the antihyperlipidemic effect of ethanolic extract of rhizomes of Alpinia galanga L. and its chloroform fraction in Triton-induced hyperlipidemic rats. Bioactivity guided fractionation was followed by chromatographic studies. Flash chromatography was done for the most active fraction resulting in the isolation of 5-(hydroxymethyl) furfural. Animals were administered with i.p. injection of Triton WR 1339 at dose of 400 mg/kg body weight. After 24 hr of Triton administration, the ethanolic extract and its fraction were administered orally at doses of 200 and 400 mg/kg body weight in rats. The treatment was continued for 5 days with a view to see the effect on lipid profile. Serum samples were subjected to biochemical analysis. The study dose dependently inhibited the total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) level, and significantly increased high-density lipoprotein (HDL) level. Phytochemical screening revealed the presence of tannins, coumarins, flavanoids, sterols, and glycosides. Phytochemical investigation of the chloroform fraction of A. galanga L. resulted in the isolation of 5-(hydroxymethyl) furfural. UV λmax was found to be 276 nm for the isolated component. Acute treatment caused a stimulatory effect on the HDL level and inhibition in TC and TG elevation induced by triton.

  19. 16-Dehydropregnenolone lowers serum cholesterol by up-regulation of CYP7A1 in hyperlipidemic male hamsters.

    PubMed

    Ramakrishna, Rachumallu; Kumar, Durgesh; Bhateria, Manisha; Gaikwad, Anil Nilkanth; Bhatta, Rabi Sankar

    2017-04-01

    16-Dehydropregnenolone (DHP) has been developed and patented as a promising antihyperlipidemic agent by CSIR-Central Drug Research Institute (CSIR-CDRI), India. Although DHP is implicated in controlling cholesterol homeostasis, the mechanism underlying its pharmacological effect in hyperlipidemic disease models is poorly understood. In the present study, we postulated that DHP lowers serum lipids through regulating the key hepatic genes accountable for cholesterol metabolism. The hypothesis was tested on golden Syrian hamsters fed with high-fat diet (HFD) following oral administration of DHP at a dose of 72mg/kg body weight for a period of one week. The serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total bile acids (TBA) in feces were measured. Real time comparative gene expression studies were performed for CYP7A1, LXRα and PPARα level in liver tissue of hamsters. The results revealed that the DHP profoundly decreased the levels of serum TC, TG, LDL-C and atherogenic index (AI), whilst elevated the HDL-C/TC ratio. Besides, DHP exhibited an anti-hyperlipidemic effect in the HFD induced hyperlipidemic hamsters by means of: (1) up-regulating the gene expression of CYP7A1 encoded cholesterol 7α-hydroxylase, that promotes the catabolism of cholesterol to bile acid; (2) inducing the gene expression of transcription factors LXRα and PPARα; (3) increasing the TBA excretion through feces. Collectively, the findings presented confer the hypolipidemic activity of DHP via up-regulation of hepatic CYP7A1 pathway that promotes cholesterol-to-bile acid conversion and bile acid excretion.

  20. Preservation of vascular DDAH activity contributes to the protection of captopril against endothelial dysfunction in hyperlipidemic rabbits.

    PubMed

    Lin, Yuan; Feng, Mei; Lu, Chang-Wu; Lei, Yan-Ping; He, Zhi-Min; Xiong, Yan

    2017-03-05

    Endothelial dysfunction plays a pivotal role in the pathogenesis of atherosclerosis. Endogenous inhibitor of nitric oxide synthase (NOS) asymmetric dimethylarginine (ADMA) has been recognized as an independent risk factor of endothelial dysfunction and the biomarker of atherosclerosis. This study was to investigate whether endogenous ADMA and its metabolic enzyme dimethylarginine dimethylaminohydrolase (DDAH) were involved in mechanisms of captopril protection against endothelial dysfunction in high fat diet feeding rabbits. Half of model rabbits were treated with captopril (10mg/kg/d, i.g.) for 12w. Vascular morphology and serum lipid profiles were detected. Serum ADMA concentration were assayed by high performance liquid chromatography. Recombinant DDAH2 gene adenoviruses were ex vivo transferred to thoracic aortas of high fat diet feeding rabbits. Endothelium-dependent relaxation of aortas response to acetylcholine and DDAH activity were measured. Atherosclerosis was confirmed in high fat diet feeding rabbits by increased serum lipid profiles and morphologic changes of vascular wall. Serum ADMA levels were significantly increased in hyperlipidemic rabbits accompanied with impairment of endothelium-dependent relaxation and inhibition of DDAH activity in thoracic aortas. Captopril treatment not only decreased vascular intima thickening and serum ADMA concentration but also preserved vascular DDAH activity and endothelium-dependent relaxation in hyperlipidemic rabbits without influence on serum lipid profiles. Similar beneficial effects on endothelial function and DDAH activity could be achieved by DDAH2 gene transfection. These results indicated that captopril could protect against injuries of vascular morphology and endothelial function in hyperlipidemic rabbits, the mechanisms may be related to the preservation of DDAH activity and decrease of ADMA accumulation in vascular endothelium. Copyright © 2017. Published by Elsevier B.V.

  1. Enhanced oxidative stress in neutrophils from hyperlipidemic guinea pig.

    PubMed

    Maeda, Kensaku; Yasunari, Kenichi; Sato, Eisuke F; Inoue, Masayasu

    2005-07-01

    Inhibitors of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase are antilipidemic agents (statins) widely used for the prevention of cardiovascular diseases. Recent studies have suggested that the overall benefits of statin therapy cannot be accounted for solely by its antilipidemic effect. To obtain further insight into the mechanism of action of statins, we studied the effect of pitavastatin on the generation of reactive oxygen species (ROS) by peritoneal polymorphonuclear leukocytes (PMN) obtained from control and hyperlipidemic guinea pigs. Flow cytometric analysis revealed that the amount of ROS generated by PMN from the hyperlipidemic animals that had been administered a laurate-containing diet (LD) for 4 weeks was larger than that from the normal diet (ND) group (837% increase, ND; 82.17 arbitrary units, LD; 688.10 arbitrary units, P < 0.01, n = 6). Administration of pitavastatin to the LD group significantly decreased plasma levels of total cholesterol (TC) and low-density lipoprotein (LDL) with a reduction in ROS generation by PMN (19% decrease, LD control; 688.10 arbitrary units, LD + pitavastatin; 556.87 arbitrary units, P < 0.01, n = 6). Western blotting analysis revealed that the expression of protein kinase C alpha (PKC alpha) and betaI was higher in PMN from the LD group than in PMN from the ND group (PKC alpha; 74% increase, PKC betaI; 339% increase, P < 0.05, n = 4, respectively). Furthermore, expression of NADPH oxidase gp91phox in PMN from the LD group was higher than that in PMN from the ND group (18% increase, P < 0.05, n = 4). By administration of pitavastatin to the LD group, the expression of PKC alpha, betaI and gp91phox was suppressed compared with the control LD group (PKC alpha; 41% decrease, PKC beta; 28% decrease, gp91phox; 56% decrease, P < 0.05, n = 4, respectively). These results indicate that PMN from hyperlipidemic animals is associated with an accelerated respiratory burst of ROS by increasing the expression of PKC alpha, beta

  2. Fimasartan Ameliorates Nonalcoholic Fatty Liver Disease through PPARδ Regulation in Hyperlipidemic and Hypertensive Conditions

    PubMed Central

    Jang, Yoo-Na; Han, Yoon-Mi; Kim, Hyun-Min; Jeong, Jong-Min

    2017-01-01

    To investigate the effects of fimasartan on nonalcoholic fatty liver disease in hyperlipidemic and hypertensive conditions, the levels of biomarkers related to fatty acid metabolism were determined in HepG2 and differentiated 3T3-L1 cells treated by high fatty acid and liver and visceral fat tissue samples of spontaneously hypertensive rats (SHRs) given high-fat diet. In HepG2 cells and liver tissues, fimasartan was shown to increase the protein levels of peroxisome proliferator-activated receptor delta (PPARδ), phosphorylated 5′ adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylated acetyl-CoA carboxylase (p-ACC), malonyl-CoA decarboxylase (MCD), medium chain acyl-CoA dehydrogenase (MCAD), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and it led to a decrease in the protein levels of 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSDH1), fatty acid synthase (FAS), and tumor necrosis factor-alpha (TNF-α). Fimasartan decreased lipid contents in HepG2 and differentiated 3T3-L1 cells and liver tissues. In addition, fimasartan increased the adiponectin level in visceral fat tissues. The antiadipogenic effects of fimasartan were offset by PPARδ antagonist (GSK0660). Consequently, fimasartan ameliorates nonalcoholic fatty liver disease mainly through the activation of oxidative metabolism represented by PPARδ-AMPK-PGC-1α pathway. PMID:28386270

  3. Rosiglitazone attenuates renal injury caused by hyperlipidemic pancreatitis

    PubMed Central

    Wang, Rui; Yan, Zhaopeng; Wu, Xingmao; Ji, Kaiqiang; Wang, Haiyuan; Zang, Bin

    2015-01-01

    Hyperlipidemic pancreatitis (HP) is a serious inflammatory disease with very high mortality and multiple organ injuries including renal injury. Rosiglitazone (Ros), an agonist of peroxisome proliferator activated receptor-γ (PPAR-γ), was reported to show a protective role against pancreatitis. However, whether Ros has an effect on renal injury caused by HP is not yet clear. In the present study, the function of Ros was explored using ELISA, RT-PCR, western blot, PAS staining and immunohistochemistry. Results of this study showed that Ros could inhibit the activation of NF-κB and MAPK P38 signaling pathways, relieve inflammatory response and inhibit cell apoptosis, thus attenuating renal injury caused by HP. This study suggested that Ros might be a promising drug for the treatment of renal injury caused by HP and also laid theoretical foundation for the development of renal injury treatment. PMID:26191125

  4. Almonds reduce biomarkers of lipid peroxidation in older hyperlipidemic subjects.

    PubMed

    Jenkins, David J A; Kendall, Cyril W C; Marchie, Augustine; Josse, Andrea R; Nguyen, Tri H; Faulkner, Dorothea A; Lapsley, Karen G; Blumberg, Jeffrey

    2008-05-01

    Nut consumption has been associated with reduced coronary heart disease (CHD) risk. In addition to cholesterol-lowering properties, almonds have been shown to lower oxidized LDL concentrations. However, little is known regarding their effects on other markers of oxidative stress. The dose-response effects of whole almonds, taken as snacks, were compared with low-saturated fat (<5% energy) whole-wheat muffins (control) in the therapeutic diets of hyperlipidemic subjects. In a randomized crossover study, 27 hyperlipidemic men and women consumed 3 isoenergetic (mean 423 kcal/d or 1770 kJ/d) supplements each for 1 mo. Supplements consisted of full-dose almonds (73 +/- 3 g/d), half-dose almonds plus half-dose muffins (half-dose almonds), and full-dose muffins (control). Subjects were assessed at wk 0, 2 and 4. Mean body weights differed < or = 300 g between treatments, although the weight loss on the half-dose almond treatment was greater than on the control (P < 0.01). At 4 wk, the full-dose almonds reduced serum concentrations of malondialdehyde (MDA) (P = 0.040) and creatinine-adjusted urinary isoprostane output (P = 0.026) compared with the control. Serum concentrations of alpha- or gamma-tocopherol, adjusted or unadjusted for total cholesterol, were not affected by the treatments. Almond antioxidant activity was demonstrated by their effect on 2 biomarkers of lipid peroxidation, serum MDA and urinary isoprostanes, and supports the previous finding that almonds reduced oxidation of LDL-C. Antioxidant activity provides an additional possible mechanism, in addition to lowering cholesterol, that may account for the reduction in CHD risk with nut consumption.

  5. PBPK MODELING OF DELTAMETHRIN IN RATS

    EPA Science Inventory

    The pyrethroid pesticide deltamethrin is cleared nearly twice as rapidly in human liver microsomes compared to rat liver microsomes. A species difference such as this could influence the toxic potency of deltamethrin between rats and humans. PBPK modeling is a tool that can be ut...

  6. PBPK MODELING OF DELTAMETHRIN IN RATS

    EPA Science Inventory

    The pyrethroid pesticide deltamethrin is cleared nearly twice as rapidly in human liver microsomes compared to rat liver microsomes. A species difference such as this could influence the toxic potency of deltamethrin between rats and humans. PBPK modeling is a tool that can be ut...

  7. Gravitational Biology: The Rat Model

    NASA Technical Reports Server (NTRS)

    1997-01-01

    In this session, Session JP3, the discussion focuses on the following topics: Morphology of brain, pituitary and thyroid in the rats exposed to altered gravity; Biochemical Properties of B Adrenoceptors After Spaceflight (LMS-STS78) or Hindlimb Suspension in Rats; Influence of Hypergravity on the Development of Monoaminergic Systems in the Rat Spinal Cord; A Vestibular Evoked Potentials (VsEPs) Study of the Function of the Otolith Organs in Different Head Orientations with respect to Earth Gravity Vector in the Rat; Quantitative Observations on the Structure of Selected Proprioceptive Components in Adult Rats that Underwent About Half of their Fetal Development in Space; Effects of a Nine-Day Shuttle Mission on the Development of the Neonatal Rat Nervous System, A Behavioral Study; Muscle Atrophy Associated to Microgravity in Rat, Basic Data For Countermeasures; Simulated Weightlessness by Unloading in the Rat, Results of a Time Course Study of Biochemical Events Occurring During Unloading and Lack of Effect of a rhBNP-2 Treatment on Bone Formation and Bone Mineral Content in Unloading Rats; and Cytological Mechanism of the Osteogenesis Under Microgravity Conditions.

  8. Hyperglycemic and hyperlipidemic conditions alter cardiac cell biomechanical properties.

    PubMed

    Michaelson, Jarett; Hariharan, Venkatesh; Huang, Hayden

    2014-06-03

    Currently, many diabetic cardiomyopathy (DC) studies focus on either in vitro molecular pathways or in vivo whole-heart properties such as ejection fraction. However, as DC is primarily a disease caused by changes in structural and functional properties, such studies may not precisely identify the influence of hyperglycemia or hyperlipidemia in producing specific cellular changes, such as increased myocardial stiffness or diastolic dysfunction. To address this need, we developed an in vitro approach to examine how structural and functional properties may change as a result of a diabetic environment. Particle-tracking microrheology was used to characterize the biomechanical properties of cardiac myocytes and fibroblasts under hyperglycemia or hyperlipidemic conditions. We showed that myocytes, but not fibroblasts, exhibited increased stiffness under diabetic conditions. Hyperlipidemia, but not hyperglycemia, led to increased cFos expression. Although direct application of reactive oxygen species had only limited effects that altered myocyte properties, the antioxidant N-acetylcysteine had broader effects in limiting glucose or fatty-acid alterations. Changes consistent with clinical DC alterations occur in cells cultured in elevated glucose or fatty acids. However, the individual roles of glucose, reactive oxygen species, and fatty acids are varied, suggesting multiple pathway involvement.

  9. Hyperglycemic and Hyperlipidemic Conditions Alter Cardiac Cell Biomechanical Properties

    PubMed Central

    Michaelson, Jarett; Hariharan, Venkatesh; Huang, Hayden

    2014-01-01

    Currently, many diabetic cardiomyopathy (DC) studies focus on either in vitro molecular pathways or in vivo whole-heart properties such as ejection fraction. However, as DC is primarily a disease caused by changes in structural and functional properties, such studies may not precisely identify the influence of hyperglycemia or hyperlipidemia in producing specific cellular changes, such as increased myocardial stiffness or diastolic dysfunction. To address this need, we developed an in vitro approach to examine how structural and functional properties may change as a result of a diabetic environment. Particle-tracking microrheology was used to characterize the biomechanical properties of cardiac myocytes and fibroblasts under hyperglycemia or hyperlipidemic conditions. We showed that myocytes, but not fibroblasts, exhibited increased stiffness under diabetic conditions. Hyperlipidemia, but not hyperglycemia, led to increased cFos expression. Although direct application of reactive oxygen species had only limited effects that altered myocyte properties, the antioxidant N-acetylcysteine had broader effects in limiting glucose or fatty-acid alterations. Changes consistent with clinical DC alterations occur in cells cultured in elevated glucose or fatty acids. However, the individual roles of glucose, reactive oxygen species, and fatty acids are varied, suggesting multiple pathway involvement. PMID:24896111

  10. Evaluation of therapeutic effect of omega-6 linoleic acid and thymoquinone enriched extracts from Nigella sativa oil in the mitigation of lipidemic oxidative stress in rats.

    PubMed

    Ahmad, Shafeeque; Beg, Zafarul H

    2016-06-01

    Nigella sativa belongs to the Ranunculaceae family. The therapeutic role of methanolic extract (ME) and volatile oil (VO) fractionated from N. sativa seed oil was investigated for antiperoxidative and antioxidant effects in atherogenic suspension fed rats. We examined the protective effects of ME and VO on the enzymatic and nonenzymatic antioxidants status in erythrocytes and the livers of atherogenic suspension fed rats. As a marker of lipid peroxidation, we estimated the conjugated diene, lipid hydroperoxide, and malondialdehyde concentrations in plasma in the following groups of rats: normolipidemic control, hyperlipidemic control, hyperlipidemic methanolic extract, and hyperlipidemic volatile oil. ME 500 mg or VO 100 mg/kg body weight of male rat was orally administrated for 30 d. Pretreatment of hyperlipidemic rats with these test extracts resulted in a significant decrease (P < 0.001) in the level of lipid peroxidation markers, conjugated diene, lipid hydroperoxide, and malondialdehyde (16-50%) compared to the hyperlipidemic control rats. In addition, ME and VO significantly (P < 0.001) elevated the hepatic and erythrocyte superoxide dismutase, catalase, and glutathione reductase activities (19-58%) compared to the hyperlipidemic rats. In liver homogenate of hyperlipidemic-ME and hyperlipidemic-VO, the glutathione-S-transferase activity was protected by 93% and 89%, and in erythrocytes, the glutathione peroxidase activity was protected by 90% and 77%, respectively. Interestingly, reduced glutathione level and activities of ATPases were protected to near normal levels. Pretreatment of rats with the test extracts replenished effectively (P < 0.001) the plasma total antioxidant power by an average of 88% against free radicals. The lipidemic oxidative stress was effectively mitigated by antiperoxidative activities of ME and VO. Thus, these test extracts, especially ME, may be used as antioxidant as well as hypolipidemic agents in the form of natural food

  11. [Study on industrialized extraction technology and function of hyperlipidemic regulating of Laminaria japonica polysaccharides].

    PubMed

    Yuan, Ze-Zhi; Cheng, Kai-Ming; Huang, Wen; Dilshat; Feng, Dong-Ru

    2010-11-01

    To study the industrialized extraction technology and the function of hyperlipidemic regulating of Laminaria japonica polysaccharides. With the orthogonal design L9 (3(4)), different influential elements of the industrialized extraction technology of Laminaria japonica polysaccharides were investigated. Mice treated with different doses of polysaccharides were applied to investigate its-function of hyperlipidemic regulating for 15 days. 5% Na2CO3, 3 hours and 80 degrees C was the best extraction condition, and the extraction rate was 2.13%. Different groups of polysaccharides with different levels of purity and dose lowered the TG, TC level of the mice in various degree. Laminaria japonica polysaccharides have obvious effect on hyperlipidemic regulating.

  12. Consensus Modeling of Oral Rat Acute Toxicity

    EPA Science Inventory

    An acute toxicity dataset (oral rat LD50) with about 7400 compounds was compiled from the ChemIDplus database. This dataset was divided into a modeling set and a prediction set. The compounds in the prediction set were selected so that they were present in the modeling set used...

  13. Consensus Modeling of Oral Rat Acute Toxicity

    EPA Science Inventory

    An acute toxicity dataset (oral rat LD50) with about 7400 compounds was compiled from the ChemIDplus database. This dataset was divided into a modeling set and a prediction set. The compounds in the prediction set were selected so that they were present in the modeling set used...

  14. Impact of Light/Dark Cycle Patterns on Oxidative Stress in an Adriamycin-Induced Nephropathy Model in Rats

    PubMed Central

    Tasset, Inmaculada; Túnez, Isaac

    2014-01-01

    The principal goal of this study was to determine the effect of the photoperiod on oxidative damage biomarkers in rats submitted to different light/darkness patterns, in a hyperlipidemic nephropathy model (induced by adriamycin), as well as its possible relationship with melatonin and leptin secretion rhythms. To test this hypothesis, six different groups were used (N = 6 rats per group): control (12 h/12h light:dark); exposure to permanent illumination (24 h light); exposure to darkness (22 h dark); injected with adriamycin, 12h/12h light:dark; injected with adriamycin + exposure to permanent illumination and injected with adriamycin + exposure to darkness (22 h dark). The different photoperiods were begun two weeks prior to medication and were maintained up to the day of the animal's sacrifice, ten days after medication. The following parameters were analysed: i) weight evolution; ii) in plasma: urea, creatinine, uric acid, total proteins, albumen, lactate dehydrogenase, creatinine-quinase, aspartate aminotransferase, alanine aminotransferase and total cholesterol; iii) in urine: urea, creatinine, total proteins and microalbumen; iv) biomarkers of oxidative damage in kidneys, heart, liver and brain: lipoperoxides, total glutathione, reduced glutathione, catalase, glutathione peroxidase, glutathione reductase and glutathione transferase; v) melatonin (pineal gland tissue and plasma) and leptin (plasma). From the results obtained it was concluded that the administration of adriamycin generated oxidative stress in renal, cerebral, hepatic and cardiac tissue. Additionally, in the healthy animal, but of a lesser relevance in the adriamycin animal, permanent light worsened the oxidative stress, whereas darkness improved it. This could be related to the circadian rhythm of the inverse release shown by melatonin and leptin, accentuating the release of melatonin in the darkness phase and that of leptin in the light phase. The correlation between melatonin and leptin

  15. Modeling Alzheimer's disease in transgenic rats.

    PubMed

    Do Carmo, Sonia; Cuello, A Claudio

    2013-10-25

    Alzheimer's disease (AD) is the most common form of dementia. At the diagnostic stage, the AD brain is characterized by the accumulation of extracellular amyloid plaques, intracellular neurofibrillary tangles and neuronal loss. Despite the large variety of therapeutic approaches, this condition remains incurable, since at the time of clinical diagnosis, the brain has already suffered irreversible and extensive damage. In recent years, it has become evident that AD starts decades prior to its clinical presentation. In this regard, transgenic animal models can shed much light on the mechanisms underlying this "pre-clinical" stage, enabling the identification and validation of new therapeutic targets. This paper summarizes the formidable efforts to create models mimicking the various aspects of AD pathology in the rat. Transgenic rat models offer distinctive advantages over mice. Rats are physiologically, genetically and morphologically closer to humans. More importantly, the rat has a well-characterized, rich behavioral display. Consequently, rat models of AD should allow a more sophisticated and accurate assessment of the impact of pathology and novel therapeutics on cognitive outcomes.

  16. A rat model for hepatitis E virus

    PubMed Central

    Mishra, Niraj; Verbeken, Erik; Ramaekers, Kaat; Dallmeier, Kai

    2016-01-01

    ABSTRACT Hepatitis E virus (HEV) is one of the prime causes of acute viral hepatitis, and chronic hepatitis E is increasingly recognized as an important problem in the transplant setting. Nevertheless, the fundamental understanding of the biology of HEV replication is limited and there are few therapeutic options. The development of such therapies is partially hindered by the lack of a robust and convenient animal model. We propose the infection of athymic nude rats with the rat HEV strain LA-B350 as such a model. A cDNA clone, pLA-B350, was constructed and the infectivity of its capped RNA transcripts was confirmed in vitro and in vivo. Furthermore, a subgenomic replicon, pLA-B350/luc, was constructed and validated for in vitro antiviral studies. Interestingly, rat HEV proved to be less sensitive to the antiviral activity of α-interferon, ribavirin and mycophenolic acid than genotype 3 HEV (a strain that infects humans). As a proof-of-concept, part of the C-terminal polymerase sequence of pLA-B350/luc was swapped with its genotype 3 HEV counterpart: the resulting chimeric replicon replicated with comparable efficiency as the wild-type construct, confirming that LA-B350 strain is amenable to humanization (replacement of certain sequences or motifs by their counterparts from human HEV strains). Finally, ribavirin effectively inhibited LA-B350 replication in athymic nude rats, confirming the suitability of the rat model for antiviral studies. PMID:27483350

  17. The Helsinki Rat Microsurgical Sidewall Aneurysm Model

    PubMed Central

    Marbacher, Serge; Marjamaa, Johan; Abdelhameed, Essam; Hernesniemi, Juha; Niemelä, Mika; Frösen, Juhana

    2014-01-01

    Experimental saccular aneurysm models are necessary for testing novel surgical and endovascular treatment options and devices before they are introduced into clinical practice. Furthermore, experimental models are needed to elucidate the complex aneurysm biology leading to rupture of saccular aneurysms. Several different kinds of experimental models for saccular aneurysms have been established in different species. Many of them, however, require special skills, expensive equipment, or special environments, which limits their widespread use. A simple, robust, and inexpensive experimental model is needed as a standardized tool that can be used in a standardized manner in various institutions. The microsurgical rat abdominal aortic sidewall aneurysm model combines the possibility to study both novel endovascular treatment strategies and the molecular basis of aneurysm biology in a standardized and inexpensive manner. Standardized grafts by means of shape, size, and geometry are harvested from a donor rat's descending thoracic aorta and then transplanted to a syngenic recipient rat. The aneurysms are sutured end-to-side with continuous or interrupted 9-0 nylon sutures to the infrarenal abdominal aorta. We present step-by-step procedural instructions, information on necessary equipment, and discuss important anatomical and surgical details for successful microsurgical creation of an abdominal aortic sidewall aneurysm in the rat. PMID:25350840

  18. Digital replantation teaching model in rats.

    PubMed

    Ad-El, D D; Harper, A; Hoffman, L A

    2000-01-01

    Replant surgery is a complex procedure that requires advanced microsurgical skills and is usually performed as an emergency operation, lasting many hours. For these reasons, teaching replantation is difficult. Although teaching models exist, they are often too general or complicated for routine use and do not simulate the stages and the pitfalls of human replant surgery. We have designed a model that is simple and imitates human replant surgery. After reviewing the rat anatomy, students dissect and replant a rat hind limb that has been sharply amputated by the instructor. They follow the same principles of "real" surgery like debridement, minimizing ischemia time, and stable fixation before anatomosis of vessels. After marking the structures, bony fixation followed by vessel and nerve anastomosis are performed. Muscle is reattached to the skin and limb vascularity evaluated. After we designed this model, plastic surgery residents performed the technique on 10 rats. An 80% limb viability rate was achieved. This model is simple to perform, simulates all the relevant structures and pitfalls of human surgery, and the rats are relatively cheap and can be used for other parallel projects.

  19. Effect of atorvastatin and diet on non-alcoholic fatty liver disease activity score in hyperlipidemic chickens.

    PubMed

    Martín-Castillo, Antonia; Castells, Maria Teresa; Adánez, Gracia; Polo, Maria Teresa Sánchez; Pérez, Bartolomé García; Ayala, Ignacio

    2010-04-01

    Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease (NAFLD), which includes from simple steatosis and steatohepatitis, to the most severe cirrhosis and carcinoma, which develops in the absence of excessive alcohol intake. NAFLD is the most common liver disorder in affluent societies. There is no proven treatment for NAFLD/NASH. One of the most frequent adverse effects of statins is an increase in hepatic aminotransferases. Studies that evaluate if the benefits of statins overcome the risks in NASH are lacking. The present study was conceived to explore the effect of both atorvastatin and diet on regression of steatohepatitis, using a chicken experimental model induced by a hyperlipidemic diet (HD). Plasma lipid levels, liver enzymes and hepatic histopathology, as well as image analysis were performed to determine changes in liver lipid deposits and inflammatory infiltration. Features of steatosis, cell-ballooning, and inflammation were scored to obtain the NAFLD activity score (NAS). A severe level of steatosis was found in animals fed on HD. Atorvastatin treated groups showed smaller size of lipid deposits and a lower level of inflammation than non-treated groups. Atorvastatin therapy induced a significant reduction of hepatocellular damage, even though in the animals which continuously received a hyperlipidemic diet. The combination of atorvastatin therapy and a standard diet produced the lowest decrease of NAS. Our results show that atorvastatin therapy not only decreased plasmatic levels of cholesterol and triglycerides, but also induced a reduction of liver steatosis, inflammation and hepatocellular damage, without increasing plasmatic aminotransferase levels.

  20. Effects of Apple Consumption on Lipid Profile of Hyperlipidemic and Overweight Men

    PubMed Central

    Vafa, Mohammad Reza; Haghighatjoo, Elham; Shidfar, Farzad; Afshari, Shirin; Gohari, Mahmood Reza; Ziaee, Amir

    2011-01-01

    Objectives: Fruits and vegetables may be beneficial on lipid profile of hyperlipidemic subjects. The present study was aimed to verify the effect of golden delicious apple on Lipid Profile in hyperlipidemic and overweight men. Methods: Forty six hyperlipidemic and overweight men were randomly divided into two groups. Intervention group received 300g golden delicious apple per day for 8 weeks. Control group had the regular dietary regimen for the same period of time. Blood samples were analyzed for serum triglycerides (TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), very low density lipoprotein-cholesterol (VLDL), apolipoprotein B (Apo B), lipoprotein a (Lp a) and LDL/HDL ratio at baseline and after intervention. Results: Total polyphenols and fibers were 485 mg/kg and 4.03 g/100g in fresh apple respectively. After 8 weeks, significant statistical differences were observed considering the TG and VLDL levels between two groups, but no significant differences were observed regarding TC, LDL-C, HDL-C, Apo (B), Lp (a) and LDL/HDL ratio. Conclusions: Consumption of Golden delicious apple may be increased serum TG and VLDL in hyperlipidemic and overweight men. We need more studies to assay the effect of apple consumption on serum TC, LDL-C, HDL-C, Apo (B), Lp (a) and LDL/HDL ratio. PMID:21603015

  1. MODELING OPERANT BEHAVIOR IN THE PARKINSONIAN RAT

    PubMed Central

    Avila, Irene; Reilly, Mark P.; Sanabria, Federico; Posadas-Sánchez, Diana; Chavez, Claudia L.; Banerjee, Nikhil; Killeen, Peter; Castañeda, Edward

    2009-01-01

    Mathematical principles of reinforcement (MPR; Killeen, 1994) is a quantitative model of operant behavior that contains 3 parameters representing motor capacity (δ), motivation (a), and short term memory (λ). The present study applied MPR to characterize the effects of bilateral infusions of 6-OHDA into the substantia nigra pars compacta in the rat, a model of Parkinson’s disease. Rats were trained to lever press under a 5-component fixed ratio (5, 15, 30, 60, and 100) schedule of food reinforcement. Rats were tested for 15 days prior to dopamine lesions and again for 15 days post-lesion. To characterize functional loss relative to lesion size, rats were grouped according to the extent and the degree of lateralization of their dopamine loss. Response rates decreased as a function of dopamine depletion, primarily at intermediate ratios. MPR accounted for 98% of variance in pre- and post-lesion response rates. Consistent with reported disruptions in motor behavior induced by dopaminergic lesions, estimates of δ increased when dopamine was severely depleted. There was no support for different estimates of a based on pre- and post-lesion performance of any lesion group, suggesting that dopamine loss has negligible effects on incentive motivation. The present study demonstrates the usefulness of combining operant techniques with a theoretical model to better understand the effects of a neurochemical manipulation. PMID:19073222

  2. [Effect of astaxanthin on preeclampsia rat model].

    PubMed

    Xuan Rong-rong; Gao Xin; Wu, Wei; Chen, Hai-min

    2014-10-01

    The effect of astaxanthin on N(Ω)-nitro-L-arginine methyl ester (L-NAME) induced preeclampsia disease rats was investigated. Thirty pregnant Sprague-Dawley rats were randomly divided into three groups (n = 10): blank group, L-NAME group and astaxanthin group. From day 5 to 20, astaxanthin group rats were treated with astaxanthin (25 mg x kg(-1) x d(-1) x bw(-1)) from pregnancy (day 5). To establish the preeclamptic rat model, L-NAME group and astaxanthin group rats were injected with L-NAME (125 mg x kg(-1) x d(-1) x bw(-1)) from days 10-20 of pregnancy. The blood pressure and urine protein were recorded. Serum of each group was collected and malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide synthase (NOS) activities were analyzed. Pathological changes were observed with HE stain. The expression of NF-κB (nuclear factor kappa B), ROCK II (Rho-associated protein kinase II), HO-1 (heme oxygenase-1) and Caspase 3 were analyzed with immunohistochemistry. L-NAME induced typical preeclampsia symptoms, such as the increased blood pressure, urinary protein, the content of MDA, etc. Astaxanthin significantly reduced the blood pressure (P < 0.01), the content of MDA (P < 0.05), and increased the activity of SOD (P < 0.05) of preeclampsia rats. The urinary protein, NO, and NOS were also decreased. HE stain revealed that after treated with astaxanthin, the thickness of basilal membrane was improved and the content of trophoblast cells and spiral arteries was reduced. Immunohistochemistry results revealed that the expressions of NF-κB, ROCK II and Caspase 3 in placenta tissue were effectively decreased, and HO-1 was increased. Results indicated that astaxanthin can improve the preeclampsia symptoms by effectively reducing the oxidative stress and inflammatory damages of preeclampsia. It revealed that astaxanthin may be benefit for prevention and treatment of preeclampsia disease.

  3. On the rat model of human osteopenias and osteoporoses

    NASA Technical Reports Server (NTRS)

    Frost, Harold M.; Jee, Webster S. S.

    1992-01-01

    The idea that rats cannot model human osteopenias errs. The same mechanisms control gains in bone mass (longitudinal bone growth and modeling drifts) and losses (BMU-based remodeling), in young and aged rats and humans. Furthermore, they respond similarly in rats and man to mechanical influences, hormones, drugs and other agents.

  4. On the rat model of human osteopenias and osteoporoses

    NASA Technical Reports Server (NTRS)

    Frost, Harold M.; Jee, Webster S. S.

    1992-01-01

    The idea that rats cannot model human osteopenias errs. The same mechanisms control gains in bone mass (longitudinal bone growth and modeling drifts) and losses (BMU-based remodeling), in young and aged rats and humans. Furthermore, they respond similarly in rats and man to mechanical influences, hormones, drugs and other agents.

  5. [Research of modified rat laryngeal transplantation model].

    PubMed

    Li, Hao; Peng, Han-wei; Zeng, Zong-yuan; Guo, Zhu-ming

    2006-07-01

    To study modified rat laryngeal transplantation model. Eighty isogeneic histocompatible F344 rats were randomized into control and experimental groups. Strome model of laryngeal transplantation was established in the the control group, and in the experimental group, the ascending pharyngeal artery was preserved and the base of the tongue, larynx and pharyngolarynx were harvested as a complex allograft followed by end-to-end anastomosis of the both allograft common carotid arteries with the recipient common carotid artery and the anterior jugular vein, respectively. The arterial and nenous patency rate and allograft viability rate were compared between the two groups. The artery and vein patency rates and graft survival rate were 30%, 15%, and 30% in the control group, and 75%, 65%, and 80% in the experimental group, respectively, showing significant difference between the two groups (P<0.05). In modified rat laryngeal transplantation model, the allograft viability rate and vessel patency rate are improved, which provides a good model for immunological study of larynx transplantation.

  6. Oxytocin administration attenuates atherosclerosis and inflammation in Watanabe Heritable Hyperlipidemic rabbits.

    PubMed

    Szeto, Angela; Rossetti, Maria A; Mendez, Armando J; Noller, Crystal M; Herderick, Edward E; Gonzales, Julie A; Schneiderman, Neil; McCabe, Philip M

    2013-05-01

    Oxytocin (OT) is a neurohypophyseal peptide traditionally associated with female reproductive functioning, and more recently with prosocial behavior. OT and its receptor are also expressed in the heart and vascular tissue and play a role in cardiovascular homeostasis. In vitro, it has been demonstrated that OT decreases NADPH-dependent superoxide production and pro-inflammatory cytokine release from vascular endothelial cells and macrophages, suggesting that OT may attenuate pathophysiological processes involved with atherosclerotic lesion formation. The present study sought to determine the effect of chronic exogenous OT administration on inflammation and atherosclerosis in an animal model of dyslipidemia and atherosclerosis, the Watanabe Heritable Hyperlipidemic (WHHL) rabbit. Twenty-two, 3-month-old WHHLs were surgically implanted with osmotic mini-pumps containing OT (n=11) or vehicle (n=11), and then were individually housed for the entire study. Blood and 24-h urine samples were taken at baseline and after 8 (midpoint) and 16 (endpoint) weeks of treatment. At endpoint, the aortas and visceral fat samples were dissected and stored for analyses. There were no group differences in body weight, serum lipids, plasma/urinary measures of oxidative stress, plasma cortisol or urinary catecholamines over the 16-week treatment. OT-treated animals exhibited significantly lower plasma C-reactive protein levels at midpoint and endpoint and developed significantly less atherosclerosis in the thoracic aorta relative to vehicle control animals at endpoint (p<0.05). Cytokine gene expression from visceral adipose tissue samples suggested that there was a decrease in adipose tissue inflammation in the OT-treated group compared to the vehicle control group, however these differences were not statistically significant. These results suggest that chronic peripheral OT administration can inhibit inflammation and atherosclerotic lesion development.

  7. Oxytocin Administration Attenuates Atherosclerosis and Inflammation in Watanabe Heritable Hyperlipidemic Rabbits

    PubMed Central

    Szeto, Angela; Rossetti, Maria A.; Mendez, Armando J.; Noller, Crystal M.; Herderick, Edward E.; Gonzales, Julie A.; Schneiderman, Neil; McCabe, Philip M.

    2012-01-01

    Oxytocin (OT) is a neurohypophyseal peptide traditionally associated with female reproductive functioning, and more recently with prosocial behavior. OT and its receptor are also expressed in the heart and vascular tissue and play a role in cardiovascular homeostasis. In vitro, it has been demonstrated that OT decreases NADPH-dependent superoxide production and pro-inflammatory cytokine release from vascular endothelial cells and macrophages, suggesting that OT may attenuate pathophysiological processes involved with atherosclerotic lesion formation. The present study sought to determine the effect of chronic exogenous OT administration on inflammation and atherosclerosis in an animal model of dyslipidemia and atherosclerosis, the Watanabe Heritable Hyperlipidemic (WHHL) rabbit. Twenty-two, 3-month-old WHHLs were surgically implanted with osmotic mini-pumps containing OT (n=11) or vehicle (n=11), and then were individually housed for the entire study. Blood and 24-hour urine samples were taken at baseline and after 8 (midpoint) and 16 (endpoint) weeks of treatment. At endpoint, the aortas and visceral fat samples were dissected and stored for analyses. There were no group differences in body weight, serum lipids, plasma/urinary measures of oxidative stress, plasma cortisol or urinary catecholamines over the 16-week treatment. OT-treated animals exhibited significantly lower plasma C-reactive protein levels at midpoint and endpoint and developed significantly less atherosclerosis in the thoracic aorta relative to vehicle control animals at endpoint (p<0.05). Cytokine gene expression from visceral adipose tissue samples suggested that there was a decrease in adipose tissue inflammation in the OT-treated group compared to the vehicle control group, however these differences were not statistically significant. These results suggest that chronic peripheral OT administration can inhibit inflammation and atherosclerotic lesion development. PMID:22998949

  8. Chronic Paraspinal Muscle Injury Model in Rat

    PubMed Central

    Cho, Tack Geun; Kim, Young Baeg

    2016-01-01

    Objective The objective of this study is to establish an animal model of chronic paraspinal muscle injury in rat. Methods Fifty four Sprague-Dawley male rats were divided into experimental group (n=30), sham (n=15), and normal group (n=9). Incision was done from T7 to L2 and paraspinal muscles were detached from spine and tied at each level. The paraspinal muscles were exposed and untied at 2 weeks after surgery. Sham operation was done by paraspinal muscles dissection at the same levels and wound closure was done without tying. Kyphotic index and thoracolumbar Cobb's angle were measured at preoperative, 2, 4, 8, and 12 weeks after the first surgery for all groups. The rats were sacrificed at 4, 8, and 12 weeks after the first surgery, and performed histological examinations. Results At 4 weeks after surgery, the kyphotic index decreased, but, Cobb's angle increased significantly in the experimental group (p<0.05), and then that were maintained until the end of the experiment. However, there were no significant differences of the kyphotic index and Cobb's angle between sham and normal groups. In histological examinations, necrosis and fibrosis were observed definitely and persisted until 12 weeks after surgery. There were also presences of regenerated muscle cells which nucleus is at the center of cytoplasm, centronucleated myofibers. Conclusion Our chronic injury model of paraspinal muscles in rats shows necrosis and fibrosis in the muscles for 12 weeks after surgery, which might be useful to study the pathophysiology of the degenerative thoracolumbar kyphosis or degeneration of paraspinal muscles. PMID:27651859

  9. Properties of Flicker ERGs in Rat Models with Retinal Degeneration

    PubMed Central

    An, Jing; Guo, Qun; Li, Li; Zhang, Zuoming

    2012-01-01

    Purpose. To describe the characteristics of rod and cone functions in rat models for congenital stationary night blindness (CSNB) and retinal cone dysfunction (RCD). Methods. Rod and cone function were isolated by recording the rod-/cone-driven flicker and blue light flicker electroretinograms (ERGs). Results. During dark adaptation, the amplitudes of flicker ERGs in CSNB rats were lower than those in control rats; the responses of RCD rats were similar to control rats. During light adaptation, the amplitudes of flicker ERGs in CSNB rats were reduced; whereas the responses of RCD rats were not detected. Blue flicker ERGs were not observed in CSNB rats at lower frequencies. The cone driven critical flicker frequencies (CFFs) in control rats were 62 Hz. The rod driven CFF of RCD rats was 20 Hz; whereas the rod-/cone-driven CFF of CSNB rats both were about 25 Hz. Conclusions. The function of the rod system was damaged completely, the cones were the source of vision in CSNB rats. Rod system function is excellent in RCD rat. The rods of albinism rats are sensitive to frequencies less than 20 Hz; whereas the cones are sensitive to frequencies up to 62 Hz. PMID:24555124

  10. Ideal Experimental Rat Models for Liver Diseases.

    PubMed

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok; Kim, Kyung Sik

    2011-05-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and diverse clinical symptoms, adverse reactions, and complications due to the pathological physiology. Also, it is not easy to reproduce identically various clinical situations in animal models. Recently, the Guide for the Care and Use of Laboratory Animals has tightened up the regulations, and therefore it is advisable to select the appropriate animals and decide upon the appropriate quantities through scientific and systemic considerations before conducting animal testing. Therefore, in this review article the authors examined various white rat animal testing models and determined the appropriate usable rat model, and the pros and cons of its application in liver disease research. The authors believe that this review will be beneficial in selecting proper laboratory animals for research purposes.

  11. Ideal Experimental Rat Models for Liver Diseases

    PubMed Central

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok

    2011-01-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and diverse clinical symptoms, adverse reactions, and complications due to the pathological physiology. Also, it is not easy to reproduce identically various clinical situations in animal models. Recently, the Guide for the Care and Use of Laboratory Animals has tightened up the regulations, and therefore it is advisable to select the appropriate animals and decide upon the appropriate quantities through scientific and systemic considerations before conducting animal testing. Therefore, in this review article the authors examined various white rat animal testing models and determined the appropriate usable rat model, and the pros and cons of its application in liver disease research. The authors believe that this review will be beneficial in selecting proper laboratory animals for research purposes. PMID:26421020

  12. Age- and sex-related differences in nuclear lipid content and nucleoside triphosphatase activity in the JCR:LA-cp corpulent rat.

    PubMed

    Czubryt, M P; Russell, J C; Sarantopoulos, J; Gilchrist, J S; Pierce, G N

    1997-11-01

    The putative role of the nuclear nucleoside triphosphatase (NTPase) is to provide energy to the nuclear pore complex for poly A(+) mRNA export. Previous work has demonstrated that liver nuclear NTPase activity is greater in 6 month old corpulent (cp/cp) female JCR:LA rats, a hyperlipidemic rat model, compared to lean (+/?) animals. This increase appeared to be related to increases in nuclear membrane cholesterol content. The current study extended these initial data to compare NTPase activity as a function of age and sex in isolated JCR:LA-cp rat liver nuclei, to further test the hypothesis that nuclear membrane cholesterol may modulate NTPase activity. NTPase activity was increased in cp/cp female animals compared to +/? females at all ages studied, with Vmax values increased by 60-176%. Membrane integrity of cp/cp female nuclei was reduced compared to +/? female nuclei. Nuclear membrane cholesterol levels increased linearly with age by 50, 150 and 250% in 3, 6 and 9 month old cp/cp females over leans. In contrast, nuclei from cp/cp males exhibited only minor, isolated changes in NTPase activity. Furthermore, there were no significant changes in nuclear cholesterol content or membrane integrity in the less hyperlipidemic male animals at any age. These data suggest that altered lipid metabolism may lead to changes in nuclear membrane structure, which in turn may alter NTPase activity and functioning of the nuclear pore complex.

  13. [Effects of sustained-release alpha-lipoic acid tablet on blood lipid, blood sugar and insulin in hyperlipidemic New Zealand rabbits].

    PubMed

    Chen, Xie-sheng; Liu, Hong; Ji, Ai-min; Yang, Yue-lian; Yao, Yu-fa; Sun, Liang; Che, Ou

    2009-04-01

    To evaluate the effect of sustained-release alpha-lipoic acid tablets (SRLA) on blood lipid, glucose and insulin levels in hyperlipidemic New Zealand rabbits. Twenty-four New Zealand rabbits were randomized into normal diet group, high-fat diet group, and high-fat diet + SRLA (300 mg/tablet) group with corresponding feed. At the beginning and 4 weeks after the feeding, the serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), blood glucose, and serum insulin were measured, and insulin sensitivity index (ISI) was calculated. Four weeks after feeding with high-fat diet, the insulin levels was elevated and the ISI lowered in the New Zealand rabbits, indicating successful establishment of the animal model of hyperlipidemia. Compared with the high-fat diet group, the serum levels of TG, TC, LDL-C and insulin were significantly reduced (P<0.05), and the ISI was significantly increased (P<0.05) in high fat diet + SRLA group. But no statistically significant difference was found in the blood glucose among the 3 groups. SRLA can significantly correct blood lipid and insulin disorders in hyperlipidemic New Zealand rabbits and prevent the occurrence of insulin resistance and hyperlipidemia.

  14. The influence of statin therapy on platelet activity markers in hyperlipidemic patients after ischemic stroke

    PubMed Central

    Chmielewski, Henryk; Kaczorowska, Beata; Przybyła, Monika; Baj, Zbigniew

    2015-01-01

    Introduction Low-density lipoprotein cholesterol (LDL-C) has been reported to increase platelet activation. Reducing the level of LDL-C with statins induces important pleiotropic effects such as platelet inhibition. This association between platelet activity and statin therapy may be clinically important in reducing the risk of ischemic stroke. We investigated the effect of simvastatin therapy on platelet activation markers (platelet CD62P, sP-selectin, and platelet-derived microparticles (PDMPs)) in hyperlipidemic patients after ischemic stroke. Material and methods The study group consisted of 21 hyperlipidemic patients after ischemic stroke confirmed by CT, and 20 healthy subjects served as controls. We assessed the CD62P expression on resting and thrombin-activated blood platelets. CD62P and PDMPs were analyzed by the use of monoclonal antibodies anti-CD61 and anti-CD62 on a flow cytometer. The level of sP-selectin in serum was measured by the ELISA (enzyme-linked immunosorbent assay) method. All markers were re-analyzed after 6 months of treatment with simvastatin (20 mg/day). Results Hyperlipidemic patients presented a significantly higher percentage of CD62+ platelets and higher reactivity to thrombin compared to control subjects. After simvastatin therapy hyperlipidemic patients showed a reduction of the percentage of resting CD62P(+) platelets (p = 0.005) and a reduction of expression and percentage of CD62P(+) platelets after activation by thrombin (median p < 0.05; percentage: p = 0.001). A decrease of sP-selectin levels (p = 0.001) and percentage of PDMPs (p < 0.05) in this group was also observed. Conclusions HMG-CoA reductase inhibitor therapy in stroke patients with hyperlipidemia may be useful not only due to the lipid-lowering effect but also because of a significant role in reduction of platelet activation and reactivity. PMID:25861297

  15. Eicosapentaenoic Acid Supplementation Changes Fatty Acid Composition and Corrects Endothelial Dysfunction in Hyperlipidemic Patients

    PubMed Central

    Yamakawa, Ken; Shimabukuro, Michio; Higa, Namio; Asahi, Tomohiro; Ohba, Kageyuki; Arasaki, Osamu; Higa, Moritake; Oshiro, Yoshito; Yoshida, Hisashi; Higa, Tohru; Saito, Taro; Ueda, Shinichiro; Masuzaki, Hiroaki; Sata, Masataka

    2012-01-01

    We investigated the effects of purified eicosapentaenoic acid (EPA) on vascular endothelial function and free fatty acid composition in Japanese hyperlipidemic subjects. In subjects with hyperlipidemia (total cholesterol ≥220 mg/dL and/or triglycerides ≥150 mg/dL), lipid profile and forearm blood flow (FBF) during reactive hyperemia were determined before and 3 months after supplementation with 1800 mg/day EPA. Peak FBF during reactive hyperemia was lower in the hyperlipidemic group than the normolipidemic group. EPA supplementation did not change serum levels of total, HDL, or LDL cholesterol, apolipoproteins, remnant-like particle (RLP) cholesterol, RLP triglycerides, or malondialdehyde-modified LDL cholesterol. EPA supplementation did not change total free fatty acid levels in serum, but changed the fatty acid composition, with increased EPA and decreased linoleic acid, γ-linolenic acid, and dihomo-γ-linolenic acid. EPA supplementation recovered peak FBF after 3 months. Peak FBF recovery was correlated positively with EPA and EPA/arachidonic acid levels and correlated inversely with dihomo-γ-linolenic acid. EPA supplementation restores endothelium-dependent vasodilatation in hyperlipidemic patients despite having no effect on serum cholesterol and triglyceride patterns. These results suggest that EPA supplementation may improve vascular function at least partly via changes in fatty acid composition. PMID:23326753

  16. MODELING VOLATILE ORGANIC COMPOUND PHARMACOKINETICS IN RAT PUPS

    EPA Science Inventory

    PBPK model predictions of internal dosimetry in young rats were compared to adult animals for benzene, chloroform (CHL), methylene chloride, methyl ethly ketone (MEK), perchloroethylene, and trichloroethylene.

  17. MODELING VOLATILE ORGANIC COMPOUND PHARMACOKINETICS IN RAT PUPS

    EPA Science Inventory

    PBPK model predictions of internal dosimetry in young rats were compared to adult animals for benzene, chloroform (CHL), methylene chloride, methyl ethly ketone (MEK), perchloroethylene, and trichloroethylene.

  18. In Vitro Antioxidant and In Vivo Hypolipidemic Effects of the King Oyster Culinary-Medicinal Mushroom, Pleurotus eryngii var. ferulae DDL01 (Agaricomycetes), in Rats with High-Fat Diet-Induced Fatty Liver and Hyperlipidemia.

    PubMed

    Choi, Jun-Hui; Kim, Dae-Won; Kim, Seung; Kim, Sung-Jun

    2017-01-01

    We investigated the effect of the culinary-medicinal mushroom Pleurotus eryngii var. ferulae DDL01 on oxidative damage in the liver and brain and a high-fat/high-cholesterol-induced hyperlipidemic model. In in vitro studies, the water extracts of the fruiting bodies showed strong scavenging activities of DPPH (139.46 ± 3.2 μg) and hydroxyl (139.46 ± 3.2 μg) radicals. Moreover, the extracts showed Fe2+ chelating and reducing abilities, as well as a large amount of polyphenols and an inhibitory effect on lipid peroxidation in the liver and brain tissues. The rats were fed a pellet diet (7.5 g/rat/day) containing P. eryngii var. ferulae DDL01 (PD) for 3 weeks. In the high-fat/high-cholesterol-induced hyperlipidemic rat model, administration of PD caused a significant decrease (P < 0.05) in the levels of serum triacylglycerols, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, aspartate aminotransferase, and alanine aminotransferase and a significant increase (P < 0.05) in the level of high-density lipoprotein cholesterol. PD administration significantly decreased high-fat/high-cholesterol-induced hepatic lipid accumulation. Treatment with the extracts (up to 500 μg/mL) did not significantly affect the viability of HepG2 and 3T3-L1 cells. Our findings suggest that this mushroom has potential as an antiatherogenic dietary source in the development of therapeutic agents and functional foods.

  19. Sensory innervation of rat contracture shoulder model.

    PubMed

    Ochiai, Nobuyasu; Ohtori, Seiji; Kenmoku, Tomonori; Yamazaki, Hironori; Ochiai, Satoko; Saisu, Takashi; Matsuki, Keisuke; Takahashi, Kazuhisa

    2013-02-01

    To date, few studies have investigated the cause of pain experienced by patients with frozen shoulder. The purposes of this study were to establish a rat contracture model and clarify the innervation pattern of the glenohumeral (GH) joint and subacromial bursa (SAB) using immunohistochemistry in the dorsal root ganglion (DRG) neurons. The rat contracture models were made by tying the animal's humerus and scapula with No. 2-0 FiberWire (Arthrex, Naples, FL, USA). Contracture was confirmed on x-ray images taken 8 weeks after the operation. Subsequently, two kinds of neurotracers, Fluoro-Gold (FG) (Fluorochrome, Denver, CO, USA) and 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI) (Molecular Probes, Eugene, OR, USA), were used to detect the GH joints and SAB separately. FG tracers were injected into GH joints, and DiI tracers were injected into the SAB. At 7 days after injection, DRGs were harvested between C1 and T1. Immunohistochemistry by use of calcitonin gene-related peptide (CGRP) was performed. CGRP is thought to be one of the causes of pain sensation in joint disease. We evaluated the percentages of FG-labeled CGRP-immunoreactive (CGRP-ir) neurons in the total number of FG-labeled neurons and of DiI-labeled CGRP-ir neurons in the total number of DiI-labeled neurons. Abduction and total arc of the rotation were statistically significantly decreased in the contracture group. Furthermore, the percentage of CGRP-ir DRG neurons was significantly higher in the contracture group in both the GH joint and SAB. These results show that pain sensation in rat shoulder contracture may be induced by the up-regulation of CGRP expression in DRG neurons. Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  20. The emerging role for rat models in gene discovery

    PubMed Central

    Dwinell, Melinda R.; Lazar, Jozef; Geurts, Aron M.

    2011-01-01

    Rat models have been used for many decades to study physiological and pathophysiological mechanisms. Prior to the release of the rat genome and new technologies for targeting gene manipulation, the rat had been the underdog in the genomics era, despite the abundance of physiological data compared to the mouse. The overarching goal of biomedical research is to improve health and advance medical science. Translating human disease gene discovery and validation in the rat, through the use of emerging technologies and integrated tools and databases, is providing power to understand the genetics, environmental influences, and biology of disease. In this review, we will briefly outline the rat models, bioinformatic tools, and technologies that are changing the landscape of translational research. The strategies used to translate disease traits to genes to function, and ultimately, to improve human health will be discussed. Finally, our perspectives on how rat models will continue to positively impact biomedical research will be provided. PMID:21732192

  1. Modified brain death model for rats.

    PubMed

    Zhang, Shuijun; Cao, Shengli; Wang, Tao; Yan, Bing; Lu, Yantao; Zhao, Yongfu

    2014-10-01

    Experimental animal models of brain death that mimic human conditions may be useful for investigating novel strategies that increase quality and quantity of organs for transplant. Brain death was induced by increasing intracranial pressure by inflating an intracranial placed balloon catheter. Brain death was confirmed by flatline electroencephalogram, physical signs of apnea, and absence of brain stem reflexes. Donor management was done after brain death. Intracranial pressure and physiologic variables were continually monitored during 9 hours' follow-up. Ninety percent of brain dead animals showed typical signs of brain death such as diabetes insipidus, hypertensive, and hypotensive periods. Donor care was performed for 9 hours after brain death, and the mean arterial pressure was maintained above 60 mm Hg. We conclude that the rat model of brain death can be performed in a standardized, reproducible, and successful way.

  2. Psychopharmacology of male rat sexual behavior: modeling human sexual dysfunctions?

    PubMed

    Olivier, B; Chan, J S W; Pattij, T; de Jong, T R; Oosting, R S; Veening, J G; Waldinger, M D

    2006-01-01

    Most of our current understanding of the neurobiology, neuroanatomy and psychopharmacology of sexual behavior and ejaculatory function has been derived from preclinical studies in the rat. When a large population of male rats is tested on sexual activity during a number of successive tests, over time individual rats display a very stable sexual behavior that is either slow, normal or fast as characterized by the number of ejaculations performed. These sexual endophenotypes are postulated as rat counterparts of premature (fast rats) or retarded ejaculation (slow rats). Psychopharmacology in these endophenotypes helps to delineate the underlying mechanisms and pathology. This is illustrated by the effects of serotonergic antidepressants and serotonergic compounds on sexual and ejaculatory behavior of rats. These preclinical studies and models contribute to a better understanding of the neurobiology of ejaculation and boost the development of novel drug targets to treat ejaculatory disorders such as premature and retarded ejaculation.

  3. ENU mutagenesis to generate genetically modified rat models.

    PubMed

    van Boxtel, Ruben; Gould, Michael N; Cuppen, Edwin; Smits, Bart M G

    2010-01-01

    The rat is one of the most preferred model organisms in biomedical research and has been extremely useful for linking physiology and pathology to the genome. However, approaches to genetically modify specific genes in the rat germ line remain relatively scarce. To date, the most efficient approach for generating genetically modified rats has been the target-selected N-ethyl-N-nitrosourea (ENU) mutagenesis-based technology. Here, we describe the detailed protocols for ENU mutagenesis and mutant retrieval in the rat model organism.

  4. Adipose Derived Stem Cells Ameliorate Hyperlipidemia-associated Detrusor-overactivity in a Rat Model System

    PubMed Central

    Huang, Yun-Ching; Shindel, Alan W.; Ning, Hongxiu; Lin, Guiting; Harraz, Ahmed M.; Wang, Guifang; Garcia, Maurice; Lue, Tom F.; Lin, Ching-Shwun

    2011-01-01

    Purpose It has been previously demonstrated that adipose tissue-derived stem cell (ADSC) can differentiate into muscle and neuron-like cells in vitro. In this study, we investigate the utility of ADSC in the treatment of overactive bladder (OAB) in obese hyperlipidemic rats (OHR). Materials and Methods Hyperlipidemia was induced in healthy rats by administration of a high fat diet. The resulting OHR were then treated with bladder injection of saline or ADSC or tail vein injection of ADSC. Bladder function was assessed by 24-h voiding behavior study and conscious cystometry. Bladder histology was assessed using immunostaining and trichrome staining followed by image analysis. Results Serum total cholesterol and low-density lipoprotein levels were significantly higher in OHR than in normal rats (p < 0.01). Micturition intervals were shorter in the saline-treated OHR relative to normal rats, OHR that received ADSC via tail vein, and OHR that received ADSC by bladder injection (143 ± 28.7 vs 407 ± 77.9 vs 281 ± 43.9 vs 368 ± 66.7 seconds respectively, p = 0.0084). Smooth muscle content of the bladder wall was significantly lower in OHR than in normal animals (p = 0.0061) while there was no significant difference between OHR groups. Nerve content and blood vessel density were lower in control than in ADSC-treated OHR. Conclusions Hyperlipidemia is associated with increased urinary frequency and diminished bladder blood vessel and nerve density in rats. Treatment with ADSC ameliorates these adverse effects and holds promise as a potential new therapy for OAB. PMID:20096880

  5. Variation in rat sciatic nerve anatomy: implications for a rat model of neuropathic pain.

    PubMed

    Asato, F; Butler, M; Blomberg, H; Gordh, T

    2000-03-01

    We discovered a variation of rat sciatic nerve anatomy as an incidental finding during the anatomical exploration of the nerve lesion site in a rat neuropathic pain model. To confirm the composition and distribution of rat sciatic nerve, macroscopic anatomical investigation was performed in both left and right sides in 24 adult Sprague-Dawley rats. In all rats, the L4 and L5 spinal nerves were fused tightly to form the sciatic nerve. However, the L6 spinal nerve did not fuse with this nerve completely as a part of the sciatic nerve, but rather sent a thin branch to it in 13 rats (54%), whereas in the remaining 11 rats (46%), L6 ran separately along with the sciatic nerve. Also, the L3 spinal nerve sent a thin branch to the L4 spinal nerve or sciatic nerve in 6 rats (25%). We conclude that the components of sciatic nerve in Sprague-Dawley rats vary from L3 to L6; however, the major components are L4 and L5 macroscopically. This finding is in contrast to the standard textbooks of rat anatomy which describe the sciatic nerve as having major contributions from L4, L5, and L6.

  6. Distraction of skeletal muscle: evolution of a rat model.

    PubMed

    Green, Stuart A; Horton, Eric; Baker, Michael; Utkan, Ali; Caiozzo, Vincent

    2002-10-01

    To better study the effects of limb lengthening on skeletal muscle, the authors developed a rat model that uses a miniature external skeletal fixator applied to the tibia of an adult Sprague-Dawley rat. The mounting and lengthening protocols follow the principles developed by Ilizarov. With the initial version of the fixator, the rats had progressive equinus contractures develop because the calf muscles resisted elongation. By incorporating a footplate in the distraction apparatus, tibial lengthening can be achieved without concomitant equinus.

  7. UPLC-Q-TOF/MS-based urine and plasma metabonomics study on the ameliorative effects of aspirin eugenol ester in hyperlipidemia rats.

    PubMed

    Ma, Ning; Karam, Isam; Liu, Xi-Wang; Kong, Xiao-Jun; Qin, Zhe; Li, Shi-Hong; Jiao, Zeng-Hua; Dong, Peng-Cheng; Yang, Ya-Jun; Li, Jian-Yong

    2017-10-01

    The main objective of this study was to investigate the ameliorative effects of aspirin eugenol ester (AEE) in hyperlipidemic rat. After five-week oral administration of AEE in high fat diet (HFD)-induced hyperlipidemic rats, the impact of AEE on plasma and urine metabonomics was investigated to explore the underlying mechanism by UPLC-Q-TOF/MS analysis. Blood lipid levels and histopathological changes of liver, stomach and duodenum were also evaluated after AEE treatment. Without obvious gastrointestinal (GI) side effects, AEE significantly relieved fatty degeneration of liver and reduced triglyceride (TG), low density lipoprotein (LDL) and total cholesterol (TCH) (P<0.01). Clear separations of metabolic profiles were observed among control, model and AEE groups by using principal component analysis (PCA) and orthogonal partial least-squares-discriminate analysis (OPLS-DA). 16 endogenous metabolites in plasma and 18 endogenous metabolites in urine involved in glycerophospholipid metabolism, fatty acid metabolism, fatty acid beta-oxidation, amino acid metabolism, TCA cycle, sphingolipid metabolism, gut microflora and pyrimidine metabolism were considered as potential biomarkers of hyperlipidemia and be regulated by AEE administration. It might be concluded that AEE was a promising drug candidate for hyperlipidemia treatment. These findings could contribute to the understanding of action mechanisms of AEE and provide evidence for further studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Hypolipidemic Effects of Alkaloids from Rhizoma Coptidis in Diet-Induced Hyperlipidemic Hamsters.

    PubMed

    He, Kai; Kou, Shuming; Zou, Zongyao; Hu, Yinran; Feng, Min; Han, Bing; Li, Xuegang; Ye, Xiaoli

    2016-05-01

    This study was conducted to evaluate the antihyperlipidemic activity of five major alkaloids in Rhizoma Coptidis using high-fat- and high-cholesterol-induced hyperlipidemic hamsters. Hyperlipidemic hamsters were treated with coptisine, berberine, jatrorrhizine, palmatine, epiberberine, and total Rhizoma Coptidis alkaloids with a dose of 46.7 mg/kg × day for 140 days. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids were examined after alkaloid treatment. The results showed that all therapy agents prevented body weight gain, reduced the serum total cholesterol, and increased the high-density lipoprotein cholesterol of hamsters. Berberine, jatrorrhizine, and total Rhizoma Coptidis alkaloids decreased the triglyceride level in hyperlipidemic hamsters, while coptisine, jatrorrhizine, palmatine, and total Rhizoma Coptidis alkaloids significantly suppressed the elevation of the low-density lipoprotein cholesterol level. The fecal excretion of bile acids was significantly elevated by berberine, coptisine, jatrorrhizine, palmatine, total Rhizoma Coptidis alkaloids, and orlistat. Notably, total Rhizoma Coptidis alkaloids possess a much stronger lipid-lowering effect than the pure Rhizoma Coptidis alkaloids. Quantitative reverse transcription-polymerase chain reaction analyses revealed that Rhizoma Coptidis alkaloids could retard the synthesis of cholesterol by downregulating the mRNA expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase and accelerate the clearance of lipids by upregulating the low-density lipoprotein receptor, cholesterol 7α-hydroxylase, and uncoupling protein-2 expression. These findings highlight the critical role of Rhizoma Coptidis alkaloids in hyperlipidemia treatment. Thus, they need to be considered in future therapeutic approaches.

  9. Role of paraoxonase-1 in bone anabolic effects of parathyroid hormone in hyperlipidemic mice

    SciTech Connect

    Lu, Jinxiu; Cheng, Henry; Atti, Elisa; Shih, Diana M.; Demer, Linda L.; Tintut, Yin

    2013-02-01

    Highlights: ► Anabolic effects of PTH were tested in hyperlipidemic mice overexpressing PON1. ► Expression of antioxidant regulatory genes was induced in PON1 overexpression. ► Bone resorptive activity was reduced in PON1 overexpressing hyperlipidemic mice. ► PON1 restored responsiveness to intermittent PTH in bones of hyperlipidemic mice. -- Abstract: Hyperlipidemia blunts anabolic effects of intermittent parathyroid hormone (PTH) on cortical bone, and the responsiveness to PTH are restored in part by oral administration of the antioxidant ApoA-I mimetic peptide, D-4F. To evaluate the mechanism of this rescue, hyperlipidemic mice overexpressing the high-density lipoprotein-associated antioxidant enzyme, paraoxonase 1 (Ldlr{sup −/−}PON1{sup tg}) were generated, and daily PTH injections were administered to Ldlr{sup −/−}PON1{sup tg} and to littermate Ldlr{sup −/−} mice. Expression of bone regulatory genes was determined by realtime RT-qPCR, and cortical bone parameters of the femoral bones by micro-computed tomographic analyses. PTH-treated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTH receptor (PTH1R), activating transcription factor-4 (ATF4), and osteoprotegerin (OPG) in femoral cortical bone, as well as significantly greater cortical bone mineral content, thickness, and area in femoral diaphyses compared with untreated Ldlr{sup −/−}PON1{sup tg} mice. In contrast, in control mice (Ldlr{sup −/−}) without PON1 overexpression, PTH treatment did not induce these markers. Calvarial bone of PTH-treated Ldlr{sup −/−}PON1{sup tg} mice also had significantly greater expression of osteoblastic differentiation marker genes as well as BMP-2-target and Wnt-target genes. Untreated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTHR1 than untreated Ldlr{sup −/−} mice, whereas sclerostin expression was reduced. In femoral cortical bones, expression levels of transcription factors, Fox

  10. A New Rat Model of Cisplatin-induced Neuropathic Pain

    PubMed Central

    Lin, Hai; Heo, Bong Ha

    2015-01-01

    Background Chemotherapy-induced peripheral neuropathy is a major side effect of anti-cancer drugs, and our knowledge of its mechanisms is lacking. Several models for chemotherapy-induced neuropathy have been introduced. However, the outcomes of these models differ significantly among laboratories. Our object was to create a model of chemotherapy-induced neuropathy in rats with cancer. Methods Female Sprague-Dawley rats were used. Mammary rat metastasis tumor (MRMT-1) cells were implanted subcutaneously in rats. Chemotherapy-induced peripheral neuropathy was induced by injection of cisplatin once a day for four days. The responses to mechanical and thermal stimuli were examined using von Frey filaments, acetone, and radiant heat. Results Cisplatin (2 mg/kg/day) produced mechanical allodynia, while it did not induce cold allodynia or thermal hyperalgesia. This dose of cisplatin could work successfully against cancer. Body weight loss was not observed in cisplatin-treated rats, nor were other abnormal behaviors noted in the same rats. Conclusions Repeated injection of intraperitoneal cisplatin induced peripheral neuropathic pain in rats. Thus, this type of rat model has broad applicability in studies related to searching for the mechanism of cisplatin-induced mechanical allodynia and agents for the treatment of neuropathic pain. PMID:26495078

  11. A Rat Excised Larynx Model of Vocal Fold Scar

    ERIC Educational Resources Information Center

    Welham, Nathan V.; Montequin, Douglas W.; Tateya, Ichiro; Tateya, Tomoko; Choi, Seong Hee; Bless, Diane M.

    2009-01-01

    Purpose: To develop and evaluate a rat excised larynx model for the measurement of acoustic, aerodynamic, and vocal fold vibratory changes resulting from vocal fold scar. Method: Twenty-four 4-month-old male Sprague-Dawley rats were assigned to 1 of 4 experimental groups: chronic vocal fold scar, chronic vocal fold scar treated with 100-ng basic…

  12. A Rat Excised Larynx Model of Vocal Fold Scar

    ERIC Educational Resources Information Center

    Welham, Nathan V.; Montequin, Douglas W.; Tateya, Ichiro; Tateya, Tomoko; Choi, Seong Hee; Bless, Diane M.

    2009-01-01

    Purpose: To develop and evaluate a rat excised larynx model for the measurement of acoustic, aerodynamic, and vocal fold vibratory changes resulting from vocal fold scar. Method: Twenty-four 4-month-old male Sprague-Dawley rats were assigned to 1 of 4 experimental groups: chronic vocal fold scar, chronic vocal fold scar treated with 100-ng basic…

  13. Spaceflight alters bone mechanics and modeling drifts in growing rats.

    PubMed

    Vajda, E G; Wronski, T J; Halloran, B P; Bachus, K N; Miller, S C

    2001-08-01

    Alterations in bone metabolism may be a particularly serious consequence of spaceflight and a major obstacle to long-term space exploration. The effects of spaceflight on bone mechanics are unclear. This study examined the effects of spaceflight on bone mechanics in a growing rat model during a 17-d mission aboard the space shuttle (STS-78). There were 18 rats that were divided into 3 experimental groups: flight rats (n = 6), ground-based control rats housed in an animal enclosure module (AEM, n = 6), and ground-based control rats housed in standard vivarium caging (n = 6). At the conclusion of the mission, rat femurs were tested in three-point bending followed by static and dynamic bone histomorphometry. Maximum stress was unaffected by spaceflight, but flexural rigidity was significantly decreased in flight animals. Much of the decrease appeared to be the result of decreases in tissue properties (elastic modulus) rather than structural changes within the bone. No significant differences in cortical bone mass or geometry were observed. In contrast, endocortical resorption was significantly decreased in flight rats accompanied by a nonsignificant decrease in periosteal bone formation, suggesting alterations in bone modeling drifts during spaceflight. For nearly all measured indices, ground-based AEM rats displayed values intermediate to flight and ground-based vivarium rats. Spaceflight can impair tissue properties in femoral cortical bone during growth without significant decreases in bone mass or geometry.

  14. Generation of TALEN-mediated FH knockout rat model.

    PubMed

    Yu, Dandan; Zhong, Yali; Li, Xiaoran; Li, Yaqing; Li, Xiaoli; Cao, Jing; Fan, Zhirui; Fan, Huijie; Yuan, Long; Xu, Benling; Yuan, Yuan; Zhang, Hongquan; Ji, Zhenyu; Wen, Jian-Guo; Zhang, Mingzhi; Nesland, Jahn M; Suo, Zhenhe

    2016-09-20

    Transcription activator-like effector nucleases (TALENs) are valuable tools for precise genome engineering of laboratory animals. Here we utilized this technique for efficient site-specific gene modification to create a fumarate hydratase (FH) gene knockout rat model, in which there was an 11 base-pair deletion in the first exon of the FH gene in 111 rats. 18 live-born targeted mutation offsprings were produced from 80 injected zygotes with 22.5% efficiency, indicating high TALEN knockout success in rat zygots. Only heterozygous deletion was observed in the offsprings. Sixteen pairs of heterozygous FH knockout (FH+/-) rats were arranged for mating experiments for six months without any homozygous KO rat identified. Sequencing from the pregnant rats embryo samples showed no homozygous FH KO, indicating that homozygous FH KO is embryonically lethal. Comparatively, the litter size was decreased in both male and female FH+/- KO rats. There was no behaviour difference between the FH+/- KO and the control rats except that the FH+/- KO male rats showed significantly higher body weight in the 16-week observation period. Clinical haematology and biochemical examinations showed hematopoietic and kidney dysfunction in the FH+/- KO rats. Small foci of anaplastic lesions of tubular epithelial cells around glomeruli were identified in the FH+/- kidney, and these anaplastic cells were comparatively positive for Ki67, p53 and Sox9, and such findings are most probably related to the kidney dysfunction reflected by the biochemical examinations of the rats. In conclusion, we have successfully established an FH+/- KO rat model, which will be useful for further functional FH studies.

  15. Generation of TALEN-mediated FH knockout rat model

    PubMed Central

    Yu, Dandan; Zhong, Yali; Li, Xiaoran; Li, Yaqing; Li, Xiaoli; Cao, Jing; Fan, Zhirui; Fan, Huijie; Yuan, Long; Xu, Benling; Yuan, Yuan; Zhang, Hongquan; Ji, Zhenyu; Wen, Jian-Guo; Zhang, Mingzhi; Nesland, Jahn M.; Suo, Zhenhe

    2016-01-01

    Transcription activator-like effector nucleases (TALENs) are valuable tools for precise genome engineering of laboratory animals. Here we utilized this technique for efficient site-specific gene modification to create a fumarate hydratase (FH) gene knockout rat model, in which there was an 11 base-pair deletion in the first exon of the FH gene in 111 rats. 18 live-born targeted mutation offsprings were produced from 80 injected zygotes with 22.5% efficiency, indicating high TALEN knockout success in rat zygots. Only heterozygous deletion was observed in the offsprings. Sixteen pairs of heterozygous FH knockout (FH+/−) rats were arranged for mating experiments for six months without any homozygous KO rat identified. Sequencing from the pregnant rats embryo samples showed no homozygous FH KO, indicating that homozygous FH KO is embryonically lethal. Comparatively, the litter size was decreased in both male and female FH+/− KO rats. There was no behaviour difference between the FH+/− KO and the control rats except that the FH+/− KO male rats showed significantly higher body weight in the 16-week observation period. Clinical haematology and biochemical examinations showed hematopoietic and kidney dysfunction in the FH+/− KO rats. Small foci of anaplastic lesions of tubular epithelial cells around glomeruli were identified in the FH+/− kidney, and these anaplastic cells were comparatively positive for Ki67, p53 and Sox9, and such findings are most probably related to the kidney dysfunction reflected by the biochemical examinations of the rats. In conclusion, we have successfully established an FH+/− KO rat model, which will be useful for further functional FH studies. PMID:27556703

  16. A novel rat model with obesity-associated retinal degeneration.

    PubMed

    Reddy, Geereddy Bhanuprakash; Vasireddy, Vidyullatha; Mandal, Md Nawajes A; Tiruvalluru, Mrudula; Wang, Xiaofei F; Jablonski, Monica M; Nappanveettil, Giridharan; Ayyagari, Radha

    2009-07-01

    A strong association between retinal degeneration and obesity has been shown in humans. However, the molecular basis of increased risk for retinal degeneration in obesity is unknown. Thus, an animal model with obesity and retinal degeneration would greatly aid the understanding of obesity-associated retinal degeneration. The retinal abnormalities in a novel rat model (WNIN-Ob) with spontaneously developed obesity are described. Histologic and immunohistochemical examination were performed on retinal sections of 2- to 12-month-old WNIN-Ob rats, and findings were compared with those of lean littermate controls. RNA from retinas of 12-month-old WNIN-Ob and lean littermate rats was used for microarray and qRT-PCR analysis. The WNIN-Ob rats developed severe obesity, with an onset at approximately 35 days. Evaluation of retinal morphology in 2- to 12-month-old WNIN-Ob and age-matched lean littermate controls revealed progressive retinal degeneration, with an onset between 4 to 6 months of age. Immunohistochemical analysis with anti-rhodopsin, anti-cone opsin, and PSD-95 antibodies further confirmed retinal degeneration, particularly rod cell loss and thinner outer plexiform layer, in the obese rat retina. Gene expression by microarray analysis and qRT-PCR established activation of stress response, tissue remodeling, impaired phototransduction, and photoreceptor degeneration in WNIN-Ob rat retina. WNIN-Ob rats develop increased stress in retinal tissue and progressive retinal degeneration after the onset of severe obesity. The WNIN-Ob rat is the first rat model to develop retinal degeneration after the onset of obesity. This novel rat model may be a valuable tool for investigating retinal degeneration associated with obesity in humans.

  17. Leptin Influences Healing in the Sprague Dawley Rat Fracture Model

    PubMed Central

    Liu, Pengcheng; Cai, Ming

    2017-01-01

    Background Leptin plays a crucial role in bone metabolism, and its level is related to bone callus formation in the fracture repair process. The objective of this study was to evaluate the effect of recombinant leptin on the healing process of femoral fractures in rats. Material/Methods Forty-eight male Sprague Dawley (SD) rats with an average body weight of 389 g (range: 376–398 g) and an average age of 10 weeks were included in this animal research, and all rats were randomly divided into two major groups. Then standardized femur fracture models were implemented in all SD rats. Rats in the control group were treated with only 0.5 mL of physiological saline, and rats in the experimental group were treated with recombinant leptin 5 μg/kg/d along with the same 0.5 mL of physiological saline for 42 days intraperitoneally. At the same time, each major group was evenly divided into three parallel subgroups for each parallel bone evaluation separately at the second, fourth, and sixth weeks. Each subgroup included eight rats. Results The total radiological evaluation results showed that the healing progress of femoral fracture in the experimental group was superior to that in the control group from the fourth week. At the sixth week, experimental group rats began to present significantly better femoral fracture healing progress than that of the control group rats. Results of biomechanics show the ultimate load (N) and deflection ultimate load (mm) of the experimental group rats was significantly increased compared with that of the control group rats from the fourth week. Conclusions Our results suggest that leptin may have a positive effect on SD rat femur fracture healing. PMID:28088810

  18. Hemodiafiltration combined with resin-mediated absorption as a therapy for hyperlipidemic acute pancreatitis.

    PubMed

    Li, Mao-qin; Shi, Zai-xiang; Xu, Ji-yuan; Lu, Bo; Li, Jia-qiong; Xu, Yan-jun; Wang, Xiao-Meng; Li, Song-mei; Mo, Xun

    2014-07-01

    The aim of this study is to investigate whether hemodiafiltration combined with resin-mediated absorption is a better therapy for hyperlipidemic acute pancreatitis. Patients (n = 67) with acute pancreatitis treated in ICU from January 2009 to December 2012 were included in this study. Seven of these 67 cases were diagnosed hyperlipidemic acute pancreatitis (HLAP). All the 7 HLAP patients went through fast, gastrointestinal decompression, anti-shock treatment, inhibition of pancreatic secretion, antiseptic treatments, and hemoperfusion (HP) combined with continuous veno venous hemodiafiltration (CVVHDF). After one round of treatment by resin adsorption, there was a significant decrease in serum triglycerides (TG) (29.78 %) and total cholesterol (TC) (24.02 %) levels (p < 0.01). TG and TC levels dropped by 49.02 and 37.66 %, respectively, after 1-day treatment of HP + CVVHDF; by 62.81 and 47.37 % on day 2 post-treatment; and by 69.57 and 49.47 % on day 3 post-treatment. All the 7 patients survived. The average time spent in the ICU was 7 ± 3.8 days, and the average duration of hospitalization was 19 ± 15.1 days. Our results show that hemoperfusion combined with hemodiafiltration is an efficient treatment as this approach can reduce plasma lipid levels effectively and reduce the risk of acute pancreatitis due to hyperlipidemia.

  19. L-4F Alters Hyperlipidemic (but not Normal) Mouse Plasma to Reduce Platelet Aggregation

    PubMed Central

    Buga, Georgette M.; Navab, Mohamad; Imaizumi, Satoshi; Reddy, Srinivasa T.; Yekta, Babak; Hough, Greg; Chanslor, Shawn; Anantharamaiah, G.M.; Fogelman, Alan M.

    2010-01-01

    Objective Hyperlipidemia is associated with platelet hyper-reactivity. We hypothesized that L-4F, an apoA-I mimetic peptide, would inhibit platelet aggregation in hyperlipidemic mice. Methods and Results Injecting L-4F into apoE null and LDL receptor null mice resulted in a significant reduction in platelet aggregation in response to agonists but there was no reduction in platelet aggregation after injection of L-4F into wild-type (WT) mice. Consistent with these results, injection of L-4F into apoE null mice prolonged bleeding time but not in WT mice. Incubating L-4F in vitro with apoE null platelet rich plasma also resulted in decreased platelet aggregation. However, incubating washed platelets from either apoE null or WT mice with L-4F did not alter aggregation. Compared to wild-type mice, unstimulated platelets from apoE null mice contained significantly more 12-HETE, thromboxane A2 (TXA2), prostaglandins D2 (PGD2) and E2 (PGE2). In response to agonists, platelets from L-4F treated apoE null mice formed significantly less TXA2, PGD2 PGE2, and 12-HETE. Conclusions By binding plasma oxidized lipids that cause platelet hyper-reactivity in hyperlipidemic mice, L-4F decreases platelet aggregation. PMID:19965777

  20. Transplant arteriosclerosis in a rat aortic model.

    PubMed Central

    Isik, F. F.; McDonald, T. O.; Ferguson, M.; Yamanaka, E.; Gordon, D.

    1992-01-01

    Transplant arteriosclerosis (TA) has emerged as an obstacle to the long-term survival of transplanted organs, especially cardiac transplants. The animal models that have been used to study TA have not been fully characterized with regard to features such as the time course of cell proliferation and the sequence of cell types arriving in the developing intimal lesion. We present a model of TA based on a transplanted segment of abdominal aorta that helps address these questions. Two strains of rats (PVG x DA) underwent orthotopic aortic transplantation without immunosuppression and were killed at 14, 20, 40, and 60 days after transplantation. The within-strain control group displayed minimal evidence of cellular rejection with minimal to absent intimal lesions. In contrast, the allograft group showed a linearly increasing intimal lesion, up through 60 days after transplantation. The mechanism of intimal thickening was by an increase in cell number at the earlier time points with the later deposition of extracellular matrix. The early intimal lesion consisted mostly of mononuclear inflammatory cells (45%) with gradually increasing presence of smooth muscle cells (SMC) in the intima between 20 and 60 days. Conversely, the media showed gradual infiltration by macrophage-type cells with virtual loss of all SMC from the media by 40 days. The proliferative index showed a peak of 6% and 8% at 20 days in both the intima and media, respectively, and was preceded by the presence of macrophages. In fact, most of the proliferating cells at the earlier time points were either monocytes/macrophages, or were immediately adjacent to monocyte-/macrophage-rich regions. This straight artery segment model of transplant arteriosclerosis provides an easily quantifiable system in which the effects of different interventions (e.g., immunosuppressive regimens) can be tested. Images Figure 2 Figure 3 Figure 6 Figure 7 Figure 8 Figure 9 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure

  1. Effects of garlicin on apoptosis in rat model of colitis

    PubMed Central

    Xu, Xi-Ming; Yu, Jie-Ping; He, Xiao-Fei; Li, Jun-Hua; Yu, Liang-Liang; Yu, Hong-Gang

    2005-01-01

    AIM: To investigate the effects of garlicin on apoptosis and expression of bcl-2 and bax in lymphocytes in rat model of ulcerative colitis (UC). METHODS: Healthy adult Sprague-Dawley rats of both sexes, weighing 180±30 g, were employed in the present study. The rat model of UC was induced by 2,4,6-trinitr-obenzene sulfonic acid (TNBS) enema. The experimental animals were randomly divided into garlicin treatment group (including high and low concentration), model control group, and normal control group. Rats in garlicin treatment group and model control group received intracolic garlicin daily at doses of 10.0 and 30.0 mg/kg and equal amount of saline respectively 24 h after colitis model was induced by alcohol and TNBS co-enema. Rats in normal control group received neither alcohol nor only TNBS but only saline enema in this study. On the 28th d of the experiment, rats were executed, the expression of bcl-2 and bax protein was determined immunohistochemically and the apoptotic cells were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method. At the same time, the rat colon mucosal damage index (CMDI) was calculated. RESULTS: In garlicin treatment group, the positive expression of bcl-2 in lymphocytes decreased and the number of apoptotic cells was more than that in model control group, CMDI was lower than that in model control group. The positive expression of bax in lymphocytes had no significant difference. CONCLUSION: Garlicin can protect colonic mucosa against damage in rat model of UC induced by TNBS enema. PMID:16052692

  2. Effects of garlicin on apoptosis in rat model of colitis.

    PubMed

    Xu, Xi-Ming; Yu, Jie-Ping; He, Xiao-Fei; Li, Jun-Hua; Yu, Liang-Liang; Yu, Hong-Gang

    2005-08-07

    To investigate the effects of garlicin on apoptosis and expression of bcl-2 and bax in lymphocytes in rat model of ulcerative colitis (UC). Healthy adult Sprague-Dawley rats of both sexes, weighing 180+/-30 g, were employed in the present study. The rat model of UC was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) enema. The experimental animals were randomly divided into garlicin treatment group (including high and low concentration), model control group, and normal control group. Rats in garlicin treatment group and model control group received intracolic garlicin daily at doses of 10.0 and 30.0 mg/kg and equal amount of saline respectively 24 h after colitis model was induced by alcohol and TNBS co-enema. Rats in normal control group received neither alcohol nor only TNBS but only saline enema in this study. On the 28th d of the experiment, rats were executed, the expression of bcl-2 and bax protein was determined immunohistochemically and the apoptotic cells were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method. At the same time, the rat colon mucosal damage index (CMDI) was calculated. In garlicin treatment group, the positive expression of bcl-2 in lymphocytes decreased and the number of apoptotic cells was more than that in model control group, CMDI was lower than that in model control group. The positive expression of bax in lymphocytes had no significant difference. Garlicin can protect colonic mucosa against damage in rat model of UC induced by TNBS enema.

  3. Cloricromene effect on the enzyme activities of the tryptophan-nicotinic acid pathway in diabetic/hyperlipidemic rabbits.

    PubMed

    Ragazzi, Eugenio; Costa, Carlo V L; Comai, Stefano; Bertazzo, Antonella; Caparrotta, Laura; Allegri, Graziella

    2006-01-18

    Since alterations of tryptophan metabolism have been reported in diabetes and atherosclerosis, it was thought of interest to investigate any role of cloricromene through the influence on the oxidative metabolism of the amino acid by using diabetic/hyperlipidemic rabbits. Male 4-month-old New Zealand white rabbits, fed a diet enriched with 1% cholesterol and 10% corn oil, were made diabetic with alloxan. During the hyperlipidemic diet, a group of rabbits was treated with cloricromene (10 mg/kg/day subcutaneously plus 1.5 mg/kg/day intravenously, for 5 weeks). The other group received saline. Normometabolic New Zealand rabbits fed standard diet, treated or not with cloricromene, were used as control. The specific activities of liver tryptophan 2,3-dioxygenase and small intestine indole 2,3-dioxygenase were not significantly changed by the drug treatment. Also the specific activities of other enzymes of the kynurenine pathway in the liver and kidneys, specifically kynurenine 3-monooxygenase, kynureninase and kynurenine-oxoglutarate transaminase, did not show any significant difference in both tissues between the two groups of rabbits. On the contrary, 3-hydroxyanthranilate 3,4-dioxygenase activity in the liver of diabetic/hyperlipidemic rabbits and control rabbits treated with cloricromene showed a slight increase in comparison with untreated animals. Conversely, the specific activity of the enzyme in kidneys was not affected by the drug treatment in diabetic/hyperlipidemic animals but was reduced in controls. Aminocarboxymuconate-semialdehyde decarboxylase specific activity remained unchanged in the liver following cloricromene treatment, instead the specific activity of the enzyme in the kidneys of the diabetic/hyperlipidemic rabbits was significantly increased by the drug, with a value more than double in comparison to untreated animals. The activity of the scavenger enzyme Cu/Zn superoxide dismutase (Cu/Zn SOD) in the small intestine was also determined and found

  4. Transgenic Rat Models for Breast Cancer Research

    DTIC Science & Technology

    1997-10-01

    superovulated rats that results in our ability to recover about half of frozen embryos as viable pups after transfer into pseudopregnant recipient rats. This...However, there are many advantages to using morulae collected from females superovulated by treatment with FSH and LH. Most notably, the numbers of...potential for a higher number of embryos per female, superovulation , if successful, represents a large savings in animal costs and investigator time

  5. The Carbohydrate Sensitive Rat as a Model of Obesity

    PubMed Central

    Nadkarni, Nachiket A.; Chaumontet, Catherine; Azzout-Marniche, Dalila; Piedcoq, Julien; Fromentin, Gilles; Tomé, Daniel; Even, Patrick C.

    2013-01-01

    Background Sensitivity to obesity is highly variable in humans, and rats fed a high fat diet (HFD) are used as a model of this inhomogeneity. Energy expenditure components (basal metabolism, thermic effect of feeding, activity) and variations in substrate partitioning are possible factors underlying the variability. Unfortunately, in rats as in humans, results have often been inconclusive and measurements usually made after obesity onset, obscuring if metabolism was a cause or consequence. Additionally, the role of high carbohydrate diet (HCD) has seldom been studied. Methodology/Findings Rats (n=24) were fed for 3 weeks on HCD and then 3 weeks on HFD. Body composition was tracked by MRI and compared to energy expenditure components measured prior to obesity. Results: 1) under HFD, as expected, by adiposity rats were variable enough to be separable into relatively fat resistant (FR) and sensitive (FS) groups, 2) under HCD, and again by adiposity, rats were also variable enough to be separable into carbohydrate resistant (CR) and sensitive (CS) groups, the normal body weight of CS rats hiding viscerally-biased fat accumulation, 3) HCD adiposity sensitivity was not related to that under HFD, and both HCD and HFD adiposity sensitivities were not related to energy expenditure components (BMR, TEF, activity cost), and 4) only carbohydrate to fat partitioning in response to an HCD test meal was related to HCD-induced adiposity. Conclusions/Significance The rat model of human obesity is based on substantial variance in adiposity gains under HFD (FR/FS model). Here, since we also found this phenomenon under HCD, where it was also linked to an identifiable metabolic difference, we should consider the existence of another model: the carbohydrate resistant (CR) or sensitive (CS) rat. This new model is potentially complementary to the FR/FS model due to relatively greater visceral fat accumulation on a low fat high carbohydrate diet. PMID:23935869

  6. Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

    PubMed Central

    Okamura, Tadashi; Pei, Xiang Yuan; Miyoshi, Ichiro; Shimizu, Yukiko; Takanashi-Yanobu, Rieko; Mototani, Yasumasa; Kanai, Takao; Satoh, Jo; Kimura, Noriko; Kasai, Noriyuki

    2013-01-01

    Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA) rat derived from Long-Evans (LE) strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction of β-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus. PMID:23691528

  7. Spontaneous trigeminal allodynia in rats: a model of primary headache.

    PubMed

    Oshinsky, Michael L; Sanghvi, Menka M; Maxwell, Christina R; Gonzalez, Dorian; Spangenberg, Rebecca J; Cooper, Marnie; Silberstein, Stephen D

    2012-10-01

    Animal models are essential for studying the pathophysiology of headache disorders and as a screening tool for new therapies. Most animal models modify a normal animal in an attempt to mimic migraine symptoms. They require manipulation to activate the trigeminal nerve or dural nociceptors. At best, they are models of secondary headache. No existing model can address the fundamental question: How is a primary headache spontaneously initiated? In the process of obtaining baseline periorbital von Frey thresholds in a wild-type Sprague-Dawley rat, we discovered a rat with spontaneous episodic trigeminal allodynia (manifested by episodically changing periorbital pain threshold). Subsequent mating showed that the trait is inherited. Animals with spontaneous trigeminal allodynia allow us to study the pathophysiology of primary recurrent headache disorders. To validate this as a model for migraine, we tested the effects of clinically proven acute and preventive migraine treatments on spontaneous changes in rat periorbital sensitivity. Sumatriptan, ketorolac, and dihydroergotamine temporarily reversed the low periorbital pain thresholds. Thirty days of chronic valproic acid treatment prevented spontaneous changes in trigeminal allodynia. After discontinuation, the rats returned to their baseline of spontaneous episodic threshold changes. We also tested the effects of known chemical human migraine triggers. On days when the rats did not have allodynia and showed normal periorbital von Frey thresholds, glycerol trinitrate and calcitonin gene related peptide induced significant decreases in the periorbital pain threshold. This model can be used as a predictive model for drug development and for studies of putative biomarkers for headache diagnosis and treatment.

  8. Anti-hyperlipidemic effect of rice bran polysaccharide and its potential mechanism in high-fat diet mice.

    PubMed

    Nie, Ying; Luo, Feijun; Wang, Long; Yang, Tao; Shi, Limin; Li, Xinhua; Shen, Junjun; Xu, Wei; Guo, Ting; Lin, Qinlu

    2017-09-04

    Hyperlipidemia occurs very often in modern society along with a high calorie intake and is regarded as one of the greatest risk factors for the prevalence of cardiac vascular disease (CVD). In this study, we investigated the anti-hyperlipidemic effect of the rice bran polysaccharides (RBP) and its mechanism in a high fat diet animal model. 60 ICR mice were randomly divided into 3 groups, which included Control, HFD (high fat diet) and HFD + RBP, and each group included 20 mice. The control group was fed with a standard diet while the other two groups were fed with HFD. In addition, the HFD + RBP group was fed with 500 mg kg(-1) of rice bran polysaccharides by intragastric administration while the other two groups were intragastrically administered with water. The results showed that RBP treatment for 10 weeks obviously decreased the body weight, liver weight and adipose tissues of mice; and it decreased the levels of total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-c) in the plasma. H&E staining of the liver tissues showed that RBP treatment decreased the size of fat droplets compared with the HFD group. Microarray analysis revealed that RBP treatment results in 80 genes being up-regulated while 72 genes were down-regulated in the tissues of liver. IPA software analysis suggested that NF-κB may play a vital role in the lipid-lowering effect of RBP. Real-time quantitative PCR confirmed that the mRNA levels of PPAR-α, PPAR-γ, PPAR-δ, SREBP-1C, FASN, ACC, SIRT and CD36, which are related to lipid metabolism, were significantly regulated by RBP supplementation compared to HFD. The western blot analysis further confirmed these altered expressions after RBP treatment. Taken together, these results suggest that the oral administration of RBP exerts lipid-lowering in high fat diet mice via regulating the lipid metabolism-related gene expression.

  9. Scavenger receptor function of mouse Fcγ receptor III contributes to progression of atherosclerosis in apolipoprotein E hyperlipidemic mice.

    PubMed

    Zhu, Xinmei; Ng, Hang Pong; Lai, Yen-Chun; Craigo, Jodi K; Nagilla, Pruthvi S; Raghani, Pooja; Nagarajan, Shanmugam

    2014-09-01

    Recent studies showed loss of CD36 or scavenger receptor-AI/II (SR-A) does not ameliorate atherosclerosis in a hyperlipidemic mouse model, suggesting receptors other than CD36 and SR-A may also contribute to atherosclerosis. In this report, we show that apolipoprotein E (apoE)-CD16 double knockout (DKO; apoE-CD16 DKO) mice have reduced atherosclerotic lesions compared with apoE knockout mice. In vivo and in vitro foam cell analyses showed apoE-CD16 DKO macrophages accumulated less neutral lipids. Reduced foam cell formation in apoE-CD16 DKO mice is not due to change in expression of CD36, SR-A, and LOX-1. This led to a hypothesis that CD16 may have scavenger receptor activity. We presented evidence that a soluble form of recombinant mouse CD16 (sCD16) bound to malondialdehyde-modified low-density lipoprotein (MDALDL), and this binding is blocked by molar excess of MDA- modified BSA and anti-MDA mAbs, suggesting CD16 specifically recognizes MDA epitopes. Interestingly, sCD16 inhibited MDALDL binding to macrophage cell line, as well as soluble forms of recombinant mouse CD36, SR-A, and LOX-1, indicating CD16 can cross-block MDALDL binding to other scavenger receptors. Anti-CD16 mAb inhibited immune complex binding to sCD16, whereas it partially inhibited MDALDL binding to sCD16, suggesting MDALDL binding site may be in close proximity to the immune complex binding site in CD16. Loss of CD16 expression resulted in reduced levels of MDALDL-induced proinflammatory cytokine expression. Finally, CD16-deficient macrophages showed reduced MDALDL-induced Syk phosphorylation. Collectively, our findings suggest scavenger receptor activity of CD16 may, in part, contribute to the progression of atherosclerosis.

  10. Novel rat model for neurocysticercosis using Taenia solium.

    PubMed

    Verastegui, Manuela R; Mejia, Alan; Clark, Taryn; Gavidia, Cesar M; Mamani, Javier; Ccopa, Fredy; Angulo, Noelia; Chile, Nancy; Carmen, Rogger; Medina, Roxana; García, Hector H; Rodriguez, Silvia; Ortega, Ynes; Gilman, Robert H

    2015-08-01

    Neurocysticercosis is caused by Taenia solium infecting the central nervous system and is the leading cause of acquired epilepsy and convulsive conditions worldwide. Research into the pathophysiology of the disease and appropriate treatment is hindered by lack of cost-effective and physiologically similar animal models. We generated a novel rat neurocysticercosis model using intracranial infection with activated T. solium oncospheres. Holtzman rats were infected in two separate groups: the first group was inoculated extraparenchymally and the second intraparenchymally, with different doses of activated oncospheres. The groups were evaluated at three different ages. Histologic examination of the tissue surrounding T. solium cysticerci was performed. Results indicate that generally infected rats developed cysticerci in the brain tissue after 4 months, and the cysticerci were observed in the parenchymal, ventricle, or submeningeal brain tissue. The route of infection did not have a statistically significant effect on the proportion of rats that developed cysticerci, and there was no dependence on infection dose. However, rat age was crucial to the success of the infection. Epilepsy was observed in 9% of rats with neurocysticercosis. In histologic examination, a layer of collagen tissue, inflammatory infiltrate cells, perivascular infiltrate, angiogenesis, spongy change, and mass effect were observed in the tissue surrounding the cysts. This study presents a suitable animal model for the study of human neurocysticercosis. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  11. Animal models of dystonia: Lessons from a mutant rat.

    PubMed

    LeDoux, Mark S

    2011-05-01

    Dystonia is a motor sign characterized by involuntary muscle contractions which produce abnormal postures. Genetic factors contribute significantly to primary dystonia. In comparison, secondary dystonia can be caused by a wide variety of metabolic, structural, infectious, toxic and inflammatory insults to the nervous system. Although classically ascribed to dysfunction of the basal ganglia, studies of diverse animal models have pointed out that dystonia is a network disorder with important contributions from abnormal olivocerebellar signaling. In particular, work with the dystonic (dt) rat has engendered dramatic paradigm shifts in dystonia research. The dt rat manifests generalized dystonia caused by deficiency of the neuronally restricted protein caytaxin. Electrophysiological and biochemical studies have shown that defects at the climbing fiber-Purkinje cell synapse in the dt rat lead to abnormal bursting firing patterns in the cerebellar nuclei, which increases linearly with postnatal age. In a general sense, the dt rat has shown the scientific and clinical communities that dystonia can arise from dysfunctional cerebellar cortex. Furthermore, work with the dt rat has provided evidence that dystonia (1) is a neurodevelopmental network disorder and (2) can be driven by abnormal cerebellar output. In large part, work with other animal models has expanded upon studies in the dt rat and shown that primary dystonia is a multi-nodal network disorder associated with defective sensorimotor integration. In addition, experiments in genetically engineered models have been used to examine the underlying cellular pathologies that drive primary dystonia. This article is part of a Special Issue entitled "Advances in dystonia".

  12. Surgical Intervention to Rescue Hirschsprung Disease in a Rat Model.

    PubMed

    Stamp, Lincon A; Obermayr, Florian; Pontell, Louise; Young, Heather M; Xie, Dan; Croaker, David H; Song, Zan-Min; Furness, John B

    2015-10-01

    Rats with a spontaneous null mutation in endothelin receptor type B or Ednrb (sl/sl; spotting lethal) lack enteric neurons in the distal bowel and usually die within the first week after birth. This early postnatal lethality limits their use for examining the potential of cell therapy to treat Hirschsprung disease, and for studies of the influence of EDNRB on the mature CNS and vascular systems. We have developed a surgical intervention to prolong the life of the spotting lethal sl/sl rat, in which we perform a colostomy on postnatal (P) day 4-6 rats to avoid the fatal obstruction caused by the lack of colonic enteric neurons. The stomas remained patent and functional and the rats matured normally following surgery. Weight gains were comparable between control and Hirschsprung phenotype (sl/sl) rats, which were followed until 4 weeks after surgery (5 weeks old). We confirmed the absence of enteric neurons in the distal colon of rats whose lives were saved by the surgical intervention. This study provides a novel approach for studying EDNRB signalling in multiple organ systems in mature rats, including an animal model to study the efficacy of cell therapy to treat Hirschsprung disease.

  13. Surgical Intervention to Rescue Hirschsprung Disease in a Rat Model

    PubMed Central

    Stamp, Lincon A; Obermayr, Florian; Pontell, Louise; Young, Heather M; Xie, Dan; Croaker, David H; Song, Zan-Min; Furness, John B

    2015-01-01

    Background/Aims Rats with a spontaneous null mutation in endothelin receptor type B or Ednrb (sl/sl; spotting lethal) lack enteric neurons in the distal bowel and usually die within the first week after birth. This early postnatal lethality limits their use for examining the potential of cell therapy to treat Hirschsprung disease, and for studies of the influence of EDNRB on the mature CNS and vascular systems. Methods We have developed a surgical intervention to prolong the life of the spotting lethal sl/sl rat, in which we perform a colostomy on postnatal (P) day 4–6 rats to avoid the fatal obstruction caused by the lack of colonic enteric neurons. Results The stomas remained patent and functional and the rats matured normally following surgery. Weight gains were comparable between control and Hirschsprung phenotype (sl/sl) rats, which were followed until 4 weeks after surgery (5 weeks old). We confirmed the absence of enteric neurons in the distal colon of rats whose lives were saved by the surgical intervention. Conclusions This study provides a novel approach for studying EDNRB signalling in multiple organ systems in mature rats, including an animal model to study the efficacy of cell therapy to treat Hirschsprung disease. PMID:26424040

  14. Chinese medicinal herbs in treating model rats with hepatic fibrosis.

    PubMed

    Zhou, Yun-Xiao; Chen, Jiu; Li, Jian-Ping; Wang, Yan-Li; Jin, Xiao-Dong

    2009-12-30

    The objective of this study was to examine the effects of Chinese medicine formula-Yu Zhang Dan (YZD, composed of Herba Lysimachiae, Rhizoma Polygoni Cuspidati, Radix Curcumae) on the model rats with hepatic fibrosis. Forty male Sprague-Dawley (SD) rats were used in the present study, and they were separated randomly into 4 groups: a normal control group (Group A, n=5), a model control (Group B, n=15), a high dose of YZD (Group C, n=10), and a low dose of YZD (Group D, n=10). Hepatic fibrosis in rats was induced by carbon tetrachloride (CCl(4)). The variation of the serum alanine transaminase (ALT), aspartate aminotransferase (AST), hyaluronate acid (HA), laminin (LN), type • • procollagen peptide (P• •NP), L-Glutathione (GSH) was respectively measured with radioimmunoassay (RIA) and detection of transforming growth factor-beta 1 (TGF-β1) and smooth muscle alpha actin (α-SMA) was conducted with immunohistochemistry. The ALT, AST HA, LN and PIII NP levels in the serum of the model control group were significantly higher than those of the normal control group (P<0.05), and both of the high dose of YZD and low dose of YZD significantly decreased the ALT, AST HA, LN and PIII NP levels of the model rats (P<0.05). The TGF-β1 and α-SMA levels of the model control group were significantly higher than those of the normal control group (P<0.05), and both of the high dose of YZD and low dose of YZD significantly decreased the TGF-β1 levels of the model rats (P<0.05) , and only the high dose of YZD significantly decreased the α-SMA levels of the model rats (P<0.05). The expression of TGF-β1 and α-SMA in the liver tissues of the rats were in the cytoplasm of the cells. It may be through decreasing the ALT, AST, HA, LN and PIII NP levels in the serum of the model rats and decreasing the expression of TGF-β1 and α-SMA in the liver tissues of the model rats that YZD significantly relieved the hepatic fibrosis.

  15. A novel model of invasive fungal rhinosinusitis in rats.

    PubMed

    Zhang, Fang; An, Yunfang; Li, Zeqing; Zhao, Changqing

    2013-01-01

    Invasive fungal rhinosinusitis (IFRS) is a life-threatening inflammatory disease that affects immunocompromised patients, but animal models of the disease are scarce. This study aimed to develop an IFRS model in neutropenic rats. The model was established in three consecutive steps: unilateral nasal obstruction with Merocel sponges, followed by administration of cyclophosphamide (CPA), and, finally, nasal inoculation with Aspergillus fumigatus. Fifty healthy Wistar rats were randomly divided into five groups, with group I as the controls, group II undergoing unilateral nasal obstruction alone, group III undergoing nasal obstruction with fungal inoculation, group IV undergoing nasal obstruction with administration of CPA, and group V undergoing nasal obstruction with administration of CPA and fungal inoculation. Hematology, histology, and mycology investigations were performed. The changes in the rat absolute neutrophil counts (ANCs) were statistically different across the groups. The administration of CPA decreased the ANCs, whereas nasal obstruction with fungal inoculation increased the ANCs, and nasal obstruction did not change them. Histological examination of the rats in group V revealed the hyphal invasion of sinus mucosa and bone, thrombosis, and tissue infarction. No pathology indicative of IFRS was observed in the remaining groups. Positive rates of fungal culture in tissue homogenates from the maxillary sinus (62.5%) and lung (25%) were found in group V, whereas groups I, II, III, and IV showed no fungal culture in the homogenates. A rat IFRS model was successfully developed through nasal obstruction, CPA-induced neutropenia, and fungal inoculation. The disease model closely mimics the pathophysiology of anthropic IFRS.

  16. Development of a Rat Model of Hypothermia

    DTIC Science & Technology

    2005-06-01

    Fall and MAJ Len Murray and their animal care technicians, SGT Jeffrey Hunter, SPC Robert Powers and SPC Melissa Valliere vi EXECUTIVE SUMMARY... Bastille . Tissue-specific extravasation of albumin-bound Evans blue in hypothermic and rewarmed rats. Can. J. Physiol. Pharmacol. 80:233-243, 2002

  17. Transgenic Rat Models for Breast Cancer Research

    DTIC Science & Technology

    1998-10-01

    production of embryos for cryopreservation can be accomplished by superovulation regimens in which FSH and LH are administered to the female rat prior to...when transferred into pseudopregnant recipients. In the past year, we have determined that the superovulation and cryopreservation procedures that we

  18. Pharmacodynamic model for chemotherapy-induced anemia in rats.

    PubMed

    Woo, Sukyung; Krzyzanski, Wojciech; Jusko, William J

    2008-06-01

    Anticancer agents often cause bone marrow toxicity resulting in progressive anemia which may influence the therapeutic effects of erythropoietic-stimulating agents. The objective of this study was to develop a pharmacodynamic (PD) model to describe chemotherapy-induced anemia in rats. Anemia was induced in male Wistar rats with a single intravenous (i.v.) injection of 60 mg/kg carboplatin. Hematological responses including reticulocytes, red blood cells (RBC), hemoglobin, and endogenous rat erythropoietin (EPO) were measured for up to 4 weeks. A catenary, lifespan-based, indirect response model served as a basic PD model to represent erythroid cellular populations in the bone marrow and blood involved in erythropoiesis. The model assumed that actively proliferating progenitor cells in the bone marrow are sensitive to anti-cancer agents and subject to an irreversible removal process. The removal rate of the target cells is proportional to drug activity concentrations and the cell numbers. An additional RBC loss from the circulation resulting from thrombocytopenia was described by a first-order process. The turnover process of rat EPO and EPO-mediated feedback inhibition mechanism regulated by hemoglobin changes were incorporated. Reticulocyte counts decreased rapidly and reached a nadir by day 3 after administration of carboplatin and returned to the baseline by day 13. This was followed by a gradual increase and the rebound peak occurred at about day 15. The hemoglobin nadir was approximately 9 g/dl observed at about 11-13 days compared to its normal value of 13 g/dl and hemoglobin returned to the baseline by day 30. The increase in endogenous rat EPO mirrored inversely hemoglobin changes and the maximum increase was observed soon after the hemoglobin nadir. The carboplatin-treated rats exhibited progressive anemia. The proposed model adequately described the time course of hematological changes after carboplatin in rats and can be a useful tool to explore

  19. A ternary model of decompression sickness in rats.

    PubMed

    Buzzacott, Peter; Lambrechts, Kate; Mazur, Aleksandra; Wang, Qiong; Papadopoulou, Virginie; Theron, Michael; Balestra, Costantino; Guerrero, François

    2014-12-01

    Decompression sickness (DCS) in rats is commonly modelled as a binary outcome. The present study aimed to develop a ternary model of predicting probability of DCS in rats, (as no-DCS, survivable-DCS or death), based upon the compression/decompression profile and physiological characteristics of each rat. A literature search identified dive profiles with outcomes no-DCS, survivable-DCS or death by DCS. Inclusion criteria were that at least one rat was represented in each DCS status, not treated with drugs or simulated ascent to altitude, that strain, sex, breathing gases and compression/decompression profile were described and that weight was reported. A dataset was compiled (n=1602 rats) from 15 studies using 22 dive profiles and two strains of both sexes. Inert gas pressures in five compartments were estimated. Using ordinal logistic regression, model-fit of the calibration dataset was optimised by maximum log likelihood. Two validation datasets assessed model robustness. In the interpolation dataset the model predicted 10/15 cases of nDCS, 3/3 sDCS and 2/2 dDCS, totalling 15/20 (75% accuracy) and 18.5/20 (92.5%) were within 95% confidence intervals. Mean weight in the extrapolation dataset was more than 2SD outside of the calibration dataset and the probability of each outcome was not predictable. This model is reliable for the prediction of DCS status providing the dive profile and rat characteristics are within the range of parameters used to optimise the model. The addition of data with a wider range of parameters should improve the applicability of the model. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Cerebral microbleeds in a neonatal rat model

    PubMed Central

    Carusillo Theriault, Brianna; Woo, Seung Kyoon; Karimy, Jason K.; Keledjian, Kaspar; Stokum, Jesse A.; Sarkar, Amrita; Coksaygan, Turhan; Ivanova, Svetlana; Gerzanich, Volodymyr

    2017-01-01

    Background In adult humans, cerebral microbleeds play important roles in neurodegenerative diseases but in neonates, the consequences of cerebral microbleeds are unknown. In rats, a single pro-angiogenic stimulus in utero predisposes to cerebral microbleeds after birth at term, a time when late oligodendrocyte progenitors (pre-oligodendrocytes) dominate in the rat brain. We hypothesized that two independent pro-angiogenic stimuli in utero would be associated with a high likelihood of perinatal microbleeds that would be severely damaging to white matter. Methods Pregnant Wistar rats were subjected to intrauterine ischemia (IUI) and low-dose maternal lipopolysaccharide (mLPS) at embryonic day (E) 19. Pups were born vaginally or abdominally at E21-22. Brains were evaluated for angiogenic markers, microhemorrhages, myelination and axonal development. Neurological function was assessed out to 6 weeks. Results mRNA (Vegf, Cd31, Mmp2, Mmp9, Timp1, Timp2) and protein (CD31, MMP2, MMP9) for angiogenic markers, in situ proteolytic activity, and collagen IV immunoreactivity were altered, consistent with an angiogenic response. Vaginally delivered pups exposed to prenatal IUI+mLPS had spontaneous cerebral microbleeds, abnormal neurological function, and dysmorphic, hypomyelinated white matter and axonopathy. Pups exposed to the same pro-angiogenic stimuli in utero but delivered abdominally had minimal cerebral microbleeds, preserved myelination and axonal development, and neurological function similar to naïve controls. Conclusions In rats, pro-angiogenic stimuli in utero can predispose to vascular fragility and lead to cerebral microbleeds. The study of microbleeds in the neonatal rat brain at full gestation may give insights into the consequences of microbleeds in human preterm infants during critical periods of white matter development. PMID:28158198

  1. Ototoxicity of boric acid powder in a rat animal model.

    PubMed

    Salihoglu, Murat; Dogru, Salim; Cesmeci, Enver; Caliskan, Halil; Kurt, Onuralp; Kuçukodaci, Zafer; Gungor, Atila

    2017-04-22

    Boric acid, which has antiseptic and acidic properties, is used to treat external and middle ear infections. However, we have not found any literature about the effect of boric acid powder on middle ear mucosa and inner ear. The purpose of this study is to investigate possible ototoxic effects of boric acid powder (BAP) on cochlear outer hair cell function and histological changes in middle ear mucosa in a rat animal model. Twenty healthy, mature Wistar albino rats were used in this study. The rats were divided into two groups, Group A and Group B, each of which consisted of 10 rats. Initially, the animals in each group underwent distortion product otoacoustic emissions (DPOAE) testing of their right and left ears. After the first DPOAE test, a surgical microscope was used to make a small perforation in both ears of the rats in each group, and a second DPOAE test was used to measure both ears in all of the rats. BAP was applied to the right middle ear of the rats using tympanic membrane perforation, and the DPOAEs were measured immediately after the BAP application. The histological changes and DPOAEs were evaluated three days later in Group A and 40 days later in Group B. No significant differences were found at all of the DPOAE frequencies. In Group A, mild inflammation of the middle ear mucosa was found on the third day after BAP application. In Group B, BAP caused mild inflammatory changes on the 40th day, which declined over time. Those changes did not lead to significant fibrosis within the mucosa. In rats, BAP causes mild inflammation in middle ear mucosa and it has no ototoxic effects on cochlear outer hair cell function in the inner ear of rats. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  2. Increased GABAB receptor signaling in a rat model for schizophrenia.

    PubMed

    Selten, Martijn M; Meyer, Francisca; Ba, Wei; Vallès, Astrid; Maas, Dorien A; Negwer, Moritz; Eijsink, Vivian D; van Vugt, Ruben W M; van Hulten, Josephus A; van Bakel, Nick H M; Roosen, Joey; van der Linden, Robert J; Schubert, Dirk; Verheij, Michel M M; Kasri, Nael Nadif; Martens, Gerard J M

    2016-09-30

    Schizophrenia is a complex disorder that affects cognitive function and has been linked, both in patients and animal models, to dysfunction of the GABAergic system. However, the pathophysiological consequences of this dysfunction are not well understood. Here, we examined the GABAergic system in an animal model displaying schizophrenia-relevant features, the apomorphine-susceptible (APO-SUS) rat and its phenotypic counterpart, the apomorphine-unsusceptible (APO-UNSUS) rat at postnatal day 20-22. We found changes in the expression of the GABA-synthesizing enzyme GAD67 specifically in the prelimbic- but not the infralimbic region of the medial prefrontal cortex (mPFC), indicative of reduced inhibitory function in this region in APO-SUS rats. While we did not observe changes in basal synaptic transmission onto LII/III pyramidal cells in the mPFC of APO-SUS compared to APO-UNSUS rats, we report reduced paired-pulse ratios at longer inter-stimulus intervals. The GABAB receptor antagonist CGP 55845 abolished this reduction, indicating that the decreased paired-pulse ratio was caused by increased GABAB signaling. Consistently, we find an increased expression of the GABAB1 receptor subunit in APO-SUS rats. Our data provide physiological evidence for increased presynaptic GABAB signaling in the mPFC of APO-SUS rats, further supporting an important role for the GABAergic system in the pathophysiology of schizophrenia.

  3. Mapping genetic determinants of kidney damage in rat models.

    PubMed

    Schulz, Angela; Kreutz, Reinhold

    2012-07-01

    During the last two decades, significant progress in our understanding of the development of kidney diseases has been achieved by unravelling the mechanisms underlying rare familial forms of human kidney diseases. Due to the genetic heterogeneity in human populations and the complex multifactorial pathogenesis of the disease phenotypes, the dissection of the genetic basis of common chronic kidney diseases (CKD) remains a difficult task. In this regard, several inbred rat models provide valuable complementary tools to uncover the genetic basis of complex renal disease phenotypes that are related to common forms of CKD. In this review, data obtained in nine experimental rat models, including the Buffalo (BUF), Dahl salt-sensitive (SS), Fawn-hooded hypertensive (FHH), Goto-Kakizaki (GK), Lyon hypertensive (LH), Munich Wistar Frömter (MWF), Sabra hypertension-prone (SBH), spontaneously hypertensive rat (SHR) and stroke-prone spontaneously hypertensive rat (SHRSP) inbred strains, that contributed to the genetic dissection of renal disease phenotypes are presented. In this panel of inbred strains, a large number of quantitative trait loci (QTL) linked to albuminuria/proteinuria and other functional or structural kidney abnormalities could be identified by QTL mapping analysis and follow-up studies including consomic and congenic rat lines. The comprehensive exploitation of the genotype-renal phenotype associations that are inherited in this panel of rat strains is suitable for making a significant contribution to the development of an integrated approach to the systems genetics of common CKD.

  4. Establishment of a rat model for canine necrotizing meningoencephalitis (NME).

    PubMed

    Park, E-S; Uchida, K; Nakayama, H

    2014-11-01

    The pathogenesis of necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis (NLE), and granulomatous meningoencephalomyelitis (GME) is still uncertain, although they are considered immune-mediated diseases. The purpose of the present study is to generate a rodent model(s) of these diseases. Rats were injected with rat cerebral or cerebellar homogenate. Rats injected with cerebral homogenate (Cbr) exhibited vacuolar or malacic changes mainly in the cerebral cortex. CD3-positive T cells and Iba-1-positive and CD163-negative microglia infiltrated and activated around the lesions. IgG deposited in the glial fibrillary acid protein (GFAP)-positive glia limitans from the early phase, and CD3-positive T cells attached to GFAP-positive astrocytes. Autoantibodies against GFAP were detected in the sera. These pathological features of Cbr rats were consistent with those of canine NME. In contrast, rats injected with cerebral homogenate (Cbe) exhibited demyelinating lesions with inflammatory reactions in the cerebellum, brainstem, and spinal cord. The presence of demyelination and autoantibodies against myelin proteins in Cbe rats was similar to murine experimental autoimmune encephalitis and differed from NME, NLE, and GME. All the present findings indicate that autoantibodies together with microglia and T cells may play a major role in the pathogenesis of idiopathic canine meningoencephalomyelitis. © The Author(s) 2014.

  5. Increased GABAB receptor signaling in a rat model for schizophrenia

    PubMed Central

    Selten, Martijn M.; Meyer, Francisca; Ba, Wei; Vallès, Astrid; Maas, Dorien A.; Negwer, Moritz; Eijsink, Vivian D.; van Vugt, Ruben W. M.; van Hulten, Josephus A.; van Bakel, Nick H. M.; Roosen, Joey; van der Linden, Robert J.; Schubert, Dirk; Verheij, Michel M. M.; Kasri, Nael Nadif; Martens, Gerard J. M.

    2016-01-01

    Schizophrenia is a complex disorder that affects cognitive function and has been linked, both in patients and animal models, to dysfunction of the GABAergic system. However, the pathophysiological consequences of this dysfunction are not well understood. Here, we examined the GABAergic system in an animal model displaying schizophrenia-relevant features, the apomorphine-susceptible (APO-SUS) rat and its phenotypic counterpart, the apomorphine-unsusceptible (APO-UNSUS) rat at postnatal day 20–22. We found changes in the expression of the GABA-synthesizing enzyme GAD67 specifically in the prelimbic- but not the infralimbic region of the medial prefrontal cortex (mPFC), indicative of reduced inhibitory function in this region in APO-SUS rats. While we did not observe changes in basal synaptic transmission onto LII/III pyramidal cells in the mPFC of APO-SUS compared to APO-UNSUS rats, we report reduced paired-pulse ratios at longer inter-stimulus intervals. The GABAB receptor antagonist CGP 55845 abolished this reduction, indicating that the decreased paired-pulse ratio was caused by increased GABAB signaling. Consistently, we find an increased expression of the GABAB1 receptor subunit in APO-SUS rats. Our data provide physiological evidence for increased presynaptic GABAB signaling in the mPFC of APO-SUS rats, further supporting an important role for the GABAergic system in the pathophysiology of schizophrenia. PMID:27687783

  6. Laryngeal transplantation in the setting of cancer: a rat model.

    PubMed

    Shipchandler, Taha Z; Lorenz, Robert R; Lee, Walter T; Teker, Aysenur Meric; Dan, Olivia; Strome, Marshall

    2008-12-01

    Traditional immunosuppressive regimens make laryngeal transplantation in cancer patients prohibitive because of the increased risk of recurrence. Everolimus, a recently developed immunosuppressant, has demonstrated significant antitumor properties. The purpose of this study was to examine the effects of everolimus alone and in combination with other immunosuppressants on tumor growth in a combined laryngeal transplantation and tumor model. Animal, prospective, randomized, controlled, and blinded. One million squamous cell carcinoma cells (SCC-158) were injected intravenously into a total of 40 rats 1 day before laryngeal transplantation. Rats were divided into four groups differing by immunosuppressive regimens. Lung surface metastases were counted 21 days after inoculation, and numerical transplantation rejection scores were recorded. A separate experiment for comparison was performed with no transplant on 24 rats, but with the same immunosuppressive treatment groups. The median number of lung surface metastases were: a) control (i.e., no immunosuppression): 85; b) everolimus 1.0 mg/kg: 25; c) tacrolimus 1.2 mg/kg: 1650; d) everolimus 1.0 mg/kg + tacrolimus 0.05 mg/kg: 1300. Rats receiving everolimus alone showed a statistically significant decrease in pulmonary surface metastases compared with the other groups. Transplanted rats had no difference in their outcomes when compared with non-transplanted rats. Everolimus significantly decreases SCC-158 growth in our combined transplantation and tumor model compared with controls and other immunosuppressants.

  7. A New Model of Severe Hemorrhagic Shock in Rats

    PubMed Central

    Rönn, Thomas; Lendemans, Sven; de Groot, Herbert; Petrat, Frank

    2011-01-01

    We here introduce a fixed-pressure model of hemorrhagic shock in rats that maximizes effects on mean arterial blood pressure (MAP) during shock and yet maintains high reproducibility and controllability. The MAP of rats was adjusted to 25 to 30 mm Hg by blood withdrawals during 30 min. After a shock period of 60 min, rats were resuscitated either with lactated Ringer solution (LR) only or with the collected blood 3-fold diluted with LR (LR + blood) and monitored for further 150 min. Throughout the experiment, vital parameters and plasma marker enzyme activities and creatinine concentration were assessed. Thereafter, liver, kidneys, small intestine, heart, and lung were harvested and evaluated histopathologically. Vital parameters, plasma marker enzyme activities, creatinine concentration, and histopathology indicated pronounced but reliable and reproducible systemic effects and marked organ damage due to hemorrhagic shock and resuscitation. In contrast to rats that received LR + blood, which survived the postresuscitation period, rats receiving LR only invariably died shortly after resuscitation. The hemorrhagic shock model we present here maximally affects MAP and yet is highly reproducible in rats, allowing the study of various aspects of hemorrhagic shock and resuscitation under clinically relevant conditions. PMID:22330349

  8. Detection of visual signals by rats: A computational model

    EPA Science Inventory

    We applied a neural network model of classical conditioning proposed by Schmajuk, Lam, and Gray (1996) to visual signal detection and discrimination tasks designed to assess sustained attention in rats (Bushnell, 1999). The model describes the animals’ expectation of receiving fo...

  9. Detection of visual signals by rats: A computational model

    EPA Science Inventory

    We applied a neural network model of classical conditioning proposed by Schmajuk, Lam, and Gray (1996) to visual signal detection and discrimination tasks designed to assess sustained attention in rats (Bushnell, 1999). The model describes the animals’ expectation of receiving fo...

  10. Modeling Alzheimer’s disease in transgenic rats

    PubMed Central

    2013-01-01

    Alzheimer’s disease (AD) is the most common form of dementia. At the diagnostic stage, the AD brain is characterized by the accumulation of extracellular amyloid plaques, intracellular neurofibrillary tangles and neuronal loss. Despite the large variety of therapeutic approaches, this condition remains incurable, since at the time of clinical diagnosis, the brain has already suffered irreversible and extensive damage. In recent years, it has become evident that AD starts decades prior to its clinical presentation. In this regard, transgenic animal models can shed much light on the mechanisms underlying this “pre-clinical” stage, enabling the identification and validation of new therapeutic targets. This paper summarizes the formidable efforts to create models mimicking the various aspects of AD pathology in the rat. Transgenic rat models offer distinctive advantages over mice. Rats are physiologically, genetically and morphologically closer to humans. More importantly, the rat has a well-characterized, rich behavioral display. Consequently, rat models of AD should allow a more sophisticated and accurate assessment of the impact of pathology and novel therapeutics on cognitive outcomes. PMID:24161192

  11. Terahertz reflectometry of burn wounds in a rat model

    PubMed Central

    Arbab, M. Hassan; Dickey, Trevor C.; Winebrenner, Dale P.; Chen, Antao; Klein, Mathew B.; Mourad, Pierre D.

    2011-01-01

    We present sub-millimeter wave reflectometry of an experimental rat skin burn model obtained by the Terahertz Time-Domain Spectroscopy (THz-TDS) technique. Full thickness burns, as confirmed by histology, were created on rats (n = 4) euthanized immediately prior to the experiments. Statistical analysis shows that the burned tissue exhibits higher reflectivity compared to normal skin over a frequency range between 0.5 and 0.7 THz (p < 0.05), likely due to post-burn formation of interstitial edema. Furthermore, we demonstrate that a double Debye dielectric relaxation model can be used to explain the terahertz response of both normal and less severely burned rat skin. Finally, our data suggest that the degree of conformation between the experimental burn measurements and the model for normal skin can potentially be used to infer the extent of burn severity. PMID:21833370

  12. Physiologically based pharmacokinetic modeling of deltamethrin: Development of a rat and human diffusion-limited model

    EPA Science Inventory

    Mirfazaelian et al. (2006) developed a physiologically based pharmacokinetic (PBPK) model for the pyrethroid pesticide deltamethrin in the rat. This model describes gastrointestinal tract absorption as a saturable process mediated by phase III efflux transporters which pump delta...

  13. Physiologically based pharmacokinetic modeling of deltamethrin: Development of a rat and human diffusion-limited model

    EPA Science Inventory

    Mirfazaelian et al. (2006) developed a physiologically based pharmacokinetic (PBPK) model for the pyrethroid pesticide deltamethrin in the rat. This model describes gastrointestinal tract absorption as a saturable process mediated by phase III efflux transporters which pump delta...

  14. Transgenic Rat Models for Breast Cancer Research

    DTIC Science & Technology

    1999-10-01

    Introduction 6 6. Body 9 7. Key Research Accomplishments 15 8. Reportable Outcomes 15 9. Conclusions 16 10. References 17 11. Bibliography 20 12. Personnel 20...seen in human breast cancer (2-4). Third, a high percentage of the resulting rat mammary cancers are hormonally responsiveness, closely mimicking that...13, 17), activated c-neu (18-20), wild type c-neu (21), deregulated growth hormone (22), and deregulated transforming growth factor a (23-25) has

  15. Morphofunctional analysis of experimental model of esophageal achalasia in rats.

    PubMed

    Sabirov, A G; Raginov, I S; Burmistrov, M V; Chelyshev, Y A; Khasanov, R Sh; Moroshek, A A; Grigoriev, P N; Zefirov, A L; Mukhamedyarov, M A

    2010-10-01

    We carried out a detailed analysis of rat model of esophageal achalasia previously developed by us. Manifest morphological and functional disorders were observed in experimental achalasia: hyperplasia of the squamous epithelium, reduced number of nerve fibers, excessive growth of fibrous connective tissue in the esophageal wall, high contractile activity of the lower esophageal sphincter, and reduced motility of the longitudinal muscle layer. Changes in rat esophagus observed in experimental achalasia largely correlate with those in esophageal achalasia in humans. Hence, our experimental model can be used for the development of new methods of disease treatment.

  16. Effect of young barley leaf extract and adlay on plasma lipids and LDL oxidation in hyperlipidemic smokers.

    PubMed

    Yu, Ya-Mei; Chang, Weng-Cheng; Liu, Chu-Sun; Tsai, Ching-Min

    2004-06-01

    Forty hyperlipidemic patients, smokers and non-smokers, were studied. Subjects received 15 g young barley leaf extract (BL) or 60 g adlay daily for four weeks. Overnight fasting blood samples were drawn immediately prior to and after four weeks of supplementation. Blood samples were analyzed for plasma lipid profiles and their susceptibility to low-density lipoprotein (LDL) oxidation. The plasma total and LDL-cholesterol (LDL-C) levels were reduced following treatment with either BL or adlay; furthermore, the lag phase of LDL oxidation increased after either supplementation. However, it seemed that BL had stronger antioxidative effect on the prevention of LDL oxidation than adlay. Our results also indicated that the antioxidative effect was less pronounced in smokers than in non-smokers. Therefore, supplementation with BL or adlay can decrease plasma lipids and inhibit LDL oxidation in hyperlipidemic smokers and/or non-smokers.

  17. Modeling Hypercalciuria in the Genetic Hypercalciuric Stone-Forming Rat

    PubMed Central

    Frick, Kevin K.; Krieger, Nancy S.; Bushinsky, David A.

    2015-01-01

    Purpose of Review In this review we discuss how the Genetic Hypercalciuric Stone-Forming (GHS) rats, which closely model idiopathic hypercalciuria and stone formation in humans, provide insights into the pathophysiology and consequences of clinical hypercalciuria. Recent Findings Hypercalciuria in the GHS rats is due to a systemic dysregulation of calcium transport, as manifest by increased intestinal calcium absorption, increased bone resorption and decreased renal tubule calcium reabsorption. Increased levels of vitamin D receptor in intestine, bone and kidney appear to mediate these changes. The excess receptors are biologically active and increase tissue sensitivity to exogenous vitamin D. Bones of GHS rats have decreased bone mineral density (BMD) as compared with Sprague Dawley rats, and exogenous 1,25(OH)2D3 exacerbates the loss of BMD. Thiazide diuretics improve the BMD in GHS rats. Summary Studying GHS rats allows direct investigation of the effects of alterations in diet and utilization of pharmacologic therapy on hypercalciuria, urine supersaturation, stone formation and bone quality in ways that are not possible in humans. PMID:26050120

  18. Fluvastatin reduced liver injury in rat model of extrahepatic cholestasis.

    PubMed

    Demirbilek, Savaş; Tas, Erkan; Gurunluoglu, Kubilay; Akin, Melih; Aksoy, Rauf T; Emre, Memet H; Aydin, Nasuhi E; Ay, Selma; Ozatay, Nilufer

    2007-02-01

    Inhibitors of 3-hydroxy-3methylglutarly coenzyme A, reductase, namely statins, exert pleiotropic actions beyond lipid-lowering effects. In ex vivo and in vitro studies, statins have antioxidative and antiinflammatory effects. Herein, we sought to determine whether treatment with fluvastatin (FV) would be beneficial in a rat model of common bile duct ligation (BDL)-induced liver injury. Female rats were subjected to a sham (n=10) or BDL (n=20). Obstructive jaundice was induced in rats by the ligation and division of the common bile duct. Three days after operation, rats subjected to CBDL were randomized to receive treatment with either FV (10 mg/kg) or saline every day over a 10 days experimental period. High levels of alanine aminotransferase, aspartate aminotransferase, and gamma glutamyltransferase decreased significantly (P<0.05) in animals treated with FV with compared to saline-administrated BDL animals. Compared with sham-operated rats, CBDL rats showed significantly higher levels of total nitrite and nitrate, malondihaldehyde, tumor necrosis factor alpha, myeloperoxidase, and lower concentrations of glutathione, superoxide dismutase, and catalase in the liver tissue (P<0.001). All of these changes were significantly attenuated (P<0.05) by treatment with FV after CBDL. CBDL was associated with increased apoptosis and nuclear factor kappa beta expression in saline-treated rats. Treatment with FV also decreased these parameters. These data support the view that FV ameliorates hepatic inflammation, lipid peroxidation, and tissue injury in rats subjected to CDBL. FV warrants further evaluation as an adjunctive treatment to ameliorate liver injury from extrahepatic biliary obstruction.

  19. A novel rat contact lens model for Fusarium keratitis

    PubMed Central

    Abou Shousha, Mohamed; Santos, Andrea Rachelle C.; Oechsler, Rafael A.; Iovieno, Alfonso; Maestre-Mesa, Jorge; Ruggeri, Marco; Echegaray, Jose J.; Dubovy, Sander R.; Perez, Victor L.; Miller, Darlene; Alfonso, Eduardo C.

    2013-01-01

    Purpose The aim of this study was to develop and characterize a new contact lens–associated fungal keratitis rat model and to assess the ability of non-invasive spectral-domain optical coherence tomography (SD-OCT) to detect pathological changes in vivo in fungal keratitis. Methods We used SD-OCT to image and measure the cornea of Sprague Dawley rats. Fusarium infection was initiated in the rat eye by fitting Fusarium solani–soaked contact lenses on the experimental eye, while the control animals received contact lenses soaked in sterile saline. The fungal infection was monitored with periodic slit-lamp examination and in vivo SD-OCT imaging of the rat eye, and confirmed by histology, counting of viable fungi in the infected rat cornea, and PCR with specific primers for Fusarium sp. Results We imaged and measured the rat cornea with SD-OCT. Custom-made contact lenses were developed based on the OCT measurements. Incubation of contact lenses in a F. solani suspension resulted in biofilm formation. We induced contact lens–associated Fusarium keratitis by fitting the rat eyes for 4 h with the Fusarium-contaminated contact lenses. The SD-OCT images of the cornea correlated well with the slit-lamp and histopathological results and clearly defined clinical signs of infection, namely, increased corneal thickening, loss of epithelial continuity, hyper-reflective areas representing infiltrates, and endothelial plaques characteristic of fungal infection. Moreover, in three cases, SD-OCT detected the infection without any clear findings on slit-lamp examination. Infection was confirmed with histological fungal staining, PCR, and microbiological culture positivity. Conclusions We developed a highly reproducible rat contact lens model and successfully induced contact lens–associated Fusarium keratitis in this model. The clinical presentation of contact lens–associated Fusarium keratitis in the rat model is similar to the human condition. SD-OCT is a valuable tool that

  20. Rodent models in neuroscience research: is it a rat race?

    PubMed

    Ellenbroek, Bart; Youn, Jiun

    2016-10-01

    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.

  1. Proteomic Analysis of the Effect of DHA-Phospholipids from Large Yellow Croaker Roe on Hyperlipidemic Mice.

    PubMed

    Liang, Peng; Zhang, Min; Cheng, Wenjian; Lin, Wenxiong; Chen, Lijiao

    2017-06-28

    Previously, we found that phospholipids derived from large yellow croaker (Pseudosciaena crocea) roe had a higher level of docosahexaenoic acid (DHA-PL), which had beneficial effects on lipid metabolism. However, the mechanism by which DHA-PL from P. crocea roe exerts these effects has not yet been illuminated. Herein, we investigated the underlying molecular action of DHA-PL by examining changes in liver protein expression in control, hyperlipidemic, and DHA-PL-treated mice. A total of 16 proteins, 9 up-regulated and 7 down-regulated, were identified and classified into several metabolic pathways, such as fat digestion and absorption, peroxisome proliferator activated receptor (PPAR) signaling, and antigen processing and presentation; the largest functional class found was that of fat digestion and absorption. We revealed Apoa1 to be a biomarker of DHA-PL effects on hyperlipidemic mice by DHA-PL diet. These results not only improve our current understanding of hyperlipidemic regulation by DHA-PL, but also suggest that DHA-PL should be applied as a beneficial food additive.

  2. Effects of Ramadan fasting on serum lipid profiles on 2 hyperlipidemic groups with or without diet pattern.

    PubMed

    Afrasiabi, Abbas; Hassanzadeh, Susan; Sattarivand, Reza; Mahboob, Soltanali

    2003-01-01

    The effects of Ramadan fasting, with low fat and low calorie diet, on blood lipid and lipoprotein levels were studied. Results revealed reduction of plasma lipid levels and anthropometric parameters in the hyperlipidemic cases. To find out whether such reductions were due to nutritional diet or Ramadan fasting, we conducted a study to evaluate effects of Ramadan fasting on 2 separate hyperlipidemic groups with or without nutritional diet regimen. This study was carried out at Madani Heart Hospital, Tabriz, Iran, during the year 1998. Thirty-eight hyperlipidemic healthy men voluntarily enrolled into 2 groups, group I, 22 men on low fat and low calorie diet and group II, 16 men without any special diet interference. The blood lipid profile tests were measured 4 times (3 weeks before, first week, last week and one month after Ramadan). To evaluate nutritional composition, 12 times in non-successive days, 24 hour nutrition recalls were obtained from all individuals during the study. Analysis of data revealed that only triglyceride in both groups reduced in the beginning of Ramadan compared to 3 weeks before. During Ramadan, with a reduction of 300 Kcal/day in comparison to before Ramadan, no changes were seen concerning anthropometric parameters and serum lipids levels. It seems that the effect of Ramadan fasting on serum lipid levels may be closely related to the nutritional diet. For reduction of plasma lipid levels, it would be necessary to omit at least one term meal or reduce energy by 500 Kcal or more per day.

  3. Hepatic expression of long-chain acyl-CoA synthetase 3 is upregulated in hyperlipidemic hamsters.

    PubMed

    Wu, Minhao; Liu, Haiyan; Chen, Wei; Fujimoto, Yasuyuki; Liu, Jingwen

    2009-11-01

    Members of the mammalian long-chain acyl-CoA synthetase (ACSL) family are key enzymes for cellular fatty acid metabolism that catalyze the initial step in activation of long-chain fatty acids. However, the specificity of individual isoforms of ACSL to the lipid metabolic process is not well studied. In addition, the regulation of expression of individual ACSL isoforms under hyperlipidemic conditions is largely unknown. We cloned the hamster ACSL3 cDNA coding region and generated specific antibodies recognizing the ACSL3 protein. We next observed the changes in ACSL3 mRNA and protein expression in hamsters fed a standard chow diet or a high fat and high cholesterol (HFHC) diet. HFHC feeding significantly increased ACSL3 mRNA and protein expression in liver and to a lesser extent in muscle but not in adipose, brain, heart, or testis. Additionally, ACSL3 mRNA abundance was differentially regulated by the nutritional status in different tissues with liver, muscle, and adipose being the most sensitive tissues. Importantly, the hepatic ACSL3 mRNA expression pattern in response to fasting and refeeding in hyperlipidemic hamsters differed from that observed in normal chow-fed hamsters. Together, these results provide the first in vivo evidence of altered regulation of hepatic ACSL3 expression under hyperlipidemic conditions and suggest important regulatory roles for this enzyme in lipid metabolism.

  4. A new composite facial and scalp transplantation model in rats.

    PubMed

    Ulusal, Betul G; Ulusal, Ali E; Ozmen, Selahattin; Zins, James E; Siemionow, Maria Z

    2003-10-01

    There are limited sources of autogenous tissue available for reconstruction of severe facial and scalp deformities caused by extensive tumor ablation, burns, or trauma. Allografts from cadaveric sources may serve as a reconstructive alternative. However, technical and immunological aspects of harvesting and transplanting face and scalp flaps limit the routine use of such procedures. For evaluation of the feasibility of composite-tissue reconstruction, an experimental model of composite face/scalp flap transplantation in rats was designed. Technical aspects of the model, survival rates, and the complications encountered during development of the model are presented. A total of 64 animals, in three experimental groups, were studied. In group I, the anatomical study group (n = 6), the anatomical features of the face and scalp region in rats were explored. Groups II and III were the transplantation groups. Isograft transplantations were performed between identical Lewis rats (RT11 to RT11), and allografts were transplanted, across major histocompatibility complex barriers, between Lewis-Brown Norway rats (RT1l/n) and Lewis rats (RT11). In group II (the control group, n = 8), transplantation of nonvascularized composite face/scalp isografts and allografts was performed. In group III (the transplantation group, n = 50), vascularized face/scalp isografts (n = 36) and allografts (n = 14) were transplanted. Complications included partial or total flap necrosis, death attributable to food aspiration, and poor general condition. To prevent acute and chronic allograft rejection, cyclosporine A (16 mg/kg per day) therapy was initiated 24 hours after transplantation; the dose was tapered to 2 mg/kg per day within 4 weeks and was maintained at that level thereafter. Long-term survival (>170 days) was achieved, without any signs of rejection, with low-dose (2 mg/kg per day) cyclosporine A therapy. This is the first report documenting successful composite face/scalp flap

  5. Spontaneous Trigeminal Allodynia in Rats: A Model of Primary Headache

    PubMed Central

    Oshinsky, Michael L.; Sanghvi, Menka M.; Maxwell, Christina R.; Gonzalez, Dorian; Spangenberg, Rebecca J.; Cooper, Marnie; Silberstein, Stephen D.

    2014-01-01

    Animal models are essential for studying the pathophysiology of headache disorders and as a screening tool for new therapies. Most animal models modify a normal animal in an attempt to mimic migraine symptoms. They require manipulation to activate the trigeminal nerve or dural nociceptors. At best, they are models of secondary headache. No existing model can address the fundamental question: How is a primary headache spontaneously initiated? In the process of obtaining baseline periorbital von Frey thresholds in a wild-type Sprague-Dawley rat, we discovered a rat with spontaneous episodic trigeminal allodynia (manifested by episodically changing periorbital pain threshold). Subsequent mating showed that the trait is inherited. Animals with spontaneous trigeminal allodynia allow us to study the pathophysiology of primary recurrent headache disorders. To validate this as a model for migraine, we tested the effects of clinically proven acute and preventive migraine treatments on spontaneous changes in rat periorbital sensitivity. Sumatriptan, ketorolac, and dihydroergotamine temporarily reversed the low periorbital pain thresholds. Thirty days of chronic valproic acid treatment prevented spontaneous changes in trigeminal allodynia. After discontinuation, the rats returned to their baseline of spontaneous episodic threshold changes. We also tested the effects of known chemical human migraine triggers. On days when the rats did not have allodynia and showed normal periorbital von Frey thresholds, glycerol trinitrate and calcitonin gene related peptide induced significant decreases in the periorbital pain threshold. This model can be used as a predictive model for drug development and for studies of putative biomarkers for headache diagnosis and treatment. PMID:22963523

  6. 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.

  7. Reducing Fear of the Laboratory Rat: A Participant Modeling Approach.

    ERIC Educational Resources Information Center

    Barber, Nigel

    1994-01-01

    Reports on the use of participant modeling in a study of 56 college-level students to reduce fear of laboratory rats. Discovers that even mild exposure reduced fear significantly. Finds that women were more fearful initially but that their fear reduction was equal to that of men. (CFR)

  8. PHARMACOKINETIC/PHARMACODYNAMIC MODELING OF PERMETHRIN IN THE RAT

    EPA Science Inventory

    A physiologically-based pharmacokinetic (PBPK) model was used to describe pharmacokinetics of permethrin and calibrated using experimental data on the concentration time-course of cis- and trans-permethrin in rat blood and brain tissues following oral administration...

  9. PHARMACOKINETIC/PHARMACODYNAMIC MODELING OF PERMETHRIN IN THE RAT

    EPA Science Inventory

    A physiologically-based pharmacokinetic (PBPK) model was used to describe pharmacokinetics of permethrin and calibrated using experimental data on the concentration time-course of cis- and trans-permethrin in rat blood and brain tissues following oral administration...

  10. Analgesic Effect of Xenon in Rat Model of Inflammatory Pain.

    PubMed

    Kukushkin, M L; Igon'kina, S I; Potapov, S V; Potapov, A V

    2017-02-01

    The analgesic effects of inert gas xenon were examined on rats. The formalin model of inflammatory pain, tail-flick test, and hot-plate test revealed the antinociceptive effects of subanesthetizing doses of inhalation anesthetic xenon. Inhalation of 50/50 xenon/oxygen mixture moderated the nociceptive responses during acute and tonic phases of inflammatory pain.

  11. Calcium Balance in A Rat Space Flight Model

    NASA Technical Reports Server (NTRS)

    Arnaud, Sara B.; Navidi, M.; Holton, Emily M. (Technical Monitor)

    1997-01-01

    One of the main characteristics of calcium (Ca) metabolism during space flight and the human bed rest model for microgravity is negative Ca balance, attributed, to an increase in urinary Ca excretion and depressed intestinal Ca absorption. No differences or less positive Ca balances are reported after skeletal unloading in similar studies in weaning or juvenile rats. To determine Ca balances and evaluate the Ca endocrine system in mature rats exposed to a space flight model which unloaded the hind limbs by tail suspension, we modified the cage to quantify dietary, fecal and urinary Ca. Five 2-5 d balance periods in 8 loaded (C) and 8 unloaded (S) rats were compared during a 4 week study in 6 month old 490 g male rats. The first period revealed negative balances of -16+/-3 and -14+/-5 mg/d which reflected adaptation to the cages, the change in diet from Purina to AIN 76 and weight loss in both C and S. Average Ca balances in rats fed 0.1% Ca and 0.3% phosphorus (Pi) diets, remained negative in S and were less than C after 6 -10 d (-2.9 vs 0.12 mg/d, p<.05) but not thereafter. In spite of eating 10% more food than C, initial weight loss, restored in C, was never recovered in S. Fecal excretion exceeded dietary intake by -3.7% in S and reflected absorption and retention of 8.4% dietary Ca in C. Urinary Ca was the same fraction of dietary intake in S and C (9.0 vs 8.6%, NS). Serum Ca, Pi, parathyroid hormone and 1,25-dihydroxyvitamin D were the same in both groups after 28 days. In contrast to the human, a major determinant of negative Ca balance in the mature rat exposed to a space flight model appears to be losses from gastrointestinal Ca secretion, rather than urinary Ca excretion.

  12. Calcium Balance in A Rat Space Flight Model

    NASA Technical Reports Server (NTRS)

    Arnaud, Sara B.; Navidi, M.; Holton, Emily M. (Technical Monitor)

    1997-01-01

    One of the main characteristics of calcium (Ca) metabolism during space flight and the human bed rest model for microgravity is negative Ca balance, attributed, to an increase in urinary Ca excretion and depressed intestinal Ca absorption. No differences or less positive Ca balances are reported after skeletal unloading in similar studies in weaning or juvenile rats. To determine Ca balances and evaluate the Ca endocrine system in mature rats exposed to a space flight model which unloaded the hind limbs by tail suspension, we modified the cage to quantify dietary, fecal and urinary Ca. Five 2-5 d balance periods in 8 loaded (C) and 8 unloaded (S) rats were compared during a 4 week study in 6 month old 490 g male rats. The first period revealed negative balances of -16+/-3 and -14+/-5 mg/d which reflected adaptation to the cages, the change in diet from Purina to AIN 76 and weight loss in both C and S. Average Ca balances in rats fed 0.1% Ca and 0.3% phosphorus (Pi) diets, remained negative in S and were less than C after 6 -10 d (-2.9 vs 0.12 mg/d, p<.05) but not thereafter. In spite of eating 10% more food than C, initial weight loss, restored in C, was never recovered in S. Fecal excretion exceeded dietary intake by -3.7% in S and reflected absorption and retention of 8.4% dietary Ca in C. Urinary Ca was the same fraction of dietary intake in S and C (9.0 vs 8.6%, NS). Serum Ca, Pi, parathyroid hormone and 1,25-dihydroxyvitamin D were the same in both groups after 28 days. In contrast to the human, a major determinant of negative Ca balance in the mature rat exposed to a space flight model appears to be losses from gastrointestinal Ca secretion, rather than urinary Ca excretion.

  13. Isolated perfused liver model: the rat and guinea pig compared.

    PubMed

    Chaïb, Samira; Charrueau, Christine; Neveux, Nathalie; Coudray-Lucas, Colette; Cynober, Luc; De Bandt, Jean-Pascal

    2004-05-01

    Although the rat is the most commonly used species for the study of hepatic metabolism, the physiology of the guinea pig is closer to human physiology. We compared the model of isolated perfused guinea pig liver with the classic model of isolated perfused rat liver, especially with respect to amino acid metabolism. After validation of an anesthetic mixture of ketamine, diazepam, and xylazine for the guinea pig, isolated perfused livers were harvested for both species. Three groups of animals were compared for the study of liver metabolic fluxes: 6-wk-old male Sprague-Dawley rats (R; 230 +/- 10 g, n = 5), young male Hartley guinea pigs (YG; 223 +/- 8 g, n = 6) matched to rats by liver weight, and adult male Hartley guinea pigs (AG; 389 +/- 5 g, n = 6) matched to rats by age. Results (mean +/- standard error of the mean) were compared by analysis of variance and Newman-Keuls tests. Both models displayed a satisfactory hepatic viability, but differences were noted, with higher portal flows (R: 3.1 +/- 0.3 versus YG: 4.5 +/- 0.3 and AG: 4.2 +/- 0.3 mL. min(-1). g(-1); P < 0.05, YG and AG versus R) and bile flows (R: 0.34 +/- 0.01 versus YG: 2.38 +/- 0.22 versus AG: 3.17 +/- 0.28 microL. min(-1). g(-1); P < 0.05, YG and AG versus R, and YG versus AG) and higher amino acid fluxes (P < 0.05) leading to greater nitrogen uptake (P < 0.05) in guinea pigs. We performed a second set of experiments to evaluate the influence of anesthesia and portal flow on this last parameter. In these experiments, rats were anesthetized with ketamine, diazepam, and xylazine and guinea pig livers were perfused at rat blood flow. Apart from a 50% anesthesia-related mortality for rats, bile flow and metabolic parameters were only slightly modified. However, some amino acid fluxes were statistically different (aspartate, serine, and histidine; P < 0.05), as confirmed by a higher transfer constant. Our results indicate that the isolated perfused guinea pig liver is a suitable model for the study of

  14. Effect of Berberine on promoting the excretion of cholesterol in high-fat diet-induced hyperlipidemic hamsters.

    PubMed

    Li, Xiao-Yang; Zhao, Zhen-Xiong; Huang, Min; Feng, Ru; He, Chi-Yu; Ma, Chao; Luo, Shi-Heng; Fu, Jie; Wen, Bao-Ying; Ren, Long; Shou, Jia-Wen; Guo, Fang; Chen, Yangchao; Gao, Xin; Wang, Yan; Jiang, Jian-Dong

    2015-08-27

    Berberine (BBR), as a new medicine for hyperlipidemia, can reduce the blood lipids in patients. Mechanistic studies have shown that BBR activates the extracellular-signal regulated kinase pathway by stabilizing low-density-lipoprotein receptor mRNA. However, aside from inhibiting the intestinal absorption of cholesterol, the effects of BBR on other metabolic pathways of cholesterol have not been reported. This study aimed to investigate the action of BBR on the excretion of cholesterol in high-fat diet-induced hyperlipidemic hamsters. Golden hamsters were fed a high-fat diet (HFD) for 6 weeks to induce hyperlipidemia, followed by oral treatment with 50 and 100 mg/kg/day of BBR or 10 and 30 mg/kg/day of lovastatin for 10 days, respectively. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), transaminases, and total bile acid in the serum, liver, bile and feces were measured using an enzyme-linked immunosorbent assay. The cholesterol (as well as coprostanol) levels in the liver, bile and feces were determined by gas chromatography-mass spectrometry. The HFD hamsters showed significantly hyperlipidemic characteristics compared with the normal hamsters. Treatment with BBR for 10 days reduced the serum TC, TG and LDL-C levels in HFD hamsters by 44-70, 34-51 and 47-71%, respectively, and this effect was both dose- and time-dependent. Initially, a large amount of cholesterol accumulated in the hyperlipidemic hamster livers. After BBR treatment, reductions in the liver cholesterol were observed by day 3 and became significant by day 7 at both doses (P < 0.001). Meanwhile, bile cholesterol was elevated by day 3 and significantly increased at day 10 (P < 0.001). BBR promoted cholesterol excretion from the liver into the bile in hyperlipidemic hamsters but not in normal hamsters, and these results provide a link between the cholesterol-lowering effect of BBR with cholesterol excretion into the bile. We conclude that BBR

  15. The mathematical whisker: A review of numerical models of the rat׳s vibrissa biomechanics.

    PubMed

    Lucianna, Facundo Adrián; Albarracín, Ana Lía; Vrech, Sonia Mariel; Farfán, Fernando Daniel; Felice, Carmelo José

    2016-07-05

    The vibrissal system of the rat refers to specialized hairs the animal uses for tactile sensory perception. Rats actively move their whiskers in a characteristic way called "whisking". Interaction with the environment produces elastic deformation of the whiskers, generating mechanical signals in the whisker-follicle complex. Advances in our understanding of the vibrissal complex biomechanics is of interest not only for the biological research field, but also for biomimetic approaches. The recent development of whisker numerical models has contributed to comprehending its sophisticated movements and its interactions with the follicle. The great diversity of behavioral patterns and complexities of the whisker-follicle ensemble encouraged the creation of many different biomechanical models. This review analyzes most of the whisker biomechanical models that have been developed so far. This review was written so as to render it accessible to readers coming from different research areas.

  16. Mixed-gas model for predicting decompression sickness in rats.

    PubMed

    Lillo, R S; Parker, E C

    2000-12-01

    A mixed-gas model for rats was developed to further explore the role of different gases in decompression and to provide a global model for possible future evaluation of its usefulness for human prediction. A Hill-equation dose-response model was fitted to over 5,000 rat dives by using the technique of maximum likelihood. These dives used various mixtures of He, N(2), Ar, and O(2) and had times at depth up to 2 h and varied decompression profiles. Results supported past findings, including 1) differences among the gases in decompression risk (He < N(2) < Ar) and exchange rate (He > Ar approximately N(2)), 2) significant decompression risk of O(2), and 3) increased risk of decompression sickness with heavier animals. New findings included asymmetrical gas exchange with gas washout often unexpectedly faster than uptake. Model success was demonstrated by the relatively small errors (and their random scatter) between model predictions and actual incidences. This mixed-gas model for prediction of decompression sickness in rats is the first such model for any animal species that covers such a broad range of gas mixtures and dive profiles.

  17. Gradient Echo MRI Characterization of Development of Atherosclerosis in the Abdominal Aorta in Watanabe Heritable Hyperlipidemic Rabbits

    SciTech Connect

    Wang, Yi-Xiang J. Kuribayashi, Hideto; Wagberg, Maria; Holmes, Andrew P.; Tessier, Jean J.; Waterton, John C.

    2006-08-15

    Purpose. The Watanabe Heritable Hyperlipidemic (WHHL) rabbit provides an important model of spontaneous atherosclerosis. With a strain of WHHL rabbits which do not develop abdominal aorta lumen stenosis even with advanced atherosclerosis, we studied the MRI-histology correlation, and the natural progression of atherosclerosis in the abdominal aorta. In addition, intra-reader segmentation repeatability and scan-rescan reproducibility were assessed. Methods. Two batches of female WHHL rabbits were used. The first batch of 6 rabbits was scanned at 20 weeks old. A second batch of 17 rabbits was scanned at 50 weeks old and then randomly divided into two subgroups: 8 were killed for histologic investigation; 9 were kept alive for follow-up, with repeat scanning a week later to assess scan-rescan reproducibility, and again at 73 weeks old to assess disease progression. MR images were acquired at 4.7 T using a chemical shift selective fat suppression gradient echo with a saturation band suppressing blood signal within the aortic lumen. Five slices per animal were acquired, centered around the renal artery region of the abdominal aorta, with in-plane resolution of 0.195 mm and slice thickness of 3 mm. Results. The coefficient of variation for intra-reader reproducibility for aortic wall thickness measurements was 2.5% for repeat segmentations of the same scans on the same day, but segmentations of these same scans made 8 months later showed a systematic change, suggesting that intra-reader bias as well as increased variability could compromise assessments made over time. Comparative analyses were therefore performed in one postprocessing session. The coefficient of variation for scan-rescan reproducibility for aortic wall thickness was 5.5% for nine pairs of scans acquired a week apart and segmented on the same day. Good MRI-histology correlation was obtained. The MRI-measured mean aortic wall thickness of animals at 20 weeks of age was 76% that of animals at 50 weeks of

  18. A new rat model for studies of hypokinesia and antiorthostasis

    NASA Technical Reports Server (NTRS)

    Musacchia, X. J.; Deavers, D. R.

    1982-01-01

    A new rat model (suspension and immobilization) is described for induction of hypokinesia and orthostatic manipulations. Hypokinetic responses were comparable to those in prolonged bed rest and weightlessness in humans, body or limb casted and small cage restrained animals. Responses to antiorthostasis (15 to 20 deg head down tilt) in rats were similar to those in neutral bouyancy tests in humans and animals and to those in prolonged bed rest in humans. During seven days of hypokinesia there was an atrophy of the gastrocnemius and increased excretion of urinary nitrogeneous end products. The antiorthostatic (AOH) 15 to 20 deg head down tilt resulted in diuresis, natriuresis and kaliuresis. No comparable responses were observed in orthostatic hypokinetic (OH) rats. Readaptation from AOH and OH occurred during one week recovery in metabolic cage conditions.

  19. A new rat model for studies of hypokinesia and antiorthostasis

    NASA Technical Reports Server (NTRS)

    Musacchia, X. J.; Deavers, D. R.

    1982-01-01

    A new rat model (suspension and immobilization) is described for induction of hypokinesia and orthostatic manipulations. Hypokinetic responses were comparable to those in prolonged bed rest and weightlessness in humans, body or limb casted and small cage restrained animals. Responses to antiorthostasis (15 to 20 deg head down tilt) in rats were similar to those in neutral bouyancy tests in humans and animals and to those in prolonged bed rest in humans. During seven days of hypokinesia there was an atrophy of the gastrocnemius and increased excretion of urinary nitrogeneous end products. The antiorthostatic (AOH) 15 to 20 deg head down tilt resulted in diuresis, natriuresis and kaliuresis. No comparable responses were observed in orthostatic hypokinetic (OH) rats. Readaptation from AOH and OH occurred during one week recovery in metabolic cage conditions.

  20. Dimensions of emotionality in a rat model of innate anxiety.

    PubMed

    Ohl, F; Toschi, N; Wigger, A; Henniger, M S; Landgraf, R

    2001-04-01

    Emotionality is thought to be multidimensional, with "anxiety" representing one dimension. Dissecting emotional dimensions in animal models is an essential prerequisite for investigating the neurobiological mechanisms that underlie anxiety. The authors used factor analysis to investigate emotional dimensions in normal rats and rats bred for either high or low anxiety-related behavior. Hyperanxious rats were reduced in emotional dimensions in the elevated plus-maze by selection pressure, and a modified hole board test revealed a dissection of their emotionality with precisely defined dimensions. This enabled clear differentiation of "anxiety" from other emotional dimensions including risk assessment behavior and exploration. Factors extracted by analyzing data from a multiple-test battery corresponded to particular test characteristics rather than to emotional dimensions. The approach used might help to develop specific treatment strategies for anxiety disorders.

  1. Chlorogenic acid decreases retinal vascular hyperpermeability in diabetic rat model.

    PubMed

    Shin, Joo Young; Sohn, Joonhong; Park, Kyu Hyung

    2013-04-01

    To evaluate the effect of chlorogenic acid (CGA), a polyphenol abundant in coffee, on retinal vascular leakage in the rat model of diabetic retinopathy, Sprague-Dawley rats were divided into four groups: controls, streptozotocin-induced diabetic rats, and diabetic rats treated with 10 and 20 mg/kg chlorogenic acid intraperitoneally daily for 14 days, respectively. Blood-retinal barrier (BRB) breakdown was evaluated using FITC-dextran. Vascular endothelial growth factor (VEGF) distribution and expression level was evaluated with immunohistochemistry and Western blot analysis. Expression of tight junction proteins, occludin and claudin-5, and zonula occludens protein, ZO-1 was also evaluated with immunohistochemistry and Western blot analysis. BRB breakdown and increased vascular leakage was found in diabetic rats, with increased VEGF expression and down-regulation of occludin, claudin-5, and ZO-1. CGA treatment effectively preserved the expression of occludin, and decreased VEGF levels, leading to less BRB breakdown and less vascular leakage. CGA may have a preventive role in BRB breakdown in diabetic retinopathy by preserving tight junction protein levels and low VEGF levels.

  2. Relative hypersecretion of proinsulin in rat model of NIDDM.

    PubMed

    Leahy, J L; Halban, P A; Weir, G C

    1991-08-01

    The plasma ratio of proinsulin to insulin is raised in individuals with non-insulin-dependent diabetes mellitus (NIDDM). Increased secretion of proinsulin relative to insulin is thought to be the cause, although differential changes in clearance have not been ruled out. This study was conducted in a rat model of NIDDM, 90% pancreatectomized (Px) rats, to investigate the pathophysiology of this observation. Proinsulin storage and secretion were assessed with high-performance liquid chromatography separation of the insulins and the proinsulins, followed by quantification of the peaks by insulin radioimmunoassay. In Px rats, the relative proportion of proinsulin in pancreas extracts was twice that of control (sham-operated) rats (15.6 +/- 1.4 vs. 8.3 +/- 1.4%, P less than 0.01). Samples obtained from the portal vein during in vitro pancreas perfusion also had an elevated proinsulin fraction (Px, 10.3 +/- 3.0; sham, 3.0 +/- 0.6%; P less than 0.006). In summary, 90% Px rats share many pathophysiological features with NIDDM, including loss of normal proinsulin homeostasis. Our results suggest that chronic hyperglycemia causes an intrinsic change in beta-cells that is characterized by the increased storage and secretion of proinsulin.

  3. Sonic hedgehog expression in a rat model of chronic pancreatitis

    PubMed Central

    Wang, Luo-Wei; Lin, Han; Lu, Yi; Xia, Wei; Gao, Jun; Li, Zhao-Shen

    2014-01-01

    AIM: To analyze the activation of sonic hedgehog (SHh) signaling pathways in a rat model of chronic pancreatitis. METHODS: Forty Wistar rats were randomly divided into 2 groups: experimental group and control group (20 rats in each group). Dibutyltin dichloride was infused into the tail vein of the rats to induce chronic pancreatitis in the experimental group. The same volume of ethanol and glycerol mixture was infused in the control group. The expression of Ptch, Smo and Gli were analyzed using immunohistochemistry, and real-time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Compared with the control group, significant histological changes in terms of the areas of abnormal architecture, glandular atrophy, fibrosis, pseudo tubular complexes, and edema were observed at week 4 in the experimental group. The expression of Ptch1, Smo and Gli1 in the pancreatic tissue increased significantly in the experimental group. Using RT-PCR, mRNA levels of Ptch, Smo and Gli in the experimental group increased significantly compared with the control group. CONCLUSION: The SHh signaling pathway is aberrantly activated in rats with chronic pancreatitis. The SHh signaling pathway plays an important role in the development of chronic pancreatitis. These results may be helpful in studies focusing on the relationship between chronic pancreatitis and pancreatic cancer. PMID:24782623

  4. Gene expression in the bladder carcinoma rat model.

    PubMed

    Ariel, Ilana; Ayesh, Suhail; Gofrit, Ofer; Ayesh, Basim; Abdul-Ghani, Rula; Pizov, Galina; Smith, Yoav; Sidi, Ami A; Birman, Tatiana; Schneider, Tamar; de Groot, Nathan; Hochberg, Abraham

    2004-10-01

    We investigated gene expression in N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced rat bladder carcinoma in order to test its applicability as a model for the study of novel therapeutic modalities, particularly gene therapy. We administered BBN in the drinking water to Wistar rats for up to 30 wk and induced papillary transitional cell carcinoma (TCC), which is similar to the most prevalent type of human bladder cancer. Tumor evolution was similar to that found in previous studies. However, we described the morphological stages according to modern human bladder carcinoma terminology. Our main goal was to examine the expression levels of the H19 gene, of the insulin-like growth factor 2 (Igf2) transcripts expressed from promoters P2 and P3 and of the telomerase subunits that we had previously investigated as tools for targeted gene therapy of bladder cancer. We detected at 30 wk of BBN exposure significant upregulation of these sequences in the rat bladder tumors, similar to our previous findings in human bladder cancer. To reinforce the similarity of this model to the corresponding human disease, we searched for additional tumor-specific genes documented as having altered expression in human bladder carcinoma, using cDNA expression arrays (Clontech). We suggest that BBN-induced rat bladder cancer has morphological, biological, and molecular parallels to human bladder cancer and is an attractive model for studying novel alternatives of therapeutic intervention. Copyright 2004 Wiley-Liss, Inc.

  5. Rat model of focal cerebral ischemia in the dominant hemisphere

    PubMed Central

    Zhang, Hua; Shen, Yan; Wang, Wei; Gao, Huanmin

    2015-01-01

    In the human brain, the dominant hemisphere is more complex than the non-dominant hemisphere. Hence, cerebral ischemia of the dominant hemisphere often leads to serious consequences. This study aims to establish a rodent model of focal cerebral ischemia in the dominant hemisphere. The quadruped feeding test was used to screen 70 male Sprague Dawley rats. From this test, 48 rats with right paw preference were selected and randomly assigned numbers. Half were assigned to the dominant hemisphere ischemia (DHI) group, and the other half were assigned to the non-dominant hemisphere ischemia (NDHI) group. The middle cerebral artery was occluded 2 h before reperfusion. Neurological functions were tested. TTC and HE staining were performed. The volume of cerebral infarction was calculated. Rats in the DHI group had significantly worse neurological scores than rats in the NDHI group (P < 0.05). TTC staining indicated ischemia had more severe consequences in the dominant hemisphere than in the non-dominant hemisphere. The dominant hippocampus indicated severe neuronal loss and disorderly cellular arrangement. The volume of cerebral infarction was also greater in the DHI group compared to the NDHI group (P < 0.05). Compared to MCA occlusion in the non-dominant hemisphere, MCA occlusion in the dominant hemisphere caused greater impairment in neurological functions. The proposed rodent model is reliable and has high levels of reproducibility. Therefore, his model can be reliably for investigating the mechanism of focal cerebral ischemia in the dominant hemisphere of human brains. PMID:25785023

  6. Experimental model of heterotopic ossification in Wistar rats

    PubMed Central

    Zotz, T.G.G.; de Paula, J.B.; Moser, A.D.L.

    2012-01-01

    Heterotopic ossification (HO) is a metaplastic biological process in which there is newly formed bone in soft tissues adjacent to large joints, resulting in joint mobility deficit. In order to determine which treatment techniques are more appropriate for such condition, experimental models of induced heterotopic bone formation have been proposed using heterologous demineralized bone matrix implants and bone morphogenetic protein and other tissues. The objective of the present experimental study was to identify a reliable protocol to induce HO in Wistar rats, based on autologous bone marrow (BM) implantation, comparing 3 different BM volumes and based on literature evidence of this HO induction model in larger laboratory animals. Twelve male Wistar albino rats weighing 350/390 g were used. The animals were anesthetized for blood sampling before HO induction in order to quantify serum alkaline phosphatase (ALP). HO was induced by BM implantation in both quadriceps muscles of these animals, experimental group (EG). Thirty-five days after the induction, another blood sample was collected for ALP determination. The results showed a weight gain in the EG and no significant difference in ALP levels when comparing the periods before and after induction. Qualitative histological analysis confirmed the occurrence of heterotopic ossification in all 12 EG rats. In conclusion, the HO induction model was effective when 0.35 mL autologous BM was applied to the quadriceps of Wistar rats. PMID:22473322

  7. Ameliorative effect of melatonin against increased intestinal permeability in diabetic rats: possible involvement of MLCK-dependent MLC phosphorylation.

    PubMed

    Yang, Xiaoping; Zou, Duobing; Tang, Songtao; Fan, Tingting; Su, Huan; Hu, Ruolei; Zhou, Qing; Gui, Shuyu; Zuo, Li; Wang, Yuan

    2016-05-01

    The increased intestinal permeability and functional impairment play an important role in type 2 diabetes (T2D), and melatonin may possess enteroprotection properties. Therefore, we used streptozotocin-induced diabetic rat model to investigate the regulation of intestinal permeability by melatonin. Rats were randomly divided into three groups, including control, diabetes mellitus (DM), and DM rats treated with melatonin. Melatonin was administered (10 mg/kg/day) by gavage for 24 weeks. The DM rats significantly increased the serum fasting blood glucose and lipid levels, which were alleviated by melatonin treatment. Importantly, the intestinal epithelial permeability was significantly increased in DM rats but was ameliorated following treatment with melatonin. These findings also indicated the expression of myosin light chain kinase (MLCK) and phosphorylation of MLC targeting subunit (MYPT) induced myosin light chain (MLC) phosphorylation level was markedly elevated in hyperglycemic and hyperlipidemic status. They were partly associated with down-regulated membrane type 1 and 2 (MT1 and MT2) expression, and up-regulated Rho-associated protein kinase (ROCK) expression and increased extracellular signal-regulated kinase (ERK) phosphorylation. However, the changes in target protein expression were reversed by melatonin. In conclusion, our results show melatonin beneficial effects on impaired intestinal epithelial permeability in T2D by suppressing ERK/MLCK- and ROCK/MCLP-dependent MLC phosphorylation.

  8. New rat models of iron sucrose-induced iron overload.

    PubMed

    Vu'o'ng Lê, Bá; Khorsi-Cauet, Hafida; Villegier, Anne-Sophie; Bach, Véronique; Gay-Quéheillard, Jérôme

    2011-07-01

    The majority of murine models of iron sucrose-induced iron overload were carried out in adult subjects. This cannot reflect the high risk of iron overload in children who have an increased need for iron. In this study, we developed four experimental iron overload models in young rats using iron sucrose and evaluated different markers of iron overload, tissue oxidative stress and inflammation as its consequences. Iron overload was observed in all iron-treated rats, as evidenced by significant increases in serum iron indices, expression of liver hepcidin gene and total tissue iron content compared with control rats. We also showed that total tissue iron content was mainly associated with the dose of iron whereas serum iron indices depended essentially on the duration of iron administration. However, no differences in tissue inflammatory and antioxidant parameters from controls were observed. Furthermore, only rats exposed to daily iron injection at a dose of 75 mg/kg body weight for one week revealed a significant increase in lipid peroxidation in iron-treated rats compared with their controls. The present results suggest a correlation between iron overload levels and the dose of iron, as well as the duration and frequency of iron injection and confirm that iron sucrose may not play a crucial role in inflammation and oxidative stress. This study provides important information about iron sucrose-induced iron overload in rats and may be useful for iron sucrose therapy for iron deficiency anemia as well as for the prevention and diagnosis of iron sucrose-induced iron overload in pediatric patients.

  9. Mg2+-dependent ATPase activity in cardiac myofibrils from the insulin-resistant JCR:LA-cp rat.

    PubMed

    Misra, T; Russell, J C; Clark, T A; Pierce, G N

    2001-01-01

    There is a great deal of information presently available documenting a cardiomyopathic condition in insulin-deficient models of diabetes. Less information is available documenting a similar status in non insulin-dependent models of diabetes. We have studied the functional integrity of the myofibrils isolated from hearts of JCR:LA rats. The JCR:LA rat is hyperinsulinemic, hyperlipidemic, glucose intolerant and obese. As such, it carries many of the characteristics found in humans with non insulin-dependent diabetes mellitus. These animals also have many indications of heart disease. However, it is not clear if the hearts suffer from vascular complications or are cardiomyopathic in nature. We examined Mg2+-dependent myofibrillar ATPase in hearts of JCR:LA-cp/cp rats and their corresponding control animals (+/?) and found no significant differences (P> 0.05). This is in striking contrast to the depression in this activity exhibited by cardiac myofibrils isolated from insulin-deficient models of diabetes. Our data demonstrate that myofibrillar functional integrity is normal in JCR:LA-cp rats and suggest that these hearts are not in a cardiomyopathic state. Insulin status may be critical in generating a cardiomyopathic condition in diabetes.

  10. Groove model of tibia‐femoral osteoarthritis in the rat

    PubMed Central

    de Visser, Huub M.; Weinans, Harrie; Coeleveld, Katja; van Rijen, Mattie H. P.; Lafeber, Floris P. J. G.

    2016-01-01

    ABSTRACT Several experimental models of osteoarthritis in rats are used to study the pathophysiology of osteoarthritis. Many mechanically induced models have the limitation that permanent joint instability is induced by, for example, ligament transection or meniscal damage. This permanent instability will counteract the potential beneficial effects of therapy. The groove model of osteoarthritis uses a one‐time trigger, surgically induced cartilage damage on the femoral condyles, and has been validated for the canine tibia‐femoral compartment. The present study evaluates this model for the rat knee joint. The articular cartilage of the weight bearing surface of both femoral condyles and trochlea were damaged (grooved) without damaging the underlying subchondral bone. Severity of joint degeneration was histologically assessed, in addition to patella cartilage damage, and subchondral bone characteristics by means of (contrast‐enhanced) micro‐CT. Mild histological degeneration of the surgically untouched tibial plateau cartilage was observed in addition to damage of the femoral condyles, without clear synovial tissue inflammation. Contrast enhanced micro‐CT demonstrated proteoglycan loss of the surgically untouched patella cartilage. Besides, a more sclerotic structure of the subchondral bone was observed. The tibia‐femoral groove model in a rat results in mild knee joint degeneration, without permanent joint instability and joint inflammation. This makes the rat groove model a useful model to study the onset and progression of post‐traumatic non‐inflammatory osteoarthritis, creating a relatively sensitive model to study disease modifying osteoarthritic drugs. © 2016 The Authors. Journal of Orthopaedic Research published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 35:496–505, 2017. PMID:27183198

  11. Groove model of tibia-femoral osteoarthritis in the rat.

    PubMed

    de Visser, Huub M; Weinans, Harrie; Coeleveld, Katja; van Rijen, Mattie H P; Lafeber, Floris P J G; Mastbergen, Simon C

    2017-03-01

    Several experimental models of osteoarthritis in rats are used to study the pathophysiology of osteoarthritis. Many mechanically induced models have the limitation that permanent joint instability is induced by, for example, ligament transection or meniscal damage. This permanent instability will counteract the potential beneficial effects of therapy. The groove model of osteoarthritis uses a one-time trigger, surgically induced cartilage damage on the femoral condyles, and has been validated for the canine tibia-femoral compartment. The present study evaluates this model for the rat knee joint. The articular cartilage of the weight bearing surface of both femoral condyles and trochlea were damaged (grooved) without damaging the underlying subchondral bone. Severity of joint degeneration was histologically assessed, in addition to patella cartilage damage, and subchondral bone characteristics by means of (contrast-enhanced) micro-CT. Mild histological degeneration of the surgically untouched tibial plateau cartilage was observed in addition to damage of the femoral condyles, without clear synovial tissue inflammation. Contrast enhanced micro-CT demonstrated proteoglycan loss of the surgically untouched patella cartilage. Besides, a more sclerotic structure of the subchondral bone was observed. The tibia-femoral groove model in a rat results in mild knee joint degeneration, without permanent joint instability and joint inflammation. This makes the rat groove model a useful model to study the onset and progression of post-traumatic non-inflammatory osteoarthritis, creating a relatively sensitive model to study disease modifying osteoarthritic drugs. © 2016 The Authors. Journal of Orthopaedic Research published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 35:496-505, 2017.

  12. Comparison of starvation and elastase models of emphysema in the rat

    SciTech Connect

    Harkema, J.R.; Mauderly, J.L.; Gregory, R.E.; Pickrell, J.A.

    1984-01-01

    Starvation and elastase-induced changes in rat lung structure, biochemistry, and function were compared as models of human pulmonary emphysema. Ten-week-old male rats were instilled intratracheally with either porcine pancreatic elastase in saline (E) or with saline alone. A group of the saline-instilled rats were fed one third of their normal food intake until a 45% loss of body weight occurred (S). The remaining saline-instilled rats served as control animals (C). Post-treatment evaluations included in vivo respiratory function, lung histopathologic and morphometric analyses, lung tissue proteinolytic activity, and lung collagen. The E rats had in vivo respiratory function changes more similar to human emphysema than those of S rats. All lung volume subdivisions were decreased in S rats and increased in E rats. The volume-pressure curve of S rats was shifted to the right of the C curve, whereas that of E rats was shifted to the left. Forced expiratory flow rates of E rats were decreased at all lung volumes, but those of S rats were not. Both E and S rats had larger terminal air spaces and less alveolar surface area than did C rats. The S rats had more collagen per gram lung and higher proteinolytic activity than did C or E rats. These results show that, although starvation induces some changes characteristic of human emphysema, elastase-treatment provides a model more similar to the human disease. 44 references, 5 figures, 4 tables.

  13. Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure.

    PubMed

    Kuijk, Ewart W; Rasmussen, Shauna; Blokzijl, Francis; Huch, Meritxell; Gehart, Helmuth; Toonen, Pim; Begthel, Harry; Clevers, Hans; Geurts, Aron M; Cuppen, Edwin

    2016-02-26

    The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as cystic organoids, were characterized by high expression of the stem cell marker Lgr5, by the expression of liver progenitor and duct markers, and by low expression of hepatocyte markers, oval cell markers, and stellate cell markers. Prolonged cultures of rat liver organoids depended on high levels of WNT-signalling and the inhibition of BMP-signaling. Upon transplantation of clonal lines to a Fah(-/-) Il2rg(-/-) rat model of liver failure, the rat liver stem cells engrafted into the host liver where they differentiated into areas with FAH and Albumin positive hepatocytes. Rat liver stem cell lines hold potential as consistent reliable cell sources for pharmacological, toxicological or metabolic studies. In addition, rat liver stem cell lines may contribute to the development of regenerative medicine in liver disease. To our knowledge, the here described liver stem cell lines represent the first organoid culture system in the rat.

  14. Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure

    PubMed Central

    Kuijk, Ewart W.; Rasmussen, Shauna; Blokzijl, Francis; Huch, Meritxell; Gehart, Helmuth; Toonen, Pim; Begthel, Harry; Clevers, Hans; Geurts, Aron M.; Cuppen, Edwin

    2016-01-01

    The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as cystic organoids, were characterized by high expression of the stem cell marker Lgr5, by the expression of liver progenitor and duct markers, and by low expression of hepatocyte markers, oval cell markers, and stellate cell markers. Prolonged cultures of rat liver organoids depended on high levels of WNT-signalling and the inhibition of BMP-signaling. Upon transplantation of clonal lines to a Fah−/− Il2rg−/− rat model of liver failure, the rat liver stem cells engrafted into the host liver where they differentiated into areas with FAH and Albumin positive hepatocytes. Rat liver stem cell lines hold potential as consistent reliable cell sources for pharmacological, toxicological or metabolic studies. In addition, rat liver stem cell lines may contribute to the development of regenerative medicine in liver disease. To our knowledge, the here described liver stem cell lines represent the first organoid culture system in the rat. PMID:26915950

  15. Emphysema model in rats treated intratracheally with elastase

    SciTech Connect

    Yokoyama, E.; Nambu, Z.; Uchiyama, I.; Kyono, H.

    1987-04-01

    Pulmonary functions, morphology, and morphometry were examined in rats at 3, 7, and 10 weeks after a single intratracheal administration of 6.5 units of porcine pancreatic elastase in order to obtain a model of pulmonary emphysema which would be suitable for studying the responses of emphysematous lungs to atmospheric pollutants. Functional residual capacity and residual volume of the elastase-treated rats increased at all the times studied, but their total lung capacity increased only at 7 and 10 weeks compared with those of the saline-treated control rats. The increase in static lung compliance and the decrease in peak flow and maximum flow at 50% of total lung capacity during forced expiration were also observed in all except the 3-week elastase animals. The elastase-treated lungs showed morphological changes characteristic of emphysematous lesions. The increase in mean linear intercept length and the decrease in total alveolar surface area were demonstrated by these elastase-treated lungs. Based on these results, they conclude that an adequate and suitable model of pulmonary emphysemia could be obtained in rats 7-10 weeks after treatment with the present dose of elastase.

  16. Local insulin therapy affects fracture healing in a rat model.

    PubMed

    Park, Andrew G; Paglia, David N; Al-Zube, Loay; Hreha, Jeremy; Vaidya, Swaroopa; Breitbart, Eric; Benevenia, Joseph; O'Connor, J Patrick; Lin, Sheldon S

    2013-05-01

    A significant number of lower extremity fractures result in mal-union necessitating effective treatments to restore ambulation. Prior research in diabetic animal fracture models demonstrated improved healing following local insulin application to the fracture site and indicated that local insulin therapy can aid bone regeneration, at least within an insulin-dependent diabetic animal model. This study tested whether local insulin therapy could accelerate femur fracture repair in normal, non-diabetic rats. High (20 units) and low (10 units) doses of insulin were delivered in a calcium sulfate carrier which provided sustained release of the exogenous insulin for 7 days after fracture. Histomorphometry, radiographic scoring, and torsional mechanical testing were used to measure fracture healing. The fracture calluses from rats treated with high-dose insulin had significantly more cartilage than untreated rats after 7 and 14 days of healing. After 4 weeks of healing, femurs from rats treated with low-dose insulin had significantly higher radiographic scores and mechanical strength (p < 0.05), compared to the no treatment control groups. The results of this study suggest that locally delivered insulin is a potential therapeutic agent for treating bone fractures. Further studies are necessary, such as large animal proof of concepts, prior to the clinical use of insulin for bone fracture treatment.

  17. Osteoporotic rat models for evaluation of osseointegration of bone implants.

    PubMed

    Alghamdi, Hamdan S; van den Beucken, Jeroen J J P; Jansen, John A

    2014-06-01

    Osseointegration of dental and orthopedic bone implants is the important process that leads to mechanical fixation of implants and warrants implant functionality. In view of increasing numbers of osteoporotic patients, bone implant surface optimization strategies with instructive and drug-loading ability have been heavily explored. However, few animal models are available to study the effect of novel implant surface modifications in osteoporotic conditions. Since laboratory rats comply with a number of practical advantages, including the reliability of several methods for rapid induction of osteoporotic conditions, the present work aimed to define the use of the femoral condyle in osteoporotic female and male rats as a suitable implantation model to study osseointegration of bone implants. The method describes the procedures for induction (by hypogonadism) and assessment (by in vivo micro-computed tomography [CT]) of osteoporotic conditions in both female and male rats. The implantation site architecture (femoral condyle bone properties and dimensions) was comparatively evaluated for female and male rats, and the implant installation procedures are described. Finally, the possible analytical techniques to evaluate bone responses via mechanical tests, ex vivo micro-CT, and histological methods are provided.

  18. Composite hemiface/calvaria transplantation model in rats.

    PubMed

    Yazici, Ilker; Unal, Sakir; Siemionow, Maria

    2006-11-01

    Extensive craniomaxillofacial deformities including bone and soft-tissue defects are always challenging for reconstructive surgeons. The purpose of this study was to extend application of the face/scalp transplantation model in the rat by incorporation of the vascularized calvarial bone, based on the same vascular pedicle, as a new treatment option for extensive craniomaxillofacial deformities with large bone defects. Seven composite hemiface/calvaria transplantations were performed across major histocompatibility complex barrier between Lewis-Brown Norway and Lewis rats. Seven donor and seven recipient rats were used in this study. Hemicalvarial bone and face grafts were dissected on the same pedicle of the common carotid artery and jugular vein and were transplanted to the deepithelialized donor faces. All rats received tapered and continuous doses of cyclosporine A monotherapy. Evaluation methods included flap angiography, daily inspection, computed tomographic scan, and bone histology. Flap angiography demonstrated the vascular supply of the bone. The average survival time was 154 days. There were no signs of rejection and there was no flap loss noted at 220 days posttransplantation. Bone histology at days 7, 30, 63, and 100 after transplantation revealed viable bone at all time points, and computed tomographic scans taken at days 14, 30, and 100 revealed normal bones without resorption. For extensive face deformities involving large bone and soft-tissue defects, this new osteomusculocutaneous hemiface/calvaria flap model may serve to create new reconstructive options for covering during one surgical procedure.

  19. Antioxidant and anti-hyperlipidemic effects of mycelia zinc polysaccharides by Pleurotus eryngii var. tuoliensis.

    PubMed

    Xu, Nuo; Ren, Zhenzhen; Zhang, Jianjun; Song, Xinling; Gao, Zheng; Jing, Huijuan; Li, Shangshang; Wang, Shouxian; Jia, Le

    2017-02-01

    The aims of this work were designed to investigate the hepatoprotective and antioxidant effects of acidic- and alkali-extractable mycelia zinc polysaccharides (AcMZPS, AlMZPS) from Pleurotus eryngii var. tuoliensis on high-fat-high-cholesterol emulsion-induced hyperlipidemic mice. The in vivo experiments demonstrated that both AcMZPS and AlMZPS had potential hepatoprotective effects by significantly decreasing the levels of LDL-C, VLDL-C, TC, TG, ALT, AST, ALP, MDA and LPO, and remarkably increasing the HDL-C, SOD, GSH-Px, and CAT in serum lipid/liver homogenate, respectively. In addition, four polysaccharide fractions of AcMZPS-1, AcMZPS-2, AlMZPS-1, and AlMZPS-2, purified from AcMZPS and AlMZPS using DEAE chromatography, respectively, were subjected to monosaccharide composition analysis and valuated for the in vitro antioxidant activity. The results obtained in present study suggested that AcMZPS, AlMZPS and their purified fractions could be used as functional foods and natural drugs in preventing the hyperlipidemia and non-alcoholic fatty liver.

  20. Pentosan polysulfate inhibits atherosclerosis in Watanabe heritable hyperlipidemic rabbits: differential modulation of metalloproteinase-2 and -9.

    PubMed

    Lupia, Enrico; Zheng, Feng; Grosjean, Fabrizio; Tack, Ivan; Doublier, Sophie; Elliot, Sharon J; Vlassara, Helen; Striker, Gary E

    2012-02-01

    Pentosan polysulfate (PPS), a heparinoid compound essentially devoid of anticoagulant activity, modulates cell growth and decreases inflammation. We investigated the effect of PPS on the progression of established atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. After severe atherosclerosis developed on an atherogenic diet, WHHL rabbits were treated with oral PPS or tap water for 1 month. The aortic intima-to-media ratio and macrophage infiltration were reduced, plaque collagen content was increased, and plaque fibrous caps were preserved by PPS treatment. Plasma lipid levels and post-heparin hepatic lipase activity remained unchanged. However, net collagenolytic activity in aortic extracts was decreased, and the levels of matrix metalloproteinase (MMP)-2 and tissue inhibitor of metalloproteinase (TIMP) activity were increased by PPS. Moreover, PPS treatment decreased tumor necrosis factor α (TNFα)-stimulated proinflammatory responses, in particular activation of nuclear factor-κB and p38, and activation of MMPs in macrophages. In conclusion, oral PPS treatment prevents progression of established atherosclerosis in WHHL rabbits. This effect may be partially mediated by increased MMP-2 and TIMP activities in the aortic wall and reduced TNFα-stimulated inflammation and MMP activation in macrophages. Thus, PPS may be a useful agent in inhibiting the progression of atherosclerosis.

  1. Resistance training with soy vs whey protein supplements in hyperlipidemic males

    PubMed Central

    DeNysschen, Carol A; Burton, Harold W; Horvath, Peter J; Leddy, John J; Browne, Richard W

    2009-01-01

    Background Most individuals at risk for developing cardiovascular disease (CVD) can reduce risk factors through diet and exercise before resorting to drug treatment. The effect of a combination of resistance training with vegetable-based (soy) versus animal-based (whey) protein supplementation on CVD risk reduction has received little study. The study's purpose was to examine the effects of 12 weeks of resistance exercise training with soy versus whey protein supplementation on strength gains, body composition and serum lipid changes in overweight, hyperlipidemic men. Methods Twenty-eight overweight, male subjects (BMI 25–30) with serum cholesterol >200 mg/dl were randomly divided into 3 groups (placebo (n = 9), and soy (n = 9) or whey (n = 10) supplementation) and participated in supervised resistance training for 12 weeks. Supplements were provided in a double blind fashion. Results All 3 groups had significant gains in strength, averaging 47% in all major muscle groups and significant increases in fat free mass (2.6%), with no difference among groups. Percent body fat and waist-to-hip ratio decreased significantly in all 3 groups an average of 8% and 2%, respectively, with no difference among groups. Total serum cholesterol decreased significantly, again with no difference among groups. Conclusion Participation in a 12 week resistance exercise training program significantly increased strength and improved both body composition and serum cholesterol in overweight, hypercholesterolemic men with no added benefit from protein supplementation. PMID:19284589

  2. Cyclooxygenase-2 in Endothelial and Vascular Smooth Muscle Cells Restrains Atherogenesis in Hyperlipidemic Mice

    PubMed Central

    Tang, Soon Yew; Monslow, James; Todd, Leslie; Lawson, John; Puré, Ellen; FitzGerald, Garret A.

    2014-01-01

    Background Placebo controlled trials of nonsteroidal antinflammatory drugs (NSAIDs) selective for inhibition of COX-2 reveal an emergent cardiovascular hazard in patients selected for low risk of heart disease. Postnatal global deletion of COX-2 accelerates atherogenesis in hyperlipidemic mice, a process delayed by selective enzyme deletion in macrophages. Methods and Results Here, selective depletion of COX-2 in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) depressed biosynthesis of prostaglandin (PG)I2 and PGE2, elevated blood pressure and accelerated atherogenesis in Ldlr knockout (KO) mice. Deletion of COX-2 in VSMCs and ECs coincided with an increase in COX-2 expression in lesional macrophages and increased biosynthesis of thromboxane. Increased accumulation of less organized intimal collagen, laminin, α-smooth muscle actin and matrix-rich fibrosis was also apparent in lesions of the mutants. Conclusions Although atherogenesis is accelerated in global COX-2 KOs, consistent with evidence of risk transformation during chronic NSAID administration, this masks the contrasting effects of enzyme depletion in macrophages versus VSMCs and ECs. Targeting delivery of COX-2 inhibitors to macrophages may conserve their efficacy while limiting cardiovascular risk. PMID:24519928

  3. Acoustic noise improves motor learning in spontaneously hypertensive rats, a rat model of attention deficit hyperactivity disorder.

    PubMed

    Söderlund, Göran B W; Eckernäs, Daniel; Holmblad, Olof; Bergquist, Filip

    2015-03-01

    The spontaneously hypertensive (SH) rat model of ADHD displays impaired motor learning. We used this characteristic to study if the recently described acoustic noise benefit in learning in children with ADHD is also observed in the SH rat model. SH rats and a Wistar control strain were trained in skilled reach and rotarod running under either ambient noise or in 75 dBA white noise. In other animals the effect of methylphenidate (MPH) on motor learning was assessed with the same paradigms. To determine if acoustic noise influenced spontaneous motor activity, the effect of acoustic noise was also determined in the open field activity paradigm. We confirm impaired motor learning in the SH rat compared to Wistar SCA controls. Acoustic noise restored motor learning in SH rats learning the Montoya reach test and the rotarod test, but had no influence on learning in Wistar rats. Noise had no effect on open field activity in SH rats, but increased corner time in Wistar. MPH completely restored rotarod learning and performance but did not improve skilled reach in the SH rat. It is suggested that the acoustic noise benefit previously reported in children with ADHD is shared by the SH rat model of ADHD, and the effect is in the same range as that of stimulant treatment. Acoustic noise may be useful as a non-pharmacological alternative to stimulant medication in the treatment of ADHD.

  4. Combating Combination of Hypertension and Diabetes in Different Rat Models

    PubMed Central

    Rosenthal, Talma; Younis, Firas; Alter, Ariela

    2010-01-01

    Rat experimental models are used extensively for studying physiological mechanisms and treatments of hypertension and diabetes co-existence. Each one of these conditions is a major risk factor for cardiovascular disease (CVD), and the combination of the two conditions is a potent enhancer of CVD. Five major animal models that advanced our understanding of the mechanisms and therapeutic approaches in humans are discussed in this review: Zucker, Goto-Kakizaki, SHROB, SHR/NDmcr-cp and Cohen Rosenthal diabetic hypertensive (CRDH) rats. The use of various drugs, such as angiotensin-converting enzyme (ACE) inhibitors (ACEIs), various angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs), to combat the effects of concomitant pathologies on the combination of diabetes and hypertension, as well as the non-pharmacological approach are reviewed in detail for each rat model. Results from experiments on these models indicate that classical factors contributing to the pathology of hypertension and diabetes combination—Including hypertension, hyperglycemia, hyperinsulinemia and hyperlipidemia—can now be treated, although these treatments do not completely prevent renal complications. Animal studies have focused on several mechanisms involved in hypertension/diabetes that remain to be translated into clinical medicine, including hypoxia, oxidative stress, and advanced glycation. Several target molecules have been identified that need to be incorporated into a treatment modality. The challenge continues to be the identification and interpretation of the clinical evidence from the animal models and their application to human treatment. PMID:27713282

  5. Particulate matter inhalation exacerbates cardiopulmonary injury in a rat model of isoproterenol-induced cardiomyopathy

    EPA Science Inventory

    Ambient particulate matter (PM) exposure is linked to cardiovascular events and death, especially among individuals with heart disease. A model of toxic cardiomyopathy was developed in Spontaneously Hypertensive Heart Failure (SHHF) rats to explore potential mechanisms. Rats were...

  6. Particulate matter inhalation exacerbates cardiopulmonary injury in a rat model of isoproterenol-induced cardiomyopathy

    EPA Science Inventory

    Ambient particulate matter (PM) exposure is linked to cardiovascular events and death, especially among individuals with heart disease. A model of toxic cardiomyopathy was developed in Spontaneously Hypertensive Heart Failure (SHHF) rats to explore potential mechanisms. Rats were...

  7. Rat clonidine mydriasis model: imidazoline receptors are not involved.

    PubMed

    Yu, Yongxin; Koss, Michael C

    2005-01-15

    The clonidine mydriasis model in rats has been widely applied in preclinical research to characterize alpha(2)-adrenoceptor antagonistic properties of drugs. The present study was undertaken to pharmacologically determine if imidazoline I(1) receptors are also involved in this model system. Sigmoid dose-response curves for pupillary dilation were produced in pentobarbital anesthetized rats by intravenous administration of increasing doses of agonists (guanabenz for alpha(2)-adrenoceptors, clonidine for both alpha(2)-adrenoceptors and imidazoline I(1) receptors, and rilmenidine for imidazoline I(1) receptors). Two antagonists (RS 79948 for alpha(2)-adrenoceptors and efaroxan for imidazoline I(1) receptors) were used to antagonize the mydriasis elicited by those three agonists, with antagonistic potencies calculated. In additional experiments, we examined the effect of the selective imidazoline I(1) receptor antagonist, AGN 192403, on clonidine-induced mydriasis. The results showed that pupillary response curves elicited by guanabenz, clonidine and rilmenidine were competitively antagonized by both RS 79948 (0.03-1 mg/kg) and efaroxan (0.03-1 mg/kg) in a dose-related fashion. The potencies of either antagonist against the three agonists were not significantly different. AGN 192403 (5 mg/kg) did not significantly shift the clonidine mydriasis curve. These results suggest that imidazoline I(1) receptors are not functionally involved in the rat clonidine mydriasis model and support this in vivo system as a useful model for studies of alpha(2)-adrenoceptors.

  8. Experimental model of arthritis induced by Paracoccidioides brasiliensis in rats.

    PubMed

    Loth, Eduardo Alexandre; Biazin, Samia Khalil; Paula, Claudete Rodrigues; Simão, Rita de Cássia Garcia; de Franco, Marcello Fabiano; Puccia, Rosana; Gandra, Rinaldo Ferreira

    2012-09-01

    Paracoccidioidomycosis (PCM), a disease caused by the fungus Paracoccidioides brasiliensis (Pb), is highly prevalent in Brazil, where it is the principal cause of death by systemic mycoses. The disease primarily affects men aged 30-50 year old and usually starts as a pulmonary focus and then may spread to other organs and systems, including the joints. The present study aimed to develop an experimental model of paracoccidioidomycotic arthritis. Two-month-old male Wistar rats (n = 48) were used, divided in 6 groups: test groups EG/15 and EG/45 (received one dose of 100 μl of saline containing 10(5) Pb viable yeasts in the knee); heat killed Pb-group HK/15 and HK/45 (received a suspension of 10(5) Pb nonviable yeasts in the knee) and control groups CG/15 and CG/45 (received only sterile saline in the knee). The rats were killed 15 and 45 days postinoculation. In contrast with the control rats, the histopathology of the joints of rats of the test groups (EG/15 and EG/45) revealed a picture of well-established PCM arthritis characterized by extensive sclerosing granulomatous inflammation with numerous multiple budding fungal cells. The X-ray examination revealed joint alterations in these groups. Only metabolic active fungi evoked inflammation. The experimental model was able to induce fungal arthritis in the knees of the rats infected with metabolic active P. brasiliensis. The disease tended to be regressive and restrained by the immune system. No evidence of fungal dissemination to the lungs was observed.

  9. Creation of Consistent Burn Wounds: A Rat Model

    PubMed Central

    Cai, Elijah Zhengyang; Ang, Chuan Han; Raju, Ashvin; Tan, Kong Bing; Hing, Eileen Chor Hoong; Loo, Yihua; Wong, Yong Chiat; Lee, Hanjing; Lim, Jane; Moochhala, Shabbir M; Hauser, Charlotte AE

    2014-01-01

    Background Burn infliction techniques are poorly described in rat models. An accurate study can only be achieved with wounds that are uniform in size and depth. We describe a simple reproducible method for creating consistent burn wounds in rats. Methods Ten male Sprague-Dawley rats were anesthetized and dorsum shaved. A 100 g cylindrical stainless-steel rod (1 cm diameter) was heated to 100℃ in boiling water. Temperature was monitored using a thermocouple. We performed two consecutive toe-pinch tests on different limbs to assess the depth of sedation. Burn infliction was limited to the loin. The skin was pulled upwards, away from the underlying viscera, creating a flat surface. The rod rested on its own weight for 5, 10, and 20 seconds at three different sites on each rat. Wounds were evaluated for size, morphology and depth. Results Average wound size was 0.9957 cm2 (standard deviation [SD] 0.1845) (n=30). Wounds created with duration of 5 seconds were pale, with an indistinct margin of erythema. Wounds of 10 and 20 seconds were well-defined, uniformly brown with a rim of erythema. Average depths of tissue damage were 1.30 mm (SD 0.424), 2.35 mm (SD 0.071), and 2.60 mm (SD 0.283) for duration of 5, 10, 20 seconds respectively. Burn duration of 5 seconds resulted in full-thickness damage. Burn duration of 10 seconds and 20 seconds resulted in full-thickness damage, involving subjacent skeletal muscle. Conclusions This is a simple reproducible method for creating burn wounds consistent in size and depth in a rat burn model. PMID:25075351

  10. Chronic gastritis rat model and role of inducing factors

    PubMed Central

    Xiang, Zun; Si, Jian-Min; Huang, Huai-De

    2004-01-01

    AIM: To establish an experimental animal model of chronic gastritis in a short term and to investigate the effects of several potential inflammation-inducing factors on rat gastric mucosa. METHODS: Twenty-four healthy, male SD rats were treated with intragastric administration of 600 mL/L alcohol, 20 mmol/L sodium deoxycholate and 0.5 g/L ammonia (factor A), forage containing low levels of vitamins (factor B), and/or indomethacin (factor C), according to an L8(27) orthogonal design. After 12 wk, gastric antral and body mucosae were pathologically examined. RESULTS: Chronic gastritis model was successfully induced in rats treated with factor A for 12 wk. After the treatment of animals, the gastric mucosal inflammation was significantly different from that in controls, and the number of pyloric glands at antrum and parietal cells at body were obviously reduced (P < 0.01). Indomethacin induced gastritis but without atrophy, and short-term vitamin deficiency failed to induce chronic gastritis and gastric atrophy. In addition, indomethacin and vitamin deficiency had no synergistic effect in inducing gastritis with the factor A. No atypical hyperplasia and intestinal metaplasia in the gastric antrum and body were observed in all rats studied. CONCLUSION: Combined intragastric administration of 600 mL/L alcohol, 20 mmol/L sodium deoxycholate and 0.5 g/L ammonia induces chronic gastritis and gastric atrophy in rats. Indomethacin induces chronic gastritis only. The long-term roles of these factors in gastric inflammation and carcinogenesis need to be further elucidated. PMID:15457578

  11. The rat caudal nerves: a model for experimental neuropathies.

    PubMed

    Schaumburg, Herbert H; Zotova, Elena; Raine, Cedric S; Tar, Moses; Arezzo, Joseph

    2010-06-01

    This study provides a detailed investigation of the anatomy of the rat caudal nerve along its entire length, as well as correlated nerve conduction measures in both large and small diameter axons. It determines that rodent caudal nerves provide a simple, sensitive experimental model for evaluation of the pathophysiology of degeneration, recovery, and prevention of length-dependent distal axonopathy. After first defining the normal anatomy and electrophysiology of the rat caudal nerves, acrylamide monomer, a reliable axonal toxin, was administered at different doses for escalating time periods. Serial electrophysiological recordings were obtained, during intoxication, from multiple sites along caudal and distal sciatic nerves. Multiple sections of the caudal and sciatic nerves were examined with light and electron microscopy. The normal distribution of conduction velocities was determined and acrylamide-induced time- and dose-related slowing of velocities at the vulnerable ultraterminal region was documented. Degenerative morphological changes in the distal regions of the caudal nerves appeared well before changes in the distal sciatic nerves. Our study has shown that (1) rat caudal nerves have a complex neural structure that varies along a distal-to-proximal gradient and (2) correlative assessment of both morphology and electrophysiology of rat caudal nerves is easily achieved and provides a highly sensitive index of the onset and progression of the length-dependent distal axonopathy.

  12. Evaluation of two experimental models of hepatic encephalopathy in rats.

    PubMed

    García-Moreno, L M; Conejo, N M; González-Pardo, H; Aller, M A; Nava, M P; Arias, J; Arias, J L

    2005-01-01

    The serious neuropsychological repercussions of hepatic encephalopathy have led to the creation of several experimental models in order to better understand the pathogenesis of the disease. In the present investigation, two possible causes of hepatic encephalopathy, cholestasis and portal hypertension, were chosen to study the behavioral impairments caused by the disease using an object recognition task. This working memory test is based on a paradigm of spontaneous delayed non-matching to sample and was performed 60 days after surgery. Male Wistar rats (225-250 g) were divided into three groups: two experimental groups, microsurgical cholestasis (N = 20) and extrahepatic portal hypertension (N = 20), and a control group (N = 20). A mild alteration of the recognition memory occurred in rats with cholestasis compared to control rats and portal hypertensive rats. The latter group showed the poorest performance on the basis of the behavioral indexes tested. In particular, only the control group spent significantly more time exploring novel objects compared to familiar ones (P < 0.001). In addition, the portal hypertension group spent the shortest time exploring both the novel and familiar objects (P < 0.001). These results suggest that the existence of portosystemic collateral circulation per se may be responsible for subclinical encephalopathy.

  13. Culture Model of Rat Portal Myofibroblasts

    PubMed Central

    El Mourabit, Haquima; Loeuillard, Emilien; Lemoinne, Sara; Cadoret, Axelle; Housset, Chantal

    2016-01-01

    Myofibroblasts are matrix-producing cells with contractile properties, usually characterized by de novo expression of alpha-smooth muscle actin, that arise in fibrotic diseases. Hepatic stellate cells (HSCs), known as perisinusoidal cells containing auto-fluorescent vitamin A, are the major although not exclusive source of myofibroblasts in the injured liver. Portal myofibroblasts (PMFs) have been defined as liver myofibroblasts derived from cells that are distinct from HSCs and located in the portal tract. Here, we describe the protocol we have established to obtain rat PMFs in culture. In this method, the biliary tree is (i) separated from the liver parenchyma by in situ enzymatic perfusion of the liver, (ii) minced and further digested in vitro, until bile duct segments are isolated by sequential filtration. Bile duct isolates free of HSC contaminants, form small cell clusters, which initially comprise a large majority of epithelial cells. In culture conditions (fetal bovine serum) that provide a growth advantage to mesenchymal cells over epithelial cells, the epithelial cells die and detach from the substrate, while spindle-shaped cells outgrow from the periphery of the cell clusters, as shown by video-microscopy. These cells are highly proliferative and after 4–5 days, the culture is composed exclusively of fully differentiated myofibroblasts, which express alpha-smooth muscle actin and collagen 1, and secrete abundant collagen. We found no evidence for epithelial-mesenchymal transition, i.e., no co-expression of alpha-smooth muscle actin and cytokeratin at any stage, while cytokeratin becomes undetectable in the confluent cells. PMFs obtained by this method express the genes that were previously reported to be overexpressed in non-HSC or portal fibroblast-derived liver myofibroblasts as compared to HSC-derived myofibroblasts, including the most discriminant, collagen 15, fibulin 2, and Thy-1. After one passage, PMFs retain the same phenotypic features as in

  14. Culture Model of Rat Portal Myofibroblasts.

    PubMed

    El Mourabit, Haquima; Loeuillard, Emilien; Lemoinne, Sara; Cadoret, Axelle; Housset, Chantal

    2016-01-01

    Myofibroblasts are matrix-producing cells with contractile properties, usually characterized by de novo expression of alpha-smooth muscle actin, that arise in fibrotic diseases. Hepatic stellate cells (HSCs), known as perisinusoidal cells containing auto-fluorescent vitamin A, are the major although not exclusive source of myofibroblasts in the injured liver. Portal myofibroblasts (PMFs) have been defined as liver myofibroblasts derived from cells that are distinct from HSCs and located in the portal tract. Here, we describe the protocol we have established to obtain rat PMFs in culture. In this method, the biliary tree is (i) separated from the liver parenchyma by in situ enzymatic perfusion of the liver, (ii) minced and further digested in vitro, until bile duct segments are isolated by sequential filtration. Bile duct isolates free of HSC contaminants, form small cell clusters, which initially comprise a large majority of epithelial cells. In culture conditions (fetal bovine serum) that provide a growth advantage to mesenchymal cells over epithelial cells, the epithelial cells die and detach from the substrate, while spindle-shaped cells outgrow from the periphery of the cell clusters, as shown by video-microscopy. These cells are highly proliferative and after 4-5 days, the culture is composed exclusively of fully differentiated myofibroblasts, which express alpha-smooth muscle actin and collagen 1, and secrete abundant collagen. We found no evidence for epithelial-mesenchymal transition, i.e., no co-expression of alpha-smooth muscle actin and cytokeratin at any stage, while cytokeratin becomes undetectable in the confluent cells. PMFs obtained by this method express the genes that were previously reported to be overexpressed in non-HSC or portal fibroblast-derived liver myofibroblasts as compared to HSC-derived myofibroblasts, including the most discriminant, collagen 15, fibulin 2, and Thy-1. After one passage, PMFs retain the same phenotypic features as in

  15. Mathematical model of glucose-insulin homeostasis in healthy rats.

    PubMed

    Lombarte, Mercedes; Lupo, Maela; Campetelli, German; Basualdo, Marta; Rigalli, Alfredo

    2013-10-01

    According to the World Health Organization there are over 220 million people in the world with diabetes and 3.4 million people died in 2004 as a consequence of this pathology. Development of an artificial pancreas would allow to restore control of blood glucose by coupling an infusion pump to a continuous glucose sensor in the blood. The design of such a device requires the development and application of mathematical models which represent the gluco-regulatory system. Models developed by other research groups describe very well the gluco-regulatory system but have a large number of mathematical equations and require complex methodologies for the estimation of its parameters. In this work we propose a mathematical model to study the homeostasis of glucose and insulin in healthy rats. The proposed model consists of three differential equations and 8 parameters that describe the variation of: blood glucose concentration, blood insulin concentration and amount of glucose in the intestine. All parameters were obtained by setting functions to the values of glucose and insulin in blood obtained after oral glucose administration. In vivo and in silico validations were performed. Additionally, a qualitative analysis has been done to verify the aforementioned model. We have shown that this model has a single, biologically consistent equilibrium point. This model is a first step in the development of a mathematical model for the type I diabetic rat.

  16. Developing a rat model of dilated cardiomyopathy with improved survival* #

    PubMed Central

    Shen, Li-juan; Lu, Shu; Zhou, Yong-hua; Li, Lan; Xing, Qing-min; Xu, Yong-liang

    2016-01-01

    To compare the continuous infusion and intermittent bolus injection administration protocols of doxorubicin (Dox) under the same cumulative dose (12 mg/kg), and establish a rat dilated cardiomyopathy model with improved survival, a total of 150 Sprague-Dawley (SD) rats were divided into three groups: a control group, administered with normal saline; a Dox 1 group, administration twice a week at 1 mg/kg; a Dox 2, administration once a week at 2 mg/kg. Mortality rates in the Dox 1 and Dox 2 groups were 22% and 48%, respectively (P<0.05). As shown by echocardiography, both Dox groups exhibited significant chamber dilatation and reduced cardiac function (all P<0.05 vs. control). Plasma brain natriuretic peptide and C-reactive protein concentrations were significantly increased (P<0.05) with both Dox regimens. The concentrations of Caspase-3 in myocardial tissues of rats significantly increased in both doxorubicin regimens. Myocardial metabolism imaging by histology and 18F-fluoro-deoxyglucose-positron emission tomography (18FDG-PET) both revealed decreased myocardial viability and necrosis, and even interstitial fibrosis, in left ventricles (LVs) in both Dox groups. Serum creatinine and aspartate aminotransferase concentrations were significantly higher in the Dox 2 model than in the Dox 1 model. Doxorubicin given at both regimens induced dilated cardiomyopathy, while its administration at lower doses with more frequent infusions reduced the mortality rate. PMID:27921402

  17. The Laboratory Rat as an Animal Model for Osteoporosis Research

    PubMed Central

    Lelovas, Pavlos P; Xanthos, Theodoros T; Thoma, Sofia E; Lyritis, George P; Dontas, Ismene A

    2008-01-01

    Osteoporosis is an important systemic disorder, affecting mainly Caucasian women, with a diverse and multifactorial etiology. A large variety of animal species, including rodents, rabbits, dogs, and primates, have been used as animal models in osteoporosis research. Among these, the laboratory rat is the preferred animal for most researchers. Its skeleton has been studied extensively, and although there are several limitations to its similarity to the human condition, these can be overcome through detailed knowledge of its specific traits or with certain techniques. The rat has been used in many experimental protocols leading to bone loss, including hormonal interventions (ovariectomy, orchidectomy, hypophysectomy, parathyroidectomy), immobilization, and dietary manipulations. The aim of the current review is not only to present the ovariectomized rat and its advantages as an appropriate model for the research of osteoporosis, but also to provide information about the most relevant age and bone site selection according to the goals of each experimental protocol. In addition, several methods of bone mass evaluation are assessed, such as biochemical markers, densitometry, histomorphometry, and bone mechanical testing, that are used for monitoring and evaluation of this animal model in preventive or therapeutic strategies for osteoporosis. PMID:19004367

  18. Anti-hyperlipidemic sesquiterpenes and new sesquiterpene glycosides from the leaves of artichoke (Cynara scolymus L.): structure requirement and mode of action.

    PubMed

    Shimoda, Hiroshi; Ninomiya, Kiyofumi; Nishida, Norihisa; Yoshino, Tomoe; Morikawa, Toshio; Matsuda, Hisashi; Yoshikawa, Masayuki

    2003-01-20

    The methanolic extract from the leaves of artichoke (Cynara scolymus L.) was found to suppress serum triglyceride elevation in olive oil-loaded mice. Through bioassay-guided separation, sesquiterpenes (cynaropicrin, aguerin B, and grosheimin) were isolated as the active components together with new sesquiterpene glycosides (cynarascolosides A, B, and C). The oxygen functional groups at the 3- and 8-positions and exo-methylene moiety in alpha-methylene-gamma-butyrolactone ring were found to be essential for the anti-hyperlipidemic activity of guaiane-type sesquiterpene. In addition, inhibition of gastric emptying was shown to be partly involved in anti-hyperlipidemic activity.

  19. [Leveling the hyperlipidemic effect of beta-adrenoblockers by means of antiatherogenic vegetarian diet].

    PubMed

    Medkova, I L; Ieromuzo, A A; Ivanov, A N; Mosiakina, L I; Biriukova, L S

    2004-01-01

    The purpose of the study was to examine the capacities of correction of impaired lipid metabolism in patients with CHD receiving selective beta-adrenoblockers (beta-AB) by using an antiatherogenic milk-and-vegetable diet. According to the type of antiatherogenic diet, 67 patients were divided into 2 groups: 1) 42 patients were on an antiatherogenic vegetarian diet (a vegetarian group--VG) and 2) 25 patients received routine mixed diet No. 10c (a control group--CG). At the same time all the patients received similar antianginal drug therapy including the selective beta-AB atenolol in a dose of 50 mg/day. The vegetarian diet without special hypolipidemic therapy had a marked normalizing effect on the serum lipid spectrum in patients with CHD. Thus, in VG, by the end of treatment, the level of total cholesterol significantly decreased by 16% while in the controls it increased by 13%. High-density lipoprotein cholesterol increased in VG and decreased in CG, therefore the atherogenicity coefficient considerably rose. These were true for triglycerides and very low-density lipoprotein cholesterol. These parameters significantly decreased in VG (by more than 30%) and increased in CG (by 16%). Among the clinical symptoms, a more pronounced decrease in blood pressure in the patients on vegetarian diet and a more significant increase in their exercise tolerance. Balanced antiatherogenic milk-and-vegetable diet in patients with coronary heart disease prevents the hyperlipidemic effect caused by the selective beta-AB atenolol and it is an agent for preventing its negative effect on lipid metabolism.

  20. Effects of anethum graveolens and garlic on lipid profile in hyperlipidemic patients

    PubMed Central

    Kojuri, Javad; Vosoughi, Amir R; Akrami, Majid

    2007-01-01

    Background hyperlipidemia as a major risk factor of atherosclerosis is treated with different drugs. Concerning length of therapy and vast majority of side effects, herbal medication may be suitable substitute for these drugs. Methods In this single-blind, placebo controlled study, lipid profiles of 150 hyperlipidemic patients in cardiology outpatient department of Shiraz University of Medical Sciences were checked at same conditions. They were divided into three equal groups randomly (each composing of 50 patients). They were given enteric-coated garlic powder tablet (equal to 400 mg garlic, 1 mg allicin) twice daily, anethum tablet (650 mg) twice daily, and placebo tablet. All patients were put on NCEP type Π diet and Six weeks later, lipid profiles were checked. Results In garlic group: total cholesterol (decreased by 26.82 mg/dl, 12.1% reduction, and P-value: .000), and LDL-cholesterol (decreased by 22.18 mg/dl, 17.3% reduction, and P-value: .000) dropped. HDL-cholesterol (increased by 10.02 mg/dl, 15.7% increase, and P-value: .000) increased. Although triglyceride dropped by 13.72 mg/dl (6.3%) but this was not significant statistically (P-value: .222). In anethum group: surprisingly, triglyceride increased by 14.74 mg/dl (6.0%). Anethum could reduce total cholesterol by 0.4 % and LDL-cholesterol by 6.3% but these were not significant statistically (P-value: .828, and .210, respectively). Conclusion Anethum has no significant effect on lipid profile, but garlic tablet has significant favorable effect on cholesterol, LDL-cholesterol, and HDL-cholesterol. Garlic may play an important role in therapy of hypercholesterolemia. PMID:17328819

  1. Effects of anethum graveolens and garlic on lipid profile in hyperlipidemic patients.

    PubMed

    Kojuri, Javad; Vosoughi, Amir R; Akrami, Majid

    2007-03-01

    hyperlipidemia as a major risk factor of atherosclerosis is treated with different drugs. Concerning length of therapy and vast majority of side effects, herbal medication may be suitable substitute for these drugs. In this single-blind, placebo controlled study, lipid profiles of 150 hyperlipidemic patients in cardiology outpatient department of Shiraz University of Medical Sciences were checked at same conditions. They were divided into three equal groups randomly (each composing of 50 patients). They were given enteric-coated garlic powder tablet (equal to 400 mg garlic, 1 mg allicin) twice daily, anethum tablet (650 mg) twice daily, and placebo tablet. All patients were put on NCEP type Pi diet and Six weeks later, lipid profiles were checked. In garlic group: total cholesterol (decreased by 26.82 mg/dl, 12.1% reduction, and P-value: .000), and LDL-cholesterol (decreased by 22.18 mg/dl, 17.3% reduction, and P-value: .000) dropped. HDL-cholesterol (increased by 10.02 mg/dl, 15.7% increase, and P-value: .000) increased. Although triglyceride dropped by 13.72 mg/dl (6.3%) but this was not significant statistically (P-value: .222). In anethum group: surprisingly, triglyceride increased by 14.74 mg/dl (6.0%). Anethum could reduce total cholesterol by 0.4 % and LDL-cholesterol by 6.3% but these were not significant statistically (P-value: .828, and .210, respectively). Anethum has no significant effect on lipid profile, but garlic tablet has significant favorable effect on cholesterol, LDL-cholesterol, and HDL-cholesterol. Garlic may play an important role in therapy of hypercholesterolemia.

  2. MRI study of atherosclerotic plaque progression using ultrasmall superparamagnetic iron oxide in Watanabe heritable hyperlipidemic rabbits.

    PubMed

    Kaneko, C; Nitta, N; Tsuchiya, K; Watanabe, S; Nitta-Seko, A; Ohta, S; Otani, H; Sonoda, A; Murata, K; Shiomi, M

    2015-09-01

    The purpose of this study was to evaluate plaque progression by using MRI with ultrasmall superparamagnetic iron oxide (USPIO) and by histopathological studies. We divided 12 Watanabe heritable hyperlipidemic (WHHL) rabbits into 4 groups based on their age (3, 9, 14 and 26 months) and injected them intravenously with 0.8 mmol (Fe) kg(-1) of USPIO (size, 32 nm; concentration, 15 mg dl(-1)). On the fifth post-injection day, they were again given an intravenous injection with 40 μmol kg(-1) of the same USPIO, and MR angiography (MRA) was performed. The signal-to-noise ratio (SNR) in regions of interest in the wall of the upper abdominal aorta was calculated on coronal images. Specimens from the same level of the aorta were subjected to iron staining and RAM-11 immunostaining and used for histopathological study. For statistical analysis of the MRA and histopathological findings, we used analysis of variance [Tukey's honest significant difference (HSD) test]. In 9-month-old rabbits, the SNR was significantly lower than in rabbits of the other ages (p < 0.01), and the area of RAM-11 (DAKO Corporation, Glostrup, Denmark) and iron uptake in the aortic wall was significantly larger (RAM-11, p < 0.01; iron, p < 0.05). These areas were the smallest in 3-month-old rabbits. Histopathologically, the number of macrophages was the greatest in 9-month-old rabbits. Our findings indicate that the SNR on MRI scans reflects the number of macrophages in the aortic wall of WHHL rabbits. USPIO-enhanced MRI visualized the accumulation of macrophages in early atherosclerotic plaques of WHHL rabbits in the course of natural progression.

  3. Role of Neutrophils in Exacerbation of Brain Injury After Focal Cerebral Ischemia in Hyperlipidemic Mice.

    PubMed

    Herz, Josephine; Sabellek, Pascal; Lane, Thomas E; Gunzer, Matthias; Hermann, Dirk M; Doeppner, Thorsten R

    2015-10-01

    Inflammation-related comorbidities contribute to stroke-induced immune responses and brain damage. We previously showed that hyperlipidemia exacerbates ischemic brain injury, which is associated with elevated peripheral and cerebral granulocyte numbers. Herein, we evaluate the contribution of neutrophils to the exacerbation of ischemic brain injury. Wild-type mice fed with a normal chow and ApoE knockout mice fed with a high cholesterol diet were exposed to middle cerebral artery occlusion. CXCR2 was blocked using the selective antagonist SB225002 (2 mg/kg) or neutralizing CXCR2 antiserum. Neutrophils were depleted using an anti-Ly6G antibody. At 72 hours post ischemia, immunohistochemistry, flow cytometry, and real-time polymerase chain reaction were performed to determine cerebral tissue injury and immunologic changes in the blood, bone marrow, and brain. Functional outcome was assessed by accelerated rota rod and tight rope tests at 4, 7, and 14 days post ischemia. CXCR2 antagonization reduced neurological deficits and infarct volumes that were exacerbated in hyperlipidemic ApoE-/- mice. This effect was mimicked by neutrophil depletion. Cerebral neutrophil infiltration and peripheral neutrophilia, which were increased on ischemia in hyperlipidemia, were attenuated by CXCR2 antagonization. This downscaling of neutrophil responses was associated with increased neutrophil apoptosis and reduced levels of CXCR2, inducible nitric oxide synthase, and NADPH oxidase 2 expression on bone marrow neutrophils. Our data demonstrate a role of neutrophils in the exacerbation of ischemic brain injury induced by hyperlipidemia. Accordingly, CXCR2 blockade, which prevents neutrophil recruitment into the brain, might be an effective option for stroke treatment in patients with hyperlipidemia. © 2015 American Heart Association, Inc.

  4. [Anti-inflammatory effect of high-density lipoprotein on the cardiovascular system of hyperlipidemic mice].

    PubMed

    Garcia, José Antonio D; de Lima, Ciderléia Castro; Messora, Luiza B; Cruz, Aline F; Marques, Ana P S; Simão, Talita P; Soares, Evelise Aline; Cristina Costa Resck, M; Incerpi, Erika K; de Mello Oliveira, Nelma; dos Santos, Leandro

    2011-10-01

    LDLr-/- mice are spontaneously hyperlipidemic and resistant to the development of neointimal lesions. This study aimed to determine the factor that prevents the inflammatory process and neointimal lesions and insulin resistance in LDLr-/- mice. Three groups of 3-month-old male mice were used: wild-type mice (WT group); LDLr-/- mice fed a standard diet (S group); and LDLr-/- mice fed a high-fat diet (HF group). After 15 days, blood was collected for analysis of plasma lipids, glucose and insulin. The HOMA index was calculated to determine insulin resistance. The heart and aorta were removed for histological study. Histological sections of the heart were processed immunohistochemically with anti-CD40L antibodies to evaluate the inflammatory process. Histological sections of the aorta were stained with hematoxylin/eosin and picrosirius red to assess morphological and morphometric alterations. The S mice were resistant to the inflammatory process, as shown by low immunoreactivity to CD40L, with high plasma HDL levels, and did not develop insulin resistance, even with moderate hyperlipidemia compared to WT. The HF mice showed severe hyperlipidemia, increased cardiac immunoreactivity to CD40L, pronounced morphological changes in the aortic wall and insulin resistance, associated with a decrease in plasma HDL levels, compared to S. This severe hyperlipidemia in the HF mice can be considered the major metabolic factor inducing oxidative stress in the cardiovascular system, increasing the lipid peroxidation of HDL and hence its removal by the liver, with consequent lowering of plasma HDL levels. High HDL plasma levels are a protective factor against the development of cardiovascular inflammation and insulin resistance in LDLr-/- mice, preventing the development of neointimal lesions. Copyright © 2011 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  5. Rat models of asthma and chronic obstructive lung disease.

    PubMed

    Martin, James G; Tamaoka, Meiyo

    2006-01-01

    The rat has been extensively used to model asthma and somewhat less extensively to model chronic obstructive pulmonary disease (COPD). The features of asthma that have been successfully modeled include allergen-induced airway constriction, eosinophilic inflammation and allergen-induced airway hyperresponsiveness. T-cell involvement has been directly demonstrated using adoptive transfer techniques. Both CD4+ and CD8+ T cells are activated in response to allergen challenge in the sensitized rat and express Thelper2 cytokines (IL-4, IL-5 and IL-13). Repeated allergen exposure causes airway remodeling. Dry gas hyperpnea challenge also evokes increases in lung resistance, allowing exercise-induced asthma to be modeled. COPD is modeled using elastase-induced parenchymal injury to mimic emphysema. Cigarette smoke-induced airspace enlargement occurs but requires months of cigarette exposure. Inflammation and fibrosis of peripheral airways is an important aspect of COPD that is less well modeled. Novel approaches to the treatment of COPD have been reported including treatments aimed at parenchymal regeneration.

  6. Stem cell therapy in intracerebral hemorrhage rat model

    PubMed Central

    Cordeiro, Marcos F; Horn, Ana P

    2015-01-01

    Intracerebral hemorrhage (ICH) is a very complex pathology, with many different not fully elucidated etiologies and prognostics. It is the most severe subtype of stroke, with high mortality and morbidity rates. Unfortunately, despite the numerous promising preclinical assays including neuroprotective, anti-hypertensive, and anti-inflammatory drugs, to this moment only symptomatic treatments are available, motivating the search for new alternatives. In this context, stem cell therapy emerged as a promising tool. However, more than a decade has passed, and there is still much to be learned not only about stem cells, but also about ICH itself, and how these two pieces come together. To date, rats have been the most widely used animal model in this research field, and there is much more to be learned from and about them. In this review, we first summarize ICH epidemiology, risk factors, and pathophysiology. We then present different methods utilized to induce ICH in rats, and examine how accurately they represent the human disease. Next, we discuss the different types of stem cells used in previous ICH studies, also taking into account the tested transplantation sites. Finally, we summarize what has been achieved in assays with stem cells in rat models of ICH, and point out some relevant issues where attention must be given in future efforts. PMID:25914768

  7. Respiratory deficits in a rat model of Parkinson's disease.

    PubMed

    Tuppy, M; Barna, B F; Alves-Dos-Santos, L; Britto, L R G; Chiavegatto, S; Moreira, T S; Takakura, A C

    2015-06-25

    Parkinson's disease (PD) is a neurodegenerative disease characterized by loss of the dopaminergic nigrostriatal pathway. In addition to deficits in voluntary movement, PD involves a disturbance of breathing regulation. However, the cause and nature of this disturbance are not well understood. Here, we investigated breathing at rest and in response to hypercapnia (7% CO2) or hypoxia (8% O2), as well as neuroanatomical changes in brainstem regions essential for breathing, in a 6-hydroxydopamine (6-OHDA) rat model of PD. Bilateral injections of 6-OHDA (24μg/μl) into the striatum decreased tyrosine hydroxylase (TH(+))-neurons in the substantia nigra pars compacta (SNpc), transcription factor phox2b-expressing neurons in the retrotrapezoid nucleus and neurokinin-1 receptors in the ventral respiratory column. In 6-OHDA-lesioned rats, respiratory rate was reduced at rest, leading to a reduction in minute ventilation. These animals also showed a reduction in the tachypneic response to hypercapnia, but not to hypoxia challenge. These results suggest that the degeneration of TH(+) neurons in the SNpc leads to impairment of breathing at rest and in hypercapnic conditions. Our data indicate that respiratory deficits in a 6-OHDA rat model of PD are related to downregulation of neural systems involved in respiratory rhythm generation. The present study suggests a new avenue to better understand the respiratory deficits observed in chronic stages of PD. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. 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

  9. Achilles tendinosis: a morphometrical study in a rat model.

    PubMed

    Silva, Rafael Duarte; Glazebrook, Mark Anthony; Campos, Vinicius Castro; Vasconcelos, Anilton Cesar

    2011-01-01

    This study addresses the morphopathogenesis of Achilles tendinosis, using a rat model and presenting quantitative analysis of time-dependent histological changes. Thirty Wistar rats were used, randomly split in experimental and control groups. Animals of the experimental group were submitted to a treadmill running scheme. Five animals of each group were euthanized at four, eight and sixteen weeks. Achilles tendons were collected and processed routinely for histopath sections. Slides were stained by Hematoxylin-Eosin, Picrosirius Red, Alcian Blue, AgNOR, TUNEL and evaluated morphometrically. Cellular density decreased slightly along the time and was higher in the experimental group than in controls at fourth, eighth and sixteenth weeks. Fiber microtearing, percentual of reticular fibers and glycosaminoglycans content increased along the time and were higher in experimental group than in controls at all-time intervals. AgNOR labeling here interpreted as a marker of transcription activity was higher in the experimental groups than in controls at all-time intervals. Apoptotic cells were more frequent and diffusely distributed in tendinosis samples than in control groups. These results suggest that as mechanical overload is becoming chronic, cellular turnover and matrix deposition increases leading to tendinosis. The combination of staining techniques and morphometry used here to describe the evolution of lesions occurring in a rat model system has proved to be suited for the study of induced Achilles tendinosis.

  10. Metabolic alteration in obese diabetes rats upon treatment with Centella asiatica extract.

    PubMed

    Maulidiani; Abas, F; Khatib, A; Perumal, V; Suppaiah, V; Ismail, A; Hamid, M; Shaari, K; Lajis, N H

    2016-03-02

    'Pegaga' is a traditional Malay remedy for a wide range of complaints. Among the 'pegaga', Centella asiatica has been used as a remedy for diabetes mellitus. Thus, we decided to validate this claim by evaluating the in vivo antidiabetic property of C. asiatica (CA) on T2DM rat model using the holistic (1)H NMR-based metabolomics approach. In this study, an obese diabetic (mimic of T2DM condition) animal model was developed using Sprague-Dawley rats fed with a high-fat diet and induced into diabetic condition by the treatment of a low dose of streptozotocin (STZ). The effect of C. asiatica extract on the experimental animals was followed based on the changes observed in the urinary and serum metabolites, measured by (1)H NMR of urine and blood samples collected over the test period. A long-term treatment of obese diabetic rats with CA extract could reverse the glucose and lipid levels, as well as the tricarboxylic acid cycle and amino acid metabolic disorders, back towards normal states. Biochemical analysis also showed an increase of insulin production in diabetic rats upon treatment of CA extract. This study has provided evidence that clearly supported the traditional use of CA as a remedy for diabetes. NMR-based metabolomics was successfully applied to show that CA produced both anti-hyperglycemic and anti-hyperlipidemic effects on a rat model. In addition to increasing the insulin secretion, the CA extract also ameliorates the metabolic pathways affected in the induced diabetic rats. This study further revealed the potential usage of CA extract in managing diabetes mellitus and the results of this work may contribute towards the further understanding of the underlying molecular mechanism of this herbal remedy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. A rat model of spontaneous myopathy and malignant hyperthermia.

    PubMed Central

    Gonzalez, L. E.; Meléndez-Vásquez, C. V.; Gregson, N. A.; File, S. E.

    1998-01-01

    Malignant hyperthermia is a main cause of death during general anesthesia, particularly in children. However, research has been hampered by the lack of a convenient animal model, the only one available being a special strain of pig. In this study, we describe spontaneous myopathy and a fatal syndrome of generalized muscle rigidity triggered by halothane in an outbred strain of rat. Histological examination of skeletal muscle reveals severe abnormalities indicating chronic underlying myopathy. The association of histological abnormalities with an acute, fatal syndrome clinically resembling malignant hyperthermia provides a strong basis for a new and extremely useful animal model to study this fatal disorder. Images Figure 1 Figure 2 PMID:9546371

  12. Streptozotocin-Induced Diabetic Models in Mice and Rats.

    PubMed

    Furman, Brian L

    2015-09-01

    Streptozotocin (STZ) is an antibiotic that produces pancreatic islet β-cell destruction and is widely used experimentally to produce a model of type 1 diabetes mellitus (T1DM). Detailed in this unit are protocols for producing STZ-induced insulin deficiency and hyperglycemia in mice and rats. Also described are protocols for creating animal models for type 2 diabetes using STZ. These animals are employed for assessing the pathological consequences of diabetes and for screening potential therapies for the treatment of this condition.

  13. Retention modeling of diesel exhaust particles in rats and humans.

    PubMed

    Yu, C P; Yoon, K J

    1991-05-01

    The objective of this study was to predict the lung burden in rats and humans of diesel exhaust particles from automobile emissions by means of a mathematical model. We previously developed a model to predict the deposition of diesel exhaust particles in the lungs of these species. In this study, the clearance and retention of diesel exhaust particles deposited in the lung are examined. A diesel particle is composed of a carbonaceous core (soot) and adsorbed organics. These materials can be removed from the lung after deposition by two mechanisms: (1) mechanical clearance, provided by mucociliary transport in the ciliated airways as well as macrophage phagocytosis and migration in the nonciliated airways, and (2) clearance by dissolution. To study the clearance of diesel exhaust particles from the lung, we used a compartmental model consisting of four anatomical compartments: nasopharyngeal, tracheobronchial, alveolar, and the lung-associated lymph node compartments. We also assumed a particle model made up of material components according to the characteristics of clearance: (1) a carbonaceous core of about 80 percent of particle mass, (2) slowly cleared organics of about 10 percent of particle mass, and (3) fast-cleared organics accounting for the remaining 10 percent of particle mass. The kinetic equations of the retention model were first developed for Fischer-344 rats. The transport rates of each material component of diesel exhaust particles (soot, slowly cleared organics, and fast-cleared organics) were derived using available experimental data and several mathematical approximations. The lung burden results calculated from the model showed that although the organics were cleared at nearly constant rates, the alveolar clearance rate of diesel soot decreased with increasing lung burden. This is consistent with existing experimental observations. At low lung burdens, the alveolar clearance rate of diesel soot was a constant, equal to the normal clearance rate

  14. Resibufogenin corrects hypertension in a rat model of human preeclampsia.

    PubMed

    Vu, Hop; Ianosi-Irimie, Monica; Danchuk, Svitlana; Rabon, Edd; Nogawa, Toshihiko; Kamano, Yoshiaki; Pettit, G Robert; Wiese, Thomas; Puschett, Jules B

    2006-02-01

    The study of the pathogenesis of preeclampsia has been hampered by a relative dearth of animal models. We developed a rat model of preeclampsia in which the excretion of a circulating inhibitor of Na/K ATPase, marinobufagenin (MBG), is elevated. These animals develop hypertension, proteinuria, and intrauterine growth restriction. The administration of a congener of MBG, resibufogenin (RBG), reduces blood pressure to normal in these animals, as is the case when given to pregnant animals rendered hypertensive by the administration of MBG. Studies of Na/K ATPase inhibition by MBG and RBG reveal that these agents are equally effective as inhibitors of the enzyme.

  15. In vivo photoacoustic imaging of osteosarcoma in a rat model

    NASA Astrophysics Data System (ADS)

    Hu, Jun; Yu, Menglei; Ye, Fei; Xing, Da

    2011-02-01

    Osteosarcoma is one of the most common primary malignant tumors of the bone and the second leading cause of cancer-related deaths in the pediatric age group. Confirmed diagnosis and prompt treatment of osteosarcoma are critical for effective prognosis. In this study, we investigate the application of photoacoustic imaging (PAI) for the detection of osteosarcoma in an animal model. Cross-section images of a normal rat leg and a tumorous rat leg were successfully reconstructed in vivo. Morphological changes and the development of the implanted osteosarcoma were accurately mapped with time-dependent photoacoustic images. Furthermore, we evaluate the use of gold nanorods as contrast agents for imaging osteosarcoma with PAI. This is the first study that uses PAI to detect osteosarcoma in vivo, and the results suggest that PAI has the potential clinical application for detecting osteosarcoma in the early stage.

  16. Studies on sensitivity of zebrafish as a model organism for Parkinson's disease: Comparison with rat model

    PubMed Central

    Makhija, Dinesh T.; Jagtap, Aarti G.

    2014-01-01

    Objective: To determine the utility of zebra fish as an animal model for Parkinson's disease (PD) in comparison with rat model. Materials and Methods: MTT assay was performed on rat and zebrafish brain synaptosomal fractions using rotenone as a neurotoxic agent. Quercetin and resveratrol were used as standards to compare anti-apoptotic activity in both organisms. Catalepsy was induced in zebrafish by exposing them to haloperidol (9 μM) solution. Drug-treated groups were exposed to bromocriptine and pramipexole, 30 min prior to haloperidol exposure at the dose of 2, 5, and 10 μg/mL. Swimming speed, time spent in the bottom of the tank, and complete cataleptic time were evaluated to assess behavioral changes. In rats, catalepsy was induced using haloperidol (1.25 mg/kg i.p.). Drug-treated groups received bromocriptine (2.5 mg/kg.) and pramipexole (1 mg/kg) orally. Bar test, block test, and locomotor activity were carried out to assess behavioral changes. Results: Resveratrol and quercetin showed comparable inhibition of apoptosis in rats and zebrafish. In anti-cataleptic study, bromocriptine and pramipexole-treated groups showed significant difference (P < 0.05) in behavioral parameters as compared to haloperidol control group in both the experimental organisms. Results obtained from fish model were in correlation with rat model. Conclusion: Findings of the present study revealed that zebrafish model is highly sensitive and can be used for basic screening of drugs against PD. PMID:24554909

  17. Subcutaneous rotenone rat model of Parkinson's disease: Dose exploration study.

    PubMed

    Zhang, Zhen-Nian; Zhang, Jing-Si; Xiang, Jun; Yu, Zhong-Hai; Zhang, Wen; Cai, Min; Li, Xiang-Ting; Wu, Ting; Li, Wen-Wei; Cai, Ding-Fang

    2017-01-15

    Subcutaneous administration of rotenone has recently attracted attention because of its convenience, simplicity and efficacy in replicating features of Parkinson's disease (PD) in animal models. However, the wide range of doses reported in the literature makes it difficult to evaluate the effectiveness of this technique objectively. The aim of the present study was to identify the optimum dose of subcutaneous rotenone for establishing a model of PD. We injected male Wistar rats subcutaneously with one of three doses of rotenone (1.5, 2, or 2.5mg/kg) daily for 5 weeks. Rotenone caused a dose-dependent increase in α-synuclein in the substantia nigra. Furthermore, at 2 and 2.5mg/kg, rotenone caused a significant decrease in the number of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra, and dopamine in the striatum. However, mortality at 2.5mg/kg was 46.7%, compared with just 6.7% at 2mg/kg; the high mortality observed at 2.5mg/kg would limit its application. The 2mg/kg dose showed no detrimental effect on body weight after 5 weeks of daily injections. Furthermore, rats in the 2mg/kg group showed a longer latency to descend from a horizontal bar and a grid wall, decreased rearing, and shorter latency to fall from a rotarod than rats that received vehicle or saline. Mitochondrial damage, observed by transmission electron microscopy, was also evident at this dose. Together, our data indicate that daily subcutaneous injection of 2mg/kg rotenone in rats facilitates the formation of α-synuclein and reproduces the typical features of PD, while maintaining low mortality. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Experience Modulates Vicarious Freezing in Rats: A Model for Empathy

    PubMed Central

    Atsak, Piray; Orre, Marie; Bakker, Petra; Cerliani, Leonardo; Roozendaal, Benno

    2011-01-01

    The study of the neural basis of emotional empathy has received a surge of interest in recent years but mostly employing human neuroimaging. A simpler animal model would pave the way for systematic single cell recordings and invasive manipulations of the brain regions implicated in empathy. Recent evidence has been put forward for the existence of empathy in rodents. In this study, we describe a potential model of empathy in female rats, in which we studied interactions between two rats: a witness observes a demonstrator experiencing a series of footshocks. By comparing the reaction of witnesses with or without previous footshock experience, we examine the role of prior experience as a modulator of empathy. We show that witnesses having previously experienced footshocks, but not naïve ones, display vicarious freezing behavior upon witnessing a cage-mate experiencing footshocks. Strikingly, the demonstrator's behavior was in turn modulated by the behavior of the witness: demonstrators froze more following footshocks if their witness froze more. Previous experiments have shown that rats emit ultrasonic vocalizations (USVs) when receiving footshocks. Thus, the role of USV in triggering vicarious freezing in our paradigm is examined. We found that experienced witness-demonstrator pairs emitted more USVs than naïve witness-demonstrator pairs, but the number of USVs was correlated with freezing in demonstrators, not in witnesses. Furthermore, playing back the USVs, recorded from witness-demonstrator pairs during the empathy test, did not induce vicarious freezing behavior in experienced witnesses. Thus, our findings confirm that vicarious freezing can be triggered in rats, and moreover it can be modulated by prior experience. Additionally, our result suggests that vicarious freezing is not triggered by USVs per se and it influences back onto the behavior of the demonstrator that had elicited the vicarious freezing in witnesses, introducing a paradigm to study empathy

  19. Azithromycin reduces inflammation in a rat model of acute conjunctivitis

    PubMed Central

    Fernandez-Robredo, Patricia; Recalde, Sergio; Moreno-Orduña, Maite; García-García, Laura; Zarranz-Ventura, Javier; García-Layana, Alfredo

    2013-01-01

    Purpose Macrolide antibiotics are known to have various anti-inflammatory effects in addition to their antimicrobial activity, but the mechanisms are still unclear. The effect of azithromycin on inflammatory molecules in the lipopolysaccharide-induced rat conjunctivitis model was investigated. Methods Twenty-four Wistar rats were divided into two groups receiving topical ocular azithromycin (15 mg/g) or vehicle. In total, six doses (25 µl) were administered as one dose twice a day for three days before subconjunctival lipopolysaccharide injection (3 mg/ml). Before the rats were euthanized, mucus secretion, conjunctival and palpebral edema and redness were evaluated. Real-time polymerase chain reaction was used to determine gene expression for interleukin-6, cyclooxygenase-2, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, and MMP-9. Interleukin-6 was determined with enzyme-linked immunosorbent assay, nuclear factor-kappa B with western blot, and MMP-2 activity with gelatin zymogram. Four eyes per group were processed for histology and subsequent periodic acid-Schiff staining and CD68 for immunofluorescence. The Student t test or the Wilcoxon test for independent samples was applied (SPSS v.15.0). Results Azithromycin-treated animals showed a significant reduction in all clinical signs (p<0.05) compared to controls. Interleukin-6 (p<0.05), nuclear factor-kappa B protein expression (p<0.01), and MMP-2 activity (p<0.05) in conjunctival homogenates were significantly reduced compared with the control animals. MMP-2 gene expression showed a tendency to decrease in the azithromycin group (p=0.063). Mucus secretion by goblet cells and the macrophage count in conjunctival tissue were also decreased in the azithromycin group (p<0.05). Conclusions These results suggest that azithromycin administration ameliorates induced inflammation effects in a rat model of acute conjunctivitis. PMID:23378729

  20. Azithromycin reduces inflammation in a rat model of acute conjunctivitis.

    PubMed

    Fernandez-Robredo, Patricia; Recalde, Sergio; Moreno-Orduña, Maite; García-García, Laura; Zarranz-Ventura, Javier; García-Layana, Alfredo

    2013-01-01

    Macrolide antibiotics are known to have various anti-inflammatory effects in addition to their antimicrobial activity, but the mechanisms are still unclear. The effect of azithromycin on inflammatory molecules in the lipopolysaccharide-induced rat conjunctivitis model was investigated. Twenty-four Wistar rats were divided into two groups receiving topical ocular azithromycin (15 mg/g) or vehicle. In total, six doses (25 µl) were administered as one dose twice a day for three days before subconjunctival lipopolysaccharide injection (3 mg/ml). Before the rats were euthanized, mucus secretion, conjunctival and palpebral edema and redness were evaluated. Real-time polymerase chain reaction was used to determine gene expression for interleukin-6, cyclooxygenase-2, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, and MMP-9. Interleukin-6 was determined with enzyme-linked immunosorbent assay, nuclear factor-kappa B with western blot, and MMP-2 activity with gelatin zymogram. Four eyes per group were processed for histology and subsequent periodic acid-Schiff staining and CD68 for immunofluorescence. The Student t test or the Wilcoxon test for independent samples was applied (SPSS v.15.0). Azithromycin-treated animals showed a significant reduction in all clinical signs (p<0.05) compared to controls. Interleukin-6 (p<0.05), nuclear factor-kappa B protein expression (p<0.01), and MMP-2 activity (p<0.05) in conjunctival homogenates were significantly reduced compared with the control animals. MMP-2 gene expression showed a tendency to decrease in the azithromycin group (p=0.063). Mucus secretion by goblet cells and the macrophage count in conjunctival tissue were also decreased in the azithromycin group (p<0.05). These results suggest that azithromycin administration ameliorates induced inflammation effects in a rat model of acute conjunctivitis.

  1. A Rat Model for Muscle Regeneration in the Soft Palate

    PubMed Central

    Carvajal Monroy, Paola L.; Grefte, Sander; Kuijpers-Jagtman, Anne M.; Helmich, Maria P. A. C.; Ulrich, Dietmar J. O.; Von den Hoff, Johannes W.; Wagener, Frank A. D. T. G.

    2013-01-01

    Background Children with a cleft in the soft palate have difficulties with speech, swallowing, and sucking. Despite successful surgical repositioning of the muscles, optimal function is often not achieved. Scar formation and defective regeneration may hamper the functional recovery of the muscles after cleft palate repair. Therefore, the aim of this study is to investigate the anatomy and histology of the soft palate in rats, and to establish an in vivo model for muscle regeneration after surgical injury. Methods Fourteen adult male Sprague Dawley rats were divided into four groups. Groups 1 (n = 4) and 2 (n = 2) were used to investigate the anatomy and histology of the soft palate, respectively. Group 3 (n = 6) was used for surgical wounding of the soft palate, and group 4 (n = 2) was used as unwounded control group. The wounds (1 mm) were evaluated by (immuno)histochemistry (AZAN staining, Pax7, MyoD, MyoG, MyHC, and ASMA) after 7 days. Results The present study shows that the anatomy and histology of the soft palate muscles of the rat is largely comparable with that in humans. All wounds showed clinical evidence of healing after 7 days. AZAN staining demonstrated extensive collagen deposition in the wound area, and initial regeneration of muscle fibers and salivary glands. Proliferating and differentiating satellite cells were identified in the wound area by antibody staining. Conclusions This model is the first, suitable for studying muscle regeneration in the rat soft palate, and allows the development of novel adjuvant strategies to promote muscle regeneration after cleft palate surgery. PMID:23554995

  2. High-fat diet-induced obesity Rat model: a comparison between Wistar and Sprague-Dawley Rat

    PubMed Central

    Marques, Cláudia; Meireles, Manuela; Norberto, Sónia; Leite, Joana; Freitas, Joana; Pestana, Diogo; Faria, Ana; Calhau, Conceição

    2016-01-01

    ABSTRACT In the past decades, obesity and associated metabolic complications have reached epidemic proportions. For the study of these pathologies, a number of animal models have been developed. However, a direct comparison between Wistar and Sprague-Dawley (SD) Rat as models of high-fat (HF) diet-induced obesity has not been adequately evaluated so far. Wistar and SD rats were assigned for 2 experimental groups for 17 weeks: standard (St) and high-fat (HF) diet groups. To assess some of the features of the metabolic syndrome, oral glucose tolerance tests, systolic blood pressure measurements and blood biochemical analysis were performed throughout the study. The gut microbiota composition of the animals of each group was evaluated at the end of the study by real-time PCR. HF diet increased weight gain, body fat mass, mesenteric adipocyte's size, adiponectin and leptin plasma levels and decreased oral glucose tolerance in both Wistar and SD rats. However, the majority of these effects were more pronounced or earlier detected in Wistar rats. The gut microbiota of SD rats was less abundant in Bacteroides and Prevotella but richer in Bifidobacterium and Lactobacillus comparatively to the gut microbiota of Wistar rats. Nevertheless, the modulation of the gut microbiota by HF diet was similar in both strains, except for Clostridium leptum that was only reduced in Wistar rats fed with HF diet. In conclusion, both Wistar and SD Rat can be used as models of HF diet-induced obesity although the metabolic effects caused by HF diet seemed to be more pronounced in Wistar Rat. Differences in the gut microbial ecology may account for the worsened metabolic scenario observed in Wistar Rat. PMID:27144092

  3. Rat testis as a radiobiological in vivo model for radionuclides.

    PubMed

    Grafström, G; Jönsson, B-A; El Hassan, A M; Tennvall, J; Strand, S-E

    2006-01-01

    The radiobiological effect of intracellularly localised radionuclides emitting low energy electrons (Auger electrons) has received much attention. Most in vivo studies reported have been performed in the mouse testis. We have investigated the rat testis as an in vivo radiobiological model, with sperm-head survival, testis weight loss and also alteration in the blood plasma hormone levels of FSH and LH as radiobiological endpoints. Validation of the rat testis model was evaluated by using mean absorbed doses of up to 10 Gy from intratesticularly (i.t.) injected (111)In oxine or local X-ray irradiation. Biokinetics of the i.t. injected radionuclide was analysed by scintillation camera imaging and used in the absorbed dose estimation. By the analysis of the autoradiographs, the activity distribution was revealed. Cell fractionation showed (111)In to be mainly associated with the cell nuclei. External irradiations were monitored by thermoluminescence dosimeters. The sperm-head survival was the most sensitive radiobiological parameter correlated to the mean absorbed dose, with a D(37) of 2.3 Gy for (111)In oxine and 1.3 Gy for X rays. The levels of plasma pituitary gonadal hormones FSH and LH were elevated for absorbed doses >7.7 Gy. This investigation shows that the radiobiological model based on the rat testis has several advantages compared with the previously commonly used mouse testis model. The model is appropriate for further investigations of basic phenomena such as radiation geometry, intracellular kinetics and heterogeneity, crucial for an understanding of the biological effect of low-energy electrons.

  4. A series of rat segmental forelimb ectopic implantation models.

    PubMed

    Zhou, Xianyu; Luo, Xusong; Gao, Bowen; Liu, Fei; Gu, Chuan; Yu, Qingxiong; Li, Qingfeng; Zhu, Hainan

    2017-05-09

    Temporary ectopic implantation has been performed in clinical practice to salvage devascularized amputated tissues for delayed replantation purpose. In this study, we established a series of segmental forelimb ectopic implantation models in rats, including forelimb, forearm, forepaw, digit, and double forelimbs, to mimic the clinical context. Time of amputated limbs harvesting in donors and ectopic implantation process in recipients were recorded. Survival time and mortalities of recipients were also recorded. Sixty days after ectopic implantation, a full-field laser perfusion imager (FLPI) was used to detect the blood flow of amputated limbs and micro-CT imaging was used to examine bone morphological changes. Histological sections of amputated limbs were stained with hematoxylin and eosin to evaluate pathological changes. Implanted amputated limbs in all models achieved long term survival and there were no obvious morphological and histological changes were found according to results of micro-CT and histology study. Thus, a series of rat segmental forelimb temporary ectopic implantation models have been well established. To our knowledge, this is the first rodent animal model related to forelimb temporary ectopic implantation. These models might facilitate further research related to salvage, reconstruction and better aesthetic and functional outcome of upper extremity/digit in temporary ectopic implantation scenario.

  5. The utility of Apc-mutant rats in modeling human colon cancer.

    PubMed

    Irving, Amy A; Yoshimi, Kazuto; Hart, Marcia L; Parker, Taybor; Clipson, Linda; Ford, Madeline R; Kuramoto, Takashi; Dove, William F; Amos-Landgraf, James M

    2014-11-01

    Prior to the advent of genetic engineering in the mouse, the rat was the model of choice for investigating the etiology of cancer. Now, recent advances in the manipulation of the rat genome, combined with a growing recognition of the physiological differences between mice and rats, have reignited interest in the rat as a model of human cancer. Two recently developed rat models, the polyposis in the rat colon (Pirc) and Kyoto Apc Delta (KAD) strains, each carry mutations in the intestinal-cancer-associated adenomatous polyposis coli (Apc) gene. In contrast to mouse models carrying Apc mutations, in which cancers develop mainly in the small intestine rather than in the colon and there is no gender bias, these rat models exhibit colonic predisposition and gender-specific susceptibility, as seen in human colon cancer. The rat also provides other experimental resources as a model organism that are not provided by the mouse: the structure of its chromosomes facilitates the analysis of genomic events, the size of its colon permits longitudinal analysis of tumor growth, and the size of biological samples from the animal facilitates multiplexed molecular analyses of the tumor and its host. Thus, the underlying biology and experimental resources of these rat models provide important avenues for investigation. We anticipate that advances in disease modeling in the rat will synergize with resources that are being developed in the mouse to provide a deeper understanding of human colon cancer.

  6. The utility of Apc-mutant rats in modeling human colon cancer

    PubMed Central

    Irving, Amy A.; Yoshimi, Kazuto; Hart, Marcia L.; Parker, Taybor; Clipson, Linda; Ford, Madeline R.; Kuramoto, Takashi; Dove, William F.; Amos-Landgraf, James M.

    2014-01-01

    Prior to the advent of genetic engineering in the mouse, the rat was the model of choice for investigating the etiology of cancer. Now, recent advances in the manipulation of the rat genome, combined with a growing recognition of the physiological differences between mice and rats, have reignited interest in the rat as a model of human cancer. Two recently developed rat models, the polyposis in the rat colon (Pirc) and Kyoto Apc Delta (KAD) strains, each carry mutations in the intestinal-cancer-associated adenomatous polyposis coli (Apc) gene. In contrast to mouse models carrying Apc mutations, in which cancers develop mainly in the small intestine rather than in the colon and there is no gender bias, these rat models exhibit colonic predisposition and gender-specific susceptibility, as seen in human colon cancer. The rat also provides other experimental resources as a model organism that are not provided by the mouse: the structure of its chromosomes facilitates the analysis of genomic events, the size of its colon permits longitudinal analysis of tumor growth, and the size of biological samples from the animal facilitates multiplexed molecular analyses of the tumor and its host. Thus, the underlying biology and experimental resources of these rat models provide important avenues for investigation. We anticipate that advances in disease modeling in the rat will synergize with resources that are being developed in the mouse to provide a deeper understanding of human colon cancer. PMID:25288683

  7. Studies on the antihyperlipidemic properties of Averrhoa bilimbi fruit in rats.

    PubMed

    Ambili, Savithri; Subramoniam, Appian; Nagarajan, Natesan Shanmugam

    2009-01-01

    Averrhoa bilimbi Linn. fruit and its extracts were screened for antihypercholesterolemic activity using Triton-induced hypercholesterolemia in rats as a model. The fruit and its water extract, but not alcohol and hexane extracts, showed remarkable antihypercholesterolemic activity. An active fraction, which showed activity at a low dose of 0.8 mg/kg, was purified from the water extract. An active component was isolated from the active fraction, which showed optimum activity at a dose of 0.3 mg/kg. The efficacy of the fruit was tested in chronic high-fat diet fed hyperlipidemic rats. The fruit (125 mg/kg) as well as its water extract (50 mg/kg) were found to be effective in lowering lipids in the high-fat diet fed rats. The fruit was subjected to preliminary general toxicity evaluation in mice. Oral administration of the fruit homogenate daily for 15 days did not result in any toxic symptoms up to a dose of 1 g/kg studied. Thus, this fruit can be used as a dietary ingredient to prevent as well as treat hyperlipidemia.

  8. 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.

  9. Surgery Results in Exaggerated and Persistent Cognitive Decline in a Rat Model of the Metabolic Syndrome

    PubMed Central

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

    2017-01-01

    Background 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. Methods 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. Results 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. Conclusion 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. PMID:23353794

  10. Generation of a New Model Rat: Nrf2 Knockout Rats Are Sensitive to Aflatoxin B1 Toxicity.

    PubMed

    Taguchi, Keiko; Takaku, Misaki; Egner, Patricia A; Morita, Masanobu; Kaneko, Takehito; Mashimo, Tomoji; Kensler, Thomas W; Yamamoto, Masayuki

    2016-07-01

    THE TRANSCRIPTION FACTOR NRF2: (NF-E2-related-factor 2) REGULATES A BATTERY OF ANTIOXIDATIVE STRESS-RESPONSE GENES AND DETOXICATION GENES, AND NRF2 KNOCKOUT LINES OF MICE HAVE BEEN CONTRIBUTING CRITICALLY TO THE CLARIFICATION OF ROLES THAT NRF2 PLAYS FOR CELL PROTECTION HOWEVER, THERE ARE APPARENT LIMITATIONS IN USE OF THE MOUSE MODELS FOR INSTANCE, RATS EXHIBIT MORE SUITABLE FEATURES FOR TOXICOLOGICAL OR PHYSIOLOGICAL EXAMINATIONS THAN MICE IN THIS STUDY, WE GENERATED 2 LINES OF NRF2 KNOCKOUT RATS BY USING A GENOME EDITING TECHNOLOGY; 1 LINE HARBORS A 7-BP DELETION Δ7 AND THE OTHER LINE HARBORS A 1-BP INSERTION +1 IN THE NRF2 GENE IN THE LIVERS OF RATS HOMOZYGOUSLY DELETING THE NRF2 GENE, AN ACTIVATOR OF NRF2 SIGNALING, CDDO-IM, COULD NOT INDUCE EXPRESSION OF REPRESENTATIVE NRF2 TARGET GENES TO EXAMINE ALTERED TOXICOLOGICAL RESPONSE, WE TREATED THE NRF2 KNOCKOUT RATS WITH AFLATOXIN B1 AFB1, A CARCINOGENIC MYCOTOXIN THAT ELICITS GENE MUTATIONS THROUGH BINDING OF ITS METABOLITES TO DNA AND FOR WHICH THE RAT HAS BEEN PROPOSED AS A REASONABLE SURROGATE FOR HUMAN TOXICITY INDEED, IN THE NRF2 KNOCKOUT RAT LIVERS THE ENZYMES OF THE AFB1 DETOXICATION PATHWAY WERE SIGNIFICANTLY DOWNREGULATED SINGLE DOSE ADMINISTRATION OF AFB1 INCREASED HEPATOTOXICITY AND BINDING OF AFB1-N7-GUANINE TO HEPATIC DNA IN NRF2 KNOCKOUT RATS COMPARED WITH WILD-TYPE NRF2 KNOCKOUT RATS REPEATEDLY TREATED WITH AFB1 WERE PRONE TO LETHALITY AND CDDO-IM WAS NO LONGER PROTECTIVE THESE RESULTS DEMONSTRATE THAT NRF2 KNOCKOUT RATS ARE QUITE SENSITIVE TO AFB1 TOXICITIES AND THIS RAT GENOTYPE EMERGES AS A NEW MODEL ANIMAL IN TOXICOLOGY.

  11. Comparison of BISAP, Ranson, MCTSI, and APACHE II in Predicting Severity and Prognoses of Hyperlipidemic Acute Pancreatitis in Chinese Patients

    PubMed Central

    Liu, Jing; Xing, Yun; Du, Lichuan; Chen, Jing; Liu, Xin; Hao, Jianyu

    2016-01-01

    In recent years, with the developing of living standard, hyperlipidemia becomes the second major reason of acute pancreatitis. It is important to predict the severity and prognosis at early stage of hyperlipidemic acute pancreatitis (HLAP). We compared the BISAP, Ranson, MCTSI, and APACHE II scoring system in predicting MSAP and SAP, local complications, and mortality of HLAP. A total of 326 diagnosed hyperlipidemic acute pancreatitis patients from August 2006 to July 2015 were studied retrospectively. Our result showed that all four scoring systems can be used to predict the severity, local complications, and mortality of HLAP. Ranson did not have significant advantage in predicting severity and prognosis of HLAP compared to other three scoring systems. APACHE II was the best in predicting severity of HLAP, but it had shortcoming in predicting local complications. MCTSI had outstanding performance in predicting local complications, but it was poor in predicting severity and mortality. BISAP score had high accuracy in assessment of severity, local complications, and mortality of HLAP, but the accuracy still needs to be improved in the future. PMID:27882045

  12. Comparison of BISAP, Ranson, MCTSI, and APACHE II in Predicting Severity and Prognoses of Hyperlipidemic Acute Pancreatitis in Chinese Patients.

    PubMed

    Yang, Lixin; Liu, Jing; Xing, Yun; Du, Lichuan; Chen, Jing; Liu, Xin; Hao, Jianyu

    2016-01-01

    In recent years, with the developing of living standard, hyperlipidemia becomes the second major reason of acute pancreatitis. It is important to predict the severity and prognosis at early stage of hyperlipidemic acute pancreatitis (HLAP). We compared the BISAP, Ranson, MCTSI, and APACHE II scoring system in predicting MSAP and SAP, local complications, and mortality of HLAP. A total of 326 diagnosed hyperlipidemic acute pancreatitis patients from August 2006 to July 2015 were studied retrospectively. Our result showed that all four scoring systems can be used to predict the severity, local complications, and mortality of HLAP. Ranson did not have significant advantage in predicting severity and prognosis of HLAP compared to other three scoring systems. APACHE II was the best in predicting severity of HLAP, but it had shortcoming in predicting local complications. MCTSI had outstanding performance in predicting local complications, but it was poor in predicting severity and mortality. BISAP score had high accuracy in assessment of severity, local complications, and mortality of HLAP, but the accuracy still needs to be improved in the future.

  13. Animal model of rapid crystalloid infusion in rats.

    PubMed

    Orgaes, Flavio Stillitano; Oliveira Neto, Fausto Viterbo de; Mendes, Flavio Henrique; Yabiku, Renato Florio

    2013-04-01

    To describe an animal model of rapid intravenous infusion with different volumes of crystalloid and discuss the clinical findings. Fifty six male Wistar rats were used, divided randomly in seven groups (n = 8). The rats of groups 1 to 6 received lactated Ringer's solution intravenously, in the rate of 25 ml/min, with different volumes proportional to blood volume (BV). The rats of group 0 were submitted to the same procedure, but did not receive the fluid (control group). The data included respiratory rate, heart rate, saturation of peripheral oxygen (SpO(2)) in two times (before and after the infusion), and upshots (respiratory arrest and death). Dunnett's test and ANOVA were used. The clinical signs significantly changed in the 2, 2.5 and 3 fold BV groups. The respiratory arrest was observed in the 1.5, 2, 2.5 and 3 fold BV groups, but death was present only in 2.5 and 3 fold BV groups. The infusion of crystalloid in the same volume of blood volume did not cause significant variation in respiratory and heart rate, saturation of peripheral oxygen and did not induce respiratory arrest. The infusion of a volume of 3 fold blood volume was lethal to all animals.

  14. Preemptive analgesic effects of midazolam and diclofenac in rat model

    PubMed Central

    Hasani, Antigona; Soljakova, Marija; Jakupi, Muharrem; Ustalar-Ozgen, Serpil

    2011-01-01

    The aim of the present study was to investigate the preemptive analgesic effects of intraperitoneally administrated midazolam and diclofenac, before acute and inflammatory induced pain in rat model. One hundred twenty-eight (n=8 in each group) male Sprague Dawley rats were included in the study. Paw movements in response to thermal stimulation or paw flinching in response to formalin injection were compared after midazolam (0.1, 1, 5 and 10 mg/kg) and diclofenac (10 mg/kg), intraperitoneal administration. Saline was used as a control. Preemptive analgesic effect was significant in both tests when diclofenac and midazolam was administrated before the pain stimuli (p<0.01 and p<0.001). Intraperitoneal injection of midazolam in doses 5 and 10 mg/kg, increase the response time in hot plate test and decrease the number of flinches in formalin test (p<0.01 vs. p<0.001). ED50 of midazolam (with diclofenac) in hot plate test was 2.02 mg/kg (CI95% =-3.47-5.03 mg); and, 0.9 mg/kg (CI95% =-0.87-4.09 mg) in phase I and 0.7 mg/kg (CI95% = 0.48-6.63 mg) in phase II, in formalin test. Intraperitoneally administered midazolam and diclofenac had preemptive analgesic effects on acute thermal, and inflammatory induced pain in rats. PMID:21619559

  15. Antifibrotic effect of heparin on liver fibrosis model in rats

    PubMed Central

    Shah, Binita; Shah, Gaurang

    2012-01-01

    AIM: To evaluate the effect of chronic thrombin inhibition by heparin on experimentally induced chronic liver injury (liver fibrosis) in rats. METHODS: Chronic liver injury (liver fibrosis) was induced in Wistar rats by oral administration of carbon tetrachloride (CCl4) for 7 wk, an animal model with persistent severe hepatic fibrosis. Intravenous administration of the thrombin antagonist (heparin) started 1 wk after the start of CCl4 intoxication for 6 wk. After completion of treatment (7 wk), markers of hepatic dysfunction were measured and changes evaluated histopathologically. RESULTS: Higher serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), total, direct and indirect bilirubin levels, as well as lower fibrinogen levels, were found in CCl4 intoxicated rats. Heparin, silymarin and combination of drug (heparin and silymarin) treatment for 6 wk prevented a rise in SGOT, SGPT, ALP, total, direct and indirect bilirubin levels and improved fibrinogen levels. Deterioration in hepatic function determined by the fibrosis area was retarded, as evident from hepatic histopathology. Total protein levels were not changed in all groups. CONCLUSION: Heparin, a thrombin antagonist, preserved hepatic function and reduced severity of hepatic dysfunction/fibrogenesis. Combination of heparin and silymarin produced additional benefits on liver fibrosis. PMID:23494756

  16. Triptolide ameliorates colonic fibrosis in an experimental rat model

    PubMed Central

    TAO, QINGSONG; WANG, BAOCHAI; ZHENG, YU; LI, GUANWEI; REN, JIANAN

    2015-01-01

    Triptolide is known to exert anti-inflammatory and immunomodulatory activities; however, its impact on intestinal fibrosis has not been previously examined. Based on our previous studies of the suppressive activity of triptolide on human colonic subepithelial myofibroblasts and the therapeutic efficacy of triptolide in Crohn’s disease, it was hypothesized that triptolide may have beneficial effects on intestinal fibrosis. In the present study, colonic fibrosis was induced in rats by 6 weekly repeated administration with a low-dose of 2,4,6-trinitrobenzene sulfonic acid (TNBS) and was then treated with triptolide or PBS daily (control) simultaneously. Extracellular matrix (ECM) deposition in the colon was examined with image analysis of Masson Trichrome staining. Total collagen levels in colonic homogenates were measured by a Sircol assay. Collagen Iα1 transcripts and collagen I protein were measured ex vivo in the isolated colonic subepithelial myofibroblasts by reverse transcription-quantitative polymerase chain reaction and immunoblot analysis, respectively. The results indicated that triptolide decreased ECM deposition and collagen production in the colon, and inhibited collagen Iα1 transcripts and collagen I protein expression in the isolated subepithelial myofibroblasts of the rats with colonic fibrosis. In conclusion, triptolide ameliorates colonic fibrosis in the experimental rat model, suggesting triptolide may be a promising compound for inflammatory bowel disease treatment. PMID:25845760

  17. Ozone enema: a model of microscopic colitis in rats.

    PubMed

    Eliakim, R; Karmeli, F; Rachmilewitz, D; Cohen, P; Zimran, A

    2001-11-01

    Ozone is one of the most powerful oxidants available, with many applications in industry and medicine. Medically relevant features of ozone include bacterial and virucidal properties, disinfection, sterilization, circulatory stimulation, and disruption of malignant cells. Ozone therapy is administered in various ways, including intravenously, intramuscularly, and intrarectally. The latter modality is used for the treatment of colitis and hepatitis. Our aim was to examine the effect of ozone water enema on normal and inflamed rat colonic mucosa. Ozone water (20 microg/ml) was prepared via ozone generator and administered intrarectally (0.5 ml) daily. Rats were killed one, three, and seven days after rectal ozone water administration, and their colons resected, rinsed, and weighed (grams per 10 cm). Damage was assessed macro- and microscopically and tissue processed for myeloperoxidase and nitric oxide synthase activity. Rats receiving saline served as controls. In an additional experiment colitis was induced by intrarectal iodoacetamide. Ozone therapy caused no macroscopic damage. Ozone therapy induced microscopic colitis, which lasted for at least a week and was accompanied by increase in segmental weight, myeloperoxidase and nitric oxide activity, and prostaglandin E2 generation. Ozone therapy had no protective effect on inflamed mucosa. In conclusion, ozone water therapy had a deleterious effect on normal colonic mucosa, suggesting intrarectal administration be reevaluated. Ozone water enema may serve as a model of microscopic colitis.

  18. Thermal imaging of brain tumors in a rat glioma model

    NASA Astrophysics Data System (ADS)

    Papaioannou, Thanassis; Thompson, Reid C.; Kateb, Babak; Sorokoumov, Oleg; Grundfest, Warren S.; Black, Keith L.

    2002-05-01

    We have explored the capability of thermal imaging for the detection of brain tumors in a rat glioma mode. Fourteen Wistar rats were injected stereotactically with 100,000 C6 glioma cells. Approximately one and two weeks post implantation, the rats underwent bilateral craniotomy and the exposed brain surface was imaged with a short wave thermal camera. Thermal images were obtained at both low (approximately 28.7 degree(s)C) and high (approximately 38 degree(s)C) core temperatures. Temperature gradients between the tumor site and the contralateral normal brain were calculated. Overall, the tumors appeared cooler than normal brain, for both high and low core temperatures. Average temperature difference between tumor and normal brain were maximal in more advanced tumors (two weeks) and at higher core temperatures. At one week (N equals 6), the average temperature gradient between tumor and normal sites was 0.1 degree(s)C and 0.2 degree(s)C at low and high core temperatures respectively (P(greater than)0.05). At two weeks (N equals 8), the average temperature gradient was 0.3 degree(s)C and 0.7 degree(s)C at low and high core temperatures respectively (P<0.05). We conclude that thermal imaging can detect temperature differences between tumor and normal brain tissue in this model, particularly in more advanced tumors. Thermal imaging may provide a novel means to identify brain tumors intraoperatively.

  19. Efficacy and Safety of Echinacoside in a Rat Osteopenia Model

    PubMed Central

    Yang, Xiaolin; Li, Fei; Yang, Yanan; Shen, Jinyang; Zou, Run; Zhu, Panpan; Zhang, Chunfeng; Yang, Zhonglin; Li, Ping

    2013-01-01

    This study aimed to investigate the efficacy and safety of echinacoside (ECH) using an osteopenia rat model. Forty-eight 6-month-old female Sprague-Dawley rats were randomly divided into one sham-operated group (SHAM) and five OVX (ovariectomized) subgroups: SHAM with vehicle 0.5% carboxymethylcellulose sodium (0.5% CMC-Na) and OVX with vehicle (OVX), OVX with 17β-estradiol (E2), and OVX with ECH of graded doses (ECH-L, ECH-M, and ECH-H). The effects of ECH and E2 on serum biochemical parameters, bone mineral density (BMD), bone biomechanical properties, bone microarchitecture, and immunohistochemistry were examined, and safety assessments were also evaluated. The results showed that ECH treatments improved total femur BMD, bone microarchitecture, and biomechanical properties and decreased serum marker levels in comparison to OVX group. Moreover, ECH administration significantly increased osteoprotegerin (OPG) level, and decreased receptor activator of nuclear factor-κB ligand (RANKL) level in serum, as well as in proximal femur. Importantly, ECH treatment ameliorated the lipid parameters without the overall incidences of adverse events of uterus and mammary gland compared to OVX and SHAM groups. This study demonstrated that administration of ECH for 12 weeks can effectively and safely prevent OVX-induced osteoporosis in rats via increasing the OPG/RANKL ratio. PMID:23573159

  20. Genetically selected alcohol preferring rats to model human alcoholism

    PubMed Central

    Ciccocioppo, Roberto

    2016-01-01

    Animal models have been successfully developed to mimic and study alcoholism. These models have the unique feature of allowing the researcher to control for the genetic characteristics of the animal, alcohol exposure and environment. Moreover, these animal models allow pharmacological, neurochemical and behavioural manipulations otherwise impossible. Unquestionably, one of the major contributions to the understanding of the neurobiological basis of alcoholism comes from data that have been obtained from the study of genetically selected alcohol-preferring rat lines and from the consequences that alcohol drinking and environmental manipulations (/i.e., protracted alcohol drinking, intoxication, exposure to stress etc) have on them. In fact, if on the one hand genetic factors may account for about 50–60% of the risk of developing alcohol dependence, on the other hand protracted alcohol exposure is a necessary precondition to actually develop the disease, while environmental vulnerability factors may be crucial for disease progression. The present article will offer an overview of the different genetically selected alcohol preferring rat lines developed and used to study alcoholism. The predictive, face and construct validity of these animal models and the translational significance of findings achieved through their use will be critically discussed. PMID:22328453

  1. A modified rat model of isolated bilateral pulmonary contusion

    PubMed Central

    WANG, SHAOHUA; RUAN, ZHENG; ZHANG, JIE; ZHENG, JIN

    2012-01-01

    The aim of the present study was to create a feasible specific rat model of isolated bilateral pulmonary contusion (PC) and to evaluate the relationship between severity of hypoxemia and quantity of contusion lesions. Anesthetized rats were placed in a prone position. Injury energy ranging from 2.1 to 3.0 J was produced by a falling weight passed through a specially designed arched shield to the bilateral chest wall of rats. After injury (4 h), the contusion volume was measured using computer-generated three-dimensional reconstruction from a chest computed tomographic scan and expressed as a percentage of total lung volume. Arterial partial pressure of oxygen (PaO2) in blood gas analysis and contusion volume percentage were used to assess the severity of contusion. Heart and lung biopsy was used to confirm the diagnosis and rule out the existence of myocardial contusion. There were 3 cases of death and 1 case of death in the 3.0 J and the 2.4 J group, respectively. PaO2 in the 2.7 J group was significantly lower than that in the lower energy groups (P<0.001). The percentage of pulmonary contusion in the 2.7 J group was significantly higher compared to that of the lower energy groups (P<0.001). PaO2 was negatively correlated with contusion percentage (R2=0.76). Hemorrhage, edema and neutrophil infiltration were determined by lung biopsy. No evidence of myocardial contusion was documented in multiple heart biopsies. The method illustrated in this research effectively duplicates isolated bilateral pulmonary contusion in rats, the severity of which is highly correlated with the contusion size. Thus, 2.7 J can be regarded as the maximal energy for sublethal injury. PMID:23181112

  2. Mechanism of auditory hypersensitivity in human autism using autism model rats.

    PubMed

    Ida-Eto, Michiru; Hara, Nao; Ohkawara, Takeshi; Narita, Masaaki

    2017-04-01

    Auditory hypersensitivity is one of the major complications in autism spectrum disorder. The aim of this study was to investigate whether the auditory brain center is affected in autism model rats. Autism model rats were prepared by prenatal exposure to thalidomide on embryonic day 9 and 10 in pregnant rats. The superior olivary complex (SOC), a complex of auditory nuclei, was immunostained with anti-calbindin d28k antibody at postnatal day 50. In autism model rats, SOC immunoreactivity was markedly decreased. Strength of immunostaining of SOC auditory fibers was also weak in autism model rats. Surprisingly, the size of the medial nucleus of trapezoid body, a nucleus exerting inhibitory function in SOC, was significantly decreased in autism model rats. Auditory hypersensitivity may be, in part, due to impairment of inhibitory processing by the auditory brain center. © 2016 Japan Pediatric Society.

  3. Photon and electron absorbed fractions calculated from a new tomographic rat model

    NASA Astrophysics Data System (ADS)

    Peixoto, P. H. R.; Vieira, J. W.; Yoriyaz, H.; Lima, F. R. A.

    2008-10-01

    This paper describes the development of a tomographic model of a rat developed using CT images of an adult male Wistar rat for radiation transport studies. It also presents calculations of absorbed fractions (AFs) under internal photon and electron sources using this rat model and the Monte Carlo code MCNP. All data related to the developed phantom were made available for the scientific community as well as the MCNP inputs prepared for AF calculations in that phantom and also all estimated AF values, which could be used to obtain absorbed dose estimates—following the MIRD methodology—in rats similar in size to the presently developed model. Comparison between the rat model developed in this study and that published by Stabin et al (2006 J. Nucl. Med. 47 655) for a 248 g Sprague-Dawley rat, as well as between the estimated AF values for both models, has been presented.

  4. Anti‐diabetic and Anti‐hyperlipidemic Effects and Safety of Salacia reticulata and Related Species

    PubMed Central

    Ray, Sidhartha

    2015-01-01

    Extracts of Salacia reticulata Wight (Hypocrataceae) roots, stems, and leaves have been used in Asia for hundreds of years for the folkloric treatment of diabetes and other health problems. Constituents that have been identified as exhibiting anti‐diabetic effects include salacinol, kotalanol, ponkorinol, salaprinol, and their corresponding de‐0‐sulfonated compounds. Mangiferin, kotalagenin 16‐acetate and various proanthocyanidin oligomers have also been isolated. Studies indicate that Salacia extracts modulate multiple targets that influence carbohydrate and lipid metabolism including α‐glucosidase, aldose reductase, pancreatic lipase, peroxisomal proliferator‐activated receptor‐α, glucose transporter‐4 mediated glucose uptake, and angiotensin II type 1 receptor. Furthermore, Salacia extracts exhibit free radical scavenging, antioxidant and hepatoprotectant activities. In human studies, Salacia extracts have been shown to decrease plasma glucose and insulin levels, decrease HbA1c, and modulate serum lipid levels with no adverse effects being reported. Similar results have been demonstrated in rat and mouse models as well as in vitro systems. Safety of S. reticulata and other Salacia species as S. oblonga and S. chinensis in rats and mice indicate that extracts are exceedingly safe. No clinical studies have examined the effects of Salacia extracts on human weight loss, although weight loss and decreases in weight gain have been demonstrated in animal models. Because of the large number of pharmacologically active compounds, it is difficult to establish standards for extracts. © 2015 The Authors. Phytotheraphy Research published by John Wiley & Sons Ltd. PMID:26031882

  5. Development of a Vascularized Heterotopic Neonatal Rat Heart Transplantation Model.

    PubMed

    Shimada, Shogo; Del Nido, Pedro J; Friehs, Ingeborg

    2016-01-01

    Rodent adult-to-adult heterotopic heart transplantation is a well-established animal model, and the detailed surgical technique with several modifications has been previously described. In immature donor organ transplantation, however, the surgical technique needs to be revised given the smaller size and fragility of the donor graft. Here, we report our surgical technique for heterotopic abdominal (AHTx) and femoral (FHTx) neonatal rat heart transplantation based on an experience of over 300 cases. Heterotopic heart transplantation was conducted in syngeneic Lewis rats. Neonatal rats (postnatal day 2-4) served as donors. AHTx was performed by utilizing the conventional adult-to-adult transplant method with specific modifications for optimal aortotomy and venous anastomosis. In the FHTx, the donor heart was vascularized by connecting the donor's aorta and pulmonary artery to the recipient's right femoral artery and vein, respectively, in an end-to-end manner. A specifically fashioned butterfly-shaped rubber sheet was used to align the target vessels properly. The transplanted graft was visually assessed for its viability and was accepted as a technical success when the viability met specific criteria. Successfully transplanted grafts were subject to further postoperative evaluation. Forty cases (AHTx and FHTx; n = 20 each) were compared regarding perioperative parameters and outcomes. Both models were technically feasible (success rate: AHTx 75% vs. FHTx 70%) by refining the conventional heterotopic transplant technique. Injury to the fragile donor aorta and congestion of the graft due to suboptimal venous connection were predominant causes of failure, leading to refractory bleeding and poor graft viability. Although the FHTx required significantly longer operation time and graft ischemic time, the in situ graft viabilities were comparable. The FHTx provided better postoperative monitoring as it enabled daily graft palpation and better echocardiographic

  6. Novel rat tail discitis model using bioluminescent Staphylococcus aureus.

    PubMed

    Bostian, Phillip A; Karnes, Jonathan M; Cui, Shari; Robinson, Lisa J; Daffner, Scott D; Witt, Michelle R; Emery, Sanford E

    2016-12-05

    Management of spondylodiscitis is a challenging clinical problem requiring medical and surgical treatment strategies. The purpose of this study was to establish a rat model of spondylodiscitis that utilizes bioluminescent Staphylococcus aureus (S. aureus), thus permitting in vivo surveillance of infection intensity. Inocula of the bioluminescent S. aureus strain XEN36 were created in concentrations of 10(2) CFU/0.1 ml, 10(4)  CFU/0.1 ml, and 10(6)  CFU/0.1 ml. Three groups of rats were injected with the bacteria in the most proximal intervertebral tail segment. The third most proximal tail segment was injected with saline as a control. Bioluminescence was measured at baseline, 3 days, and weekly for a total of 6 weeks. Detected bioluminescence for each group peaked at day 3 and returned to baseline in 21 days. The average intensity was highest for the experimental group injected with the most concentrated bacterial solution (10(6)  CFU/0.1 ml). Radiographic analysis revealed loss of intervertebral disc space and evidence of osseous bridging. Saline-injected spaces exhibited no decrease in intervertebral spacing as compared to distal sites. Histologic analysis revealed neutrophilic infiltrates, destruction of the annulus fibrosus and nucleus pulposus, destruction of vertebral endplates, and osseous bridging. Saline-injected discs exhibited preserved annulus fibrosus and nucleus pulposus on histology. This study demonstrates that injection of bioluminescent S. aureus into the intervertebral disc of a rat tail is a viable animal model for spondylodiscitis research. This model allows for real-time, in vivo quantification of infection intensity, which may decrease the number of animals required for infection studies of the intervertebral disc. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

  7. Differentiated analysis of orthodontic tooth movement in rats with an improved rat model and three-dimensional imaging.

    PubMed

    Kirschneck, Christian; Proff, Peter; Fanghaenel, Jochen; Behr, Michael; Wahlmann, Ulrich; Roemer, Piero

    2013-12-01

    Rat models currently available for analysis of orthodontic tooth movement often lack differentiated, reliable and precise measurement systems allowing researchers to separately investigate the individual contribution of tooth tipping, body translation and root torque to overall displacement. Many previously proposed models have serious limitations such as the rather inaccurate analysis of the effects of orthodontic forces on rat incisors. We therefore developed a differentiated measurement system that was used within a rat model with the aim of overcoming the limitations of previous studies. The first left upper molar and the upper incisors of 24 male Wistar rats were subjected to a constant orthodontic force of 0.25 N by means of a NiTi closed coil spring for up to four weeks. The extent of the various types of tooth movement was measured optometrically with a CCD microscope camera and cephalometrically by means of cone beam computed tomography (CBCT). Both types of measurement proved to be reliable for consecutive measurements and the significant tooth movement induced had no harmful effects on the animals. Movement kinetics corresponded to known physiological processes and tipping and body movement equally contributed to the tooth displacement. The upper incisors of the rats were significantly deformed and their natural eruption was effectively halted. The results showed that our proposed measurement systems used within a rat model resolved most of the inadequacies of previous studies. They are reliable, precise and physiological tools for the differentiated analysis of orthodontic tooth movement while simultaneously preserving animal welfare.

  8. Keratoepithelioplasty in rat: development of a model and histological study.

    PubMed

    Amano, S; Sawa, M; Ishii, Y

    1992-01-01

    A model for keratoepithelioplasty (KEP) was developed using the Lewis rat, and histological studies were performed using this model. The entire corneal epithelium was removed mechanically and a 1.5-mm width of the conjunctiva including the limbus was excised. An oval corneal lamellar graft (3 x 1.5 mm) with an intact epithelium taken from another Lewis rat was transplanted on the denuded limbus. Biomicroscopic observations showed much less vascular invasion in the part of the cornea adjacent to the lenticule than in other parts of the cornea, and the cornea remained clear adjacent to the lenticule. Histologically, a few vessels were observed in the corneal stroma under the lenticule. Epithelial cells on the lenticule specimens showed histological characteristics of the corneal epithelium. These findings indicate that one of the functions of KEP is to block neovascularization in the newly developing corneal epithelium by transplanting the lenticule between the corneal epithelium and conjunctival vessels. The present study also confirmed that this model is useful in the research of the pathophysiological mechanism of KEP.

  9. [Histological study of a model of keratoepithelioplasty in the rat].

    PubMed

    Amano, S; Sawa, M; Ishii, Y

    1992-11-01

    A model for keratoepithelioplasty (KEP) was developed using the Lewis rat, and histological studies were performed using the model. The entire corneal epithelium was removed using a spatula and a 1.5-mm-width of the conjunctiva including the limbus was excised. An oval corneal lamellar graft (3 x 1.5 mm) with an intact epithelium taken from another Lewis rat was transplanted on the denuded limbus. Biomicroscopic observation showed significantly less vascular invasion in the part of the cornea adjacent to the lenticule than in other part of cornea, and clear cornea was maintained in the cornea adjacent to the lenticule. Histologically only few vessels were recognized in the lenticule, and the epithelial cells on the lenticule showed histological characteristics of corneal epithelium. These results indicate that surgical function of KEP can be obtained because the lenticules keep distance between corneal epithelium and conjunctival vessels. And it is also confirmed that this model is useful in research on the pathophysiological mechanism of KEP.

  10. Modeling postpartum depression in rats: theoretic and methodological issues.

    PubMed

    Li, Ming; Chou, Shinn-Yi

    2016-07-18

    The postpartum period is when a host of changes occur at molecular, cellular, physiological and behavioral levels to prepare female humans for the challenge of maternity. Alteration or prevention of these normal adaptions is thought to contribute to disruptions of emotion regulation, motivation and cognitive abilities that underlie postpartum mental disorders, such as postpartum depression. Despite the high incidence of this disorder, and the detrimental consequences for both mother and child, its etiology and related neurobiological mechanisms remain poorly understood, partially due to the lack of appropriate animal models. In recent decades, there have been a number of attempts to model postpartum depression disorder in rats. In the present review, we first describe clinical symptoms of postpartum depression and discuss known risk factors, including both genetic and environmental factors. Thereafter, we discuss various rat models that have been developed to capture various aspects of this disorder and knowledge gained from such attempts. In doing so, we focus on the theories behind each attempt and the methods used to achieve their goals. Finally, we point out several understudied areas in this field and make suggestions for future directions.

  11. Fluorescing fatty acids in rat fatty liver models.

    PubMed

    Croce, Anna C; Ferrigno, Andrea; Di Pasqua, Laura G; Berardo, Clarissa; Mannucci, Barbara; Bottiroli, Giovanni; Vairetti, Mariapia

    2017-06-01

    The autofluorescence (AF) of NAD(P)H and flavins has been at the basis of many in-situ studies of liver energy metabolism and functionality. Conversely, few data have been so far reported on fluorescing lipids. In this work we investigated the AF of liver lipid extracts from two fatty liver models, Wistar rats fed with MCD diet for 12 days (Wi-MCD), and obese (fa/fa) Zucker rats. Among the most abundant fatty acids in the lipid extracts, indicated by mass spectrometry, arachidonic acid (AA) exhibited higher quantum yield than the other fluorescing fatty acids (FLFA), and red shifted AF spectrum. This allowed to estimate the AA contribution to the overall emission of lipid extracts by curve fitting analysis. AA prevailed in obese Zucker livers, accounting for the different AF spectral profiles between the two models. AF and mass spectrometry indicated also a different balance between the fluorescing fraction and the overall amount of AA in the two models. The ability of AF to detect directly AA and FLFA was demonstrated, suggesting its supportive role as tool in wide-ranging applications, from the control of animal origin food, to experimental investigations on liver fat accumulation, lipotoxicity and disease progression, with potential translation to the clinics. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Modeling postpartum depression in rats: theoretic and methodological issues

    PubMed Central

    Ming, LI; Shinn-Yi, CHOU

    2016-01-01

    The postpartum period is when a host of changes occur at molecular, cellular, physiological and behavioral levels to prepare female humans for the challenge of maternity. Alteration or prevention of these normal adaptions is thought to contribute to disruptions of emotion regulation, motivation and cognitive abilities that underlie postpartum mental disorders, such as postpartum depression. Despite the high incidence of this disorder, and the detrimental consequences for both mother and child, its etiology and related neurobiological mechanisms remain poorly understood, partially due to the lack of appropriate animal models. In recent decades, there have been a number of attempts to model postpartum depression disorder in rats. In the present review, we first describe clinical symptoms of postpartum depression and discuss known risk factors, including both genetic and environmental factors. Thereafter, we discuss various rat models that have been developed to capture various aspects of this disorder and knowledge gained from such attempts. In doing so, we focus on the theories behind each attempt and the methods used to achieve their goals. Finally, we point out several understudied areas in this field and make suggestions for future directions. PMID:27469254

  13. Progesterone Treatment in Two Rat Models of Ocular Ischemia

    PubMed Central

    Allen, Rachael S.; Olsen, Timothy W.; Sayeed, Iqbal; Cale, Heather A.; Morrison, Katherine C.; Oumarbaeva, Yuliya; Lucaciu, Irina; Boatright, Jeffrey H.; Pardue, Machelle T.; Stein, Donald G.

    2015-01-01

    Purpose. To determine whether the neurosteroid progesterone, shown to have protective effects in animal models of traumatic brain injury, stroke, and spinal cord injury, is also protective in ocular ischemia animal models. Methods. Progesterone treatment was tested in two ocular ischemia models in rats: a rodent anterior ischemic optic neuropathy (rAION) model, which induces permanent monocular optic nerve stroke, and the middle cerebral artery occlusion (MCAO) model, which causes transient ischemia in both the retina and brain due to an intraluminal filament that blocks the ophthalmic and middle cerebral arteries. Visual function and retinal histology were assessed to determine whether progesterone attenuated retinal injury in these models. Additionally, behavioral testing and 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining in brains were used to compare progesterone's neuroprotective effects in both retina and brain using the MCAO model. Results. Progesterone treatment showed no effect on visual evoked potential (VEP) reduction and retinal ganglion cell loss in the permanent rAION model. In the transient MCAO model, progesterone treatment reduced (1) electroretinogram (ERG) deficits, (2) MCAO-induced upregulation of glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP), and (3) retinal ganglion cell loss. As expected, progesterone treatment also had significant protective effects in behavioral tests and a reduction in infarct size in the brain. Conclusions. Progesterone treatment showed protective effects in the retina following MCAO but not rAION injury, which may result from mechanistic differences with injury type and the therapeutic action of progesterone. PMID:26024074

  14. Effect of thyroid hormone status and concomitant medication on statin induced adverse effects in hyperlipidemic patients.

    PubMed

    Berta, E; Harangi, M; Zsíros, N; Nagy, E V; Paragh, G; Bodor, M

    2014-06-01

    Statins are effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, adverse effects induced by statins are the major barrier of maximalizing cardiovascular risk reduction. Hypothyroidism and administration of drugs metabolized on the same cytochrome P450 (CYPP450) pathways where statin biotransformation occurs represent a significant risk factor for statin induced adverse effects including myopathy. Simvastatin, atorvastatin and lovastatin are metabolized by CYP3A4, fluvastatin by CYP2C9, while rosuvastatin by CYP2C9 and 2C19. We investigated the levels of the free thyroid hormones and CYP metabolism of concomitant medication in 101 hyperlipidemic patients (age 61.3 +/- 9.9 ys) with statin induced adverse effects including myopathy (56 cases; 55.4%), hepatopathy (39 cases; 38.6%) and gastrointestinal adverse effects (24 cases; 23.8%). Abnormal thyroid hormone levels were found in 5 patients (4.95%); clinical hypothyroidism in 2 and hyperthyroidism in 3 cases. 11 patients had a positive history for hypothyroidism (10.9%). Myopathy occured in one patient with hypothyroidism and two patients with hyperthyroidism. There were no significant differences in the TSH, fT4 and fT3 levels between patients with statin induced myopathy and patients with other types of adverse effects. 78 patients (77.2%) were administered drugs metabolized by CYP isoforms also used by statins (3A4: 66 cases (65.3%); 2C9: 67 cases (66.3%); 2C19: 54 cases (53.5%)). Patients with myopathy took significantly more drugs metabolized by CYP3A4 compared to patients with other types of adverse effects (p < 0.05). More myopathy cases were found in patients on simvastatin treatment (52% vs. 38%, ns.), while significantly less patients with myopathy were on fluvastatin treatment (13% vs. 33%, p < 0.05) compared to patients with other types of statin induced adverse effects. Both abnormal thyroid hormone status and administration of drugs metabolized by CYP

  15. Metabolic Cages for a Space Flight Model in the Rat

    NASA Technical Reports Server (NTRS)

    Harper, Jennifer S.; Mulenburg, Gerald M.; Evans, Juli; Navidi, Meena; Wolinsky, Ira; Arnaud, Sara B.

    1994-01-01

    A variety of space flight models are available to mimic the physiologic changes seen in the rat during weightlessness. The model reported by Wronski and Morey-Holton has been widely used by many investigators, in musculoskeletal physiologic studies especially, resulting in accumulation of an extensive database that enables scientists to mimic space flight effects in the 1-g environment of Earth. However, information on nutrition or gastrointestinal and renal function in this space flight model is limited by the difficulty in acquiring uncontaminated metabolic specimens for analysis. In the Holton system, a traction tape harness is applied to the tail, and the rat's hindquarters are elevated by attaching the harness to a pulley system. Weight-bearing hind limbs are unloaded, and there is a headward fluid shift. The tail-suspended rats are able to move freely about their cages on their forelimbs and tolerate this procedure with minimal signs of stress. The cage used in Holton's model is basically a clear acrylic box set on a plastic grid floor with the pulley and tail harness system attached to the open top of the cage. Food is available from a square food cup recessed into a corner of the floor. In this system, urine, feces, and spilled food fall through the grid floor onto absorbent paper beneath the cage and cannot be separated and recovered quantitatively for analysis in metabolic balance studies. Commercially available metabolic cages are generally cylindrical and have been used with a centrally located suspension apparatus in other space flight models. The large living area, three times as large as most metabolic cages, and the free range of motion unique to Holton's model, essential for musculoskeletal investigations, were sacrificed. Holton's cages can accommodate animals ranging in weight from 70 to 600 g. Although an alternative construction of Holton's cage has been reported, it does not permit collection of separate urine and fecal samples. We describe

  16. Metabolic Cages for a Space Flight Model in the Rat

    NASA Technical Reports Server (NTRS)

    Harper, Jennifer S.; Mulenburg, Gerald M.; Evans, Juli; Navidi, Meena; Wolinsky, Ira; Arnaud, Sara B.

    1994-01-01

    A variety of space flight models are available to mimic the physiologic changes seen in the rat during weightlessness. The model reported by Wronski and Morey-Holton has been widely used by many investigators, in musculoskeletal physiologic studies especially, resulting in accumulation of an extensive database that enables scientists to mimic space flight effects in the 1-g environment of Earth. However, information on nutrition or gastrointestinal and renal function in this space flight model is limited by the difficulty in acquiring uncontaminated metabolic specimens for analysis. In the Holton system, a traction tape harness is applied to the tail, and the rat's hindquarters are elevated by attaching the harness to a pulley system. Weight-bearing hind limbs are unloaded, and there is a headward fluid shift. The tail-suspended rats are able to move freely about their cages on their forelimbs and tolerate this procedure with minimal signs of stress. The cage used in Holton's model is basically a clear acrylic box set on a plastic grid floor with the pulley and tail harness system attached to the open top of the cage. Food is available from a square food cup recessed into a corner of the floor. In this system, urine, feces, and spilled food fall through the grid floor onto absorbent paper beneath the cage and cannot be separated and recovered quantitatively for analysis in metabolic balance studies. Commercially available metabolic cages are generally cylindrical and have been used with a centrally located suspension apparatus in other space flight models. The large living area, three times as large as most metabolic cages, and the free range of motion unique to Holton's model, essential for musculoskeletal investigations, were sacrificed. Holton's cages can accommodate animals ranging in weight from 70 to 600 g. Although an alternative construction of Holton's cage has been reported, it does not permit collection of separate urine and fecal samples. We describe

  17. [Development of peripheral neuropathy rat model induced by 1-bromopropane].

    PubMed

    Wang, Qing-hua; Zhong, Zhi-xia; Chen, Jing-jing; Xie, Ke-qin; Zhao, Xiu-lan

    2012-10-01

    To observe the peripheral neurotoxicity of 1-bromopropane (1-BP) by developing an animal model of peripheral neuropathy through oral administration of 1-BP. Forty male Wistar rats were randomly and equally divided into low-dose group (200 mg/kg), medium-dose group (400 mg/kg), high-dose group (800 mg/kg), and control group. The rats in the low-dose, medium-dose, and high-dose groups were orally given 1-BP (dissolved in corn oil), while the rats in the control group were orally given an equal volume of corn oil. The oral administration (0.2 ml/100 g BW) was performed once per day, 5 days per week, for 16 consecutive weeks. Neurobehavioral indices including gait score, hindlimb grip strength, and hindlimb landing foot splay were recorded periodically. Hematological and biochemical parameters were also measured during and after 1-BP exposure. The gait scores were significantly higher in the high-dose group (after 8 ∼ 16 weeks of 1-BP exposure), medium-dose group (after 14 ∼ 16 weeks of 1-BP exposure), and low-dose group (after 15 ∼ 16 weeks of 1-BP exposure) than in the control group (P < 0.05, P < 0.01). Compared with the control group, the high-dose group showed significantly decreased hindlimb grip strength after 9, 12, and 14 weeks of 1-BP exposure (P < 0.05, P < 0.01), with the hindlimbs paralyzed after 16 weeks of 1-BP exposure. After 16 weeks of 1-BP exposure, the hindlimb grip strengths of rats in the medium-dose and low-dose groups were decreased to 72.6% and 91.2% of the control value (P < 0.01, P < 0.05). Compared with the control group, the high-dose group showed significantly increased hindlimb landing foot splay after 12, 14, and 16 weeks of 1-BP exposure, and the medium-dose group showed significantly increased hindlimb landing foot splay after 14 and 16 weeks of 1-BP exposure (P < 0.05, P < 0.01). The high-dose and medium-dose groups showed significantly higher serum alanine aminotransferase (ALT) activity than the control group after 8 weeks of

  18. The MAM-E17 schizophrenia rat model: Comprehensive behavioral analysis of pre-pubertal, pubertal and adult rats.

    PubMed

    Kállai, Veronika; Tóth, Attila; Gálosi, Rita; Péczely, László; Ollmann, Tamás; Petykó, Zoltán; László, Kristóf; Kállai, János; Szabó, Imre; Karádi, Zoltán; Lénárd, László

    2017-08-14

    The MAM-E17 model is one of the most accepted schizophrenia rat models, which follows the neurodevelopmental theory of the disease. While symptoms of MAM-E17 rats were studied extensively, their examinations were usually restricted to adulthood and in a few cases to prepuberty. It is well known, however, that schizophrenia symptoms often start at puberty or early adulthood. Therefore the purpose of this study was to investigate the behavioral characteristics of MAM-E17 rats in various tests throughout three different age-periods, namely in prepuberty, late puberty and adulthood. In open field test, MAM-E17 rats displayed increased locomotor activity, elevated sniffing frequency and, as tendency, enhanced rearing activity. The elevated activity turned up in late puberty and remained there in adulthood, too. There was also a deficient prepulse inhibition (PPI) of startle response in late puberty and adulthood, but not before puberty. In rotarod task, MAM-treated rats performed better than control rats. The enhanced performance on rotarod was only present in late puberty and adulthood. In elevated plus maze test MAM-treated rats displayed diminished anxiety mostly in prepuberty. Histological analysis revealed reduced volume and cell disarray in the dorsal hippocampus. This is the first comprehensive study about symptoms of MAM-E17 rats manifested in behavioral tests carried out in prepuberty, late puberty and adulthood. Results display the age-dependent appearance of schizophrenia symptoms in the same rats. The present findings provide basic information to accomplish the schizophrenia related animal research, as well as can also confer further data to develop preventive treatment for human patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Spatial memory impairments in a prediabetic rat model.

    PubMed

    Soares, E; Prediger, R D; Nunes, S; Castro, A A; Viana, S D; Lemos, C; De Souza, C M; Agostinho, P; Cunha, R A; Carvalho, E; Fontes Ribeiro, C A; Reis, F; Pereira, F C

    2013-10-10

    Diabetes is associated with an increased risk for brain disorders, namely cognitive impairments associated with hippocampal dysfunction underlying diabetic encephalopathy. However, the impact of a prediabetic state on cognitive function is unknown. Therefore, we now investigated whether spatial learning and memory deficits and the underlying hippocampal dysfunction were already present in a prediabetic animal model. Adult Wistar rats drinking high-sucrose (HSu) diet (35% sucrose solution during 9 weeks) were compared to controls' drinking water. HSu rats exhibited fasting normoglycemia accompanied by hyperinsulinemia and hypertriglyceridemia in the fed state, and insulin resistance with impaired glucose tolerance confirming them as a prediabetic rodent model. HSu rats displayed a poorer performance in hippocampal-dependent short- and long-term spatial memory performance, assessed with the modified Y-maze and Morris water maze tasks, respectively; this was accompanied by a reduction of insulin receptor-β density with normal levels of insulin receptor substrate-1 pSer636/639, and decreased hippocampal glucocorticoid receptor levels without changes of the plasma corticosterone levels. Importantly, HSu animals exhibited increased hippocampal levels of AMPA and NMDA receptor subunits GluA1 and GLUN1, respectively, whereas the levels of protein markers related to nerve terminals (synaptophysin) and oxidative stress/inflammation (HNE, RAGE, TNF-α) remained unaltered. These findings indicate that 9 weeks of sucrose consumption resulted in a metabolic condition suggestive of a prediabetic state, which translated into short- and long-term spatial memory deficits accompanied by alterations in hippocampal glutamatergic neurotransmission and abnormal glucocorticoid signaling. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Characterisation of a rat model of bortezomib induced painful neuropathy.

    PubMed

    Duggett, Natalie A; Flatters, Sarah J L

    2017-10-03

    Bortezomib (Velcade®) is a breakthrough treatment for multiple myeloma, significantly improving patient survival. However, its use is limited by painful neuropathy often resulting in dose reduction/cessation of first-line treatment due to lack of treatment. The aim of this study was to characterise a clinically-relevant rat model of bortezomib-induced painful neuropathy, using established evoked measures and novel ethological techniques, to aid drug discovery. Adult male Sprague-Dawley rats were injected intraperitoneally (i.p.) with 0.1, 0.2mg kg(-1) Bortezomib, or its vehicle, on days 0, 3, 7 and 10. Multiple behavioural approaches were utilised; mechanical hypersensitivity, cold allodynia, heat hypersensitivity, motor co-ordination, burrowing and voluntary wheel running. At maximal bortezomib-induced mechanical hypersensitivity, 200mg kg(-1) ethosuximide/vehicle and 100mg kg(-1) PBN (Phenyl N-tert-butylnitrone)/vehicle were administered i.p., in separate experiments, and mechanical hypersensitivity assessed 1, 3 and 24 hours later. Bortezomib induced dose-related mechanical hypersensitivity for up to 80 days. Bortezomib induced short-term cold allodynia, but no significant change in heat hypersensitivity, motor co-ordination, voluntary wheel running and burrowing behaviour compared to vehicle-treated controls. Systemic PBN and ethosuximide significantly ameliorated bortezomib-induced mechanical hypersensitivity compared to vehicle-controls. These data characterise a reproducible, rat model of clinical-grade bortezomib-induced neuropathy demonstrating long-lasting pain behaviours to evoked stimuli. Inhibition by ethosuximide and PBN suggests involvement of calcium and/or ROS in bortezomib-induced painful neuropathy. These drugs could be used as preclinical positive controls to assess novel analgesics. As ethosuximide is widely-used clinically, translation to the clinic to treat bortezomib-induced painful neuropathy may be possible. This article is protected by

  1. Hypertension and vulnerability to hemorrhagic shock in a rat model.

    PubMed

    Reynolds, Penny S; Song, Kyle Seokhan; Tamariz, Francisco J; Wayne Barbee, R

    2015-02-01

    Trauma mortality may be increased in the presence of preexisting diseases such as chronic hypertension. We hypothesized that systemic and microvascular alterations accompanying chronic hypertension would increase the vulnerability to hemorrhage relative to normotensive controls in a rat model of hemorrhagic shock. We present a novel comparative hemorrhage model of shock vulnerability, quantified by "vulnerability curves" expressing physiological response to hemorrhage as a function of three matched shock metrics: cumulative blood volume, mean arterial pressure (MAP), and oxygen delivery (Do2). Responses were central hemodynamics and respiratory and muscle oxygenation obtained for one hypertensive (spontaneously hypertensive [SHR]) and two normotensive (Sprague-Dawley, Wistar-Kyoto) rat strains. Hemorrhagic shock was induced by incremental (0.5 mL) hemorrhage to cardiovascular collapse in anesthetized and mechanically ventilated animals. Shock vulnerability of SHR rats was primarily pressure-driven; in general, SHR exhibited the expected patterns of more rapid deterioration in MAP and Vo2 over smaller ranges of blood loss and Do2. Sternotomy-related depression of CO and thus Do2 in SHR meant that we could not test hypotheses related to the role of Do2 and contribution to perfusion differences between normotensive and hypertensive subjects. Insensitivity of lactate to strain effects suggests that lactate may be a reliable biomarker of shock status. Unexpected similarities between Wistar-Kyoto and SHR suggest strain-related effects other than those related to hypertension per se contribute to hemorrhage response; body size effects and genetic relationships could not be ruled out. Future studies should incorporate phylogenetically based methods to examine the role of hypertension and physiological response to hemorrhage across multiple strains.

  2. A Model of Insulin Resistance and Nonalcoholic Steatohepatitis in Rats

    PubMed Central

    Svegliati-Baroni, Gianluca; Candelaresi, Cinzia; Saccomanno, Stefania; Ferretti, Gianna; Bachetti, Tiziana; Marzioni, Marco; De Minicis, Samuele; Nobili, Liliana; Salzano, Renata; Omenetti, Alessia; Pacetti, Deborah; Sigmund, Soeren; Benedetti, Antonio; Casini, Alessandro

    2006-01-01

    Insulin resistance induces nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH). We used a high-fat, high-calorie solid diet (HFD) to create a model of insulin resistance and NASH in nongenetically modified rats and to study the relationship between visceral adipose tissue and liver. Obesity and insulin resistance occurred in HFD rats, accompanied by a progressive increase in visceral adipose tissue tumor necrosis factor (TNF)-α mRNA and in circulating free fatty acids. HFD also decreased adiponectin mRNA and peroxisome proliferator-activated receptor (PPAR)-α expression in the visceral adipose tissue and the liver, respectively, and induced hepatic insulin resistance through TNF-α-mediated c-Jun N-terminal kinase (JNK)-dependent insulin receptor substrate-1Ser307 phosphorylation. These modifications lead to hepatic steatosis accompanied by oxidative stress phenomena, necroinflammation, and hepatocyte apoptosis at 4 weeks and by pericentral fibrosis at 6 months. Supplementation of n-3 polyunsaturated fatty acid, a PPARα ligand, to HFD-treated animals restored hepatic adiponectin and PPARα expression, reduced TNF-α hepatic levels, and ameliorated fatty liver and the degree of liver injury. Thus, our model mimics the most common features of NASH in humans and provides an ideal tool to study the role of individual pathogenetic events (as for PPARα down-regulation) and to define any future experimental therapy, such as n-3 polyunsaturated fatty acid, which ameliorated the degree of liver injury. PMID:16936261

  3. Alendronate enhances osseous healing in a rat calvarial defect model.

    PubMed

    Toker, Hulya; Ozdemir, Hakan; Ozer, Hatice; Eren, Kaya

    2012-11-01

    The aim of this study was to evaluate the effect of alendronate on osseous wound healing in an experimental model. Critical size defects were created in calvaria of 40 male Wistar rats. The animals were divided into four groups of 10 animals each: autogenous bone graft group; autogenous bone graft with systemic alendronate group (0.01 mg/kg body weight per day for 8 weeks); autogenous bone graft with local alendronate group (1mg/mL for 5 min); non-treatment (control) group. Animals were sacrificed after 8 weeks; osteoblast number, lamellar bone formation, and area of newly formed bone were analysed. The osteoblast number significantly increased in the autogenous bone graft with local alendronate group compared to the autogenous bone graft group (p<0.05). Both systemic and local application of the alendronate significantly increased the new bone formation compared to the autogenous bone graft group (p<0.05) with no significant difference between local or systemic use (p>0.05). Local alendronate and autogenous bone graft use significantly increased the total bone area compared to autogenous bone graft alone (p<0.05). Alendronate enhances the new bone formation by autogenous bone graft in the rat calvarial defect model suggesting that the inhibition of the osteoclastic activity allows an increased rate of bone apposition, which could be applicable to the inflammation-induced destruction of the periodontal tissues during disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Modeling Symptoms of Attention-Deficit Hyperactivity Disorder in a Rat Model of Fetal Alcohol Syndrome.

    PubMed

    Atalar, Elmas Gülcan; Uzbay, Tayfun; Karakaş, Sirel

    2016-11-01

    Several studies indicate the similarity between the symptoms of fetal alcohol syndrome and attention-deficit hyperactivity disorder (ADHD). This study hypothesized that prenatal exposure to ethanol (EtOH) can be used as an animal model of ADHD in Wistar rats. At the first stage of the study, alcohol was delivered to the pregnant dams (237-252 g) by intra-gastric route throughout Gestation Days 8-20 at a dose of 6 g/kg/day. Untreated control group with isocaloric sucrose intubation was also included. Of the 16 male pups (174-180 g), 8 were in the fetal alcohol effects (FAE) group and 8 were in the untreated control group. Subjects went through behavior shaping, discrimination learning and reversal learning. Number of sessions to learn the tasks, response frequency to inhibitory (S-) and excitatory (S+) stimulus features, response latency and inter-response time (IRT) were measured. Significant differences were obtained on only the reversal task. Rats with FAE needed greater number of sessions to learn the reversal task, and they had a higher frequency of incorrect responses in specifically the latter part of the sessions. Our results suggest that reversal learning of FAE rats exhibits deficit in the inhibition of pre-learned responses. Responses behaviorally mimicked attention deficit and impulsivity symptoms of human ADHD. However, the experimental design of the study was not conducive to hyperactivity. Accordingly, rats with FEA can be an alternative to other models since it is not, for example, based on a symptom that is atypical (such as hypertension) to ADHD. Significant difference was obtained in a reversal task between male rats prenatally exposed to ethanol and matched controls. The greater number of sessions for learning and higher frequency of incorrect responses behaviorally mimicked symptoms of ADHD, suggesting that rats with fetal ethanol effects can serve as a useful animal model. © The Author 2016. Medical Council on Alcohol and Oxford University

  5. Relationship between Immunological Abnormalities in Rat Models of Diabetes Mellitus and the Amplification Circuits for Diabetes.

    PubMed

    Takeda, Yuji; Shimomura, Tomoko; Asao, Hironobu; Wakabayashi, Ichiro

    2017-01-01

    A better understanding of pathogenic mechanisms is required in order to treat diseases. However, the mechanisms of diabetes mellitus and diabetic complications are extremely complex. Immune reactions are involved in the pathogenesis of diabetes and its complications, while diabetes influences immune reactions. Furthermore, both diabetes and immune reactions are influenced by genetic and environmental factors. To address these issues, animal models are useful tools. So far, various animal models of diabetes have been developed in rats, which have advantages over mice models in terms of the larger volume of tissue samples and the variety of type 2 diabetes models. In this review, we introduce rat models of diabetes and summarize the immune reactions in diabetic rat models. Finally, we speculate on the relationship between immune reactions and diabetic episodes. For example, diabetes-prone Biobreeding rats, type 1 diabetes model rats, exhibit increased autoreactive cellular and inflammatory immune reactions, while Goto-Kakizaki rats, type 2 diabetes model rats, exhibit increased Th2 reactions and attenuation of phagocytic activity. Investigation of immunological abnormalities in various diabetic rat models is useful for elucidating complicated mechanisms in the pathophysiology of diabetes. Studying immunological alterations, such as predominance of Th1/17 or Th2 cells, humoral immunity, and innate immune reactions, may improve understanding the structure of amplification circuits for diabetes in future studies.

  6. Relationship between Immunological Abnormalities in Rat Models of Diabetes Mellitus and the Amplification Circuits for Diabetes

    PubMed Central

    Shimomura, Tomoko; Asao, Hironobu; Wakabayashi, Ichiro

    2017-01-01

    A better understanding of pathogenic mechanisms is required in order to treat diseases. However, the mechanisms of diabetes mellitus and diabetic complications are extremely complex. Immune reactions are involved in the pathogenesis of diabetes and its complications, while diabetes influences immune reactions. Furthermore, both diabetes and immune reactions are influenced by genetic and environmental factors. To address these issues, animal models are useful tools. So far, various animal models of diabetes have been developed in rats, which have advantages over mice models in terms of the larger volume of tissue samples and the variety of type 2 diabetes models. In this review, we introduce rat models of diabetes and summarize the immune reactions in diabetic rat models. Finally, we speculate on the relationship between immune reactions and diabetic episodes. For example, diabetes-prone Biobreeding rats, type 1 diabetes model rats, exhibit increased autoreactive cellular and inflammatory immune reactions, while Goto-Kakizaki rats, type 2 diabetes model rats, exhibit increased Th2 reactions and attenuation of phagocytic activity. Investigation of immunological abnormalities in various diabetic rat models is useful for elucidating complicated mechanisms in the pathophysiology of diabetes. Studying immunological alterations, such as predominance of Th1/17 or Th2 cells, humoral immunity, and innate immune reactions, may improve understanding the structure of amplification circuits for diabetes in future studies. PMID:28299342

  7. A Rat Drinking in the Dark Model for Studying Ethanol and Sucrose Consumption

    PubMed Central

    Holgate, Joan Y.; Shariff, Masroor; Mu, Erica W. H.; Bartlett, Selena

    2017-01-01

    Background: The intermittent access 2-bottle choice (IA2BC) and drinking in the dark (DID) models were developed for studying rodent binge-like consumption. Traditionally, IA2BC was used with rats and DID with mice. Recently, IA2BC was adapted to study mouse ethanol consumption. However, it is unknown whether DID is suitable for rats or if one rat model is more advantageous than another for studying binge-like consumption. Methods: Male Wistar rats consumed 20% ethanol or 5% sucrose using IA2BC or DID for 12 weeks. IA2BC drinking sessions occurred on alternate days (Mondays–Fridays) and lasted 24 h, whereas DID sessions ran 4 h/day, 5 days/week (Monday–Friday). Average consumption/session, week and hour was measured. To explore DID model suitability for screening novel compounds for controlling ethanol and sucrose intake, varenicline (2 mg/kg) or vehicle was administered to DID rats. Results: IA2BC rats consume more ethanol/session and similar amounts of ethanol/week than DID rats. While, IA2BC rats consume more sucrose/session and week than DID rats. Although IA2BC rats had more ethanol and sucrose access time, DID rats had greater ethanol and sucrose intake/hour. Varenicline significantly reduced ethanol and sucrose consumption in DID rats, consistent with previously published IA2BC studies. Conclusions: Despite the shorter access time, the rat DID model induced higher initial intake and greater consumption/hour for both ethanol and sucrose. The shorter duration of DID sessions did not prevent detection of varenicline-induced reductions in ethanol or sucrose consumption, suggesting the DID model may be suitable for studying binge-like ethanol and sucrose consumption. PMID:28275340

  8. QSAR Modeling of Rat Acute Toxicity by Oral Exposure

    PubMed Central

    Zhu, Hao; Martin, Todd M.; Ye, Lin; Sedykh, Alexander; Young, Douglas M.; Tropsha, Alexander

    2009-01-01

    Few Quantitative Structure-Activity Relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity endpoints. In this study, a comprehensive dataset of 7,385 compounds with their most conservative lethal dose (LD50) values has been compiled. A combinatorial QSAR approach has been employed to develop robust and predictive models of acute toxicity in rats caused by oral exposure to chemicals. To enable fair comparison between the predictive power of models generated in this study versus a commercial toxicity predictor, TOPKAT (Toxicity Prediction by Komputer Assisted Technology), a modeling subset of the entire dataset was selected that included all 3,472 compounds used in the TOPKAT’s training set. The remaining 3,913 compounds, which were not present in the TOPKAT training set, were used as the external validation set. QSAR models of five different types were developed for the modeling set. The prediction accuracy for the external validation set was estimated by determination coefficient R2 of linear regression between actual and predicted LD50 values. The use of the applicability domain threshold implemented in most models generally improved the external prediction accuracy but expectedly led to the decrease in chemical space coverage; depending on the applicability domain threshold, R2 ranged from 0.24 to 0.70. Ultimately, several consensus models were developed by averaging the predicted LD50 for every compound using all 5 models. The consensus models afforded higher prediction accuracy for the external validation dataset with the higher coverage as compared to individual constituent models. The validated consensus LD50 models developed in this study can be used as reliable computational predictors of in vivo acute toxicity. PMID:19845371

  9. Role of aldosterone in the remnant kidney model in the rat.

    PubMed Central

    Greene, E L; Kren, S; Hostetter, T H

    1996-01-01

    The renin-angiotensin-aldosterone system (RAAS) participates in the injury sustained by the remnant kidney. Our studies assessed the importance of aldosterone in that model and the response of aldosterone to drugs interfering with the RAAS. Initially, four groups of rats were studied: SHAM-operated rats, untreated remnant rats (REM), REM rats treated with losartan and enalapril (REM AIIA), and REM AIIA rats infused with exogenous aldosterone (REM AIIA + ALDO). The last group was maintained with aldosterone levels comparable to those in untreated REM rats by constant infusion of exogenous aldosterone. REM rats had larger adrenal glands and a > 10-fold elevation in plasma aldosterone compared to SHAM. REM AIIA rats demonstrated significant suppression of the hyperaldosteronism as well as marked attenuation of proteinuria, hypertension, and glomerulosclerosis compared to REM. REM AIIA + ALDO rats manifested greater proteinuria, hypertension, and glomerulosclerosis than REM AIIA rats. Indeed, by 4 wk of observation all of these features of the experimental disease were similar in magnitude in REM AIIA + ALDO and untreated REM. In separate REM rats spironolactone administration did not reduce glomerular sclerosis but did transiently reduce proteinuria, lowered arterial pressure, and lessened cardiac hypertrophy. In summary, aldosterone contributes to hypertension and renal injury in the remnant kidney model. PMID:8770880

  10. Laser thresholds in pulp exposure: a rat animal model

    NASA Astrophysics Data System (ADS)

    White, Joel M.; Goodis, Harold E.; Kudler, Joel J.

    1995-05-01

    Laser technology is now being clinically investigated for the removal of carious enamel and dentin. This study used an animal model to evaluate histological pulpal effects from laser exposure. The molars of 24 Sprague-Dawley rats (n equals 264) were exposed to either a pulsed 1.06 micrometers Nd:YAG laser (120 microseconds, 320 micrometer diameter fiber), air rotor drill preparation or left untreated as controls. The following treatment conditions were investigated: control group (n equals 54); high speed drill with carbide bur (n equals 39); laser exposure at 50 mJ/p at 10 Hz (n equals 27), 100 mJ/p at 10 Hz (n equals 66) and 100 mJ/p at 20 Hz (n equals 39). A sixth treatment condition was investigated: root surface hypersensitivity, which included incremental laser exposure from 30 to 100 mJ/p at 10 Hz (n equals 39). The animals were euthanized either immediately after treatment, at one week, or at one month. The jaws were fixed and bioprepared. Remaining dentin thickness was measured, and ranged from 0.17 +/- 0.04 mm to 0.35 +/- 0.09 mm. The pulp tissue was examined for histologic inflammatory response. No evidence of pulpal involvement or adverse pulpal effects were found at any time period in teeth receiving 50 mJ/p. When histologic samples were compared with controls, all observations were similar. Of the 210 exposed teeth, 2 teeth receiving 100 mJ/p demonstrated abscess formation and were exfoliated. Further, in the rat molar when remaining dentin thickness was less than 0.5 mm, exposed to 100 mJ/p, threshold pulpal effects occurred. The response of rat pulp to laser exposure indicated no histologically measurable response to pulsed laser energy at 50 mJ/p.

  11. A BBDR-HPT Axis Model for the Pregnant Rat and Fetus: Evaluation of Iodide Deficiency

    EPA Science Inventory

    A biologically based dose response (BBDR) model for the hypothalamic-pituitarythyroid (HPT) axis for the pregnant rat and fetus is being developed to advance understanding of thyroid hormone disruptions and developmental neurotoxicity (DNT). The model for the pregnant rat and fet...

  12. A BBDR-HPT Axis Model for the Pregnant Rat and Fetus: Evaluation of Iodide Deficiency

    EPA Science Inventory

    A biologically based dose response (BBDR) model for the hypothalamic-pituitarythyroid (HPT) axis for the pregnant rat and fetus is being developed to advance understanding of thyroid hormone disruptions and developmental neurotoxicity (DNT). The model for the pregnant rat and fet...

  13. Metformin and atorvastatin reduce adhesion formation in a rat uterine horn model.

    PubMed

    Yilmaz, Bulent; Aksakal, Orhan; Gungor, Tayfun; Sirvan, Levent; Sut, Necdet; Kelekci, Sefa; Soysal, Sunullah; Mollamahmutoglu, Leyla

    2009-03-01

    The aim of the present study was to determine whether atorvastatin and metformin are effective in preventing adhesions in a rat uterine horn model. A total of 40 non-pregnant, female Wistar albino rats, weighing 180-210 g, were used as a model for post-operative adhesion formation. The rats were randomized into four groups after seven standard lesions were inflicted in each uterine horn and lower abdominal sidewall using bipolar cauterization. The rats were given atorvastatin 2.5 mg/kg/day, p.o. (10 rats), atorvastatin 30 mg/kg/day, p.o. (10 rats), metformin 50 mg/kg/day, p.o. (10 rats) and no treatment was applied in the control group (10 rats). The animals were killed 2 weeks later and adhesions were scored both clinically and pathologically by authors blinded to groups. One rat in the control group died before the end of the 2 week period. Total clinical adhesion scores regarding extent, severity and degree of adhesions and histopathological findings including inflammation and fibrosis were significantly lower in the metformin (P < 0.001 and P < 0.01, respectively) and atorvastatin 30 mg/kg/day (P < 0.001 and P < 0.01, respectively) groups when compared with control group. Metformin and atorvastatin are both effective for prevention of adhesion formation in a rat uterine horn model.

  14. Laparoscopic splenectomy and nephrectomy in a rat model. Description of a new technique.

    PubMed

    Giuffrida, M C; Marquet, R L; Kazemier, G; Wittich, P; Bouvy, N D; Bruining, H A; Bonjer, H J

    1997-05-01

    In experimental studies on the effects of laparoscopic procedures on tumor biology, a localized tumor model is desirable. The spleen and the kidney are preferable, because these organs are amenable to tumor placement and subsequent removal. This study describes the technique of laparoscopic splenectomy and nephrectomy in the rat model. Pneumoperitoneum was established by CO2 insufflation. Laparoscopic splenectomy involved two-handed dissection, intracorporeal ligation, and division of gastrosplenic attachments and hilar and short gastric vessels. Laparoscopic nephrectomy was done by intracorporeal ligation and division of the renal vessels and the ureter after mobilization of the kidney. Laparoscopic splenectomy was performed in six rats; laparoscopic nephrectomy was done in six rats. Operative time ranged from 45 to 90 min for splenectomy and from 40 to 65 min for nephrectomy. Postoperatively, two rats died from hemorrhage. Necropsy of the rats after 10 days revealed adhesion in three rats after splenectomy and in four rats after nephrectomy. Inflammatory processes were found around the silk ligatures in all rats after splenectomy; in two rats wound infections occurred at the port sites. Laparoscopic splenectomy and nephrectomy in the rat proved technically feasible and may provide new localized tumor models suitable to be used in further studies on the oncological effects of laparoscopic surgery.

  15. Dual regulating effects of gastrodin on extracellular dopamine concentration in rats models of Tourette's syndrome.

    PubMed

    Zhang, Feng; Li, Anyuan

    2015-01-01

    Evaluate the dual regulating effects of gastrodin on striatal extracellular dopamine (DA) concentration in Tourette's syndrome (TS) rat models, and explore the underlying pharmacological mechanisms. Seventy Wistar rats were randomly divided into control group and TS model group. The former was intraperitoneally injected with saline (0.9%), while in the later, the rats were injected with Apomorphine (Apo) and 3,3'-iminodipropionitrile (IDPN) respectively to manipulate two kinds of TS rat models. Both Apo and IDPN induced rats were further assigned to three conditions, and the related rats were treated respectively by oral gavage with saline, gastrodin and Haloperidol (Hal). Data of stereotypy of the rats were collected. After 8 weeks, the extracellular content of DA and HVA in striatum were examined by intracerebral microdialysis and follow-up high-performance liquid chromatography (HPLC), and the expression of dopamine transporter (DAT) was probed by Western blot. Gastrodin improved the stereotyped behaviors in TS rats. Furthermore, it down-regulated the elevated striatal extracellular DA concentration in Apo-induced rats and up-regulated the decreased DA content in the rats exposed to IDPN. Meanwhile, a dramatic down-regulation was detected in DAT protein expression in Apo + GAS group, while an opposite profile was showed in the IDPN + GAS group. The dual regulating effects of gastrodin on extracellular DA level have been established, and the related mechanisms would be the dual regulating effects of gastrodin on the expression of DAT, a glycoprotein in the regulation of the extracellular DA concentration.

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

    SciTech Connect

    Miller, Frederick J.; Asgharian, Bahman; Schroeter, Jeffry D.; Price, Owen; Corley, Richard A.; Einstein, Daniel R.; Jacob, Rick E.; Cox, Timothy C.; Kabilan, Senthil; Bentley, Timothy

    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 model 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.

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

    SciTech Connect

    Miller, Frederick J.; Asgharian, Bahman; Schroeter, Jeffry D.; Price, Owen; Corley, Richard A.; Einstein, Daniel R.; Jacob, Rick E.; Cox, Timothy C.; Kabilan, Senthil; Bentley, Timothy

    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 model 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.

  18. Electroacupuncture analgesia in rat ankle sprain pain model: neural mechanisms.

    PubMed

    Kim, Hee Young; Koo, Sung Tae; Kim, Jae Hyo; An, Kyungeh; Chung, Kyungsoon; Chung, Jin Mo

    2010-02-01

    Acupuncture, an alternative medical therapy with a long history, is appealing because it can activate endogenous analgesic mechanisms by minimally invasive means. The mechanisms of acupuncture, however, are not well understood yet. The following sentence was removed from our original manuscript. One of the major problems impeding understanding of the acupuncture mechanism is lack of experimental models that mimic various forms of persistent pain that respond to acupuncture in humans. In this review, we summarize and discuss previous and recent findings regarding electroacupuncture-induced analgesia in an ankle sprain pain model and the potential underlying mechanisms of acupuncture. A novel model of ankle sprain pain is introduced recently and the mechanism of electroacupuncture-induced analgesia in this model has been explored. The following sentence was removed from our original manuscript. This model provides a reproducible and quantifiable index of persistent pain at the ankle joint in rats. Acupuncture at a remote site produces long-lasting and powerful analgesia. The consistent analgesic effect of acupuncture in this model has allowed us to pursue the underlying neural mechanisms. These studies provide insight into the mechanisms of acupuncture analgesia in one particular form of persistent pain, and hopefully will allow us to expand our knowledge to other painful conditions.

  19. Scavenger receptor function of mouse FcγRIII contributes to progression of atherosclerosis in apoE hyperlipidemic mice1

    PubMed Central

    Zhu, Xinmei; Ng, Hang Pong; Lai, Yen-Chun; Craigo, Jodi K.; Nagilla, Pruthvi S.; Raghani, Pooja; Nagarajan, Shanmugam

    2014-01-01

    Recent studies showed loss of CD36 or scavenger receptor-AI/II (SR-A) does not ameliorate atherosclerosis in hyperlipidemic mouse model, suggesting receptors other than CD36 and SR-A may also contribute to atherosclerosis. In this report, we show that apoE-CD16 double knockout mice (apoE-CD16 DKO) have reduced atherosclerotic lesions compared with apoE KO mice. In vivo and in vitro foam cells analyses showed apoE-CD16 DKO macrophages accumulated less neutral lipids. Reduced foam cell formation in apoE-CD16 DKO mice is not due to change in expression of CD36, SR-A and LOX-1. This led to a hypothesis that CD16 may have scavenger receptor activity. We presented evidence that a soluble form of recombinant mouse CD16 (sCD16) bound to malondialdehyde-modified low-density lipoprotein (MDALDL), and this binding is blocked by molar excess of MDA-BSA and anti-MDA mAbs, suggesting CD16 specifically recognizes MDA epitopes. Interestingly, sCD16 inhibited MDALDL binding to macrophage cell line as well as sCD36, sSR-A and sLOX-1, indicating CD16 can cross-block MDALDL binding to other scavenger receptors. Anti-CD16 mAb inhibited IC binding to sCD16, while partially inhibited MDALDL binding to sCD16, suggesting MDALDL binding site may be in close proximity to the IC binding site in CD16. Loss of CD16 expression resulted in reduced levels of MDALDL induced pro-inflammatory cytokine expression. Finally, CD16 deficient macrophages showed reduced MDALDL-induced Syk phosphorylation. Collectively our findings suggest scavenger receptor activity of CD16 may in part contribute to the progression of atherosclerosis. PMID:25038257

  20. Modeling the Nonlinear Motion of the Rat Central Airways.

    PubMed

    Ibrahim, G; Rona, A; Hainsworth, S V

    2016-01-01

    Advances in volumetric medical imaging techniques allowed the subject-specific modeling of the bronchial flow through the first few generations of the central airways using computational fluid dynamics (CFD). However, a reliable CFD prediction of the bronchial flow requires modeling of the inhomogeneous deformation of the central airways during breathing. This paper addresses this issue by introducing two models of the central airways motion. The first model utilizes a node-to-node mapping between the discretized geometries of the central airways generated from a number of successive computed tomography (CT) images acquired dynamically (without breath hold) over the breathing cycle of two Sprague-Dawley rats. The second model uses a node-to-node mapping between only two discretized airway geometries generated from the CT images acquired at end-exhale and at end-inhale along with the ventilator measurement of the lung volume change. The advantage of this second model is that it uses just one pair of CT images, which more readily complies with the radiation dosage restrictions for humans. Three-dimensional computer aided design geometries of the central airways generated from the dynamic-CT images were used as benchmarks to validate the output from the two models at sampled time-points over the breathing cycle. The central airway geometries deformed by the first model showed good agreement to the benchmark geometries within a tolerance of 4%. The central airway geometry deformed by the second model better approximated the benchmark geometries than previous approaches that used a linear or harmonic motion model.

  1. Experimental models for cancellous bone healing in the rat

    PubMed Central

    Bernhardsson, Magnus; Sandberg, Olof; Aspenberg, Per

    2015-01-01

    Background and purpose — Cancellous bone appears to heal by mechanisms different from shaft fracture healing. There is a paucity of animal models for fractures in cancellous bone, especially with mechanical evaluation. One proposed model consists of a screw in the proximal tibia of rodents, evaluated by pull-out testing. We evaluated this model in rats by comparing it to the healing of empty drill holes, in order to explain its relevance for fracture healing in cancellous bone. To determine the sensitivity to external influences, we also compared the response to drugs that influence bone healing. Methods — Mechanical fixation of the screws was measured by pull-out test and related to the density of the new bone formed around similar, but radiolucent, PMMA screws. The pull-out force was also related to the bone density in drill holes at various time points, as measured by microCT. Results — The initial bone formation was similar in drill holes and around the screw, and appeared to be reflected by the pull-out force. Both models responded similarly to alendronate or teriparatide (PTH). Later, the models became different as the bone that initially filled the drill hole was resorbed to restore the bone marrow cavity, whereas on the implant surface a thin layer of bone remained, making it change gradually from a trauma-related model to an implant fixation model. Interpretation — The similar initial bone formation in the different models suggests that pull-out testing in the screw model is relevant for assessment of metaphyseal bone healing. The subsequent remodeling would not be of clinical relevance in either model. PMID:26200395

  2. NO2 inhalation enhances asthma susceptibility in a rat model.

    PubMed

    Han, Ming; Ji, Xiaotong; Li, Guangke; Sang, Nan

    2017-10-07

    Nitrogen dioxide (NO2) is a major air pollutant. Epidemiologic studies have found that NO2 exposure is associated with an increased risk of asthma. Nevertheless, the potential molecular mechanisms remain unclear. In this study, we investigated the effect of NO2 inhalation on the occurrence of allergic airway inflammation and its underlying mechanisms. Firstly, male Wistar rats were exposed to 2 and 5 mg/m(3) NO2 (28 days, 5 h/day). The results showed that NO2 exposure could induce pulmonary inflammatory response, mucus formation, and Th1/Th2 imbalance in the lung of normal rats, resulting in allergic asthma-like features. Secondly, male Wistar rats were exposed to 5 mg/m(3) NO2 (42 days, 5 h/day), sensitized with ovalbumin (OVA), challenged with aerosolized OVA, and characterized in asthma models. Results showed that NO2 exposure aggravated lung inflammation in the OVA-sensitized rats, accompanied by the increase in inflammatory cell infiltration, mucus hypersecretion, and collagen deposition. Furthermore, NO2 exposure promoted the increase in the expression of mucin gene (MUC5AC) and pro-inflammatory factors [interleukin (IL)-1β, intercellular adhesion molecule-1 (ICAM-1), and IL-6] as well as serum OVA-specific immunoglobulin E (IgE) production. Taken together, we established that NO2 exposure promotes allergic airway inflammation and increases the asthma susceptibility. The underlying mechanisms involve the promotion of activation of interleukin-4/signal transducer and activator of transcription-6 (IL-4/STAT6) pathway [IL-4 receptor (IL-4R) α, janus kinase (JAK) 1, JAK 3, and STAT6] and related transcription factor [T cell-specific protein-tyrosine kinase (Lck), extracellular-regulated kinase (ERK)1/2, and nuclear factor-κB (NF-κB)]. In particular, the imbalance of Th1/Th2 cell differentiation [IL-4, interferon (IFN)-γ, GATA-binding protein-3 (GATA-3), and T-box expressed in T cells (T-bet)] plays a pivotal role in NO2-induced inflammatory responses

  3. Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability

    PubMed Central

    Brooks, Marjory B.; Turk, James R.; Guerrero, Abraham; Narayanan, Padma K.; Nolan, John P.; Besteman, Elizabeth G.; Wilson, Dennis W.; Thomas, Roberta A.; Fishman, Cindy E.; Thompson, Karol L.; Ellinger-Ziegelbauer, Heidrun; Pierson, Jennifer B.; Paulman, April; Chiang, Alan Y.; Schultze, Albert E.

    2017-01-01

    Systemic inflammation co-activates coagulation, which unchecked culminates in a lethal syndrome of multi-organ microvascular thrombosis known as disseminated intravascular coagulation (DIC). We studied an endotoxin-induced inflammatory state in rats to identify biomarkers of hemostatic imbalance favoring hypercoagulability. Intraperitoneal injection of LPS at 15 mg/kg body weight resulted in peripheral leukopenia and widespread neutrophilic sequestration characteristic of an acute systemic inflammatory response. Early indicators of hemostatic pathway activation developed within 4 hours, including increased circulating concentrations of procoagulant extracellular vesicles (EVs), EVs expressing endothelial cell and platelet membrane markers, and high concentration of soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor-1 (PAI-1), and D-dimers. Inflammation persisted throughout the 48-hour observation period; however, increases were found in a subset of serum microRNA (miRNA) that coincided with gradual resolution of hemostatic protein abnormalities and reduction in EV counts. Dose-adjusted LPS treatment in rats provides a time-course model to develop biomarker profiles reflecting procoagulant imbalance and rebalance under inflammatory conditions. PMID:28081568

  4. Rheumatoid arthritis: identifying and characterising polymorphisms using rat models

    PubMed Central

    2016-01-01

    ABSTRACT Rheumatoid arthritis is a chronic inflammatory joint disorder characterised by erosive inflammation of the articular cartilage and by destruction of the synovial joints. It is regulated by both genetic and environmental factors, and, currently, there is no preventative treatment or cure for this disease. Genome-wide association studies have identified ∼100 new loci associated with rheumatoid arthritis, in addition to the already known locus within the major histocompatibility complex II region. However, together, these loci account for only a modest fraction of the genetic variance associated with this disease and very little is known about the pathogenic roles of most of the risk loci identified. Here, we discuss how rat models of rheumatoid arthritis are being used to detect quantitative trait loci that regulate different arthritic traits by genetic linkage analysis and to positionally clone the underlying causative genes using congenic strains. By isolating specific loci on a fixed genetic background, congenic strains overcome the challenges of genetic heterogeneity and environmental interactions associated with human studies. Most importantly, congenic strains allow functional experimental studies be performed to investigate the pathological consequences of natural genetic polymorphisms, as illustrated by the discovery of several major disease genes that contribute to arthritis in rats. We discuss how these advances have provided new biological insights into arthritis in humans. PMID:27736747

  5. Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability.

    PubMed

    Brooks, Marjory B; Turk, James R; Guerrero, Abraham; Narayanan, Padma K; Nolan, John P; Besteman, Elizabeth G; Wilson, Dennis W; Thomas, Roberta A; Fishman, Cindy E; Thompson, Karol L; Ellinger-Ziegelbauer, Heidrun; Pierson, Jennifer B; Paulman, April; Chiang, Alan Y; Schultze, Albert E

    2017-01-01

    Systemic inflammation co-activates coagulation, which unchecked culminates in a lethal syndrome of multi-organ microvascular thrombosis known as disseminated intravascular coagulation (DIC). We studied an endotoxin-induced inflammatory state in rats to identify biomarkers of hemostatic imbalance favoring hypercoagulability. Intraperitoneal injection of LPS at 15 mg/kg body weight resulted in peripheral leukopenia and widespread neutrophilic sequestration characteristic of an acute systemic inflammatory response. Early indicators of hemostatic pathway activation developed within 4 hours, including increased circulating concentrations of procoagulant extracellular vesicles (EVs), EVs expressing endothelial cell and platelet membrane markers, and high concentration of soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor-1 (PAI-1), and D-dimers. Inflammation persisted throughout the 48-hour observation period; however, increases were found in a subset of serum microRNA (miRNA) that coincided with gradual resolution of hemostatic protein abnormalities and reduction in EV counts. Dose-adjusted LPS treatment in rats provides a time-course model to develop biomarker profiles reflecting procoagulant imbalance and rebalance under inflammatory conditions.

  6. A new model of progressive pulmonary fibrosis in rats

    SciTech Connect

    Last, J.A.; Gelzleichter, T.R.; Pinkerton, K.E.; Walker, R.M.; Witschi, H. )

    1993-08-01

    Sprague-Dawley rats were exposed for 6 h daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This unique animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis and should facilitate studying underlying mechanisms and potential therapy of progressive pulmonary fibrosis.

  7. [Histostructural changes of rat cerebral cortex during hemorrhagic stroke modeling].

    PubMed

    Savos'ko, S I; Chaĭkovs'kyĭ, Iu B; Pogoriela, N Kh; Makarenko, O M

    2012-01-01

    Pathological changes during modeling of primary and secondary acute hemorrhagic stroke were studied in rats. We revealed differences in the activity of pharmacological action of medications under condition of acute stroke. The action of medications increased viability of neurons in both hemispheres of rat cerebrum at a right-side primary and secondary hemorrhagic stroke. Following secondary stroke, the amount of degenerative neurons amounted 25.5 +/- 0.8 cells/mm2, following the action ofcerebrolysin this value was 17.6 +/- 1.7 cells/ mm2 and after the action of cortexine and cerebral this value amounted 18.0 +/- 0.9 cells/mm2 and 10.7 +/- 0.4 cells/ mm2, respectively. In control animals the number of degenerative neurons did not exceed 2% and averaged 1.5 +/- 0.1 cells/mm2. Analysis of the morphological and statistical data showed that the most effective remedies under the primary and secondary hemorrhagic insult are cortexine and cerebral. Cerebral was found to be more effective.

  8. Effects of benidipine in a rat model for experimental angina.

    PubMed

    Ikeda, Jun-ichi; Matsubara, Masahiro; Yao, Kozo

    2006-12-01

    To compare the antianginal effects of 1,4-dihydropyridine-type calcium-channel blockers, we evaluated the effects of benidipine, amlodipine, nifedipine, and efonidipine on vasopressin-induced myocardial ischemia in rats, an experimental model of angina. Intravenous administration of benidipine (3 microg/kg), amlodipine (1000 microg/kg), and nifedipine (100 microg/kg) suppressed the vasopressin-induced S-wave depression, an index of myocardial ischemia. Efonidipine (100 microg/kg, i.v.) tended to inhibit the S-wave depression. At the antianginal dose of each drug, amlodipine, nifedipine, and efonidipine decreased blood pressure significantly, whereas benidipine had little effect on blood pressure at a dose of 3 microg/kg. These results indicate that benidipine, unlike the other 1,4-dihydropyridine-type calcium-channel blockers examined in this study, inhibits vasopressin-induced coronary vasospasm with fewer undesirable effects such as hypotension in rats, suggesting that benidipine may be useful in the treatment of angina pectoris.

  9. Anxiety responses and neurochemical changes in a kaolin-induced rat model of hydrocephalus.

    PubMed

    Hwang, Yong Sup; Shim, Insop; Chang, Jin Woo

    2011-04-01

    Hydrocephalus is a pathological enlargement of the ventricles of the brain, which can result from various diseases of the central nervous system. Patients with hydrocephalus frequently show motor abnormalities, such as abnormal gait and posture, as well as intellectual and emotional impairment. The present study was designed to investigate anxiety responses in rats with kaolin-induced hydrocephalus. A total of 26 Sprague-Dawley rats were used for this study. Hydrocephalus was induced in 14 Sprague-Dawley rats by injecting 0.1 ml of 20% kaolin solution into the cisterna magna; 12 rats were administered the same volume of saline in the same fashion and served as controls. Seven of the rats that were injected with kaolin and 6 of the rats injected with saline were killed 3 days after injection (Group 1); the remaining rats were killed 4 weeks after injection (Group 2) to evaluate effects related to acute and chronic hydrocephalus. The rats were tested in an elevated plus maze after induction of hydrocephalus by kaolin injection. After the animals were killed, brain sections were immunostained for cholecystokinin and neuropeptide Y. In addition, tyrosine hydroxylase immunoreactivity in the ventral tegmental area was evaluated by immunohistological staining. The rats with acute hydrocephalus showed decreased entry into and spent less time in the open arms of the elevated plus maze as compared with the control rats. The hydrocephalic rats had significantly more cholecystokinin-immunoreactive neurons and fewer neuropeptide Y-immunoreactive neurons in their brains. In addition, hydrocephalus progress in this model was positively correlated with the anxiety response. The numbers of tyrosine hydroxylase-immunoreactive neurons were decreased significantly in the hydrocephalic rats as compared with the control rats. These results suggest that the rat model of hydrocephalus is characterized by increased anxiety response and is associated with the functional impairment of the

  10. Noninvasive fatigue fracture model of the rat ulna.

    PubMed

    Tami, A E; Nasser, P; Schaffler, M B; Knothe Tate, M L

    2003-11-01

    Fatigue damage occurs in response to repeated cyclic loading and has been observed in situ in cortical bone of humans and other animals. When microcracks accumulate and coalesce, failure ensues and is referred to as fatigue fracture. Experimental study of fatigue fracture healing is inherently difficult due to the lack of noninvasive models. In this study, we hypothesized that repeated cyclic loading of the rat ulna results in a fatigue fracture. The aim of the study was to develop a noninvasive long bone fatigue fracture model that induces failure through accumulation and coalescence of microdamage and replicates the morphology of a clinical fracture. Using modified end-load bending, right ulnae of adult Sprague-Dawley rats were cyclically loaded in vivo to fatigue failure based on increased bone compliance, which reflects changes in bone stiffness due to microdamage. Preterminal tracer studies with 0.8% Procion Red solution were conducted according to protocols described previously to evaluate perfusion of the vasculature as well as the lacunocanalicular system at different time points during healing. Eighteen of the 20 animals loaded sustained a fatigue fracture of the medial ulna, i.e. through the compressive cortex. In all cases, the fracture was closed and non-displaced. No disruption to the periosteum or intramedullary vasculature was observed. The loading regime did not produce soft tissue trauma; in addition, no haematoma was observed in association with application of load. Healing proceeded via proliferative woven bone formation, followed by consolidation within 42 days postfracture. In sum, a noninvasive long bone fatigue fracture model was developed that lends itself for the study of internal remodeling of periosteal woven bone during fracture healing and has obvious applications for the study of fatigue fracture etiology.

  11. A new model of implant-related osteomyelitis in rats.

    PubMed

    Lucke, M; Schmidmaier, G; Sadoni, S; Wildemann, B; Schiller, R; Stemberger, A; Haas, N P; Raschke, M

    2003-10-15

    Infection related to osteosynthesis often has dramatic consequences for the patient. Prolonged hospitalization with systemic antibiotic therapy, several revision procedures, possible amputation, and even death may occur. To investigate the pathology of infection in orthopedic surgery, a new rat model of implant related osteomyelitis was developed. Three different concentrations (10(6), 10(3), and 10(2) colony-forming units (CFU)/10 microl) of Staphylococcus aureus were inoculated into the tibial medullary cavity with simultaneous insertion of a titanium Kirschner wire. Controls received phosphate-buffered saline (PBS). Each group consisted of 10 animals. Animals were followed for 4 weeks until sacrifice. X-rays of the tibiae were taken weekly, blood counts were analyzed, and body temperature and weight were determined. After sacrifice, infection was evaluated by histological and microbiological investigations. All animals inoculated with Staph. aureus in either concentration developed microbiological, histological, and radiological signs of osteomyelitis in correlation to the amount of inoculated bacteria. X-rays clearly revealed osseous destruction after 14 days with progression of osteomyelitis during the following weeks. CFU/g bone and bone weight after sacrifice showed dependence on the amount of inoculated CFU. The histological results confirmed the radiological findings. No significant changes in blood counts, body weight, and body temperature between the groups could be observed. The results demonstrate that it is possible to develop a model of implant-related osteomyelitis in rats with dependence on the amount of inoculated bacteria. No other promoters of infection besides intramedullary insertion of titanium Kirschner wires were used in this model.

  12. Antisense oligonucleotide inhibition of cholesteryl ester transfer protein enhances RCT in hyperlipidemic, CETP transgenic, LDLr−/− mice

    PubMed Central

    Bell, Thomas A.; Graham, Mark J.; Lee, Richard G.; Mullick, Adam E.; Fu, Wuxia; Norris, Dan; Crooke, Rosanne M.

    2013-01-01

    Due to their ability to promote positive effects across all of the lipoprotein classes, cholesteryl ester transfer protein (CETP) inhibitors are currently being developed as therapeutic agents for cardiovascular disease. In these studies, we compared an antisense oligonucleotide (ASO) inhibitor of CETP to the CETP small molecule inhibitor anacetrapib. In hyperlipidemic CETP transgenic (tg) mice, both drugs provided comparable reductions in total plasma cholesterol, decreases in CETP activity, and increases in HDL cholesterol. However, only mice treated with the antisense inhibitor showed an enhanced effect on macrophage reverse cholesterol transport, presumably due to differences in HDL apolipoprotein composition and decreases in plasma triglyceride. Additionally, the ASO-mediated reductions in CETP mRNA were associated with less accumulation of aortic cholesterol. These preliminary findings suggest that CETP ASOs may represent an alternative means to inhibit that target and to support their continued development as a treatment for cardiovascular disease in man. PMID:23801661

  13. Altered explorative strategies and reactive coping style in the FSL rat model of depression

    PubMed Central

    Magara, Salvatore; Holst, Sarah; Lundberg, Stina; Roman, Erika; Lindskog, Maria

    2015-01-01

    Modeling depression in animals is based on the observation of behaviors interpreted as analog to human symptoms. Typical tests used in experimental depression research are designed to evoke an either-or outcome. It is known that explorative and coping strategies are relevant for depression, however these aspects are generally not considered in animal behavioral testing. Here we investigate the Flinders Sensitive Line (FSL), a rat model of depression, compared to the Sprague-Dawley (SD) rat in three independent tests where the animals are allowed to express a more extensive behavioral repertoire. The multivariate concentric square field™ (MCSF) and the novel cage tests evoke exploratory behaviors in a novel environment and the home cage change test evokes social behaviors in the re-establishment of a social hierarchy. In the MCSF test, FSL rats exhibited less exploratory drive and more risk-assessment behavior compared to SD rats. When re-exposed to the arena, FSL, but not SD rats, increased their exploratory behavior compared to the first trial and displayed risk-assessment behavior to the same extent as SD rats. Thus, the behavior of FSL rats was more similar to that of SDs when the rats were familiar with the arena. In the novel cage test FSL rats exhibited a reactive coping style, consistent with the reduced exploration observed in the MCSF. Reactive coping is associated with less aggressive behavior. Accordingly, FSL rats displayed less aggressive behavior in the home cage change test. Taken together, our data show that FSL rats express altered exploratory behavior and reactive coping style. Reduced interest is a core symptom of depression, and individuals with a reactive coping style are more vulnerable to the disease. Our results support the use of FSL rats as an animal model of depression and increase our understanding of the FSL rat beyond the behavioral dimensions targeted by the traditional depression-related tests. PMID:25954168

  14. Curative effect of sesame oil in a rat model of chronic kidney disease.

    PubMed

    Liu, Chuan-Teng; Chien, Se-Ping; Hsu, Dur-Zong; Periasamy, Srinivasan; Liu, Ming-Yie

    2015-12-01

    Chronic kidney disease causes a progressive and irreversible loss of renal function. We investigated the curative effect of sesame oil, a natural, nutrient-rich, potent antioxidant, in a rat model of chronic kidney disease. Chronic kidney disease was induced by subcutaneously injecting uni-nephrectomized rats with deoxycorticosterone acetate (DOCA) and 1% NaCl [DOCA/salt] in drinking water. Four weeks later, the rats were gavaged with sesame oil (0.5 or 1 mL/kg per day) for 7 days. Renal injury, histopathological changes, hydroxyl radical, peroxynitrite, lipid peroxidation, Nrf2, osteopontin expression, and collagen were assessed 24 h after the last dose of sesame oil. Blood urea nitrogen, creatinine, urine volume, and albuminuria were significantly higher in the DOCA/salt treated rats than in control rats. Sesame oil significantly decreased these four tested parameters in DOCA/salt treated rats. In addition, creatinine clearance rate and nuclear Nrf2 expression were significantly decreased in the DOCA/salt treated rats compared to control rats. Sesame oil significantly decreased hydroxyl radical, peroxynitrite level, lipid peroxidation, osteopontin, and renal collagen deposition, but increased creatinine clearance rate and nuclear Nrf2 expression in DOCA/salt treated rats. We conclude that supplementation of sesame oil mitigates DOCA/salt induced chronic kidney disease in rats by activating Nrf2 and attenuating osteopontin expression and inhibiting renal fibrosis in rats. © 2015 Asian Pacific Society of Nephrology.

  15. The effects of carnosine in an experimental rat model of septic shock

    PubMed Central

    Sahin, Sabiha; Oter, Serdar; Burukoglu, Dilek; Sutken, Emine

    2013-01-01

    Background To examine the effect of carnosine on liver function and histological findings in experimental septic shock model, 24 Sprague-Dawley rats were used. Material/Methods Rats were divided into control, septic shock, and carnosine-treated septic shock groups. Femoral vein and artery catheterization were performed on all rats. Rats in the control group underwent laparotomy and catheterization; in the test groups, cecal ligation-perforation and bladder cannulation were added. Rats in the treatment group received a single intraperitoneal (IP) injection of 250 mg/kg carnosine 60 minutes after cecal ligation-perforation. Rats were monitored for blood pressure, heart rate, and body temperature to assess the postoperative septic response, and body fluids were replaced as necessary. At the end of 24 hours, rats were sacrificed and liver samples were collected. Results Statistically significant improvements were observed in liver function, tissue and serum MDA levels, and histological findings in rats treated with carnosine, compared to rats with untreated sepsis. HB and HCT values did not change significantly during the course of the experiment. Rats exposed to septic shock and treated with carnosine exhibited decreased sinusoidal dilatation and cellular inflammation into the portal region, compared to the sepsis group; the livers of rats in this group had near-normal histological structure. Conclusions We conclude that carnosine may be an effective treatment for oxidative damage due to liver tissue perfusion defects in cases of septic shock. PMID:23396325

  16. Novel PPAR Pan Agonist, ZBH Ameliorates Hyperlipidemia and Insulin Resistance in High Fat Diet Induced Hyperlipidemic Hamster

    PubMed Central

    Xie, Xinni; Xue, Nina; Jin, Xueyuan; Wang, Lili

    2014-01-01

    Effective and safe pharmacological interventions for hyperlipidemia remains badly needed. By incorporating the key pharmacophore of fibrates into the natural scaffold of resveratrol, a novel structural compound ZBH was constructed. In present study, we found ZBH reserved approximately one third of the sirtuin 1 (SIRT1) activation produced by resveratrol at in-vitro enzyme activity assay, directly bound to and activated all three peroxisome proliferator-activated receptor (PPAR) subtypes respectively in PPAR binding and transactivation assays. Moreover, ZBH (EC50, 1.75 µM) activate PPARα 21 fold more efficiently than the well-known PPAR pan agonist bezafibrate (EC50, 37.37 µM) in the cellular transactivation assays. In the high fat diet induced hyperlipidemic hamsters, 5-week treatment with ZBH significantly lowered serum triglyceride, total cholesterol, LDL-C, FFA, hyperinsulinemia, and improved insulin sensitivity more potently than bezafibrate. Meanwhile, serum transaminases, creatine phosphokinase and CREA levels were found not altered by ZBH intervention. Mechanism study indicated ZBH promoted the expression of PPARα target genes and SIRT1 mRNA. Hepatic lipogenesis was markedly decreased via down-regulation of lipogenic genes, and fatty acid uptake and oxidation was simultaneously increased in the liver and skeletal muscle via up-regulation of lipolysis genes. Glucose uptake and utilization was also significantly promoted in skeletal muscle. These results suggested that ZBH significantly lowered hyperlipidemia and ameliorated insulin resistance more efficiently than bezafibrate in the hyperlipidemic hamsters primarily by activating of PPARα, and SIRT1 promotion and activation. ZBH thus presents a potential new agent to combat hyperlipidemia. PMID:24759758

  17. BAFF Receptor mAb Treatment Ameliorates Development and Progression of Atherosclerosis in Hyperlipidemic ApoE−/− Mice

    PubMed Central

    Kyaw, Tin; Cui, Peng; Tay, Christopher; Kanellakis, Peter; Hosseini, Hamid; Liu, Edgar; Rolink, Antonius G.; Tipping, Peter

    2013-01-01

    Aims Option to attenuate atherosclerosis by depleting B2 cells is currently limited to anti-CD20 antibodies which deplete all B-cell subtypes. In the present study we evaluated the capacity of a monoclonal antibody to B cell activating factor-receptor (BAFFR) to selectively deplete atherogenic B2 cells to prevent both development and progression of atherosclerosis in the ApoE−/− mouse. Methods and Results To determine whether the BAFFR antibody prevents atherosclerosis development, we treated ApoE−/− mice with the antibody while feeding them a high fat diet (HFD) for 8 weeks. Mature CD93− CD19+ B2 cells were reduced by treatment, spleen B-cell zones disrupted and spleen CD20 mRNA expression decreased while B1a cells and non-B cells were spared. Atherosclerosis was ameliorated in the hyperlipidemic mice and CD19+ B cells, CD4+ and CD8+ T cells were reduced in atherosclerotic lesions. Expressions of proinflammatory cytokines, IL1β, TNFα, and IFNγ in the lesions were also reduced, while MCP1, MIF and VCAM-1 expressions were unaffected. Plasma immunoglobulins were reduced, but MDA-oxLDL specific antibodies were unaffected. To determine whether anti-BAFFR antibody ameliorates progression of atherosclerosis, we first fed ApoE−/− mice a HFD for 6 weeks, and then instigated anti-BAFFR antibody treatment for a further 6 week-HFD. CD93− CD19+ B2 cells were selectively decreased and atherosclerotic lesions were reduced by this treatment. Conclusion Anti-BAFFR monoclonal antibody selectively depletes mature B2 cells while sparing B1a cells, disrupts spleen B-cell zones and ameliorates atherosclerosis development and progression in hyperlipidemic ApoE−/− mice. Our findings have potential for clinical translation to manage atherosclerosis-based cardiovascular diseases. PMID:23560095

  18. Clinical and pathological manifestations of cardiovascular disease in rat models: the influence of acute ozone exposure

    EPA Science Inventory

    This paper shows that rat models of cardiovascular diseases have differential degrees of underlying pathologies at a young age. Rodent models of cardiovascular diseases (CVD) and metabolic disorders are used for examining susceptibility variations to environmental exposures. How...

  19. Clinical and pathological manifestations of cardiovascular disease in rat models: the influence of acute ozone exposure

    EPA Science Inventory

    This paper shows that rat models of cardiovascular diseases have differential degrees of underlying pathologies at a young age. Rodent models of cardiovascular diseases (CVD) and metabolic disorders are used for examining susceptibility variations to environmental exposures. How...

  20. Characterization of the Prediabetic State in a Novel Rat Model of Type 2 Diabetes, the ZFDM Rat.

    PubMed

    Gheni, Ghupurjan; Yokoi, Norihide; Beppu, Masayuki; Yamaguchi, Takuro; Hidaka, Shihomi; Kawabata, Ayako; Hoshino, Yoshikazu; Hoshino, Masayuki; Seino, Susumu

    2015-01-01

    We recently established a novel animal model of obese type 2 diabetes (T2D), the Zucker fatty diabetes mellitus (ZFDM) rat strain harboring the fatty mutation (fa) in the leptin receptor gene. Here we performed a phenotypic characterization of the strain, focusing mainly on the prediabetic state. At 6-8 weeks of age, fa/fa male rats exhibited mild glucose intolerance and severe insulin resistance. Although basal insulin secretion was remarkably high in the isolated pancreatic islets, the responses to both glucose stimulation and the incretin GLP-1 were retained. At 10-12 weeks of age, fa/fa male rats exhibited marked glucose intolerance as well as severe insulin resistance similar to that at the earlier age. In the pancreatic islets, the insulin secretory response to glucose stimulation was maintained but the response to the incretin was diminished. In nondiabetic Zucker fatty (ZF) rats, the insulin secretory responses to both glucose stimulation and the incretin in the pancreatic islets were similar to those of ZFDM rats. As islet architecture was destroyed with age in ZFDM rats, a combination of severe insulin resistance, diminished insulin secretory response to incretin, and intrinsic fragility of the islets may cause the development of T2D in this strain.

  1. Effectiveness of Saccharomyces boulardii in a rat model of colitis.

    PubMed

    Soyturk, Mujde; Saygili, Saba Mukaddes; Baskin, Huseyin; Sagol, Ozgul; Yilmaz, Osman; Saygili, Fatih; Akpinar, Hale

    2012-11-28

    To investigate the effects of Saccharomyces boulardii (S. boulardii) in an experimental rat model of trinitrobenzene sulfonic acid (TNBS)-induced colitis. Thirty-two Wistar albino female rats were categorized into five groups. On the first day of the study, 50 mg TNBS was administered via a rectal catheter in order to induce colitis in all rats, except those in the control group. For 14 d, the rats were fed a standard diet, without the administration of any additional supplements to either the control or TNBS groups, in addition to 1 mg/kg per day S. boulardii to the S. boulardii group, 1 mg/kg per day methyl prednisolone (MP) to the MP group. The animals in the S. boulardii + MP group were coadministered these doses of S. boulardii and MP. During the study, weight loss, stool consistency, and the presence of obvious blood in the stool were evaluated, and the disease activity index (DAI) for colitis was recorded. The intestines were examined and colitis was macro- and microscopically scored. The serum and tissue levels of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) were determined, and fungemia was evaluated in the blood samples. The mean DAI scores for the MP and S. boulardii + MP groups was significantly lower than the TNBS group (3.69 ± 0.61 vs 4.46 ± 0.34, P = 0.018 and 3.77 ± 0.73 vs 4.46 ± 0.34, P = 0.025, respectively). While no significant differences between the TNBS and the S. boulardii or MP groups could be determined in terms of serum NO levels, the level of serum NO in the S. boulardii + MP group was significantly higher than in the TNBS and S. boulardii groups (8.12 ± 4.25 μmol/L vs 3.18 ± 1.19 μmol/L, P = 0.013; 8.12 ± 4.25 μmol/L vs 3.47 ± 1.66 μmol/L, P = 0.012, respectively). The tissue NO levels in the S. boulardii, MP and S. boulardii + MP groups were significantly lower than the TNBS group (16.62 ± 2.27 μmol/L vs 29.72 ± 6.10 μmol/L, P = 0.002; 14.66 ± 5.18 μmol/L vs 29.72 ± 6.10 μmol/L, P = 0.003; 11.95 ± 2

  2. Effectiveness of Saccharomyces boulardii in a rat model of colitis

    PubMed Central

    Soyturk, Mujde; Saygili, Saba Mukaddes; Baskin, Huseyin; Sagol, Ozgul; Yilmaz, Osman; Saygili, Fatih; Akpinar, Hale

    2012-01-01

    AIM: To investigate the effects of Saccharomyces boulardii (S. boulardii) in an experimental rat model of trinitrobenzene sulfonic acid (TNBS)-induced colitis. METHODS: Thirty-two Wistar albino female rats were categorized into five groups. On the first day of the study, 50 mg TNBS was administered via a rectal catheter in order to induce colitis in all rats, except those in the control group. For 14 d, the rats were fed a standard diet, without the administration of any additional supplements to either the control or TNBS groups, in addition to 1 mg/kg per day S. boulardii to the S. boulardii group, 1 mg/kg per day methyl prednisolone (MP) to the MP group. The animals in the S. boulardii + MP group were coadministered these doses of S. boulardii and MP. During the study, weight loss, stool consistency, and the presence of obvious blood in the stool were evaluated, and the disease activity index (DAI) for colitis was recorded. The intestines were examined and colitis was macro- and microscopically scored. The serum and tissue levels of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) were determined, and fungemia was evaluated in the blood samples. RESULTS: The mean DAI scores for the MP and S. boulardii + MP groups was significantly lower than the TNBS group (3.69 ± 0.61 vs 4.46 ± 0.34, P = 0.018 and 3.77 ± 0.73 vs 4.46 ± 0.34, P = 0.025, respectively). While no significant differences between the TNBS and the S. boulardii or MP groups could be determined in terms of serum NO levels, the level of serum NO in the S. boulardii + MP group was significantly higher than in the TNBS and S. boulardii groups (8.12 ± 4.25 μmol/L vs 3.18 ± 1.19 μmol/L, P = 0.013; 8.12 ± 4.25 μmol/L vs 3.47 ± 1.66 μmol/L, P = 0.012, respectively). The tissue NO levels in the S. boulardii, MP and S. boulardii + MP groups were significantly lower than the TNBS group (16.62 ± 2.27 μmol/L vs 29.72 ± 6.10 μmol/L, P = 0.002; 14.66 ± 5.18 μmol/L vs 29.72 ± 6.10 μmol/L, P

  3. Modeling interpopulation dispersal by banner-tailed kangaroo rats

    USGS Publications Warehouse

    Skvarla, J.L.; Nichols, J.D.; Hines, J.E.; Waser, P.M.

    2004-01-01

    Many metapopulation models assume rules of population connectivity that are implicitly based on what we know about within-population dispersal, but especially for vertebrates, few data exist to assess whether interpopulation dispersal is just within-population dispersal "scaled up." We extended existing multi-stratum mark-release-recapture models to incorporate the robust design, allowing us to compare patterns of within- and between-population movement in the banner-tailed kangaroo rat (Dipodomys spectabilis). Movement was rare among eight populations separated by only a few hundred meters: seven years of twice-annual sampling captured >1200 individuals but only 26 interpopulation dispersers. We developed a program that implemented models with parameters for capture, survival, and interpopulation movement probability and that evaluated competing hypotheses in a model selection framework. We evaluated variants of the island, stepping-stone, and isolation-by-distance models of interpopulation movement, incorporating effects of age, season, and habitat (short or tall grass). For both sexes, QAICc values clearly favored isolation-by-distance models, or models combining the effects of isolation by distance and habitat. Models with probability of dispersal expressed as linear-logistic functions of distance and as negative exponentials of distance fit the data equally well. Interpopulation movement probabilities were similar among sexes (perhaps slightly biased toward females), greater for juveniles than adults (especially for females), and greater before than during the breeding season (especially for females). These patterns resemble those previously described for within-population dispersal in this species, which we interpret as indicating that the same processes initiate both within- and between-population dispersal.

  4. Development of a non-infectious rat model of acute exacerbation of idiopathic pulmonary fibrosis

    PubMed Central

    Chen, Shan-Shan; Yin, Zhao-Fang; Chen, Tao; Qiu, Hui; Wei, Ya-Ru; Du, Shan-Shan; Jin, Yue-Ping; Zhao, Meng-Meng; Wu, Qin

    2017-01-01

    Background Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease with severe pulmonary fibrosis. The main cause of IPF-associated death is acute exacerbation of IPF (AE-IPF). This study aims to develop a rat model of AE-IPF by two intratracheal perfusions with bleomycin (BLM). Methods Ninety male Sprague Dawley (SD) rats were randomized into three groups: an AE-IPF model group (BLM + BLM group), an IPF model group (BLM group), and a normal control group. Rats in the BLM + BLM group underwent a second perfusion with BLM on day 28 after the first perfusion with BLM. Rats in the other two groups received saline as the second perfusion. Six rats in each group were sacrificed on day 31, day 35, and day 42 after the first perfusion, respectively. Additional 18 rats in each group were observed for survival. Results Rats in the BLM + BLM group had significantly worse pulmonary alveolar inflammation and fibrosis than rats in the BLM group. Rats in the BLM + BLM group also developed large amounts of hyaline membrane, showed high levels of albumin (ALB) and various inflammatory factors in the bronchoalveolar lavage fluid (BALF), and had markedly increased lung water content. Furthermore, rat survival was reduced in the BLM + BLM group. The pathophysiological characteristics of rats in the BLM + BLM group resemble those of patients with AE-IPF. Conclusions A second perfusion with BLM appears to induce acute exacerbation of pulmonary fibrosis and may be used to model AE-IPF in rats. PMID:28203411

  5. Further validation of a model of fibromyalgia syndrome in the rat

    PubMed Central

    Green, Paul G.; Alvarez, Pedro; Gear, Robert W.; Mendoza, Dennis; Levine, Jon D.

    2011-01-01

    We have recently developed an animal model of fibromyalgia syndrome in the rat. In this model, rats exposed to unpredictable sound stress develop a delayed onset enhancement and prolongation of cytokine-induced mechanical hyperalgesia in muscle and skin. In this study, we tested the hypothesis that our model also manifests symptoms of common co-morbid diagnoses: irritable bowel syndrome, temporomandibular disorder and anxiety. Both visceral sensitivity and cytokine hyperalgesia in masseter muscle were present in the stressed rats. Furthermore, in an established model of irritable bowel syndrome, water avoidance, we observed significant muscle hyperalgesia. Finally, using the elevated plus maze to assess for anxiety level, we observed a significantly higher anxiety level in sound stress exposed rats. Thus, unpredictable sound stress produces a condition in the rat with several features — delayed onset visceral and temporomandibular hyperalgesia and increased anxiety, as well as cutaneous and muscle hyperalgesia — commonly found in patients with fibromyalgia syndrome. PMID:21481648

  6. Hemostatic Efficacy of Nanofibrous Matrix in Rat Liver Injury Model.

    PubMed

    Jaiswal, Amit K; Chhabra, Hemlata; Narwane, Sandipan; Rege, Nirmala; Bellare, Jayesh R

    2017-02-01

    This present study examined the hemostatic efficacy of nanofibrous matrix in a rat liver model. The nanofibrous matrix comprising gelatin and polycaprolactone was prepared by electrospinning method. Twelve animals underwent surgery and were followed-up for a month. Time taken to cease bleeding, activated partial thromboplastin time, prothrombin time, and fibrinogen concentration were measured. Histopathological examination of liver was also done of treated and control animals. All test animals showed very rapid hemostasis after application of electrospun sheet. Histopathological study showed quick recovery of liver wound in the test group as compared to the control group. The nanofibrous matrix has proven to be not only safe and effective as hemostat but has also shown its potential for liver regeneration.

  7. [Efficacy of cerebrolysin in cerebral hemorrhage model in rats].

    PubMed

    Kositsyn, N S; Svinov, M M; Goloborod'ko, E V; Bozhevalova, S V; Iablonskaia, A M

    2006-01-01

    The pharmacological efficacy of cerebrolysin (a brain-derived peptidergic drug) was studied in rats with a unilateral hemorrhagic stroke model. Cerebrolysin produces a neuroprotective effect, which is manifested by a decrease in the number of degenerated neurons in the vicinity of hematoma region in acute period and by a reduction of the neuronal loss in the early recovery phase. Besides, the administration of cerebrolysin improves the functional state as judged from the results of neurological and behavioral tests (open field, paw licking, and passive avoidance). A decrease in the hyperactivity in the open field test and the conservation of latent avoidance in the passive avoidance test demonstrate the drug influence on the maintenance of inhibitory processes deteriorated in stroke.

  8. Sepsis leads to thyroid impairment and dysfunction in rat model.

    PubMed

    Lin, Xingsheng; Shi, Songjing; Shi, Songchang

    2016-10-01

    Sepsis was a systemic response to a local infection. Apoptosis was observed in the experimental sepsis. In this study, cecal ligation and puncture (CLP)-induced sepsis was established in rats. We found that sepsis decreased thyroid hormone levels, including triiodothyronine (T3), thyroxine (T4), free T3 (fT3), and free T4 (fT4). Besides, we detected the increasing expression level of Caspase-3 and increasing ratio of TUNEL positive cells in the thyroid after sepsis. Furthermore, a series of pathological ultrastructural changes were observed in thyroid follicular epithelial cells by CLP-induced sepsis. This study established a sepsis animal model and provided the cellular and molecular basis for decoding the pathological mechanism in thyroid with the occurrence of sepsis.

  9. In Situ Perfusion Model in Rat Colon for Drug Absorption Studies: Comparison with Small Intestine and Caco-2 Cell Model.

    PubMed

    Lozoya-Agullo, Isabel; González-Álvarez, Isabel; González-Álvarez, Marta; Merino-Sanjuán, Matilde; Bermejo, Marival

    2015-09-01

    Our aim is to develop and to validate the in situ closed loop perfusion method in rat colon and to compare with small intestine and Caco-2 cell models. Correlations with human oral fraction absorbed (Fa) and human colon fraction absorbed (Fa_colon) were developed to check the applicability of the rat colon model for controlled release (CR) drug screening. Sixteen model drugs were selected and their permeabilities assessed in rat small intestine and colon, and in Caco-2 monolayers. Correlations between colon/intestine/Caco-2 permeabilities versus human Fa and human Fa_colon have been explored to check model predictability and to apply a BCS approach in order to propose a cut off value for CR screening. Rat intestine perfusion with Doluisio's method and single-pass technique provided a similar range of permeabilities demonstrating the possibility of combining data from different laboratories. Rat colon permeability was well correlated with Caco-2 cell-4 days model reflecting a higher paracellular permeability. Rat colon permeabilities were also higher than human colon ones. In spite of the magnitude differences, a good sigmoidal relationship has been shown between rat colon permeabilities and human colon fractions absorbed, indicating that rat colon perfusion can be used for compound classification and screening of CR candidates. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  10. Podocyte Injury and Albuminuria in Experimental Hyperuricemic Model Rats

    PubMed Central

    Asakawa, Shinichiro; Morimoto, Chikayuki; Shiraishi, Takeshi; Nakamura, Takashi; Tamura, Yoshifuru; Kumagai, Takanori; Hosoyamada, Makoto

    2017-01-01

    Although hyperuricemia is shown to accelerate chronic kidney disease, the mechanisms remain unclear. Accumulating studies also indicate that uric acid has both pro- and antioxidant properties. We postulated that hyperuricemia impairs the function of glomerular podocytes, resulting in albuminuria. Hyperuricemic model was induced by oral administration of 2% oxonic acid, a uricase inhibitor. Oxonic acid caused a twofold increase in serum uric acid levels at 8 weeks when compared to control animals. Hyperuricemia in this model was associated with the increase in blood pressure and the wall-thickening of afferent arterioles as well as arcuate arteries. Notably, hyperuricemic rats showed significant albuminuria, and the podocyte injury marker, desmin, was upregulated in the glomeruli. Conversely, podocin, the key component of podocyte slit diaphragm, was downregulated. Structural analysis using transmission electron microscopy confirmed podocyte injury in this model. We found that urinary 8-hydroxy-2′-deoxyguanosine levels were significantly increased and correlated with albuminuria and podocytopathy. Interestingly, although the superoxide dismutase mimetic, tempol, ameliorated the vascular changes and the hypertension, it failed to reduce albuminuria, suggesting that vascular remodeling and podocyte injury in this model are mediated through different mechanisms. In conclusion, vasculopathy and podocytopathy may distinctly contribute to the kidney injury in a hyperuricemic state. PMID:28337250

  11. A model of calcium transport along the rat nephron.

    PubMed

    Tournus, Magali; Seguin, Nicolas; Perthame, Benoît; Thomas, S Randall; Edwards, Aurélie

    2013-10-01

    We developed a mathematical model of calcium (Ca(2+)) transport along the rat nephron to investigate the factors that promote hypercalciuria. The model is an extension of the flat medullary model of Hervy and Thomas (Am J Physiol Renal Physiol 284: F65-F81, 2003). It explicitly represents all the nephron segments beyond the proximal tubules and distinguishes between superficial and deep nephrons. It solves dynamic conservation equations to determine NaCl, urea, and Ca(2+) concentration profiles in tubules, vasa recta, and the interstitium. Calcium is known to be reabsorbed passively in the thick ascending limbs and actively in the distal convoluted (DCT) and connecting (CNT) tubules. Our model predicts that the passive diffusion of Ca(2+) from the vasa recta and loops of Henle generates a significant axial Ca(2+) concentration gradient in the medullary interstitium. In the base case, the urinary Ca(2+) concentration and fractional excretion are predicted as 2.7 mM and 0.32%, respectively. Urinary Ca(2+) excretion is found to be strongly modulated by water and NaCl reabsorption along the nephron. Our simulations also suggest that Ca(2+) molar flow and concentration profiles differ significantly between superficial and deep nephrons, such that the latter deliver less Ca(2+) to the collecting duct. Finally, our results suggest that the DCT and CNT can act to counteract upstream variations in Ca(2+) transport but not always sufficiently to prevent hypercalciuria.

  12. HIV-1 Nef breaches placental barrier in rat model.

    PubMed

    Singh, Poonam; Agnihotri, Saurabh Kumar; Tewari, Mahesh Chandra; Kumar, Sadan; Sachdev, Monika; Tripathi, Raj Kamal

    2012-01-01

    The vertical transmission of HIV-1 from the mother to fetus is known, but the molecular mechanism regulating this transmission is not fully characterized. The fetus is highly protected by the placenta, which does not permit microbial pathogens to cross the placental barrier. In the present study, a rat model was established to observe the effect of HIV-1 protein Nef on placental barrier. Evans blue dye was used to assay permeability of placental barrier and fourteen day pregnant Sprague Dawley rats were injected intravenously with 2% Evans blue dye along with various concentrations of recombinant Nef. After an hour, animals were sacrificed and dye migration was observed through the assimilation of peripheral blood into fetus. Interestingly, traces of recombinant Nef protein were detected in the embryo as well as amniotic fluid and amniotic membrane along with placenta and uterus. Our study indicates that recombinant HIV-1-Nef protein breaches the placental barrier and allows the migration of Evans blue dye to the growing fetus. Further the concentration of Nef protein in blood is directly proportional to the intensity of dye migration and to the amount of Nef protein detected in uterus, placenta, amniotic membrane, amniotic fluid and embryo. Based on this study, it can be concluded that the HIV-1 Nef protein has a direct effect on breaching of the placental barrier in the model we have established in this study. Our observations will be helpful to understand the molecular mechanisms related to this breach of placental barrier by Nef in humans and may be helpful to identify specific Nef inhibitors.

  13. The rat saphenous flap: a fasciocutaneous free flap model without panniculus carnosus.

    PubMed

    Mutaf, M; Tasaki, Y; Tanaka, K; Fujii, T

    1995-10-01

    The rat saphenous flap is described as a new experimental model for free flap studies. This is a fasciocutaneous free flap based on the saphenofemoral vascular pedicle. The flap may include the entire medial aspect of the lower leg between the knee and ankle. Thirty flaps were harvested from 15 inbred rats. Each flap was transferred to the anterior neck of a recipient rat of the same inbred strain so that 15 flaps were vascularized free flaps using the standard end-to-end microvascular technique and the other 15 flaps were nonvascularized free grafts. All but two (technical failure) of the vascularized flaps showed complete survival, whereas all nonvascularized flaps completely necrosed 2 weeks after transfer. It was concluded that the rat saphenous flap has several advantages such as a long and consistent vascular pedicle, ease of harvest, and an all-or-none survival pattern. Furthermore, as a unique feature of this flap, histological analysis revealed that the rat saphenous flap is composed of the skin and underlying fascia without panniculus carnosus. We therefore suggest that the rat saphenous flap is the first true fasciocutaneous free flap model in the rat. In this paper, in addition to illustrating the anatomy of the saphenous vessels and describing a new fasciocutaneous free flap model based on these vessels, we have documented some anatomical details of the rat leg that have never been described in the literature related to the rat anatomy.

  14. Fractional ventilation mapping using inert fluorinated gas MRI in rat models of inflammation and fibrosis.

    PubMed

    Couch, Marcus J; Fox, Matthew S; Viel, Chris; Gajawada, Gowtham; Li, Tao; Ouriadov, Alexei V; Albert, Mitchell S

    2016-05-01

    The purpose of this study was to extend established methods for fractional ventilation mapping using (19) F MRI of inert fluorinated gases to rat models of pulmonary inflammation and fibrosis. In this study, five rats were instilled with lipopolysaccharide (LPS) in the lungs two days prior to imaging, six rats were instilled with bleomycin in the lungs two weeks prior to imaging and an additional four rats were used as controls. (19) F MR lung imaging was performed at 3 T with rats continuously breathing a mixture of sulfur hexafluoride and O2 . Fractional ventilation maps were obtained using a wash-out approach, by switching the breathing mixture to pure O2 , and acquiring images following each successive wash-out breath. The mean fractional ventilation (r) was 0.29 ± 0.05 for control rats, 0.23 ± 0.10 for LPS-instilled rats and 0.19 ± 0.03 for bleomycin-instilled rats. Bleomycin-instilled rats had a significantly decreased mean r value compared with controls (P = 0.010). Although LPS-instilled rats had a slightly reduced mean r value, this trend was not statistically significant (P = 0.556). Fractional ventilation gradients were calculated in the anterior/posterior (A/P) direction, and the mean A/P gradient was -0.005 ± 0.008 cm(-1) for control rats, 0.013 ± 0.005 cm(-1) for LPS-instilled rats and 0.009 ± 0.018 cm(-1) for bleomycin-instilled rats. Fractional ventilation gradients were significantly different for control rats compared with LPS-instilled rats only (P = 0.016). The ventilation gradients calculated from control rats showed the expected gravitational relationship, while ventilation gradients calculated from LPS- and bleomycin-instilled rats showed the opposite trend. Histology confirmed that LPS-instilled rats had a significantly elevated alveolar wall thickness, while bleomycin-instilled rats showed signs of substantial fibrosis. Overall, (19)F MRI may be able to detect the effects of pulmonary

  15. The HIV-1 transgenic rat model of neuroHIV

    PubMed Central

    Vigorito, Michael; Connaghan, Kaitlyn P.; Chang, Sulie L.

    2016-01-01

    Despite the ability of current combination anti-retroviral therapy (cART) to limit the progression of HIV-1 to AIDS, HIV-positive individuals continue to experience neuroHIV in the form of HIV-associated neurological disorders (HAND), which can range from subtle to substantial neurocognitive impairment. NeuroHIV may also influence substance use, abuse, and dependence in HIV-positive individuals. Because of the nature of the virus, variables such as mental health co-morbidities make it difficult to study the interaction between HIV and substance abuse in human populations. Several rodent models have been developed in an attempt to study the transmission and pathogenesis of the HIV-1 virus. The HIV-1 transgenic (HIV-1Tg) rat is a reliable model of neuroHIV because it mimics the condition of HIV-infected patients on cART. Research using this model supports the hypothesis that the presence of HIV-1 viral proteins in the central nervous system increases the sensitivity and susceptibility of HIV-positive individuals to substance abuse. PMID:25733103

  16. Rat Indwelling Urinary Catheter Model of Candida albicans Biofilm Infection

    PubMed Central

    Nett, Jeniel E.; Brooks, Erin G.; Cabezas-Olcoz, Jonathan; Sanchez, Hiram; Zarnowski, Robert; Marchillo, Karen

    2014-01-01

    Indwelling urinary catheters are commonly used in the management of hospitalized patients. Candida can adhere to the device surface and propagate as a biofilm. These Candida biofilm communities differ from free-floating Candida, exhibiting high tolerance to antifungal therapy. The significance of catheter-associated candiduria is often unclear, and treatment may be problematic considering the biofilm drug-resistant phenotype. Here we describe a rodent model for the study of urinary catheter-associated Candida albicans biofilm infection that mimics this common process in patients. In the setting of a functioning, indwelling urinary catheter in a rat, Candida proliferated as a biofilm on the device surface. Characteristic biofilm architecture was observed, including adherent, filamentous cells embedded in an extracellular matrix. Similar to what occurs in human patients, animals with this infection developed candiduria and pyuria. Infection progressed to cystitis, and a biofilmlike covering was observed over the bladder surface. Furthermore, large numbers of C. albicans cells were dispersed into the urine from either the catheter or bladder wall biofilm over the infection period. We successfully utilized the model to test the efficacy of antifungals, analyze transcriptional patterns, and examine the phenotype of a genetic mutant. The model should be useful for future investigations involving the pathogenesis, diagnosis, therapy, prevention, and drug resistance of Candida biofilms in the urinary tract. PMID:25183731

  17. An ameliorated skin flap model in rats for experimental research.

    PubMed

    Hosnuter, Mübin; Kargi, Eksal; Peksoy, Irfan; Babucçu, Orhan; Payasli, Cem

    2006-01-01

    There is a disagreement in the experimental design of random skin flaps owing to their vascular inconsistency. The definition of a reliable axial-pattern skin flap model is needed. The purpose of this study was to describe a new skin flap model to deal with entire drawbacks of existing random and axial pattern skin flap designs. This was accomplished by creating paired skin flaps including both skin and vascular pedicle on the dorsum of the same rat. This design was suitably termed as rando-axial flap. The present study offers a simple and reliable skin flap model with following advantages: (1) it has a predictable necrosis area, (2) it reveals a larger survival area (75 +/- 5%) when compared to other flaps in this study (Mann-Whitney U-test, p<0.001), (3) the vascular pedicle is consistent, (4) control and study flaps are placed on the same animal (5) it can be converted to a random, an axial or a free flap.

  18. Fischer-344 rats are unsuitable for the MCAO filament model due to their cerebrovascular anatomy.

    PubMed

    Dittmar, Michael S; Vatankhah, Bijan; Fehm, Nando P; Schuierer, Gerhard; Bogdahn, Ulrich; Horn, Markus; Schlachetzki, Felix

    2006-09-30

    Middle cerebral artery occlusion (MCAO) in Fischer-344 rats results in a small variance of infarct size. However, complications are frequent especially in aged Fisher-344 rats undergoing endovascular suture occlusion of the middle cerebral artery. Analyzing our experiences with 165 Wistar, 13 Sprague-Dawley and 10 F-344 rats, we compared the incidence of impossible thread advancement and subarachnoid hemorrhage, respectively. Magnetic resonance angiography (MRA) was applied to study the course of the internal carotid artery (ICA) in Fischer and Wistar rats. Finally, we performed a structured review of the literature from 1991 to 2005 evaluating reports on Fischer rats subjected to intraluminal filament MCAO. Complications like fruitless filament advancement or subarachnoid hemorrhage were found to be significantly more frequent in Fischer rats than in other strains. MRA revealed significantly more pronounced kinking of the ICA in F-344 than in Wistar rats. In seven publications available on filament MCAO in F-344 rats, complication rates of 50-100% were reported, corroborating our data. Surgical difficulties accompanied by high complication rates due to their cerebrovascular anatomy make Fischer rats unsuitable for filament MCAO. If the use of Fischer rats for studies on focal cerebral ischemia is indicated, other ischemia models than intraluminal suture occlusion should be chosen.

  19. Cysteamine prevents the development of lens opacity in a rat model of selenite-induced cataract.

    PubMed

    Lee, Sang-Mok; Jeong, Eui Man; Jeong, Jinho; Shin, Dong-Myung; Lee, Hyun-Ju; Kim, Hyo-Jun; Lim, Jisun; Lee, Jin-Haeng; Cho, Sung-Yup; Kim, Mee-Kum; Wee, Won-Ryang; Lee, Jin-Hak; Kim, In-Gyu

    2012-03-15

    The activation of transglutaminase 2 (TG2) by oxidative stress through TGFβ has been reported to play a crucial role in cataract formation. The authors investigated whether TG2 is involved in selenite-induced cataract formation in rats and whether cysteamine, a chemical inhibitor of TG2, can prevent cataract formation in this model. Intracellular TG2 activity was monitored in a human lens epithelial cell (HLE-B3) line and cultured rat lenses after treatment with selenite. Rat pups (13 days old) were injected subcutaneously with sodium selenite (Na(2)SeO(3); 20 μmol/kg) and intraperitoneally with cysteamine (30, 40, and 60 mg/kg) for 14 days. Lenses were evaluated photographically at days 7 and 14. The concentrations of malondialdehyde and glutathione in the lenses were determined. In HLE-B3 cells or rat lenses, selenite induced intracellular TG activity, which was inhibited by cysteamine. In selenite-treated rats, the rate of cataract formation was significantly reduced by cysteamine (P < 0.001). The mean cataract area in the lenses of cysteamine-treated rats was smaller than that of control rats (P < 0.01). The levels of total and reduced glutathione in the lenses of cysteamine-treated rats extracted at day 14 were higher than those of control rats. Cysteamine suppresses cataract formation induced by selenite in rats, suggesting that cysteamine can be used as a pharmaceutical intervention to prevent or delay cataract formation.

  20. Selective inhibition of 20-hydroxyeicosatetraenoic acid lowers blood pressure in a rat model of preeclampsia.

    PubMed

    Faulkner, Jessica L; Plenty, Nicole L; Wallace, Kedra; Amaral, Lorena M; Cunningham, Mark W; Murphy, Sydney; LaMarca, Babbette

    2017-09-22

    Little is currently known of the role(s) of the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE) in hypertensive pregnancies. We hypothesized that specific inhibition of 20-HETE would attenuate increases in blood pressure in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. Specific 20-HETE synthesis inhibitor HET0016 (1mg/kg) was administered daily to RUPP rats from gestational days 14-18. Blood pressure (BP) increased in RUPP rats and was decreased with HET0016 administration. BP was unchanged in NP+HET0016 rats. Fetal death greatly increased in RUPP rats and was reduced in RUPP+HET0016 rats. 20-HETE levels increased modestly in RUPP rats compared to NP and was reduced in both NP+HET0016 and RUPP+HET0016 rats. Furthermore, circulating levels of HETEs, EET, and DHETE were significantly altered between groups. HET0016 shifted CYP metabolism toward EETs, as indicated by a decrease in plasma 20-HETE:EETs in RUPP+HET0016 rats compared to RUPP. In conclusion, 20-HETE inhibition in RUPP rats reduces BP and fetal death, and is associated with an increase in EET/20-HETE ratio. Copyright © 2017. Published by Elsevier Inc.

  1. Protective Effect of Dihydromyricetin Against Lipopolysaccharide-Induced Acute Kidney Injury in a Rat Model.

    PubMed

    Wang, Jun-Tao; Jiao, Peng; Zhou, Yun; Liu, Qian

    2016-02-11

    BACKGROUND The present study investigated the effect of dihydromyricetin (DHM) on lipopolysaccharide (LPS)-induced acute kidney injury in a rat model. MATERIAL AND METHODS Kidney injury was induced in male Sprague-Dawley rats by injection of LPS through the tail vein. The rats were treated with 5 µg/kg body weight DHM within 12 h of the LPS administration. The urine of the rats was collected over a period of 48 h for determination of calcium and creatinine concentrations. Blood urea nitrogen in the serum was analyzed using a BC-2800 Vet Animal Auto Biochemistry Analyzer. On day 3 after treatment, the rats were sacrificed to extract the kidneys. RESULTS Treatment of the endotoxemia rats with DHM caused a significant (P<0.05) decrease in the level of kidney injury molecule‑1 and blood urea nitrogen. DHM treatment significantly (P<0.05) decreased the level of calcium in the kidney tissues compared to those of the untreated endotoxemia rats. The level of malonaldehyde (MDA) in the kidney tissues was significantly reduced in the endotoxemia rats by DHM treatment. The results from immunohistochemistry reveled a significant decrease in the expression of osteopontin (OPN) and CD44 levels. The endotoxemia rats showed significantly higher levels of TUNEL-positive stained nuclei compared to the normal controls. However, treatment of the endotoxemia rats with DHM resulted in a significant decrease in the population of TUNEL-positive cells. CONCLUSIONS DHM may be a promising candidate for the treatment of acute kidney injury.

  2. Cerebral salt wasting in subarachnoid hemorrhage rats: model, mechanism, and tool.

    PubMed

    Kojima, Jun; Katayama, Yoichi; Moro, Nobuhiro; Kawai, Hiroyuki; Yoneko, Maki; Mori, Tatsuro

    2005-04-01

    Cerebral salt wasting (CSW) frequently occurs concomitantly with aneurysmal subarachnoid hemorrhage (SAH). CSW induces excessive natriuresis and osmotic diuresis, and reduces total blood volume. As a result, the risk of symptomatic cerebral vasospasm may be elevated. Therefore, it is important to determine the mechanism of CSW. The purpose of this study was to evaluate whether the rat SAH model exhibits CSW and to investigate the relationship between CSW and natriuretic peptides. A SAH model was produced in 24 rats by perforating a cerebral artery with a nylon thread up through the common carotid artery. To evaluate CSW, urine was cumulatively collected from SAH onset to 12 hours and sodium (Na) excretion was analyzed. Body weight and hematocrit were analyzed before and after SAH onset. Concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in plasma were also analyzed. Urine volume and total Na excretion of SAH rats were significantly higher than those of sham rats (p<0.05). Body weight of SAH rats significantly decreased and hematocrit significantly increased (p < 0.05). ANP concentration was significantly decreased in SAH rats (p<0.05). However, BNP concentrations did not change. This study demonstrated for the first time that a rat SAH model exhibited CSW. It was suggested that the cause of CSW was neither ANP nor BNP. In addition, this rat SAH model will be useful for study of CSW after SAH.

  3. A RAT MODEL OF HEART FAILURE INDUCED BY ISOPROTERENOL AND A HIGH SALT DIET

    EPA Science Inventory

    Rat models of heart failure (HF) show varied pathology and time to disease outcome, dependent on induction method. We found that subchronic (4wk) isoproterenol (ISO) infusion in Spontaneously Hypertensive Heart Failure (SHHF) rats caused cardiac injury with minimal hypertrophy. O...

  4. A RAT MODEL OF HEART FAILURE INDUCED BY ISOPROTERENOL AND A HIGH SALT DIET

    EPA Science Inventory

    Rat models of heart failure (HF) show varied pathology and time to disease outcome, dependent on induction method. We found that subchronic (4wk) isoproterenol (ISO) infusion in Spontaneously Hypertensive Heart Failure (SHHF) rats caused cardiac injury with minimal hypertrophy. O...

  5. Grape powder treatment prevents anxiety-like behavior in a rat model of aging.

    PubMed

    Patki, Gaurav; Ali, Quaisar; Pokkunuri, Indira; Asghar, Mohammad; Salim, Samina

    2015-06-01

    Earlier, we have reported that grape powder (GP) treatment prevented pharmacologic and psychological stress-induced anxiety-like behavior and memory impairment in rats. Protective effects of GP were attributed to its antioxidant effects. In this study, we tested the hypothesis that age-associated behavioral and cognitive deficits such as anxiety and memory impairment will be ameliorated with GP treatment. Using a National Institute of Aging recommended rodent model of aging, we examined a potentially protective role of antioxidant-rich GP in age-associated anxiety-like behavior and memory impairment. Male Fischer 344 rats were randomly assigned into 4 groups: young rats (3 months old) provided with tap water or with 15 g/L GP dissolved in tap water for 3 weeks, aged rats (21 months old) provided with tap water or with GP-treated tap water for 3 weeks (AG-GP). Anxiety-like behavior was significantly greater in aged rats compared with young rats, GP-treated young rats, or aged control rats (P < .05). Also, GP treatment prevented age-induced anxiety-like behavior in AG-GP rats (P < .05). Neither short-term nor long-term age-associated memory deficits improved with GP treatment in AG-GP rats. Furthermore, aged rats showed increased level of physiological stress (corticosterone) and increased oxidative stress in the plasma (8-isoprostane) as well as in selected brain areas (protein carbonylation). Grape powder treatment prevented age-induced increase in corticosterone levels and plasma 8-isoprostane levels in aged rats (P < .05), whereas protein carbonylation was recovered in the amygdala region only (P < .05). Grape powder by regulating oxidative stress ameliorates age-induced anxiety-like behavior in rats, whereas age-associated memory deficits seem unaffected with GP treatment.

  6. Leukostasis and pigment epithelium-derived factor in rat models of diabetic retinopathy

    PubMed Central

    Matsuoka, Masato; Minamino, Keizo; Matsumura, Miyo

    2007-01-01

    Purpose Spontaneously diabetic Torii (SDT) rats, an animal model of type 2 diabetes, have a low incidence of neovascular formation and an absence of non-perfused areas in their retinas at the proliferative stage that presents tractional retinal detachment with fibrous proliferation. The aim of this study was to determine whether leukostasis is present in the retina, to evaluate the levels of pigment epithelium-derived factor (PEDF) and intracellular adhesion molecule-1 (ICAM-1) levels in the blood of SDT rats, and to examine the effects of PEDF on leukostasis. Methods SDT rats, streptozotocin-induced diabetic (STZ) rats, and control Sprague-Dawley (SD) rats were studied. The index of leukostasis in the retina was determined immunohistochemically by counting the number of labeled adherent leukocytes. The levels of PEDF and the soluble intracellular adhesion molecule (sICAM)-1 in the plasma were measured. To investigate the effect of PEDF and vascular endothelial growth factor (VEGF) on leukostasis, the adhesion of monocytes to human umbilical vein endothelial cells (HUVECs) was assayed in vitro. Results SDT and STZ diabetic rats showed a significant increase of retinal leukostasis compared to that of control SD rats, but SDT rats had noteworthy lower levels of leukostasis than STZ rats in long term experiments. The sICAM-1 levels and PEDF expression were up-regulated in both STZ and SDT rats, but the SDT rats showed significantly higher levels of PEDF than STZ rats. In vitro studies showed that exposure of HUVECs to VEGF increased the number of adhering monocytes, and PEDF inhibited the VEGF-induced leukostasis in a dose-dependent manner. Conclusions The inhibition of the VEGF-induced leukostasis by PEDF is most likely responsible for the low incidence of capillary occlusion and retinal neovascularization in SDT rats. PMID:17653050

  7. The Characterization of Obese Polycystic Ovary Syndrome Rat Model Suitable for Exercise Intervention

    PubMed Central

    Qiu, Shuwei; Jiang, Zhongli

    2014-01-01

    Objective To develop a new polycystic ovary syndrome (PCOS) rat model suitable for exercise intervention. Method Thirty six rats were randomly divided into three experimental groups: PCOS rats with high-fat diet (PF, n = 24), PCOS rats with ordinary diet (PO, n = 6), and control rats with ordinary diet (CO, n = 6). Two kinds of PCOS rat model were made by adjustment diet structure and testosterone injection for 28 days. After a successful animal model, PF model rats were randomly assigned to three groups: exercise with a continuation of high-fat diet (PF-EF, n = 6), sedentary with a continuation of high-fat diet (PF-SF, n = 6), exercise with an ordinary diet (PF-EO, n = 6). Fasting blood glucose (FBG) and insulin (FINS), estrogen (E2), progesterone (P), and testosterone (T) in serum were determined by RIA, and ovarian morphology was evaluated by Image-Pro plus 6.0. Results Body weight, Lee index, FINS increased significantly in PF rat model. Serum levels of E2 and T were significantly higher in PF and PO than in CO. Ovary organ index and ovarian areas were significant lower in PF than in CO. After intervention for 2 weeks, the levels of 1 h postprandial blood glucose (PBG1), 2 h postprandial blood glucose (PBG2), FINS and the serum levels of T decreased significantly in PF-EF rats and PF-EO rats. The ratio of FBG/FINS was significant higher in PF-EO rats than in PF-SF rats. Ovarian morphology showed that the numbers of preantral follicles and atretic follicles decreased significantly, and the numbers of antral follicles and corpora lutea increased significantly in the rats of PF-EF and PF-EO. Conclusion By combination of high-fat diet and testosterone injection, the obese PCOS rat model is conformable with the lifestyle habits of fatty foods and insufficient exercise, and has metabolic and reproductive characteristics of human PCOS. This model can be applied to study exercise intervention. PMID:24905232

  8. Comparative Proteomic Analysis of Two Uveitis Models in Lewis Rats

    PubMed Central

    Pepple, Kathryn L.; Rotkis, Lauren; Wilson, Leslie; Sandt, Angela; Van Gelder, Russell N.

    2015-01-01

    Purpose Inflammation generates changes in the protein constituents of the aqueous humor. Proteins that change in multiple models of uveitis may be good biomarkers of disease or targets for therapeutic intervention. The present study was conducted to identify differentially-expressed proteins in the inflamed aqueous humor. Methods Two models of uveitis were induced in Lewis rats: experimental autoimmune uveitis (EAU) and primed mycobacterial uveitis (PMU). Differential gel electrophoresis was used to compare naïve and inflamed aqueous humor. Differentially-expressed proteins were separated by using 2-D gel electrophoresis and excised for identification with matrix-assisted laser desorption/ionization–time of flight (MALDI-TOF). Expression of select proteins was verified by Western blot analysis in both the aqueous and vitreous. Results The inflamed aqueous from both models demonstrated an increase in total protein concentration when compared to naïve aqueous. Calprotectin, a heterodimer of S100A8 and S100A9, was increased in the aqueous in both PMU and EAU. In the vitreous, S100A8 and S100A9 were preferentially elevated in PMU. Apolipoprotein E was elevated in the aqueous of both uveitis models but was preferentially elevated in EAU. Beta-B2–crystallin levels decreased in the aqueous and vitreous of EAU but not PMU. Conclusions The proinflammatory molecules S100A8 and S100A9 were elevated in both models of uveitis but may play a more significant role in PMU than EAU. The neuroprotective protein β-B2–crystallin was found to decline in EAU. Therapies to modulate these proteins in vivo may be good targets in the treatment of ocular inflammation. PMID:26747776

  9. A mathematical model of the rat nephron: glucose transport

    PubMed Central

    2015-01-01

    Mathematical models of the proximal tubule (PT), loop of Henle (LOH), and distal nephron have been combined to simulate transport by rat renal tubules. The ensemble is composed of 24,000 superficial (SF) nephrons and 12,000 juxtamedullary (JM) nephrons in 5 classes (according to LOH length); all coalesce into 7,200 connecting tubules (CNT). Medullary interstitial solute concentrations are specified. The model equations require that each nephron glomerular filtration rate (GFR) satisfies a tubuloglomerular feedback (TGF) relationship, and each initial hydrostatic pressure yields a common CNT pressure; that common CNT pressure is determined from an overall distal hydraulic resistance to flow. By virtue of the greater GFR for JM nephrons, fluid delivery to SF and JM tubules is comparable. Glucose reabsorption is restricted to the PT, cotransported with one Na in the convoluted tubule (SGLT2), and two Na in the straight tubule (SGLT1). Increasing ambient glucose from 5 to 10 mM increases proximal Na reabsorption and decreases distal delivery. This is mitigated by a TGF-mediated increase in GFR, and may thus be an etiology for TGF-mediated glomerular hyperfiltration. With SGLT2 inhibition by 95%, the model predicts that under normoglycemic conditions about 60% of filtered glucose will still be reabsorbed, so that profound glycosuria is not to be expected. Compared with glucose-driven osmotic diuresis, SGLT2 inhibition provokes greater natriuresis. When hyperglycemia is superimposed on SGLT2 inhibition, the model suggests that natriuresis may be severe, reflecting synergy of a proximal diuretic and osmotic diuresis. In sum, the model captures TGF-mediated diabetic hyperfiltration and predicts glomerular protection with SGLT2 inhibition. PMID:25694480

  10. A mathematical model of the rat nephron: glucose transport.

    PubMed

    Weinstein, Alan M

    2015-05-15

    Mathematical models of the proximal tubule (PT), loop of Henle (LOH), and distal nephron have been combined to simulate transport by rat renal tubules. The ensemble is composed of 24,000 superficial (SF) nephrons and 12,000 juxtamedullary (JM) nephrons in 5 classes (according to LOH length); all coalesce into 7,200 connecting tubules (CNT). Medullary interstitial solute concentrations are specified. The model equations require that each nephron glomerular filtration rate (GFR) satisfies a tubuloglomerular feedback (TGF) relationship, and each initial hydrostatic pressure yields a common CNT pressure; that common CNT pressure is determined from an overall distal hydraulic resistance to flow. By virtue of the greater GFR for JM nephrons, fluid delivery to SF and JM tubules is comparable. Glucose reabsorption is restricted to the PT, cotransported with one Na in the convoluted tubule (SGLT2), and two Na in the straight tubule (SGLT1). Increasing ambient glucose from 5 to 10 mM increases proximal Na reabsorption and decreases distal delivery. This is mitigated by a TGF-mediated increase in GFR, and may thus be an etiology for TGF-mediated glomerular hyperfiltration. With SGLT2 inhibition by 95%, the model predicts that under normoglycemic conditions about 60% of filtered glucose will still be reabsorbed, so that profound glycosuria is not to be expected. Compared with glucose-driven osmotic diuresis, SGLT2 inhibition provokes greater natriuresis. When hyperglycemia is superimposed on SGLT2 inhibition, the model suggests that natriuresis may be severe, reflecting synergy of a proximal diuretic and osmotic diuresis. In sum, the model captures TGF-mediated diabetic hyperfiltration and predicts glomerular protection with SGLT2 inhibition. Copyright © 2015 the American Physiological Society.

  11. Dimethylarginine dimethylaminohydrolase in rat penile tissue: reduced enzyme activity is responsible for erectile dysfunction in a rat model of atherosclerosis

    PubMed Central

    Park, K; Lee, D G; Kim, S W; Paick, J-S

    2009-01-01

    Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is mainly metabolized by NG,NG-dimethylarginine dimethylaminohydrolase (DDAH). We investigated whether altered cavernosal ADMA–DDAH metabolism might cause impairment of erection in rat model of atherosclerosis (AS). Male Sprague–Dawley rats (3 months old) were divided into an AS group and a normal control (Con) group (n=20 in each group). The AS rats received AS-prone treatment (6 weeks of 1% cholesterol diet plus early 2 weeks of NG-nitro-L-arginine methyl ester (3 mg ml−1 per day) treatment). After 6 weeks, rats underwent cavernosometry measuring the maximal intracavernosal pressure/mean arterial pressure (ICP/MAP) ratios as a surrogate marker of erectile function. The amount of cavernosal ADMA was assessed by immunoblot analysis and correlated with the ICP/MAP. Isoform-specific DDAH expression was compared by immunohistochemistry. Cavernosal DDAH and NOS activity were measured. Cavernosal malondialdehyde levels were assayed to determine the degree of lipid peroxidation. Compared to the controls, the AS rats had signs of impaired erectile function. Higher cavernosal ADMA was observed in the AS rats. The cavernosal ADMA had a moderately negative correlation with the ICP/MAP. Immunohistochemistry revealed the expression of both isoforms was not affected by the presence of AS. However, significantly diminished DDAH as well as NOS activity was observed in the AS group. In addition, elevated cavernosal malondialdehyde levels were noted in the AS rats. Our study showed that decreased cavernosal DDAH activity is the cause of cavernosal ADMA accumulation leading to reduced cavernosal NOS activity and impairment of erectile function. PMID:19603041

  12. Simulating certain aspects of hypogravity: Effects on the mandibular incisors of suspended rats (PULEH model)

    NASA Technical Reports Server (NTRS)

    Simmons, D. J.; Winter, F.; Morey-Holton, E. R.

    1984-01-01

    The effect of a hypogravity simulating model on the rate of mandibular incisor formation, dentinogenesis and, amelogenesis in laboratory rats was studied. The model is the partial unloading by elevating the hindquarters. In this system, rat hindquarters are elevated 30 to 40 deg from the cage floors to completely unload the hindlimbs, but the animals are free to move about using their forelimbs. This model replicates the fluid sift changes which occur during the weightlessness of spaceflight and produces an osteopenia in the weight bearing skeletons. The histogenesis and/or mineralization rates of the mandibular incisor during the first 19d of PULEH in young growing rats are recorded.

  13. Simulating certain aspects of hypogravity: Effects on the mandibular incisors of suspended rats (PULEH model)

    NASA Technical Reports Server (NTRS)

    Simmons, D. J.; Winter, F.; Morey-Holton, E. R.

    1984-01-01

    The effect of a hypogravity simulating model on the rate of mandibular incisor formation, dentinogenesis and, amelogenesis in laboratory rats was studied. The model is the partial unloading by elevating the hindquarters. In this system, rat hindquarters are elevated 30 to 40 deg from the cage floors to completely unload the hindlimbs, but the animals are free to move about using their forelimbs. This model replicates the fluid sift changes which occur during the weightlessness of spaceflight and produces an osteopenia in the weight bearing skeletons. The histogenesis and/or mineralization rates of the mandibular incisor during the first 19d of PULEH in young growing rats are recorded.

  14. Lipid mapping of the rat brain for models of disease.

    PubMed

    Martínez-Gardeazabal, J; González de San Román, E; Moreno-Rodríguez, M; Llorente-Ovejero, A; Manuel, I; Rodríguez-Puertas, R

    2017-02-21

    Lipids not only constitute the primary component of cellular membranes and contribute to metabolism but also serve as intracellular signaling molecules and bind to specific membrane receptors to control cell proliferation, growth and convey neuroprotection. Over the last several decades, the development of new analytical techniques, such as imaging mass spectrometry (IMS), has contributed to our understanding of their involvement in physiological and pathological conditions. IMS allows researchers to obtain a wide range of information about the spatial distribution and abundance of the different lipid molecules that is crucial to understand brain functions. The primary aim of this study was to map the spatial distribution of different lipid species in the rat central nervous system (CNS) using IMS to find a possible relationship between anatomical localization and physiology. The data obtained were subsequently applied to a model of neurological disease, the 192IgG-saporin lesion model of memory impairment. The results were obtained using a LTQ-Orbitrap XL mass spectrometer in positive and negative ionization modes and analyzed by ImageQuest and MSIReader software. A total of 176 different molecules were recorded based on the specific localization of their intensities. However, only 34 lipid species in negative mode and 51 in positive were assigned to known molecules with an error of 5ppm. These molecules were grouped by different lipid families, resulting in: Phosphatidylcholines (PC): PC (34: 1)+K(+) and PC (32: 0)+K(+) distributed primarily in gray matter, and PC (36: 1)+K(+) and PC (38: 1)+Na(+) distributed in white matter. Phosphatidic acid (PA): PA (38: 3)+K(+) in white matter, and PA (38: 5)+K(+) in gray matter and brain ventricles. Phosphoinositol (PI): PI (18: 0/20: 4)-H(+) in gray matter, and PI (O-30: 1) or PI (P-30: 0)-H(+) in white matter. Phosphatidylserines (PS): PS (34: 1)-H(+) in gray matter, and PS (38: 1)-H(+) in white matter. Sphingomyelin (SM

  15. Beneficial metabolic effects of 2',3',5'-tri-acetyl-N6- (3-hydroxylaniline) adenosine in the liver and plasma of hyperlipidemic hamsters.

    PubMed

    Sun, Yang; Lian, Zeqin; Jiang, Chunying; Wang, Yinghong; Zhu, Haibo

    2012-01-01

    Pharmaceutical research of hyperlipidemia has been commonly pursued using traditional approaches. However, unbiased metabonomics attempts to explore the metabolic signature of hyperlipidemia in a high-throughput manner to understand pathophysiology of the disease process. As a new way, we performed (1)H NMR-based metabonomics to evaluate the beneficial effects of 2',3',5'-tri-acetyl-N(6)- (3-hydroxylaniline) adenosine (WS070117) on plasma and liver from hyperlipidemic Syrian golden hamsters. Both plasma and liver profiles provided a clearer distinction between the control and hyperlipidemic hamsters. Compared to control animals, hyperlipidemic hamsters showed a higher content of lipids (triglyceride and cholesterol), lactate and alanine together with a lower content of choline-containing compounds (e.g., phosphocholine, phosphatidylcholine, and glycerophosphocholine) and betaine. As a result, metabonomics-based findings such as the PCA and OPLS-DA plotting of metabolic state and analysis of potential biomarkers in plasma and liver correlated well to the assessment of biochemical assays, Oil Red O staining and in vivo ultrasonographic imaging suggesting that WS070117 was able to regulate lipid content and displayed more beneficial effects on plasma and liver than simvastatin. This work demonstrates the promise of applying (1)H NMR metabonomics to evaluate the beneficial effects of WS070117 which may be a good drug candidate for hyperlipidemia.

  16. Mathematical Model of Ammonia Handling in the Rat Renal Medulla

    PubMed Central

    Noiret, Lorette; Baigent, Stephen; Jalan, Rajiv; Thomas, S. Randall

    2015-01-01

    The kidney is one of the main organs that produces ammonia and release it into the circulation. Under normal conditions, between 30 and 50% of the ammonia produced in the kidney is excreted in the urine, the rest being absorbed into the systemic circulation via the renal vein. In acidosis and in some pathological conditions, the proportion of urinary excretion can increase to 70% of the ammonia produced in the kidney. Mechanisms regulating the balance between urinary excretion and renal vein release are not fully understood. We developed a mathematical model that reflects current thinking about renal ammonia handling in order to investigate the role of each tubular segment and identify some of the components which might control this balance. The model treats the movements of water, sodium chloride, urea, NH3 and NH4+, and non-reabsorbable solute in an idealized renal medulla of the rat at steady state. A parameter study was performed to identify the transport parameters and microenvironmental conditions that most affect the rate of urinary ammonia excretion. Our results suggest that urinary ammonia excretion is mainly determined by those parameters that affect ammonia recycling in the loops of Henle. In particular, our results suggest a critical role for interstitial pH in the outer medulla and for luminal pH along the inner medullary collecting ducts. PMID:26280830

  17. Mathematical Model of Ammonia Handling in the Rat Renal Medulla.

    PubMed

    Noiret, Lorette; Baigent, Stephen; Jalan, Rajiv; Thomas, S Randall

    2015-01-01

    The kidney is one of the main organs that produces ammonia and release it into the circulation. Under normal conditions, between 30 and 50% of the ammonia produced in the kidney is excreted in the urine, the rest being absorbed into the systemic circulation via the renal vein. In acidosis and in some pathological conditions, the proportion of urinary excretion can increase to 70% of the ammonia produced in the kidney. Mechanisms regulating the balance between urinary excretion and renal vein release are not fully understood. We developed a mathematical model that reflects current thinking about renal ammonia handling in order to investigate the role of each tubular segment and identify some of the components which might control this balance. The model treats the movements of water, sodium chloride, urea, NH3 and [Formula: see text], and non-reabsorbable solute in an idealized renal medulla of the rat at steady state. A parameter study was performed to identify the transport parameters and microenvironmental conditions that most affect the rate of urinary ammonia excretion. Our results suggest that urinary ammonia excretion is mainly determined by those parameters that affect ammonia recycling in the loops of Henle. In particular, our results suggest a critical role for interstitial pH in the outer medulla and for luminal pH along the inner medullary collecting ducts.

  18. Modeling fibrosis using fibroblasts isolated from scarred rat vocal folds

    PubMed Central

    Kishimoto, Yo; Kishimoto, Ayami Ohno; Ye, Shuyun; Kendziorski, Christina; Welham, Nathan V.

    2016-01-01

    Following injury, pathologically activated vocal fold fibroblasts (VFFs) can engage in disordered extracellular matrix (ECM) remodeling, leading to VF fibrosis and impaired voice function. Given the importance of scar VFFs to phenotypically appropriate in vitro modeling of VF fibrosis, we pursued detailed characterization of scar VFFs obtained from surgically injured rat VF mucosae, compared to those obtained from experimentally naïve, age-matched tissue. Scar VFFs initially exhibited a myofibroblast phenotype characterized by increased proliferation, increased Col1a1 transcription and collagen, type I synthesis, increased Acta2 transcription and α-smooth muscle actin synthesis, and enhanced contractile function. These features were most distinct at passage 1 (P1); we observed a coalescence of the scar and naïve VFF phenotypes at later passages. An empirical Bayes statistical analysis of the P1 cell transcriptome identified 421 genes that were differentially expressed by scar, compared to naïve, VFFs. These genes were primarily associated with the wound response, ECM regulation, and cell proliferation. Follow-up comparison of P1 scar VFFs and their in vivo tissue source showed substantial transcriptomic differences. Finally, P1 scar VFFs responded to treatment with hepatocyte growth factor and transforming growth factor-β3, two biologics with reported therapeutic value. Despite the practical limitations inherent to working with early passage cells, this experimental model is easily implemented in any suitably equipped laboratory and has the potential to improve the applicability of preclinical VF fibrosis research. PMID:27111284

  19. A Novel Model of Intravital Platelet Imaging Using CD41-ZsGreen1 Transgenic Rats

    PubMed Central

    Mizuno, Makoto; Tomizawa, Atsuyuki; Ohno, Kousaku; Jakubowski, Joseph A.; Sugidachi, Atsuhiro

    2016-01-01

    Platelets play pivotal roles in both hemostasis and thrombosis. Although models of intravital platelet imaging are available for thrombosis studies in mice, few are available for rat studies. The present effort aimed to generate fluorescent platelets in rats and assess their dynamics in a rat model of arterial injury. We generated CD41-ZsGreen1 transgenic rats, in which green fluorescence protein ZsGreen1 was expressed specifically in megakaryocytes and thus platelets. The transgenic rats exhibited normal hematological and biochemical values with the exception of body weight and erythroid parameters, which were slightly lower than those of wild-type rats. Platelet aggregation, induced by 20 μM ADP and 10 μg/ml collagen, and blood clotting times were not significantly different between transgenic and wild-type rats. Saphenous arteries of transgenic rats were injured with 10% FeCl3, and the formation of fluorescent thrombi was evaluated using confocal microscopy. FeCl3 caused time-dependent increases in the mean fluorescence intensity of injured arteries of vehicle-treated rats. Prasugrel (3 mg/kg, p.o.), administered 2 h before FeCl3, significantly inhibited fluorescence compared with vehicle-treated rats (4.5 ± 0.4 vs. 14.9 ± 2.4 arbitrary fluorescence units at 30 min, respectively, n = 8, P = 0.0037). These data indicate that CD41-ZsGreen1 transgenic rats represent a useful model for intravital imaging of platelet-mediated thrombus formation and the evaluation of antithrombotic agents. PMID:27128503

  20. 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

  1. Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model.

    PubMed

    Jennings, Paul; Weiland, Christina; Limonciel, Alice; Bloch, Katarzyna M; Radford, Robert; Aschauer, Lydia; McMorrow, Tara; Wilmes, Anja; Pfaller, Walter; Ahr, Hans J; Slattery, Craig; Lock, Edward A; Ryan, Michael P; Ellinger-Ziegelbauer, Heidrun

    2012-04-01

    Ochratoxin A (OTA) is a widely studied compound due to its role in renal toxicity and carcinogenicity. However, there is still no consensus on the exact mechanisms of toxicity or carcinogenicity. In the current study, we analysed the effect of OTA on three human renal proximal tubular models (human primary, RPTEC/TERT1 and HK-2 cells) and two rat renal proximal tubular models (rat primary and NRK-52E cells). Global transcriptomics analysis at two exposure times was performed to generate a set of 756 OTA sensitive genes. This gene set was then compared in more detail across all models and additionally to a rat in vivo renal cortex model. The results demonstrate a well-conserved response across all models. OTA resulted in deregulation of a number of pathways including cytoskeleton, nucleosome regulation, translation, transcription, ubiquitination and cell cycle pathways. Interestingly, the oxidative stress activated Nrf2 pathway was not enriched. These results point to an epigenetic action of OTA, perhaps initiated by actin binding as the actin remodelling gene, advillin was the highest up-regulated in all models. The largest model differences were observed between the human and the rat in vitro models. However, since the human in vitro models were more similar to the rat in vivo model, it is more likely that these differences are model-specific rather than species-specific per se. This study demonstrates the usefulness of in vitro cell culture models combined with transcriptomic analysis for the investigation of mechanisms of toxicity and carcinogenicity. In addition, these results provide further evidence supporting a non-genotoxic mechanism of OTA-induced carcinogenicity.

  2. Gene transfer by viral vectors into blood vessels in a rat model of retinopathy of prematurity.

    PubMed

    Chowers, I; Banin, E; Hemo, Y; Porat, R; Falk, H; Keshet, E; Pe'er, J; Panet, A

    2001-08-01

    To test the feasibility of gene transfer into hyaloid blood vessels and into preretinal neovascularisation in a rat model of retinopathy of prematurity (ROP), using different viral vectors. Newborn rats were exposed to alternating hypoxic and hyperoxic conditions in order to induce ocular neovascularisation (ROP rats). Adenovirus, herpes simplex, vaccinia, and retroviral (MuLV based) vectors, all carrying the beta galactosidase (beta-gal) gene, were injected intravitreally on postnatal day 18 (P18). Two sets of controls were also examined: P18 ROP rats injected with saline and P18 rats that were raised in room air before the viral vectors or saline were injected. Two days after injection, the rats were killed, eyes enucleated, and beta-gal expression was examined by X-gal staining in whole mounts and in histological sections. Intravitreal injection of the adenovirus and vaccinia vectors yielded marked beta-gal expression in hyaloid blood vessels in the rat ROP model. Retinal expression of beta-gal with these vectors was limited almost exclusively to the vicinity of the injection site. Injection of herpes simplex yielded a punctuate pattern of beta-gal expression in the retina but not in blood vessels. No significant beta-gal expression occurred in rat eyes injected with the retroviral vector. Adenovirus is an efficient vector for gene transfer into blood vessels in an animal model of ROP. This may be a first step towards utilising gene transfer as a tool for modulating ocular neovascularisation for experimental and therapeutic purposes.

  3. Molecular modeling of the structures of human and rat pancreatic cholesterol esterases.

    PubMed Central

    Feaster, S. R.; Quinn, D. M.; Barnett, B. L.

    1997-01-01

    Structural models have been generated for rat and human cholesterol esterases by molecular modeling. For rat cholesterol esterase, three separate models were generated according to the following procedure: (1) the cholesterol esterase sequence was aligned with those of three template enzymes: Torpedo californica acetylcholinesterase, Geotrichum candidum lipase and Candida rugosa lipase; (2) the X-ray structure coordinates of the three template enzymes were used to construct cholesterol esterase models by amino acid replacements of matched sequence positions and by making sequence insertions and deletions as required; (3) bad contracts in each of the cholesterol esterase models were relaxed by molecular dynamics and mechanics; (4) the three cholesterol esterase models were merged into one by arithmetic averaging of atomic coordinates; (5) Ramachandran analysis indicated that the model generated from the AChE template possessed the best set of phi/psi angles. Therefore, this model was subjected to molecular dynamics, with harmonic constraints imposed on the C(alpha) coordinates to drive them toward the coordinates of the averaged model. (6) Subsequent relaxation by molecular mechanics produced the final rat cholesterol esterase model. A model for human cholesterol esterase was produced by repeating steps 1-3 above, albeit with the rat cholesterol esterase model as the template. Hydrophobic and electrostatic analyses of the rat and human cholesterol esterase models suggest the structural origins of molecular recognition of hydrophobic substrates and interfaces, of charged interfaces, and of bile salt activators. PMID:9007978

  4. The Influence of a High Salt Diet on a Rat Model of Isoproterenol-Induced Heart Failure

    EPA Science Inventory

    Rat models of heart failure (HF) show varied pathology and time to disease outcome, dependent on induction method. We found that subchronic (4 weeks) isoproterenol (ISO) infusion exacerbated cardiomyopathy in Spontaneously Hypertensive Heart Failure (SHHF) rats. Others have shown...

  5. The Influence of a High Salt Diet on a Rat Model of Isoproterenol-Induced Heart Failure

    EPA Science Inventory

    Rat models of heart failure (HF) show varied pathology and time to disease outcome, dependent on induction method. We found that subchronic (4 weeks) isoproterenol (ISO) infusion exacerbated cardiomyopathy in Spontaneously Hypertensive Heart Failure (SHHF) rats. Others have shown...

  6. Establishment and identification of a hypoxia-ischemia brain damage model in neonatal rats

    PubMed Central

    YAO, DAN; ZHANG, WEIRAN; HE, XUE; WANG, JINHU; JIANG, KEWEN; ZHAO, ZHENGYAN

    2016-01-01

    The present study was designed to set up a reliable model of severe hypoxia-ischemia brain damage (HIBD) in neonatal rats and several methods were used to identify whether the model was successful. A total of 40 healthy 7-day-old Sprague-Dawley rats were randomly divided into 2 groups: The sham-surgery group (n=18) and the HIBD model group (n=22). The HIBD model was produced according to the traditional Rice method. The rats were anesthetized with ethyl ether. The left common carotid artery (CCA) was exposed, ligated and cut. Following this, the rats were exposed to hypoxia in a normobaric chamber filled with 8% oxygen and 92% nitrogen for 2 h. In the sham-surgery group, the left CCA was exposed but was not ligated, cut or exposed to hypoxia. The neurobehavioral changes of the rats were observed in the 24 h after HIBD. The brains were collected after 72 h to observe the pathological morphological changes of the brain tissue. The behavioral ability and neurobehavioral changes were studied in each group. The water maze test was used for evaluating the learning-memory ability when the rats were 28 days old. Compared with the sham-surgery group, all the HIBD model rats had a lag of motor development. The rats had evident changes in anatomy and Nissl staining, and cognitive impairment was shown through the result of the water maze. Therefore, the model of HIBD in neonatal rats is feasible and provides a reliable model for subsequent studies. PMID:27073628

  7. Virgin Coconut Oil Supplementation Prevents Bone Loss in Osteoporosis Rat Model

    PubMed Central

    Hayatullina, Zil; Muhammad, Norliza; Mohamed, Norazlina; Soelaiman, Ima-Nirwana

    2012-01-01

    Oxidative stress and free radicals have been implicated in the pathogenesis of osteoporosis. Therefore, antioxidant compounds have the potential to be used in the prevention and treatment of the disease. In this study, we investigated the effects of virgin coconut oil (VCO) on bone microarchitecture in a postmenopausal osteoporosis rat model. VCO is a different form of coconut oil as it is rich with antioxidants. Three-month-old female rats were randomly grouped into baseline, sham-operated, ovariectomized control (Ovx), and ovariectomized rats fed with 8% VCO in their diet for six weeks (Ovx+VCO). Bone histomorphometry of the right femora was carried out at the end of the study. Rats supplemented with VCO had a significantly greater bone volume and trabecular number while trabecular separation was lower than the Ovx group. In conclusion, VCO was effective in maintaining bone structure and preventing bone loss in estrogen-deficient rat model. PMID:23024690

  8. Virgin coconut oil supplementation prevents bone loss in osteoporosis rat model.

    PubMed

    Hayatullina, Zil; Muhammad, Norliza; Mohamed, Norazlina; Soelaiman, Ima-Nirwana

    2012-01-01

    Oxidative stress and free radicals have been implicated in the pathogenesis of osteoporosis. Therefore, antioxidant compounds have the potential to be used in the prevention and treatment of the disease. In this study, we investigated the effects of virgin coconut oil (VCO) on bone microarchitecture in a postmenopausal osteoporosis rat model. VCO is a different form of coconut oil as it is rich with antioxidants. Three-month-old female rats were randomly grouped into baseline, sham-operated, ovariectomized control (Ovx), and ovariectomized rats fed with 8% VCO in their diet for six weeks (Ovx+VCO). Bone histomorphometry of the right femora was carried out at the end of the study. Rats supplemented with VCO had a significantly greater bone volume and trabecular number while trabecular separation was lower than the Ovx group. In conclusion, VCO was effective in maintaining bone structure and preventing bone loss in estrogen-deficient rat model.

  9. Identifying Molecular Targets for Chemoprevention in a Rat Model

    DTIC Science & Technology

    2007-06-01

    at the 65-week time point. This example shows a relatively large patch of Leydig cells ( Ley ) adjacent to two seminiferous tubules (Tub). PhIP Rat...9, 2006 [16] Weisburger JH, Rivenson A, Reinhardt J, Braley J, Pittman B, and Zang E (2002). On the occurrence of Leydig cell tumors in the F344 rat

  10. Cellular Biochemistry and Cytogenetics in a Rat Lung Tumor Model

    DTIC Science & Technology

    1984-10-01

    Clara cells and alveolar type II cells from control and beta- naphthoflavone-pretreated rats. Cancer Res. 42:4658-4663. Kaighn, M.E., (1973), Human ...alkylation of nucleic acids of the rat by N-methyl-N-nitrosourea, dimethylnitrosamine , dimethylsulfate, and methylmethanesulfonate. Biochem. J. 110:39-47

  11. Structure-activity relationship models for rat carcinogenesis and assessing the role mutagens play in model predictivity.

    PubMed

    Carrasquer, C A; Batey, K; Qamar, S; Cunningham, A R; Cunningham, S L

    2014-01-01

    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 69-76% compared with only 47-53% for non-mutagenic carcinogens. As a surrogate for mutagenicity, comparisons between single site and multiple site carcinogen SAR models were analysed. 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.

  12. Modeling corticosteroid effects in a rat model of rheumatoid arthritis I: mechanistic disease progression model for the time course of collagen-induced arthritis in Lewis rats.

    PubMed

    Earp, Justin C; Dubois, Debra C; Molano, Diana S; Pyszczynski, Nancy A; Keller, Craig E; Almon, Richard R; Jusko, William J

    2008-08-01

    A mechanism-based model was developed to describe the time course of arthritis progression in the rat. Arthritis was induced in male Lewis rats with type II porcine collagen into the base of the tail. Disease progression was monitored by paw swelling, bone mineral density (BMD), body weights, plasma corticosterone (CST) concentrations, and tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and glucocorticoid receptor (GR) mRNA expression in paw tissue. Bone mineral density was determined by PIXImus II dual energy X-ray densitometry. Plasma CST was assayed by high-performance liquid chromatography. Cytokine and GR mRNA were determined by quantitative real-time polymerase chain reaction. Disease progression models were constructed from transduction and indirect response models and applied using S-ADAPT software. A delay in the onset of increased paw TNF-alpha and IL-6 mRNA concentrations was successfully characterized by simple transduction. This rise was closely followed by an up-regulation of GR mRNA and CST concentrations. Paw swelling and body weight responses peaked approximately 21 days after induction, whereas bone mineral density changes were greatest at 23 days after induction. After peak response, the time course in IL-1beta, IL-6 mRNA, and paw edema slowly declined toward a disease steady state. Model parameters indicate TNF-alpha and IL-1beta mRNA most significantly induce paw edema, whereas IL-6 mRNA exerted the most influence on BMD. The model for bone mineral density captures rates of turnover of cancellous and cortical bone and the fraction of each in the different regions analyzed. This small systems model integrates and quantitates multiple factors contributing to arthritis in rats.

  13. Lemon juice has protective activity in a rat urolithiasis model

    PubMed Central

    Touhami, Mohammed; Laroubi, Amine; Elhabazi, Khadija; Loubna, Farouk; Zrara, Ibtissam; Eljahiri, Younes; Oussama, Abdelkhalek; Grases, Félix; Chait, Abderrahman

    2007-01-01

    Background The use of herbal medicines (medicinal plants or phytotherapy) has recently gained popularity in Europe and the United States. Nevertheless the exact mechanism of the preventive effects of these products is still far to be clearly established, being its knowledge necessary to successfully apply these therapies to avoid stone formation. Methods The effect of oral lemon juice administration on calcium oxalate urolithiasis was studied in male Wistar rats. Rats were rendered nephrolithic by providing drinking water containing 0.75% ethylene glycol [v/v] (EG) and 2% ammonium chloride [w/v] (AC) for 10 days. In addition to EG/AC treatment, three groups of rats were also gavage-administered solutions containing 100%, 75% or 50% lemon juice [v/v] (6 μl solution/g body weight). Positive control rats were treated with EG/AC but not lemon juice. Negative control rats were provided with normal drinking water, and were administered normal water by gavage. Each group contained 6 rats. After 10 days, serum samples were collected for analysis, the left kidney was removed and assessed for calcium levels using flame spectroscopy, and the right kidney was sectioned for histopathological analysis using light microscopy. Results Analysis showed that the rats treated with EG/AC alone had higher amounts of calcium in the kidneys compared to negative control rats. This EG/AC-induced increase in kidney calcium levels was inhibited by the administration of lemon juice. Histology showed that rats treated with EG/AC alone had large deposits of calcium oxalate crystals in all parts of the kidney, and that such deposits were not present in rats also treated with either 100% or 75% lemon juice. Conclusion These data suggest that lemon juice has a protective activity against urolithiasis. PMID:17919315

  14. Lemon juice has protective activity in a rat urolithiasis model.

    PubMed

    Touhami, Mohammed; Laroubi, Amine; Elhabazi, Khadija; Loubna, Farouk; Zrara, Ibtissam; Eljahiri, Younes; Oussama, Abdelkhalek; Grases, Félix; Chait, Abderrahman

    2007-10-05

    The use of herbal medicines (medicinal plants or phytotherapy) has recently gained popularity in Europe and the United States. Nevertheless the exact mechanism of the preventive effects of these products is still far to be clearly established, being its knowledge necessary to successfully apply these therapies to avoid stone formation. The effect of oral lemon juice administration on calcium oxalate urolithiasis was studied in male Wistar rats. Rats were rendered nephrolithic by providing drinking water containing 0.75% ethylene glycol [v/v] (EG) and 2% ammonium chloride [w/v] (AC) for 10 days. In addition to EG/AC treatment, three groups of rats were also gavage-administered solutions containing 100%, 75% or 50% lemon juice [v/v] (6 microl solution/g body weight). Positive control rats were treated with EG/AC but not lemon juice. Negative control rats were provided with normal drinking water, and were administered normal water by gavage. Each group contained 6 rats. After 10 days, serum samples were collected for analysis, the left kidney was removed and assessed for calcium levels using flame spectroscopy, and the right kidney was sectioned for histopathological analysis using light microscopy. Analysis showed that the rats treated with EG/AC alone had higher amounts of calcium in the kidneys compared to negative control rats. This EG/AC-induced increase in kidney calcium levels was inhibited by the administration of lemon juice. Histology showed that rats treated with EG/AC alone had large deposits of calcium oxalate crystals in all parts of the kidney, and that such deposits were not present in rats also treated with either 100% or 75% lemon juice. These data suggest that lemon juice has a protective activity against urolithiasis.

  15. Absence of "Warm-Up" during Active Avoidance Learning in a Rat Model of Anxiety Vulnerability: Insights from Computational Modeling.

    PubMed

    Myers, Catherine E; Smith, Ian M; Servatius, Richard J; Beck, Kevin D

    2014-01-01

    Avoidance behaviors, in which a learned response causes omission of an upcoming punisher, are a core feature of many psychiatric disorders. While reinforcement learning (RL) models have been widely used to study the development of appetitive behaviors, less attention has been paid to avoidance. Here, we present a RL model of lever-press avoidance learning in Sprague-Dawley (SD) rats and in the inbred Wistar Kyoto (WKY) rat, which has been proposed as a model of anxiety vulnerability. We focus on "warm-up," transiently decreased avoidance responding at the start of a testing session, which is shown by SD but not WKY rats. We first show that a RL model can correctly simulate key aspects of acquisition, extinction, and warm-up in SD rats; we then show that WKY behavior can be simulated by altering three model parameters, which respectively govern the tendency to explore new behaviors vs. exploit previously reinforced ones, the tendency to repeat previous behaviors regardless of reinforcement, and the learning rate for predicting future outcomes. This suggests that several, dissociable mechanisms may contribute independently to strain differences in behavior. The model predicts that, if the "standard" inter-session interval is shortened from 48 to 24 h, SD rats (but not WKY) will continue to show warm-up; we confirm this prediction in an empirical study with SD and WKY rats. The model further predicts that SD rats will continue to show warm-up with inter-session intervals as short as a few minutes, while WKY rats will not show warm-up, even with inter-session intervals as long as a month. Together, the modeling and empirical data indicate that strain differences in warm-up are qualitative rather than just the result of differential sensitivity to task variables. Understanding the mechanisms that govern expression of warm-up behavior in avoidance may lead to better understanding of pathological avoidance, and potential pathways to modify these processes.

  16. Exercise activates compensatory thermoregulatory reaction in rats: a modeling study

    PubMed Central

    Yoo, Yeonjoo; LaPradd, Michelle; Kline, Hannah; Zaretskaia, Maria V.; Behrouzvaziri, Abolhassan; Rusyniak, Daniel E.; Molkov, Yaroslav I.

    2015-01-01

    The importance of exercise is increasingly emphasized for maintaining health. However, exercise itself can pose threats to health such as the development of exertional heat shock in warm environments. Therefore, it is important to understand how the thermoregulation system adjusts during exercise and how alterations of this can contribute to heat stroke. To explore this we measured the core body temperature of rats (Tc) running for 15 min on a treadmill at various speeds in two ambient temperatures (Ta = 25°C and 32°C). We assimilated the experimental data into a mathematical model that describes temperature changes in two compartments of the body, representing the muscles and the core. In our model the core body generates heat to maintain normal body temperature, and dissipates it into the environment. The muscles produce additional heat during exercise. According to the estimation of model parameters, at Ta = 25°C, the heat generation in the core was progressively reduced with the increase of the treadmill speed to compensate for a progressive increase in heat production by the muscles. This compensation was ineffective at Ta = 32°C, which resulted in an increased rate of heat accumulation with increasing speed, as opposed to the Ta = 25°C case. Interestingly, placing an animal on a treadmill increased heat production in the muscles even when the treadmill speed was zero. Quantitatively, this “ready-to-run” phenomenon accounted for over half of the heat generation in the muscles observed at maximal treadmill speed. We speculate that this anticipatory response utilizes stress-related circuitry. PMID:26472864

  17. Nonequilibrium thermodynamic model of the rat proximal tubule epithelium.

    PubMed Central

    Weinstein, A M

    1983-01-01

    The rat proximal tubule epithelium is represented as well-stirred, compliant cellular and paracellular compartments bounded by mucosal and serosal bathing solutions. With a uniform pCO2 throughout the epithelium, the model variables include the concentrations of Na, K, Cl, HCO3, H2PO4, HPO4, and H, as well as hydrostatic pressure and electrical potential. Except for a metabolically driven Na-K exchanger at the basolateral cell membrane, all membrane transport within the epithelium is passive and is represented by the linear equations of nonequilibrium thermodynamics. In particular, this includes the cotransport of Na-Cl and Na-H2PO4 and countertransport of Na-H at the apical cell membrane. Experimental constraints on the choice of ionic conductivities are satisfied by allowing K-Cl cotransport at the basolateral membrane. The model equations include those for mass balance of the nonreacting species, as well as chemical equilibrium for the acidification reactions. Time-dependent terms are retained to permit the study of transient phenomena. In the steady state the energy dissipation is computed and verified equal to the sum of input from the Na-K exchanger plus the Gibbs free energy of mass addition to the system. The parameter dependence of coupled water transport is studied and shown to be consistent with the predictions of previous analytical models of the lateral intercellular space. Water transport in the presence of an end-proximal (HCO3-depleted) luminal solution is investigated. Here the lower permeability and higher reflection coefficient of HCO3 enhance net sodium and water transport. Due to enhanced flux across the tight junction, this process may permit proximal tubule Na transport to proceed with diminished energy dissipation. PMID:6652211

  18. 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...

  19. 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...

  20. Development of a Physiologically Based Pharmacokinetic Model for Triadimefon and Triadimenol in Rats and Humans

    EPA Science Inventory

    A physiologically based pharmacokinetic (PBPK) model was developed for the conazole fungicide triadimefon and its primary metabolite, triadimenol. Rat tissue:blood partition coefficients and metabolic constants were measured in vitro for both compounds. Kinetic time course data...

  1. Development of a Physiologically Based Pharmacokinetic Model for Triadimefon and Triadimenol in Rats and Humans

    EPA Science Inventory

    A physiologically based pharmacokinetic (PBPK) model was developed for the conazole fungicide triadimefon and its primary metabolite, triadimenol. Rat tissue:blood partition coefficients and metabolic constants were measured in vitro for both compounds. Kinetic time course data...

  2. Increases in body mass of rats during spaceflight: models and measurements.

    PubMed

    Wade, C E; Ortiz, R M; Baer, L A

    2000-11-01

    To test the hypothesis that the body mass of rats is increased during spaceflight, we developed two models from the literature and obtained mass measurements during spaceflight. From studies of centrifugation (hypergravity), there is a reduction in body mass of rats dependent on the exposure gravity level. From data in 18 publications on rats subjected to hypergravity by centrifugation, we developed a model that predicted a 27% increase in body mass during the microgravity of spaceflight. Following spaceflight, with an increase in gravity on return to Earth, there is a reduction in body mass of rats for over 3 d. We related the reduction in body mass after spaceflight to the time after landing that mass measurements were made. From data in 23 publications on rats returning from spaceflight, we developed a model that predicted a 19% increase in body mass during spaceflight. Measurement of body mass of rats on days 6 and 10 of spaceflight found a 7 and 9% increase compared with ground control animals. The increase in body mass during spaceflight suggests that the rat may provide a viable model for metabolic studies in which changes during spaceflight may be predicted in part by ground-based hypergravity studies.

  3. The JCR:LA-cp rat: a novel rodent model of cystic medial necrosis.

    PubMed

    Pung, Yuh Fen; Chilian, William M; Bennett, Martin R; Figg, Nichola; Kamarulzaman, Mohd Hamzah

    2017-03-01

    Although there are multiple rodent models of the metabolic syndrome, very few develop vascular complications. In contrast, the JCR:LA-cp rat develops both metabolic syndrome and early atherosclerosis in predisposed areas. However, the pathology of the normal vessel wall has not been described. We examined JCR:LA control (+/+) or cp/cp rats fed normal chow diet for 6 or 18 mo. JCR:LA-cp rats developed multiple features of advanced cystic medial necrosis including "cysts," increased collagen formation and proteoglycan deposition around cysts, apoptosis of vascular smooth muscle cells, and spotty medial calcification. These appearances began within 6 mo and were extensive by 18 mo. JCR:LA-cp rats had reduced medial cellularity, increased medial thickness, and vessel hypoxia that was most marked in the adventitia. In conclusion, the normal chow-fed JCR:LA-cp rat represents a novel rodent model of cystic medial necrosis, associated with multiple metabolic abnormalities, vascular smooth muscle cell apoptosis, and vessel hypoxia.NEW & NOTEWORTHY Triggers for cystic medial necrosis (CMN) have been difficult to study due to lack of animal models to recapitulate the pathologies seen in humans. Our study is the first description of CMN in the rat. Thus the JCR:LA-cp rat represents a useful model to investigate the underlying molecular changes leading to the development of CMN. Copyright © 2017 the American Physiological Society.

  4. Assessment of pharmacokinetic interaction of spirulina with glitazone in a type 2 diabetes rat model.

    PubMed

    Gupta, Annu; Nair, Anroop; Kumria, Rachna; Al-Dhubiab, Bandar-E; Chattopadhyaya, Ipshita; Gupta, Sumeet

    2013-12-01

    The objective of the current study was to assess the possible pharmacokinetic interactions of spirulina with glitazones in an insulin resistance rat model. Wistar male albino rats were equally divided into five groups: insulin resistant rats+spirulina (500 mg/kg)+pioglitazone (10 mg/kg), insulin resistant rats+pioglitazone (10 mg/kg), insulin resistant rats+spirulina (500 mg/kg)+rosiglitazone (10 mg/kg), insulin resistant rats+rosiglitazone (10 mg/kg), and insulin resistant rats+spirulina (500 mg/kg). Described doses of pioglitazone, rosiglitazone, or spirulina were per orally administered and the plasma drug concentrations were determined. The pharmacokinetic parameters such as Tmax, Cmax, AUC(0-α), t1/2, and Kel were determined by plotting the drug concentration as a function of time. The data observed in this acute study indicated that there was no statistically significant difference in any of the pharmacokinetic parameters (Tmax, Cmax, AUC(0-α), t1/2, and Kel) of glitazones (pioglitazone, rosiglitazone) or spirulina, when they were coadministered. Given the promising results, this study concludes that the coadministration of spirulina does not influence the pharmacokinetics of glitazones in a type 2 diabetes rat model. Further chronic in vivo studies are recommended to assess the real time effect.

  5. Arthritic disease is more severe in older rats in a kaolin/carrageenan-induced arthritis model.

    PubMed

    Kim, Kyoung Soo; Kim, Myung-Hwan; Yeom, Mijung; Choi, Hyun Mi; Yang, Hyung-In; Yoo, Myung Chul; Hahm, Dae-Hyun

    2012-12-01

    This study examined in an arthritis animal model whether elderly onset rheumatoid arthritis (EORA) is a more severe disease than younger onset rheumatoid arthritis. Arthritis was induced by injecting 5% kaolin/carrageenan into the left tibiotarsal ankles of 18-month-old and 4-week-old rats. Various parameters were measured to evaluate the arthritic progression of kaolin/carrageenan-induced arthritis in the rats. Immunohistochemical staining of arthritic joints was performed to determine the degree of inflammation in old and young rats. Measurements of ankle volume and thickness, arthritic index, number of squeaks, and the paw pressure test showed the 18-month-old rats had more severe disease than the young rats in a kaolin/carrageenan-induced arthritis model. The degree of inflammation and MMP-1 expression of arthritic joints in old rats was significantly higher than that of young rats based on histological evaluation with hematoxylin and eosin (H&E) staining and immunochemistry. More severe disease symptoms were found in old rats with EORA, but the molecular mechanisms still remain to be elucidated. Understanding the molecular mechanisms will be helpful to develop clinical protocols to efficiently treat patients with EORA, which is difficult to control with current protocols.

  6. Degraded neural and behavioral processing of speech sounds in a rat model of Rett syndrome.

    PubMed

    Engineer, Crystal T; Rahebi, Kimiya C; Borland, Michael S; Buell, Elizabeth P; Centanni, Tracy M; Fink, Melyssa K; Im, Kwok W; Wilson, Linda G; Kilgard, Michael P

    2015-11-01

    Individuals with Rett syndrome have greatly impaired speech and language abilities. Auditory brainstem responses to sounds are normal, but cortical responses are highly abnormal. In this study, we used the novel rat Mecp2 knockout model of Rett syndrome to document the neural and behavioral processing of speech sounds. We hypothesized that both speech discrimination ability and the neural response to speech sounds would be impaired in Mecp2 rats. We expected that extensive speech training would improve speech discrimination ability and the cortical response to speech sounds. Our results reveal that speech responses across all four auditory cortex fields of Mecp2 rats were hyperexcitable, responded slower, and were less able to follow rapidly presented sounds. While Mecp2 rats could accurately perform consonant and vowel discrimination tasks in quiet, they were significantly impaired at speech sound discrimination in background noise. Extensive speech training improved discrimination ability. Training shifted cortical responses in both Mecp2 and control rats to favor the onset of speech sounds. While training increased the response to low frequency sounds in control rats, the opposite occurred in Mecp2 rats. Although neural coding and plasticity are abnormal in the rat model of Rett syndrome, extensive therapy appears to be effective. These findings may help to explain some aspects of communication deficits in Rett syndrome and suggest that extensive rehabilitation therapy might prove beneficial. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Degraded neural and behavioral processing of speech sounds in a rat model of Rett syndrome

    PubMed Central

    Engineer, Crystal T.; Rahebi, Kimiya C.; Borland, Michael S.; Buell, Elizabeth P.; Centanni, Tracy M.; Fink, Melyssa K.; Im, Kwok W.; Wilson, Linda G.; Kilgard, Michael P.

    2015-01-01

    Individuals with Rett syndrome have greatly impaired speech and language abilities. Auditory brainstem responses to sounds are normal, but cortical responses are highly abnormal. In this study, we used the novel rat Mecp2 knockout model of Rett syndrome to document the neural and behavioral processing of speech sounds. We hypothesized that both speech discrimination ability and the neural response to speech sounds would be impaired in Mecp2 rats. We expected that extensive speech training would improve speech discrimination ability and the cortical response to speech sounds. Our results reveal that speech responses across all four auditory cortex fields of Mecp2 rats were hyperexcitable, responded slower, and were less able to follow rapidly presented sounds. While Mecp2 rats could accurately perform consonant and vowel discrimination tasks in quiet, they were significantly impaired at speech sound discrimination in background noise. Extensive speech training improved discrimination ability. Training shifted cortical responses in both Mecp2 and control rats to favor the onset of speech sounds. While training increased the response to low frequency sounds in control rats, the opposite occurred in Mecp2 rats. Although neural coding and plasticity are abnormal in the rat model of Rett syndrome, extensive therapy appears to be effective. These findings may help to explain some aspects of communication deficits in Rett syndrome and suggest that extensive rehabilitation therapy might prove beneficial. PMID:26321676

  8. Determination of oxidative stress and effect of erdosteine on rhinitis medicamentosa in a rat model.

    PubMed

    Dokuyucu, Recep; Cevik, Cengiz; Ozler, Gul Soylu; Ozgur, Tumay; Arli, Cengiz; Sefil, Fatih; Yonden, Zafer

    2014-11-05

    We aimed to determine the presence of oxidative stress in rhinitis medicamentosa (RM) and to evaluate the effect of erdosteine (ED) on mucosal changes in a rat model. Twenty-four male rats were used in this experimental study. Three groups were created. Group 1 (n=8) was the control group. Two puffs of 0.05% oxymetazolin were sprayed into the nasal cavities of the remaining rats (n=16) three times daily for eight weeks. One of these 16 rats was scarified at the end of the eight weeks and examined to confirm the presence of RM. Seven of the remaining 16 rats were killed, and venous blood samples were taken (Group 2). Group 3 (n=8) received 10mg/kg of an ED suspension orally for seven days. All rats were put on formalin for light microscopy. The total antioxidant status (TAS) was similar in all groups (p=0.073). The total oxidative status (TOS) of the RM group was significantly higher than that of the control group and RM+ED group (Group 3) (p=0.003 and p=0.011, respectively). The pathological recovery of the nasal mucosa of the rats was similar in the RM+ED and control groups. The TOS was high in this RM rat model, and oxidative stress was associated with RM. ED significantly ameliorated nasal mucosal changes induced by RM, suggesting that oxidative stress may play an important role in the pathophysiology of this condition.

  9. Impulsivity trait in the early symptomatic BACHD transgenic rat model of Huntington disease.

    PubMed

    Manfré, Giuseppe; Doyère, Valérie; Bossi, Simon; Riess, Olaf; Nguyen, Huu Phuc; El Massioui, Nicole

    2016-02-15

    Impulsivity trait was characterized in 3-5 months old BACHD rats, a transgenic model of Huntington disease, using (1) the delay discounting task to assess cognitive/choice impulsivity, and (2) the Differential Reinforcement of Low Rate of Responding task to evaluate motor/action impulsivity. Transgenic animals showed a high level of choice impulsivity and, to a lesser extent, action impulsivity. Our results provide the first evidence that the transgenic BACHD rat (TG5 line) displays impulsivity disorder as early as 3 months old, as described in early symptomatic HD patients, thus adding to the face validity of the rat model.

  10. Modeling CICR in rat ventricular myocytes: voltage clamp studies

    PubMed Central

    2010-01-01

    Background The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR) in cardiac myocytes, with voltage clamp (VC) studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect Ca2+ loading of the sarcoplasmic reticulum (SR), and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR Ca2+ release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic Ca2+ concentration ([Ca2+]myo). Methods The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU), in which resides the mechanistic basis of CICR). The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed Ca2+ channels (trigger-channel and release-channel). It releases Ca2+ flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[Ca2+]myo. Results Our model reproduces measured VC data published by several laboratories, and generates graded Ca2+ release at high Ca2+ gain in a homeostatically-controlled environment where [Ca2+]myo is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR Ca2+ release, its activation by trigger Ca2+, and its refractory characteristics

  11. A PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODEL FOR TRICHLOROETHYLENE WITH SPECIFICITY FOR THE LONG EVANS RAT

    EPA Science Inventory

    A PBPK model for TCE with specificity for the male LE rat that accurately predicts TCE tissue time-course data has not been developed, although other PBPK models for TCE exist. Development of such a model was the present aim. The PBPK model consisted of 5 compartments: fat; slowl...

  12. Deferoxamine and eflornithine (DL-alpha-difluoromethylornithine) in a rat model of Pneumocystis carinii pneumonia.

    PubMed Central

    Clarkson, A B; Sarić, M; Grady, R W

    1990-01-01

    The iron chelator deferoxamine and the polyamine biosynthesis inhibitor eflornithine (DL-alpha-difluoromethylornithine) were examined for anti-Pneumocystis carinii activity in the rat model of P. carinii pneumonia. The activity of deferoxamine at 250, 500, and 1,000 mg/kg given intraperitoneally provides evidence that iron chelation is a promising novel approach to P. carinii chemotherapy. Results with eflornithine at 2, 3, and 4% in drinking water confirm and extend previously reported activity in the rat model. PMID:2285303

  13. Probucol inhibits LPS-induced microglia activation and ameliorates brain ischemic injury in normal and hyperlipidemic mice

    PubMed Central

    Jung, Yeon Suk; Park, Jung Hwa; Kim, Hyunha; Kim, So Young; Hwang, Ji Young; Hong, Ki Whan; Bae, Sun Sik; Choi, Byung Tae; Lee, Sae-Won; Shin, Hwa Kyoung

    2016-01-01

    Aim: Increasing evidence suggests that probucol, a lipid-lowering agent with anti-oxidant activities, may be useful for the treatment of ischemic stroke with hyperlipidemia via reduction in cholesterol and neuroinflammation. In this study we examined whether probucol could protect against brain ischemic injury via anti-neuroinflammatory action in normal and hyperlipidemic mice. Methods: Primary mouse microglia and murine BV2 microglia were exposed to lipopolysaccharide (LPS) for 3 h, and the release NO, PGE2, IL-1β and IL-6, as well as the changes in NF-κB, MAPK and AP-1 signaling pathways were assessed. ApoE KO mice were fed a high-fat diet containing 0.004%, 0.02%, 0.1% (wt/wt) probucol for 10 weeks, whereas normal C57BL/6J mice received probucol (3, 10, 30 mg·kg-1·d-1, po) for 4 d. Then all the mice were subjected to focal cerebral ischemia through middle cerebral artery occlusion (MCAO). The neurological deficits were scored 24 h after the surgery, and then brains were removed for measuring the cerebral infarct size and the production of pro-inflammatory mediators. Results: In LPS-treated BV2 cells and primary microglial cells, pretreatment with probucol (1, 5, 10 μmol/L) dose-dependently inhibited the release of NO, PGE2, IL-1β and IL-6, which occurred at the transcription levels. Furthermore, the inhibitory actions of probucol were associated with the downregulation of the NF-κB, MAPK and AP-1 signaling pathways. In the normal mice with MCAO, pre-administration of probucol dose-dependently decreased the infarct volume and improved neurological function. These effects were accompanied by the decreased production of pro-inflammatory mediators (iNOS, COX-2, IL-1, IL-6). In ApoE KO mice fed a high-fat diet, pre-administration of 0.1% probucol significantly reduced the infarct volume, improved the neurological deficits following MCAO, and decreased the total- and LDL-cholesterol levels. Conclusion: Probucol inhibits LPS-induced microglia activation and

  14. Extended duration local anesthetic agent in a rat paw model.

    PubMed

    Ickowicz, D E; Golovanevski, L; Domb, A J; Weiniger, C F

    2014-07-01

    Encapsulated local anesthetics extend postoperative analgesic effect following site-directed nerve injection; potentially reducing postoperative complications. Our study aim was to investigate efficacy of our improved extended duration formulation - 15% bupivacaine in poly(DL-lactic acid co castor oil) 3:7 synthesized by ring opening polymerization. In vitro, around 70% of bupivacaine was released from the p(DLLA-CO) 3:7 after 10 days. A single injection of the optimal formulation of 15% bupivacaine-polymer or plain (0.5%) bupivacaine (control), was injected via a 22G needle beside the sciatic nerve of Sprague-Dawley rats under anesthesia; followed (in some animals) by a 1cm longitudinal incision through the skin and fascia of the paw area. Behavioral tests for sensory and motor block assessment were done using Hargreave's hot plate score, von Frey filaments and rearing count. The 15% bupivacaine formulation significantly prolonged sensory block duration up to at least 48 h. Following surgery, motor block was observed for 48 h following administration of bupivacaine-polymer formulation and rearing was reduced (returning to baseline after 48 h). No significant differences in mechanical nociceptive response were observed. The optimized bupivacaine-polymer formulation prolonged duration of local anesthesia effect in our animal model up to at least 48 h.

  15. Dynamics of myelin content decrease in the rat stroke model

    NASA Astrophysics Data System (ADS)

    Kisel, A.; Khodanovich, M.; Atochin, D.; Mustafina, L.; Yarnykh, V.

    2017-08-01

    The majority of studies were usually focused on neuronal death after brain ischemia; however, stroke affects all cell types including oligodendrocytes that form myelin sheath in the CNS. Our study is focused on the changes of myelin content in the ischemic core and neighbor structures in early terms (1, 3 and 10 days) after stroke. Stroke was modeled with middle cerebral artery occlusion (MCAo) in 15 male rats that were divided into three groups by time points after operation. Brain sections were histologically stained with Luxol Fast Blue (LFB) for myelin quantification. The significant demyelination was found in the ischemic core, corpus callosum, anterior commissure, whereas myelin content was increased in caudoputamen, internal capsule and piriform cortex compared with the contralateral hemisphere. The motor cortex showed a significant increase of myelin content on the 1st day and a significant decrease on the 3rd and 10th days after MCAo. These results suggest that stroke influences myelination not only in the ischemic core but also in distant structures.

  16. Interictal EEG discoordination in a rat seizure model.

    PubMed

    Neymotin, Samuel A; Lee, Heekyung; Fenton, André A; Lytton, William W

    2010-12-01

    Cognitive and psychiatric comorbidities are common and clinically important in medial temporal lobe epilepsy and are likely caused by ongoing abnormalities in brain activity. In addition, it is unclear how the dynamics of interictal brain activity in medial temporal lobe epilepsy contributes to the generation of seizures. To investigate these issues, the authors evaluated multisite interictal EEG from a perinatal excitotoxic, hippocampal lesion rat model of medial temporal lobe epilepsy. Sample entropy, an information theoretical measure, demonstrated decreased complexity at different time scales and across all channels in epileptic animals. However, higher-order multiarea measures showed evidence of increased variability in population correlation measures. This apparent paradox was resolved by noting that although the EEG from epileptic animals was overall more stereotyped, there were frequent periods where two or more brain areas "broke off" from ongoing brain activity in epileptic animals, producing decorrelations between areas. These decorrelations were particularly apparent across the midline, suggesting impairments of interhemispheric coordination, a form of interhemispheric diaschisis. Both the observed alterations could contribute to a reduction in brain functionality: an overall reduction in complexity and a failure of interhemispheric brain coordination, suggesting a breakdown in communication between hemispheres. The authors speculate that any tendency of areas to lose communication or break away from coordinated brain activity might predispose to seizures in these areas.

  17. 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.

  18. Therapeutic effect of sunitinib on diabetes mellitus related ovarian injury: an experimental rat model study.

    PubMed

    Erbas, Oytun; Pala, Halil Gursoy; Pala, Emel Ebru; Artunc Ulkumen, Burcu; Akman, Levent; Akman, Tulay; Oltulu, Fatih; Aktug, Huseyin; Yavasoglu, Altug

    2015-05-01

    The aim of our study is to investigate the effect of sunitinib on diabetes mellitus related-ovarian injury and fibrosis in rat models. An experimental diabetes mellitus model was created in 16 rats, and eight rats with normal blood glucose levels were included in control group (Group-1). The diabetic rats were divided into two groups:diabetic control group (water given) - Group-2 and sunitinib treatment group - Group-3. After four weeks, bilateral oophorectomy was performed and ovaries were examined histologically. The groups were compared by Student's t-test, analysis of variance (ANOVA) and Mann-Whitney's U-test. There was a significant increase in no-medication (water given) diabetic rat's ovary (Group-2) in terms of follicular degeneration, stromal degeneration, stromal fibrosis and NF-kappaB immune-expression compared with control group normal rats' ovary (Group-1) (p < 0.0001). Stromal degeneration (p = 0.04), stromal fibrosis (p = 0.01), follicular degeneration (p = 0.02), NF-kappaB immune-expression (p = 0.001) significantly decreased in sunitinib-treated diabetic rat's ovary (Group-3) when compared with no-medication (water given) diabetic rat's ovary (Group-2) (p < 0.05). When we used sunitinib in the treatment of diabetic rats, ovarian injury, fibrosis and NF-kappaB immunoexpression decreased significantly. The effects of sunitinib in rat models give hope to the improved treatment of premature ovarian failure due to diabetes mellitus in humans.

  19. Heterogeneous stock rats: a new model to study the genetics of renal phenotypes

    PubMed Central

    Solberg Woods, Leah C.; Stelloh, Cary; Regner, Kevin R.; Schwabe, Tiffany; Eisenhauer, Jessica

    2010-01-01

    Chronic kidney disease is a growing medical concern, with an estimated 25.6 million people in the United States exhibiting some degree of kidney injury and/or decline in kidney function. Animal models provide great insight into the study of the genetics of complex diseases. In particular, heterogeneous stock (HS) rats represent a unique genetic resource enabling rapid fine-mapping of complex traits. However, they have not been explored as a model to study renal phenotypes. To evaluate the usefulness of HS rats in the genetics of renal traits, a time course evaluation (weeks 8–40) was performed for several renal phenotypes. As expected, a large degree of variation was seen for most renal traits. By week 24, three (of 40) rats exhibited marked proteinuria that increased gradually until week 40 and ranged from 33.7 to 80.2 mg/24 h. Detailed histological analysis confirmed renal damage in these rats. In addition, several rats consistently exhibited significant hematuria (5/41). Interestingly, these rats were not the same rats that exhibited proteinuria, indicating that susceptibility to different types of kidney injury is likely segregating within the HS population. One HS rat exhibited unilateral renal agenesis (URA), which was accompanied by a significant degree of proteinuria and glomerular and tubulointerstitial injury. The parents of this HS rat were identified and bred further. Additional offspring of this pair were observed to exhibit URA at frequency between 40% and 60%. In summary, these novel data demonstrate that HS rats exhibit variation in proteinuria and other kidney-related traits, confirming that the model harbors susceptibility alleles for kidney injury and providing the basis for further genetic studies. PMID:20219828

  20. Comparative numerical modeling of inhaled micron-sized particle deposition in human and rat nasal cavities.

    PubMed

    Shang, Yidan; Dong, Jingliang; Inthavong, Kiao; Tu, Jiyuan

    2015-01-01

    Micron-sized particle deposition in anatomically realistic models of a rat and human nasal cavity was numerically investigated. A steady laminar inhalation flow rate was applied and particles were released from the outside air. Particles showing equivalent total particle deposition fractions were classified into low, medium and high inertial particle. Typical particle sizes are 2.5, 9 and 20 μm for the human model and 1, 2 and 3 μm for the rat model, respectively. Using a surface-mapping technique the 3D nasal cavity surface was "unwrapped" into a 2D domain and the particle deposition locations were plotted for complete visual coverage of the domain surface. The total surface area comparison showed that the surface area of the human nasal model was about ten times the size of the rat model. In contrast, the regional surface area percentage analysis revealed the olfactory region of the rat model was significantly larger than all other regions making up ∼55.6% of the total surface area, while that of the human nasal model only occupying 10.5%. Flow pattern comparisons showed rapid airflow acceleration was found at the nasopharynx region and the nostril region for the human and rat model, respectively. For the human model, the main passage is the major deposition region for micro-particles. While for the rat model, it is the vestibule. Through comparing the regional deposition flux between human and rat models, this study can contribute towards better extrapolation approach of inhalation exposure data between inter-subject species.

  1. A new agent for flap survival – Hippophae rhamnoides L. (sea buckthorn): An experimental study in rats

    PubMed Central

    Emsen, Ilteris Murat

    2005-01-01

    Hippophae rhamnoides L. (sea buckthorn) is a member of the Elaeagnaceae family, and is a temperate bush native to Europe and Asia. The antioxidant activity of H rhamnoides L. has been shown in vitro cell culture and animal studies. Different fractions of H rhamnoides L. fruits inhibit 2,2-azobis-(2,4 dimethylvaleronitrile) and ascorbate iron-induced lipid peroxidations in vitro. H rhamnoides L., as well as vitamin E, decrease the malondialdehyde content in hyperlipidemic rabbit serum-cultured smooth muscle cells. The aim of the present study was to investigate, in a rat model, the potential effect of H rhamnoides L. on survival of random pattern skin flaps. For this purpose, 30 Wistar Albino rats were used, and a McFarlane-type caudally based skin flap was created on the dorsum of the rat (2.5 cm × 8 cm). Rats were divided into three groups: one control (group A) and two treatment groups (groups B and C). H rhamnoides L. was administered orally to the experimental groups: group B received a single 15 mg/kg dose per day and group C received 15 mg/kg twice per day. The areas and lengths of flap necrosis were measured in each group. The extent of necrotic flap areas were evaluated as length and area of total flap area, and differences were studied by Student’s t tests. The areas and lengths of necrosis of skin flaps decreased depending on H rhamnoides L., but viability of the flaps treated with 15 mg/kg/day was not significantly different from the control group. The rats receiving H rhamnoides L. 15 mg/kg twice per day had the highest flap survival rate (P<0.001). In conclusion, H rhamnoides L. may have a dose-dependent effect to increase flap survival in random skin flaps. PMID:24227931

  2. Tissue Engineering to Repair Diaphragmatic Defect in a Rat Model

    PubMed Central

    Liao, G. P.; Vojnits, K.; Xue, H.; Aroom, K.; Meng, F.; Pan, H. Y.; Hetz, R. A.; Corkins, C. J.; Hughes, T. G.; Triolo, F.; Johnson, A.; Moise, Kenneth J.; Lally, K. P.

    2017-01-01

    Tissue engineering is an emerging strategy for repairing damaged tissues or organs. The current study explored using decellularized rat diaphragm scaffolds combined with human amniotic fluid-derived multipotent stromal cells (hAFMSC) to provide a scaffold, stem cell construct that would allow structural barrier function during tissue ingrowth/regeneration. We created an innovative cell infusion system that allowed hAFMSC to embed into scaffolds and then implanted the composite tissues into rats with surgically created left-sided diaphragmatic defects. Control rats received decellularized diaphragm scaffolds alone. We found that the composite tissues that combined hAFMSCs demonstrated improved physiological function as well as the muscular-tendon structure, compared with the native contralateral hemidiaphragm of the same rat. Our results indicate that the decellularized diaphragm scaffolds are a potential support material for diaphragmatic hernia repair and the composite grafts with hAFMSC are able to accelerate the functional recovery of diaphragmatic hernia. PMID:28928772

  3. Physiologically based Pharmacokinetic Modeling of 1,4-Dioxane in Rats, Mice, and Humans

    SciTech Connect

    Sweeney, Lisa M.; Thrall, Karla D.; Poet, Torka S.; Corley, Rick; Weber, Thomas J.; Locey, B. J.; Clarkson, Jacquelyn; Sager, S.; Gargas, M. L.

    2008-01-01

    ABSTRACT 1,4-Dioxane (CAS No. 123-91-1) is used primarily as a solvent or as a solvent stabilizer. It can cause lung, liver and kidney damage at sufficiently high exposure levels. Two physiologically-based pharmacokinetic (PBPK) models of 1,4-dioxane and its major metabolite, hydroxyethoxyacetic acid (HEAA), were published in 1990. These models have uncertainties and deficiencies that could be addressed and the model strengthened for use in a contemporary cancer risk assessment for 1,4-dioxane. Studies were performed to fill data gaps and reduce uncertainties pertaining to the pharmacokinetics of 1,4-dioxane and HEAA in rats, mice, and humans. Three types of studies were performed:partition coefficient measurements, blood time course in mice, and in vitro pharmacokinetics using rat, mouse, and human hepatocytes. Updated PBPK models were developed based on these new data and previously available data. The optimized rate of metabolism for the mouse was significantly higher than the value previously estimated. The optimized rat kinetic parameters were similar to those in the 1990 models. Only two human studies were identified. Model predictions were consistent with one study, but did not fit the second as well. In addition, a rat nasal exposure was completed. The results confirmed water directly contacts rat nasal tissues during drinking water under bioassays. Consistent with previous PBPK models, nasal tissues were not specifically included in the model. Use of these models will reduce the uncertainty in future 1,4-dioxane risk assessments.

  4. Physiologically based pharmacokinetic modeling of 1,4-Dioxane in rats, mice, and humans.

    PubMed

    Sweeney, Lisa M; Thrall, Karla D; Poet, Torka S; Corley, Richard A; Weber, Thomas J; Locey, Betty J; Clarkson, Jacquelyn; Sager, Shawn; Gargas, Michael L

    2008-01-01

    1,4-Dioxane (CAS No. 123-91-1) is used primarily as a solvent or as a solvent stabilizer. It can cause lung, liver, and kidney damage at sufficiently high exposure levels. Two physiologically based pharmacokinetic (PBPK) models of 1,4-dioxane and its major metabolite, hydroxyethoxyacetic acid (HEAA), were published in 1990. These models have uncertainties and deficiencies that could be addressed and the model strengthened for use in a contemporary cancer risk assessment for 1,4-dioxane. Studies were performed to fill data gaps and reduce uncertainties pertaining to the pharmacokinetics of 1,4-dioxane and HEAA in rats, mice, and humans. Three types of studies were performed: partition coefficient measurements, blood time course in mice, and in vitro pharmacokinetics using rat, mouse, and human hepatocytes. Updated PBPK models were developed based on these new data and previously available data. The optimized rate of metabolism for the mouse was significantly higher than the value previously estimated. The optimized rat kinetic parameters were similar to those in the 1990 models. Only two human studies were identified. Model predictions were consistent with one study, but did not fit the second as well. In addition, a rat nasal exposure was completed. The results confirmed water directly contacts rat nasal tissues during drinking water under bioassay conditions. Consistent with previous PBPK models, nasal tissues were not specifically included in the model. Use of these models will reduce the uncertainty in future 1,4-dioxane risk assessments.

  5. Effect of Ethanol on Fluoroquinolone Efficacy in a Rat Model of Pneumococcal Pneumonia

    PubMed Central

    Olsen, Keith M.; Gentry-Nielsen, Martha; Yue, Mei; Snitily, Mary U.; Preheim, Laurel C.

    2006-01-01

    This investigation compared the effect of ethanol on fluoroquinolone antibiotic efficacy and pharmacodynamics in an ethanol-fed rat model of pneumococcal pneumonia. Male Sprague-Dawley rats received a liquid diet containing 36% of total calories as ethanol. Paired controls (pair-fed controls) were fed a liquid diet without ethanol or received rat chow. Diets began 7 days before and continued for 10 days after transtracheal infections with 10 times the 50% lethal dose of type 3 Streptococcus pneumoniae. Beginning 18 h after infection, the rats received once daily subcutaneous phosphate-buffered saline, levofloxacin, moxifloxacin, or trovafloxacin at 50 or 100 mg/kg of body weight. White blood cell counts were determined, blood samples were collected for culture, and mortality was recorded. Additional rats were killed on day 5 for pharmacodynamic studies and quantitative cultures of bronchoalveolar lavage fluid. Bacteremia occurred by day 3 in 20 of 22 untreated rats. All 22 untreated rats died by day 9. Moxifloxacin treatment was effective in all diet groups at both the 50- and 100-mg/kg doses. In contrast, 50-mg/kg doses of levofloxacin and trovafloxacin improved survival in ethanol-fed rats but were ineffective in chow-fed rats. High-dose trovafloxacin at 100 mg/kg was associated with increased mortality in pair-fed rats. The free-fraction area under the concentration-time curve/MIC ratio exceeded 50 with all antibiotics in the ethanol group but dropped below 30 with levofloxacin and trovafloxacin in the pair- and chow-fed rats, with higher mortality. Achievement of adequate antibiotic-free fraction area under the concentration-time curve/MIC ratios helps overcome ethanol-induced immune defects induced in experimental pneumococcal pneumonia. PMID:16377688

  6. Pioglitazone treatment restores in vivo muscle oxidative capacity in a rat model of diabetes.

    PubMed

    Wessels, B; Ciapaite, J; van den Broek, N M A; Houten, S M; Nicolay, K; Prompers, J J

    2015-01-01

    To determine the effect of pioglitazone treatment on in vivo and ex vivo muscle mitochondrial function in a rat model of diabetes. Both the lean, healthy rats and the obese, diabetic rats are Zucker Diabetic Fatty (ZDF) rats. The homozygous fa/fa ZDF rats are obese and diabetic. The heterozygous fa/+ ZDF rats are lean and healthy. Diabetic Zucker Diabetic Fatty rats were treated with either pioglitazone (30 mg/kg/day) or water as a control (n = 6 per group), for 2 weeks. In vivo ¹H and ³¹P magnetic resonance spectroscopy was performed on skeletal muscle to assess intramyocellular lipid (IMCL) content and muscle oxidative capacity, respectively. Ex vivo muscle mitochondrial respiratory capacity was evaluated using high-resolution respirometry. In addition, several markers of mitochondrial content were determined. IMCL content was 14-fold higher and in vivo muscle oxidative capacity was 26% lower in diabetic rats compared with lean rats, which was, however, not caused by impairments of ex vivo mitochondrial respiratory capacity or a lower mitochondrial content. Pioglitazone treatment restored in vivo muscle oxidative capacity in diabetic rats to the level of lean controls. This amelioration was not accompanied by an increase in mitochondrial content or ex vivo mitochondrial respiratory capacity, but rather was paralleled by an improvement in lipid homeostasis, that is lowering of plasma triglycerides and muscle lipid and long-chain acylcarnitine content. Diminished in vivo muscle oxidative capacity in diabetic rats results from mitochondrial lipid overload and can be alleviated by redirecting the lipids from the muscle into adipose tissue using pioglitazone treatment. © 2014 John Wiley & Sons Ltd.

  7. Effect of ethanol on fluoroquinolone efficacy in a rat model of pneumococcal pneumonia.

    PubMed

    Olsen, Keith M; Gentry-Nielsen, Martha; Yue, Mei; Snitily, Mary U; Preheim, Laurel C

    2006-01-01

    This investigation compared the effect of ethanol on fluoroquinolone antibiotic efficacy and pharmacodynamics in an ethanol-fed rat model of pneumococcal pneumonia. Male Sprague-Dawley rats received a liquid diet containing 36% of total calories as ethanol. Paired controls (pair-fed controls) were fed a liquid diet without ethanol or received rat chow. Diets began 7 days before and continued for 10 days after transtracheal infections with 10 times the 50% lethal dose of type 3 Streptococcus pneumoniae. Beginning 18 h after infection, the rats received once daily subcutaneous phosphate-buffered saline, levofloxacin, moxifloxacin, or trovafloxacin at 50 or 100 mg/kg of body weight. White blood cell counts were determined, blood samples were collected for culture, and mortality was recorded. Additional rats were killed on day 5 for pharmacodynamic studies and quantitative cultures of bronchoalveolar lavage fluid. Bacteremia occurred by day 3 in 20 of 22 untreated rats. All 22 untreated rats died by day 9. Moxifloxacin treatment was effective in all diet groups at both the 50- and 100-mg/kg doses. In contrast, 50-mg/kg doses of levofloxacin and trovafloxacin improved survival in ethanol-fed rats but were ineffective in chow-fed rats. High-dose trovafloxacin at 100 mg/kg was associated with increased mortality in pair-fed rats. The free-fraction area under the concentration-time curve/MIC ratio exceeded 50 with all antibiotics in the ethanol group but dropped below 30 with levofloxacin and trovafloxacin in the pair- and chow-fed rats, with higher mortality. Achievement of adequate antibiotic-free fraction area under the concentration-time curve/MIC ratios helps overcome ethanol-induced immune defects induced in experimental pneumococcal pneumonia.

  8. Eldecalcitol prevents endothelial dysfunction in postmenopausal osteoporosis model rats.

    PubMed

    Serizawa, Kenichi; Yogo, Kenji; Tashiro, Yoshihito; Takeda, Satoshi; Kawasaki, Ryohei; Aizawa, Ken; Endo, Koichi

    2016-02-01

    Postmenopausal women have high incidence of cardiovascular events as estrogen deficiency can cause endothelial dysfunction. Vitamin D is reported to be beneficial on endothelial function, but it remains controversial whether vitamin D is effective for endothelial dysfunction under the treatment for osteoporosis in postmenopausal women. The aim of this study was to evaluate the endothelial protective effect of eldecalcitol (ELD) in ovariectomized (OVX) rats. ELD (20  ng/kg) was orally administrated five times a week for 4 weeks from 1 day after surgery. After that, flow-mediated dilation (FMD) as an indicator of endothelial function was measured by high-resolution ultrasound in the femoral artery of living rats. ELD ameliorated the reduction of FMD in OVX rats. ELD inhibited the increase in NOX4, nitrotyrosine, and p65 and the decrease in dimer/monomer ratio of nitric oxide synthase in OVX rat femoral arteries. ELD also prevented the decrease in peroxisome proliferator-activated receptor gamma (PPARγ) in femoral arteries and cultured endothelial cells. Although PPARγ is known to inhibit osteoblastogenesis, ELD understandably increased bone mineral density of OVX rats without increase in PPARγ in bone marrow. These results suggest that ELD prevented the deterioration of endothelial function under condition of preventing bone loss in OVX rats. This endothelial protective effect