THERMOREGULATION AT A HIGH AMBIENT TEMPERATURE FOLLOWING THE ORAL ADMINISTRATION OF ETHANOL IN THE RAT

EPA Science Inventory

This study was designed to assess the thermoregulatory mechanisms responsible for the elevation in body temperature following ethanol administration when exposed to a high ambient temperature (Ta). ale rats of the Fischer 344 strain were gavaged with 20% ethanol at doses of 0, 2....

Transgenic rats with green, red, and blue fluorescence: powerful tools for bioimaging, cell trafficking, and differentiation

NASA Astrophysics Data System (ADS)

Murakami, Takashi; Kobayashi, Eiji

2005-04-01

The rat represents a perfect animal for broadening medical experiments, because its physiology has been well understood in the history of experimental animals. In addition, its larger body size takes enough advantage for surgical manipulation, compared to the mouse. Many rat models mimicking human diseases, therefore, have been used in a variety of biomedical studies including physiology, pharmacology, transplantation, and immunology. In an effort to create the specifically designed rats for biomedical research and regenerative medicine, we have developed the engineered rat system on the basis of transgenic technology and succeeded in establishing various transgenic rat strains. The transgenic rats with green fluorescent protein (GFP) were generated in the two different strains (Wistar and Lewis), in which GFP is driven under the chicken beta-actin promoter and cytomegalovirus enhancer (CAG promoter). Their GFP expression levels were different in each organ, but the Lewis line expressed GFP strongly and ubiquitously in most of the organs compared with that of Wistar. For red fluorescence, DsRed2 was transduced to the Wistar rats: one line specifically expresses DsRed2 in the liver under the mouse albumin promoter, another is designed for the Cre/LoxP system as the double reporter rat (the initial DsRed2 expression turns on GFP in the presence of Cre recombinase). LacZ-transgenic rats represent blue color, and LacZ is driven the CAG (DA) or ROSA26 promoter (Lewis). Our unique transgenic rats" system highlights the powerful performance for the elucidation of many cellular processes in regenerative medicine, leading to innovative medical treatments.

Chronic preclinical safety evaluation of EPO-018B, a pegylated peptidic erythropoiesis-stimulating agent in monkeys and rats

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

Gong, Xue-Lian; Gu, Xiao-Lei

EPO-018B, a synthetic peptide-based erythropoiesis stimulating agent (ESA), is mainly designed for treatment of anemia caused by chronic renal failure and chemotherapy against cancer. It overcomes the deficiencies of currently approved ESA, including the frequent administration of temperature-sensitive recombinant protein and anti-EPO antibody-mediated pure red cell aplasia (PRCA). This study was designed to evaluate the potential chronic toxicity of EPO-018B. Subcutaneous administration doses were designed as 0, 0.2, 1 and 10 mg/kg for six months for 160 rats (20/gender/group) and 0, 0.3, 3 and 20 mg/kg for nine months for 32 monkeys (4/gender/group) once every three weeks. The vehicles receivedmore » the same volume of physiological saline injection. All animals survived to the scheduled necropsies after six weeks (for rats) and fourteen weeks (for monkeys) recovery period, except for the two high-dose female rats and two high-dose male monkeys, which were considered related to the increased RBCs, chronic blood hyperviscosity and chronic cardiac injury. EPO-018B is supposed to be subcutaneously injected once every month and the intended human therapeutic dose is 0.025 mg/kg. The study findings at 0.2 mg/kg for rats and 0.3 mg/kg for monkeys were considered to be the study NOAEL (the no observed adverse effect level), which were more than ten times the intended human therapeutic dose. Higher doses caused adverse effects related to the liver toxicity, cardiotoxicity, appearance of neutralizing antibodies of EPO-018B and the decrease of serum glucose and cholesterol. Most treatment-induced effects were reversible or revealed ongoing recovery upon the discontinuation of treatment. The sequelae occurred in rats and monkeys were considered secondary to exaggerated pharmacology and would less likely occur in the intended patient population. As to the differences between human beings and animals, the safety of EPO-018B need to be further confirmed in the future clinical studies. - Highlights: • EPO-018B is a newly developed synthetic peptide-based ESA. • The evaluation contained studies of 6 months in rats and 9 months in monkeys. • The safety studies provided further evidences in future clinical trials. • Most toxic effects were reversible and need more evidences in clinical studies.« less

Provision of food and water in rodent whole body plethysmography safety pharmacology respiratory studies - Impact on animal welfare and data quality.

PubMed

Grant, Claire; Marks, Louise; Prior, Helen

2017-11-01

We evaluated the feasibility of providing food and water to rodents during whole body plethysmography (WBP) studies as a welfare improvement to standard conditions. Male Han Wistar rats or CD1 mice (n=8) were placed in WBP chambers and respiratory parameters recorded for approximately 6h on four separate occasions. On each occasion the animals were exposed to a different plethysmography chamber environment using a randomised design: no food/water (the standard conditions), water bottle, hydrating gel and wet food. In a further session, rats (n=8) were administered theophylline, or vehicle and respiratory parameters measured in the plethysmography chamber containing wet food. Respiratory parameters of rats were not significantly altered by the provision of water or food. Providing wet food resulted in reduced body weight loss. Administration of theophylline caused the expected increase in respiratory rate. When mice were given access to hydrating gel or wet food the respiratory parameters were significantly affected; respiratory rate and tidal volume were increased. Providing wet food resulted in reduced bodyweight loss. The provision of food and water did not impact on respiratory parameters in rats placed in WBP chambers. When provided with wet food, rats lost less bodyweight. Therefore, to improve welfare conditions for rats during WBP respiratory studies wet food should be provided when appropriate to the study design. In mice, provision of food and water led to changes in respiratory parameters, therefore these improvements in welfare conditions are not suitable for mice. Copyright © 2017. Published by Elsevier Inc.

Pre-exposure to wheel running disrupts taste aversion conditioning.

PubMed

Salvy, Sarah-Jeanne; Pierce, W David; Heth, Donald C; Russell, James C

2002-05-01

When rats are given access to a running wheel after drinking a flavored solution, they subsequently drink less of that flavor solution. It has been suggested that running produces a conditioned taste aversion (CTA). This study explored whether CTA is eliminated by prior exposure to wheel running [i.e., unconditioned stimulus (UCS) pre-exposure effect]. The rats in the experimental group (UW) were allowed to wheel run for 1 h daily for seven consecutive days of pre-exposure. Rats in the two other groups had either access to locked wheels (LW group) or were maintained in their home cages (HC group) during the pre-exposure days. All rats were then exposed to four paired and four unpaired trials using a "ABBAABBA" design. Conditioning trials were composed of one flavored liquid followed by 60-min access to wheel running. For the unpaired trials, rats received a different flavor not followed by the opportunity to run. All rats were then initially tested for water consumption followed by tests of the two flavors (paired or unpaired) in a counterbalanced design. Rats in the UW group show no CTA to the liquid paired with wheel running, whereas LW and HC groups developed CTA. These results indicate that pre-exposure to wheel running (i.e., the UCS), eliminates subsequent CTA.

Positioning Vascularized Composite Allotransplantation within the Spectrum of Transplantation

DTIC Science & Technology

2016-10-01

In the third year of this grant, we made significant progress using our rat osteomyocutaneous flap model to study the effect of rejection on...submitted in the first quarter of year 4. We have also made significant progress in using the Vevo 2100 in imaging vasculopathy in the rat model, as...transplant biopsy timepoints, with multiple slides per timepoint to scan, as well as selected slides of the rat hind-limb project that are designated for

The role of hepatic transport and metabolism in the interactions between pravastatin or repaglinide and two rOatp inhibitors in rats.

PubMed

Badolo, Lassina; Bundgaard, Christoffer; Garmer, Mats; Jensen, Bente

2013-07-16

A change in the function or expression of hepatic drug transporters may have significant effect on the efficacy or safety of orally administered drugs. Although a number of clinical drug-drug interactions associated with hepatic transport proteins have been reported, in practice it is not always straightforward to discriminate other pathways (e.g. drug metabolism) from being involved in these interactions. The present study was designed to assess the interactions between organic anion transporting polypeptide (Oatp) substrates (pravastatin or repaglinide) and inhibitors (spironolactone or diphenhydramine) in vivo in rats. The mechanisms behind the interactions were then investigated using in vitro tools (isolated hepatocytes and rat liver microsomes). The results showed a significant increase in the systemic exposures of pravastatin (2.5-fold increase in AUC) and repaglinide (1.8-fold increase in AUC) after co-administration of spironolactone to rats. Diphenhydramine increased the AUC of repaglinide by 1.4-fold. The in vivo interactions observed in rats between Oatp substrates and inhibitors may a priori be classified as transport-mediated drug-drug interactions. However, mechanistic studies performed in vitro using both isolated rat hepatocytes and rat liver microsomes showed that the interaction between pravastatin and spironolactone may be solely linked to the inhibition of pravastatin uptake in liver. On the contrary, the inhibition of cytochrome P450 seemed to be the reason for the interactions observed between repaglinide and spironolactone. Although the function and structure of transport proteins may vary between rats and humans, the approach used in the present study can be applied to humans and help to understand the role of drug transport and drug metabolism in a given drug-drug interaction. This is important to predict and mitigate the risk of drug-drug interactions for a candidate drug in pre-clinical development, it is also important for the optimal design of drug-drug interactions studies in the clinic. Copyright © 2013 Elsevier B.V. All rights reserved.

Novel non-contact retina camera for the rat and its application to dynamic retinal vessel analysis

PubMed Central

Link, Dietmar; Strohmaier, Clemens; Seifert, Bernd U.; Riemer, Thomas; Reitsamer, Herbert A.; Haueisen, Jens; Vilser, Walthard

2011-01-01

We present a novel non-invasive and non-contact system for reflex-free retinal imaging and dynamic retinal vessel analysis in the rat. Theoretical analysis was performed prior to development of the new optical design, taking into account the optical properties of the rat eye and its specific illumination and imaging requirements. A novel optical model of the rat eye was developed for use with standard optical design software, facilitating both sequential and non-sequential modes. A retinal camera for the rat was constructed using standard optical and mechanical components. The addition of a customized illumination unit and existing standard software enabled dynamic vessel analysis. Seven-minute in-vivo vessel diameter recordings performed on 9 Brown-Norway rats showed stable readings. On average, the coefficient of variation was (1.1 ± 0.19) % for the arteries and (0.6 ± 0.08) % for the veins. The slope of the linear regression analysis was (0.56 ± 0.26) % for the arteries and (0.15 ± 0.27) % for the veins. In conclusion, the device can be used in basic studies of retinal vessel behavior. PMID:22076270

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

PubMed

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

2004-01-15

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

INTEGRATED DISINFECTION BY-PRODUCTS (DBP) MIXTURES RESEARCH: GENE EXPRESSION ALTERATIONS IN PRIMARY RAT HEPATOCYTE CULTURES EXPOSED TO DBP MIXTURES FORMED BY CHLORINATION AND OZONATION/POSTCHLORINATION

EPA Science Inventory

What is the study?
This study was designed to provide data on the in vitro toxicity of water concentrates containing complex mixtures of DBPs. Rat hepatocytes in primary culture were exposed for 24 hr to full strength, 1:10 or 1:20 dilutions of chlorination or ozonation/chl...

Gender differences in CMS and the effects of antidepressant venlafaxine in rats.

PubMed

Xing, Yanli; He, Jie; Hou, Jian; Lin, Fei; Tian, Jingwei; Kurihara, Hiroshi

2013-11-01

Gender differences in susceptibility to chronic mild stress (CMS) and effects of venlafaxine in rats have been investigated in the current study. Male and female SD rats were exposed to CMS or CMS plus chronic venlafaxine administration (10mg/kg, 21days) in order to study depressive behavior in rats. Rats were tested in open field test and sucrose preference test to figure out gender differences in behavior. Then serum corticosterone and the expression of FKBP5 in hippocampus of rats were detected to explore the possible mechanism. The results showed that the CMS impact on behavioral parameters and corticosterone levels and response to venlafaxine were gender dependent. Female rats appeared more vulnerable in the dysregulation of HPA axis to CMS. Venlafaxine treatment normalized depressive-like behavior in both gender. However, venlafaxine treated male rats exhibited better improved explore behavior and anhedonia. FKBP5 might be involved in the explanation of gender differences in CMS and venlafaxine treatment. Male and female rats respond differently to chronic stress and venlafaxine continuous treatment. This results have guiding meaning in design of trials related to stress induced depression. Copyright © 2013 Elsevier Ltd. All rights reserved.

Role of ATP-sensitive potassium channels in the piracetam induced blockade of opioid effects.

PubMed

Rehni, Ashish K; Singh, Nirmal; Jindal, Seema

2007-12-01

The present study has been designed to investigate the effect of piracetam on morphine/ buprenorphine-induced antinociception in rats and effect of piracetam on morphine or minoxidil induced relaxation in KCl-precontracted isolated rat aortic ring preparation. Nociceptive threshold was measured by the tail flick test in rats. The cumulative dose responses of morphine or minoxidil were recorded in KCl-precontracted isolated rat aortic ring preparation. Piracetam attenuated buprenorphine-induced antinociception in rats. Piracetam significantly reduced the morphine and minoxidil induced relaxation in KCl precontracted isolated rat aortic ring preparation suggesting that piracetam interferes with opioid receptor and ATP-sensitive potassium channel (KATP) opener mediated responses in vitro. Thus, it may be suggested that piracetam attenuates opioid effects by an opioid receptor-KATP channel linked mechanism.

Dietary folate and choline status differentially affect lipid metabolism and behavior-mediated neurotransmitters in young rats

USDA-ARS?s Scientific Manuscript database

The relationship between choline and folate metabolisms is an important issue due to the essential role of these nutrients in brain plasticity and cognitive functions. Present study was designed to investigate whether modification of the dietary folate-choline status in young rats would affect brain...

STRUCTURE ACTIVITY RELATIONSHIP OF PHTHALATE ESTERS TO INHIBITED FETAL TESTICULAR TESTOSTERONE PRODUCTION IN THE SPRAGUE DAWLEY RAT

EPA Science Inventory

Several of the phthalate esters (widely used as plasticizers of polyvinyl chloride and other applications) have been shown to inhibit fetal testicular testosterone (T) production and Insl3 mRNA in the laboratory rat. The current study was designed to define the dose response of 7...

Neuromuscular junction formation between human stem-cell-derived motoneurons and rat skeletal muscle in a defined system.

PubMed

Guo, Xiufang; Das, Mainak; Rumsey, John; Gonzalez, Mercedes; Stancescu, Maria; Hickman, James

2010-12-01

To date, the coculture of motoneurons (MNs) and skeletal muscle in a defined in vitro system has only been described in one study and that was between rat MNs and rat skeletal muscle. No in vitro studies have demonstrated human MN to rat muscle synapse formation, although numerous studies have attempted to implant human stem cells into rat models to determine if they could be of therapeutic use in disease or spinal injury models, although with little evidence of neuromuscular junction (NMJ) formation. In this report, MNs differentiated from human spinal cord stem cells, together with rat skeletal myotubes, were used to build a coculture system to demonstrate that NMJ formation between human MNs and rat skeletal muscles is possible. The culture was characterized by morphology, immunocytochemistry, and electrophysiology, while NMJ formation was demonstrated by immunocytochemistry and videography. This defined system provides a highly controlled reproducible model for studying the formation, regulation, maintenance, and repair of NMJs. The in vitro coculture system developed here will be an important model system to study NMJ development, the physiological and functional mechanism of synaptic transmission, and NMJ- or synapse-related disorders such as amyotrophic lateral sclerosis, as well as for drug screening and therapy design.

Red algae (Gelidium amansii) reduces adiposity via activation of lipolysis in rats with diabetes induced by streptozotocin-nicotinamide.

PubMed

Yang, Tsung-Han; Yao, Hsien-Tsung; Chiang, Meng-Tsan

2015-12-01

Gelidium amansii (GA) is an edible red algae that is distributed mainly in northeastern Taiwan. This study was designed to investigate the effects of GA on plasma glucose, lipids, and adipocytokines in rats with streptozotocin-nicotinamide-induced diabetes. Rats were divided into four groups: (1) rats without diabetes fed a high-fat diet (control group); (2) rats with diabetes fed a high-fat diet; (3) rats with diabetes fed a high-fat diet with thiazolidinedione in the diet; and (4) rats with diabetes fed a high-fat diet and GA. The experimental diet and drinking water were available ad libitum for 11 weeks. After the 11-week feeding study, plasma glucose, triglyceride, and cholesterol concentrations were lower in rats with diabetes fed the GA diet than in animals with diabetes fed the control diet. In addition, cholesterol and triglyceride excretion were significantly higher in rats with diabetes fed the GA diet. Moreover, GA feeding induced lipolysis in both paraepididymal and perirenal adipose tissues. Adipose tissue (paraepididymal and perirenal) weight and triglyceride contents were lower after GA treatment. Plasma adipocytokines including tumor necrosis factor-alpha, interleukin-6, and plasminogen activator inhibitor-1 were reduced by GA feeding in rats with diabetes. The results of the current study suggest that GA feeding may regulate plasma glucose and lipid levels and prevent adipose tissue accumulation in rats with diabetes. Copyright © 2015. Published by Elsevier B.V.

Orexins Mediate Sex Differences in the Stress Response and in Cognitive Flexibility.

PubMed

Grafe, Laura A; Cornfeld, Amanda; Luz, Sandra; Valentino, Rita; Bhatnagar, Seema

2017-04-15

Women are twice as likely as men to experience stress-related psychiatric disorders. The biological basis of these sex differences is poorly understood. Orexins are altered in anxious and depressed patients. Using a rat model of repeated stress, we examined whether orexins contribute to sex differences in outcomes relevant to stress-related psychiatric diseases. Behavioral, neural, and endocrine habituation to repeated restraint stress and subsequent cognitive flexibility was examined in adult male and female rats. In parallel, orexin expression and activation were determined in both sexes, and chromatin immunoprecipitation was used to determine transcription factors acting at the orexin promoter. Designer receptors exclusively activated by designer drugs were used to inhibit orexin activation throughout repeated restraint to determine if the stress-related impairments in female rats could be reduced. Female rats exhibited impaired habituation to repeated restraint with subsequent deficits in cognitive flexibility compared with male rats. Increased orexin expression and activation were observed in female rats compared with male rats. The higher expression of orexin messenger RNA in female rats was due to actions of glucocorticoid receptors on the orexin promoter, as determined by chromatin immunoprecipitation. Inhibition of orexins using designer receptors exclusively activated by designer drugs in female rats throughout repeated restraint abolished their heightened hypothalamic-pituitary-adrenal responsivity and reduced stress-induced cognitive impairments. Orexins mediate the impairments in adaptations to repeated stress and in subsequent cognitive flexibility exhibited by female rats and provide evidence for a broader role for orexins in mediating functions relevant to stress-related psychiatric diseases. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The Presence Of Rat And House Sanitation Associated With Leptospira sp. Bacterial Infection In Rats (A Cross Sectional Study In Semarang, Central Java Province, Indonesia)

NASA Astrophysics Data System (ADS)

Setiyani, Endang; Martini, Martini; Saraswati, Lintang Dian

2018-02-01

The Gajah Mungkur sub-district in Semarang, Indonesia had highest leptospirosis cases (reported in human with seven infected and one dead) in 2015. The purpose of this study was to analyze the association between house sanitation and density of rats with Leptospira sp. infection in rats. The study design was cross sectional observational analytic. The number of 308 trapswere placed in study sites over three consecutive nights afterwards. Every houses were placed with four traps, inside and outside. Trapped rats were anesthetized with atropine dose from 0.02 to 0.05 mg/kg body weight of rats continued with Ketamine HCL dose of 50-100 mg/kg body weight of rats by injecting in the thick thigh muscle of it. After that, identification of rats by species and gender then continues with surgery in which a kidney sample was taken to confirm the presence of bacteria Leptospirasp using PCR techniques. The trap installed in 77 houses which later had further observation on house sanitation which includes the existence of a pile of used goods, food storage, garbage can, and the presence of the ceiling, windows and other ventilation.Data was analyzed using distribution frequency and bivariate chi-square test. We had 100 rats captured with live traps as the samples.The proportion of Rattusnorvegicuswas 27% (14.8% positive Leptospira sp.infection) and Rattustanezumi 73% (11%positive Leptospira sp.infection). The proportion of male and female rats were almost equal. The statistic test result was significant between the density of rats (p = 0.0001, OR 12.833, 95%CI: 1.565-105.261) and sex of rats (p = 0.019, OR 0.095, 95%CI: 0.012-0.769) with Leptospira sp. infection in rats. The number of rats may increase the infection of Leptospirasp., especially female rats and poor condition of house sanitation. It is recommended to improve house sanitation and regularly trapping rats.

Studies on distribution of para-methoxymethamphetamine (PMMA) designer drug in rats using gas chromatography-mass spectrometry.

PubMed

Rohanova, Miroslava; Balikova, Marie

2009-04-01

para-Methoxymethamphetamine (PMMA) is an abused psychedelic compound with reports of several intoxications and deaths after ingestion. However, its pharmacokinetics based on a controlled study is unknown and only partial information on its biotransformation is available. Our experimental study was designed for the time disposition profile of PMMA and its metabolites para-methoxyamphetamine (PMA), para-hydroxymethamphetamine (OH-MAM) and para-hydroxyamphetamine (OH-AM) in blood and biological tissues in rats after the bolus subcutaneous dose 40 mg/kg using a validated GC-MS method. The experimental results ascertained could be useful for subsequent evaluation of PMMA psychotropic or neurotoxic effects and the diagnostic concern of intoxication.

Team-Based Learning in a Community Health Nursing Course: Improving Academic Outcomes.

PubMed

Miles, Jane M; Larson, Kim L; Swanson, Melvin

2017-07-01

Population health concepts, such as upstream thinking, present challenging ideas to undergraduate nursing students grounded in an acute care orientation. The purpose of this study was to describe how team-based learning (TBL) influenced academic outcomes in a community health nursing course. A descriptive correlational design examined the relationship among student scores on individual readiness assurance tests (iRATs), team readiness assurance tests (tRATs), and the final examination. The sample included 221 nursing students who had completed the course. A large positive correlation was found between iRAT and final examination scores. For all students, the mean tRAT score was higher than the mean iRAT score. A moderate positive correlation existed between tRAT and final examination scores. The study contributes to understanding the effects of TBL pedagogy on student academic outcomes in nursing education. TBL is a valuable teaching method in a course requiring the application of challenging concepts. [J Nurs Educ. 2017;56(7):425-429.]. Copyright 2017, SLACK Incorporated.

Further Studies on Antioxidant Potential and Protection of Pancreatic β-Cells by Embelia ribes in Experimental Diabetes

PubMed Central

Bhandari, Uma; Jain, Neeti; Pillai, K. K.

2007-01-01

This study was designed to examine the antioxidant defense by ethanolic extract of Embelia ribes on streptozotocin-(40 mg/kg, intravenously, single-injection) induced diabetes in Wistar rats. Forty days of oral feeding the extract (100 mg/kg and 200 mg/kg) to diabetic rats resulted in significant (P < .01) decrease in blood glucose, blood glycosylated haemoglobin, serum lactate dehydrogenase, creatine kinase, and increase in blood glutathione levels as compared to pathogenic diabetic rats. Further, the extract also significantly (P < .01) decreased the pancreatic thiobarbituric acid-reactive substances (TBARS) levels and significantly (P < .01) increased the superoxide dismutase, catalase, and glutathione levels as compared to above levels in pancreatic tissue of pathogenic diabetic rats. The islets were shrunken in diabetic rats in comparison to normal rats. In the drug-treated diabetic rats, there was expansion of islets. The results of test drug were comparable to gliclazide (25 mg/kg, daily), a standard antihyperglycemic agent. The study concludes that Embelia ribes enhances the antioxidant defense against reactive oxygen species produced under hyperglycemic condition and this protects β-cells against loss, and exhibit antidiabetic property. PMID:17641739

A Novel Interactive Exoskeletal Robot for Overground Locomotion Studies in Rats.

PubMed

Song, Yun Seong; Hogan, Neville

2015-07-01

This paper introduces a newly developed apparatus, Iron Rat, for locomotion research in rodents. Its main purpose is to allow maximal freedom of voluntary overground movement of the animal while providing forceful interaction to the hindlimbs. Advantages and challenges of the proposed exoskeletal apparatus over other existing designs are discussed. Design and implementation challenges are presented and discussed, emphasizing their implications for free, voluntary movement of the animal. A live-animal experiment was conducted to assess the design. Unconstrained natural movement of the animal was compared with its movement with the exoskeletal module attached. The compact design and back-drivable implementation of this apparatus will allow novel experimental manipulations that may include forceful yet compliant dynamic interaction with the animal's overground locomotion.

Cytotoxic effect of aspartame (diet sweet) on the histological and genetic structures of female albino rats and their offspring.

PubMed

Abd Elfatah, Azza A M; Ghaly, Inas S; Hanafy, Safaa M

2012-10-01

The present study evaluated the effect of aspartame intake on the histological and genetic structures of mother albino rats and their offspring. Sixty adult female albino rats and 180 of their offspring were equally divided into two groups (control and treated), each group divided into three subgroups. Each subgroup consisted of 10 pregnant rats and 30 of their offspring. The experimental design divided into three periods: (1) the gestation period (subgroup one), (2) the gestation period and three weeks after delivery (subgroup two) and (3) animals in the third subgroup treated as subgroup two then left till the end of the ninth week after delivery. Each pregnant rat in the treated subgroups was given a single daily dose of 1 mL aspartame solution (50.4 mg) by gastric gavage throughout the time intervals of experimental design. At the end of each experimental period for control and treated subgroups, the liver of half of both control and treated groups were subjected for histological study while the liver and bone marrow of the other halves were subjected for cytogenetic studies. Body weight of both groups were recorded individually twice weekly in the morning before offering the diet. The results revealed that the rats and their offspring in the subgroups of control animals showed increases in body weight, normal histological sections, low chromosomal aberration and low DNA fragmentation. The treated animals in the three subgroups rats and their offspring revealed decreases in body weight, high histological lesions, increases in the chromosomal aberration and DNA fragmentation compared with control groups. In conclusion, the consumption of aspartame leads to histopathological lesions in the liver and alterations of the genetic system in the liver and bone marrow of mother albino rats and their offspring. These toxicological changes were directly proportional to the duration of its administration and improved after its withdrawal.

Green tea polyphenols mitigate bone loss of female rats in a chronic inflammation-induced bone loss model

USDA-ARS?s Scientific Manuscript database

The purpose of this study was to explore bioavailability, efficacy, and molecular mechanisms of green tea polyphenols (GTP) related to preventing bone loss in rats with chronic inflammation. A 2 (placebo vs. lipopolysaccharide, LPS) × 2 (no GTP vs. 0.5% GTP in drinking water) factorial design using ...

A novel vascular clip design for the reliable induction of 2-kidney, 1-clip hypertension in the rat

PubMed Central

Chelko, Stephen P.; Schmiedt, Chad W.; Lewis, Tristan H.; Lewis, Stephen J.

2012-01-01

The 2-kidney, 1-clip (2K1C) model has provided many insights into the pathogenesis of renovascular hypertension. However, studies using the 2K1C model often report low success rates of hypertension, with typical success rates of just 40–60%. We hypothesized that these low success rates are due to fundamental design flaws in the clips traditionally used in 2K1C models. Specifically, the gap widths of traditional silver clips may not be maintained during investigator handling and these clips may also be easily dislodged from the renal artery following placement. Therefore, we designed and tested a novel vascular clip possessing design features to maintain both gap width and position around the renal artery. In this initial study, application of these new clips to the left renal artery produced reliable and consistent levels of hypertension in rats. Nine-day application of clips with gap widths of 0.27, 0.25, and 0.23 mm elicited higher mean arterial blood pressures of 112 ± 4, 121 ± 6, and 135 ± 7 mmHg, respectively (n = 8 for each group), than those of sham-operated controls (95 ± 2 mmHg, n = 8). Moreover, 8 out of 8 rats in each of the 0.23 and 0.25 mm 2K1C groups were hypertensive, whereas 7 out of 8 rats in the 0.27 mm 2K1C group were hypertensive. Plasma renin concentrations were also increased in all 2K1C groups compared with sham-operated controls. In summary, this novel clip design may help eliminate the large degree of unreliability commonly encountered with the 2K1C model. PMID:22074718

A novel vascular clip design for the reliable induction of 2-kidney, 1-clip hypertension in the rat.

PubMed

Chelko, Stephen P; Schmiedt, Chad W; Lewis, Tristan H; Lewis, Stephen J; Robertson, Tom P

2012-02-01

The 2-kidney, 1-clip (2K1C) model has provided many insights into the pathogenesis of renovascular hypertension. However, studies using the 2K1C model often report low success rates of hypertension, with typical success rates of just 40-60%. We hypothesized that these low success rates are due to fundamental design flaws in the clips traditionally used in 2K1C models. Specifically, the gap widths of traditional silver clips may not be maintained during investigator handling and these clips may also be easily dislodged from the renal artery following placement. Therefore, we designed and tested a novel vascular clip possessing design features to maintain both gap width and position around the renal artery. In this initial study, application of these new clips to the left renal artery produced reliable and consistent levels of hypertension in rats. Nine-day application of clips with gap widths of 0.27, 0.25, and 0.23 mm elicited higher mean arterial blood pressures of 112 ± 4, 121 ± 6, and 135 ± 7 mmHg, respectively (n = 8 for each group), than those of sham-operated controls (95 ± 2 mmHg, n = 8). Moreover, 8 out of 8 rats in each of the 0.23 and 0.25 mm 2K1C groups were hypertensive, whereas 7 out of 8 rats in the 0.27 mm 2K1C group were hypertensive. Plasma renin concentrations were also increased in all 2K1C groups compared with sham-operated controls. In summary, this novel clip design may help eliminate the large degree of unreliability commonly encountered with the 2K1C model.

SOURCES OF VARIABILITY IN BASELINE GENE EXPRESSION IN RAT LIVER AND KIDNEY

EPA Science Inventory

Toxicogenomic studies are typically variable in design, but the impact of variations in study design and conduct on control animal gene expression has not been well characterized. A working group of the Health and Environmental Sciences Institute (HESI) Technical Committee on the...

Pubertal administration of DEHP delays puberty, suppresses testosterone production and inhibits reproductive tract development in male Sprague-Dawley and Long-Evans Rats

EPA Science Inventory

While is clear that exposure to high dosage levels of some phthalates delays the onset of puberty in the male rat it has been hypothesized that low levels of DEHP accelerate puberty by enhancing testicular androgen synthesis. The current study was designed to determine if the do...

Noninvasive Raman spectroscopy of rat tibiae: approach to in vivo assessment of bone quality

PubMed Central

Okagbare, Paul I.; Begun, Dana; Tecklenburg, Mary; Awonusi, Ayorinde; Goldstein, Steven A.

2012-01-01

Abstract. We report on in vivo noninvasive Raman spectroscopy of rat tibiae using robust fiber-optic Raman probes and holders designed for transcutaneous Raman measurements in small animals. The configuration allows placement of multiple fibers around a rat leg, maintaining contact with the skin. Bone Raman data are presented for three regions of the rat tibia diaphysis with different thicknesses of overlying soft tissue. The ability to perform in vivo noninvasive Raman measurement and evaluation of subtle changes in bone composition is demonstrated with rat leg phantoms in which the tibia has carbonated hydroxylapatite, with different carbonate contents. Our data provide proof of the principle that small changes in bone composition can be monitored through soft tissue at anatomical sites of interest in biomedical studies. PMID:23085899

Noninvasive Raman spectroscopy of rat tibiae: approach to in vivo assessment of bone quality.

PubMed

Okagbare, Paul I; Begun, Dana; Tecklenburg, Mary; Awonusi, Ayorinde; Goldstein, Steven A; Morris, Michael D

2012-09-01

We report on in vivo noninvasive Raman spectroscopy of rat tibiae using robust fiber-optic Raman probes and holders designed for transcutaneous Raman measurements in small animals. The configuration allows placement of multiple fibers around a rat leg, maintaining contact with the skin. Bone Raman data are presented for three regions of the rat tibia diaphysis with different thicknesses of overlying soft tissue. The ability to perform in vivo noninvasive Raman measurement and evaluation of subtle changes in bone composition is demonstrated with rat leg phantoms in which the tibia has carbonated hydroxylapatite, with different carbonate contents. Our data provide proof of the principle that small changes in bone composition can be monitored through soft tissue at anatomical sites of interest in biomedical studies.

Reproducibility of African giant pouched rats detecting Mycobacterium tuberculosis.

PubMed

Ellis, Haylee; Mulder, Christiaan; Valverde, Emilio; Poling, Alan; Edwards, Timothy

2017-04-24

African pouched rats sniffing sputum samples provided by local clinics have significantly increased tuberculosis case findings in Tanzania and Mozambique. The objective of this study was to determine the reproducibility of rat results. Over an 18-month period 11,869 samples were examined by the rats. Intra-rater reliability was assessed through Yule's Q. Inter-rater reliability was assessed with Krippendorff's alpha. Intra-rater reliability was high, with a mean Yule's Q of 0.9. Inter-rater agreement was fair, with Krippendorf's alpha ranging from 0.15 to 0.45. Both Intra- and Inter-rater reliability was independent of the sex of the animals, but they were positively correlated with age. Both intra- and inter-rater agreement was lowest for samples designated as smear-negative by the clinics. Overall, the reproducibility of tuberculosis detection rat results was fair and diagnostic results were therefore independent of the rats used.

Statistical power analysis of cardiovascular safety pharmacology studies in conscious rats.

PubMed

Bhatt, Siddhartha; Li, Dingzhou; Flynn, Declan; Wisialowski, Todd; Hemkens, Michelle; Steidl-Nichols, Jill

2016-01-01

Cardiovascular (CV) toxicity and related attrition are a major challenge for novel therapeutic entities and identifying CV liability early is critical for effective derisking. CV safety pharmacology studies in rats are a valuable tool for early investigation of CV risk. Thorough understanding of data analysis techniques and statistical power of these studies is currently lacking and is imperative for enabling sound decision-making. Data from 24 crossover and 12 parallel design CV telemetry rat studies were used for statistical power calculations. Average values of telemetry parameters (heart rate, blood pressure, body temperature, and activity) were logged every 60s (from 1h predose to 24h post-dose) and reduced to 15min mean values. These data were subsequently binned into super intervals for statistical analysis. A repeated measure analysis of variance was used for statistical analysis of crossover studies and a repeated measure analysis of covariance was used for parallel studies. Statistical power analysis was performed to generate power curves and establish relationships between detectable CV (blood pressure and heart rate) changes and statistical power. Additionally, data from a crossover CV study with phentolamine at 4, 20 and 100mg/kg are reported as a representative example of data analysis methods. Phentolamine produced a CV profile characteristic of alpha adrenergic receptor antagonism, evidenced by a dose-dependent decrease in blood pressure and reflex tachycardia. Detectable blood pressure changes at 80% statistical power for crossover studies (n=8) were 4-5mmHg. For parallel studies (n=8), detectable changes at 80% power were 6-7mmHg. Detectable heart rate changes for both study designs were 20-22bpm. Based on our results, the conscious rat CV model is a sensitive tool to detect and mitigate CV risk in early safety studies. Furthermore, these results will enable informed selection of appropriate models and study design for early stage CV studies. Copyright © 2016 Elsevier Inc. All rights reserved.

A novel vibrotactile system for stimulating the glabrous skin of awake freely behaving rats during operant conditioning.

PubMed

Devecioğlu, İsmail; Güçlü, Burak

2015-03-15

Rat skin is innervated by mechanoreceptive fibers similar to those in other mammals. Tactile experiments with behaving rats mostly focus on the vibrissal system which does not exist in humans. The aim of this study was to design and implement a novel vibrotactile system to stimulate the glabrous skin of behaving rats during operant conditioning. A computer-controlled vibrotactile system was developed for various tasks in which the volar surface of unrestrained rats' fore- and hindpaws was stimulated in an operant chamber. The operant chamber was built from off-the-shelf components. A highly accurate electrodynamic shaker with a novel multi-probe design was used for generating mechanical displacements. Twenty-five rats were trained for four sequential tasks: (A) middle-lever (trial start signal) press, (B) side-lever press with an associated visual cue, (C) similar to (B) with the addition of an auditory/tactile stimulus, (D) auditory/tactile detection (yes/no) task. Out of 9 rats which could complete the tactile version of this training schedule, 5 had over 70% accuracy in the tactile version of the detection task. Unlike actuators for stimulating whiskers, this system does not require a particular head/body alignment and can be used with freely behaving animals. The vibrotactile system was found to be effective for conditioning freely behaving rats based on stimuli applied on the glabrous skin. However, detection accuracies were lower compared to those in tasks involving whisker stimulation reported previously, probably due to differences in cortical processing. Copyright © 2015 Elsevier B.V. All rights reserved.

Experimental Lithium-Ion Battery Developed for Demonstration at the 2007 NASA Desert Research and Technology Studies (D-RATS) Program

NASA Technical Reports Server (NTRS)

Bennett, William R.; Baldwin, Richard S.

2010-01-01

The NASA Glenn Research Center (GRC) Electrochemistry Branch designed and built five lithium-ion battery packs for demonstration in spacesuit simulators as a part of the 2007 Desert Research and Technology Studies (D-RATS) activity at Cinder Lake, Arizona. The experimental batteries incorporated advanced, NASA-developed electrolytes and included internal protection against over-current, overdischarge and over-temperature. The 500-g experimental batteries were designed to deliver a constant power of 22 W for 2.5 hr with a minimum voltage of 13 V. When discharged at the maximum expected power output of 38.5 W, the batteries operated for 103 min of discharge time, achieving a specific energy of 130 Wh/kg. This report summarizes design details and safety considerations. Results for field trials and laboratory testing are summarized.

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

NASA Technical Reports Server (NTRS)

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

1992-01-01

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

Study of antidiarrheal and hematology profile of laboratory rat fed with yogurt containing local probiotic and purple sweet potato extract

NASA Astrophysics Data System (ADS)

Tari, A. I. N.; Handayani, C. B.; Hartati, S.

2018-03-01

The aim of this study was to evaluate the effectiveness of local probiotic in yogurt with purple sweet potato extract supplementation on the hematological parameters of albino rats (Spraque dawley). The study was conducted using a Completely Randomized Design with 30 rats divided into 6 groups. In group K-, rats were fed with distilled water from day 1 to 21. In group YTP, Rats were fed with yogurt without probiotics from day 1 to 21. YDP group was rats were fed with probiotic yogurt from day 1 to 21. In group YTP+E, rats were fed with yogurt without probiotic from day 1 to 7, interspersed with exposure to enteropathogenic Escherichia coli (EPEC) on day 8 to 14. In group YDP+E, rats were fed with probiotic yogurt from day 1 to 7, interspersed by EPEC on day 8 to 24. In group K +, rats were fed with water from day 1 to 7, then fed with EPEC on day 8 to 14, after which water was given back on day 15 to 21. The result showed that probiotic yogurt treatment with supplement of purple sweet potato extract had a significant effect (P<0,05) on feces water content, number of erythrocyte, leucocyte, and hemoglobin. The treatment of YDP had water content in feces 48.422% and the number of erythrocyte, leucocytes, and hemoglobin were 8.578 106/μl, 14.152 106/μl and 13.98 g/dL respectively.

Lymphatic Territories (Lymphosomes) in the Rat: An Anatomical Study for Future Lymphatic Research.

PubMed

Suami, Hiroo; Scaglioni, Mario F

2017-11-01

Understanding the precise anatomy in experimental animals is crucial for correct design of research projects. Rats are commonly used for scientific research in plastic surgery because of their availability in academic institutions, moderate cost, and sizable vessels for microsurgical procedures. In past publications about rat anatomy, lymphatic mapping has been limited and incomplete. The aim of this study was to comprehensively map the superficial lymphatic system in the rat. Twenty-seven Sprague-Dawley rats were used for this study. Indocyanine green fluorescence lymphography was used to identify the lymphatic vessels and lymph nodes. Under general anaesthesia, indocyanine green was injected intradermally at multiple spots along the dorsal and medial midlines, front and hind paws, ears, and tail. The course of the lymphatic vessels was traced on the skin with a marker pen and photographed. The superficial lymphatic vessels in each rat were sketched on a graphic template and all of the templates were superimposed using graphics software to define the relationship between the lymphatic vessel and sentinel node. Indocyanine green fluorescence lymphography was able to demonstrate the superficial lymphatic vessels in the rat. Six groups of regional lymph node/s were identified and lymphatic pathways to those nodes delineated. The authors' lymphosome concept was successfully applied to the rat, with six lymphosomes identified. The authors succeeded in performing superficial lymphatic mapping in the rat. The authors' anatomical findings can provide further information about the lymphatic system in the normal state and promote understanding of pathologic changes generated by surgical manipulation for future studies.

Enhanced hepatic insulin signaling in the livers of high altitude native rats under basal conditions and in the livers of low altitude native rats under insulin stimulation: a mechanistic study.

PubMed

Al Dera, Hussain; Eleawa, Samy M; Al-Hashem, Fahaid H; Mahzari, Moeber M; Hoja, Ibrahim; Al Khateeb, Mahmoud

2017-07-01

This study was designed to investigate the role of the liver in lowering fasting blood glucose levels (FBG) in rats native to high (HA) and low altitude (LA) areas. As compared with LA natives, besides the improved insulin and glucose tolerance, HA native rats had lower FBG, at least mediated by inhibition of hepatic gluconeogenesis and activation of glycogen synthesis. An effect that is mediated by the enhancement of hepatic insulin signaling mediated by the decreased phosphorylation of TSC induced inhibition of mTOR function. Such effect was independent of activation of AMPK nor stabilization of HIF1α, but most probably due to oxidative stress induced REDD1 expression. However, under insulin stimulation, and in spite of the less activated mTOR function in HA native rats, LA native rats had higher glycogen content and reduced levels of gluconeogenic enzymes with a more enhanced insulin signaling, mainly due to higher levels of p-IRS1 (tyr612).

Effect of Norbinaltorphimine on Δ9-Tetrahydrocannabinol (THC)-Induced Taste Avoidance in Adolescent and Adult Sprague-Dawley Rats

PubMed Central

Flax, Shaun M.; Wakeford, Alison G.P.; Cheng, Kejun; Rice, Kenner C.; Riley, Anthony L.

2017-01-01

Rationale The aversive effects of Δ9-tetrahydrocannabinol (THC) are mediated by activity at the kappa opioid receptor (KOR) as assessed in adult animals; however, no studies have assessed KOR involvement in the aversive effects of THC in adolescents. Given that adolescents have been reported to be insensitive to the aversive effects induced by KOR agonists, a different mechanism might mediate the aversive effects of THC in this age group. Objectives The present study was designed to assess the impact of KOR antagonism on the aversive effects of THC in adolescent and adult rats using the conditioned taste avoidance (CTA) procedure. Methods Following a single pretreatment injection of norbinaltorphimine (norBNI; 15 mg/kg), CTAs induced by THC (0, 0.56, 1.0, 1.8 and 3.2 mg/kg) were assessed in adolescent (n = 84) and adult (n = 83) Sprague Dawley rats. Results The KOR antagonist, norBNI, had weak and inconsistent effects on THC-induced taste avoidance in adolescent rats in that norBNI both attenuated and strengthened taste avoidance dependent on dose and trial. norBNI had limited impact on the final one-bottle avoidance and no effects on the two-bottle preference test. Interestingly, norBNI had no effect on THC-induced taste avoidance in adult rats as well. Conclusions That norBNI had no significant effect on THC-induced avoidance in adults and a minor and inconsistent effect in adolescents demonstrates that the aversive effects of THC are not mediated by KOR activity as assessed by the CTA design in Sprague Dawley rats. PMID:26025420

High-Impact, Self-Motivated Training Within an Enriched Environment With Single Animal Tracking Dose-Dependently Promotes Motor Skill Acquisition and Functional Recovery.

PubMed

Starkey, Michelle L; Bleul, Christiane; Kasper, Hansjörg; Mosberger, Alice C; Zörner, Björn; Giger, Stefan; Gullo, Miriam; Buschmann, Frank; Schwab, Martin E

2014-07-01

Functional recovery following central nervous system injuries is strongly influenced by rehabilitative training. In the clinical setting, the intensity of training and the level of motivation for a particular task are known to play important roles. With increasing neuroscience studies investigating the effects of training and rehabilitation, it is important to understand how the amount and type of training of individuals influences outcome. However, little is known about the influence of spontaneous "self-training" during daily life as it is often uncontrolled, not recorded, and mostly disregarded. Here, we investigated the effects of the intensity of self-training on motor skill acquisition in normal, intact rats and on the recovery of functional motor behavior following spinal cord injury in adult rats. We used a custom-designed small animal tracking system, "RatTrack," to continuously record the activity of multiple rats, simultaneously in a complex Natural Habitat-enriched environment. Naïve, adult rats performed high-intensity, self-motivated motor training, which resulted in them out-performing rats that were conventionally housed and trained on skilled movement tasks, for example, skilled prehension (grasping) and ladder walking. Following spinal cord injury the amount of self-training was correlated with improved functional recovery. These data suggest that high-impact, self-motivated training leads to superior skill acquisition and functional recovery than conventional training paradigms. These findings have important implications for the design of animal studies investigating rehabilitation and for the planning of human rehabilitation programs. © The Author(s) 2014.

Effect of norbinaltorphimine on ∆⁹-tetrahydrocannabinol (THC)-induced taste avoidance in adolescent and adult Sprague-Dawley rats.

PubMed

Flax, Shaun M; Wakeford, Alison G P; Cheng, Kejun; Rice, Kenner C; Riley, Anthony L

2015-09-01

The aversive effects of ∆(9)-tetrahydrocannabinol (THC) are mediated by activity at the kappa opioid receptor (KOR) as assessed in adult animals; however, no studies have assessed KOR involvement in the aversive effects of THC in adolescents. Given that adolescents have been reported to be insensitive to the aversive effects induced by KOR agonists, a different mechanism might mediate the aversive effects of THC in this age group. The present study was designed to assess the impact of KOR antagonism on the aversive effects of THC in adolescent and adult rats using the conditioned taste avoidance (CTA) procedure. Following a single pretreatment injection of norbinaltorphimine (norBNI; 15 mg/kg), CTAs induced by THC (0, 0.56, 1.0, 1.8, and 3.2 mg/kg) were assessed in adolescent (n = 84) and adult (n = 83) Sprague-Dawley rats. The KOR antagonist, norBNI, had weak and inconsistent effects on THC-induced taste avoidance in adolescent rats in that norBNI both attenuated and strengthened taste avoidance dependent on dose and trial. norBNI had limited impact on the final one-bottle avoidance and no effects on the two-bottle preference test. Interestingly, norBNI had no effect on THC-induced taste avoidance in adult rats as well. That norBNI had no significant effect on THC-induced avoidance in adults, and a minor and inconsistent effect in adolescents demonstrates that the aversive effects of THC are not mediated by KOR activity as assessed by the CTA design in Sprague-Dawley rats.

Lower risk taking and exploratory behavior in alcohol-preferring sP rats than in alcohol non-preferring sNP rats in the multivariate concentric square field (MCSF) test.

PubMed

Roman, Erika; Colombo, Giancarlo

2009-12-14

The present investigation continues previous behavioral profiling studies of selectively bred alcohol-drinking and alcohol non-drinking rats. In this study, alcohol-naïve adult Sardinian alcohol-preferring (sP) and non-preferring (sNP) rats were tested in the multivariate concentric square field (MCSF) test. The MCSF test has an ethoexperimental approach and measures general activity, exploration, risk assessment, risk taking, and shelter seeking in laboratory rodents. The multivariate design enables behavioral profiling in one and the same test situation. Age-matched male Wistar rats were included as a control group. Five weeks after the first MCSF trial, a repeated testing was done to explore differences in acquired experience. The results revealed distinct differences in exploratory strategies and behavioral profiles between sP and sNP rats. The sP rats were characterized by lower activity, lower exploratory drive, higher risk assessment, and lower risk taking behavior than in sNP rats. In the repeated trial, risk-taking behavior was almost abolished in sP rats. When comparing the performance of sP and sNP rats with that of Wistar rats, the principal component analysis revealed that the sP rats were the most divergent group. The vigilant behavior observed in sP rats with low exploratory drive and low risk-taking behavior is interpreted here as high innate anxiety-related behaviors and may be related to their propensity for high voluntary alcohol intake and preference. We suggest that the different lines of alcohol-preferring rats with different behavioral characteristics constitute valuable animal models that mimic the heterogeneity in human alcohol dependence.

Involvement of melatonin metabolites in the long-term inhibitory effect of the hormone on rat spinal nociceptive transmission.

PubMed

Mondaca, Mauricio; Hernández, Alejandro; Valladares, Luis; Sierralta, Walter; Noseda, Rodrigo; Soto-Moyano, Rubén

2004-02-01

There is evidence that melatonin and its metabolites could bind to nuclear sites in neurones, suggesting that this hormone is able to exert long-term functional effects in the central nervous system via genomic mechanisms. This study was designed to investigate (i) whether systemically administered melatonin can exert long-term effects on spinal cord windup activity, and (ii) whether blockade of melatonin degradation with eserine could prevent this effect. Rats receiving melatonin (10 mg/kg ip), the same dose of melatonin plus eserine (0.5 mg/kg ip), or saline were studied. Seven days after administration of the drugs or saline, spinal windup of rats was assessed in a C-fiber reflex response paradigm. Results show that rats receiving melatonin exhibited a reduction in spinal windup activity. This was not observed in the animals receiving melatonin plus eserine or saline, suggesting a role for melatonin metabolites in long-term changes of nociceptive transmission in the rat spinal cord.

Amygdala Kindling Alters Estrus Cycle and Ovarian Morphology in the Rat.

PubMed

Pan, Juan; Zhang, Lingwu; Wang, Feng; Liu, Dan; Li, P Andy; Sun, Tao

2013-11-01

The objective of this study is to explore the effects of amygdala kindling on estrus cycle and ovarian morphology. Thirty-five female rats at the age of 8 weeks were randomly designated to electrode kindled, sham-kindled, and normal controls. Kindled rats were implanted with kindling electrodes in the left basolateral amygdala and kindled by brief suprathreshold stimulations with a bipolar electrode. Estrous cycles were daily monitored through vaginal smears. Electrographic and behavioral seizures were recorded and ovarian morphology was evaluated by light and electron microscopies. Our results showed that the kindled rats lost their ovarian periodicity displayed significant ovarian enlargement. H&E staining revealed increased number of growing follicles and total follicles, as well as polycysts in the ovaries of the kindled animals compared to sham and control animals. Ultrastructural study detected numerous apoptotic granulosa cells in growing follicles and thecal cell hyperplasia with secretary granules in the thecal cells in the kindled rats. The results suggest that amygdala kindling is a risk factor for the development of polycystic ovary syndrome.

Dietary fat source alters hepatic gene expression profile and determines the type of liver pathology in rats overfed via total enteral nutrition

USDA-ARS?s Scientific Manuscript database

This study was designed to determine if the fatty acid composition of the diet affects the development and progression of nonalcoholic fatty liver disease (NAFLD). Male Sprague-Dawley rats (n = 5-6/group) were overfed low (5%) or high (70%) fat diets with different fatty acid sources: olive oil (OO,...

Novel approach of using a cocktail of designed bacteriophages against gut pathogenic E. coli for bacterial load biocontrol

PubMed Central

2014-01-01

Background This study was conducted to explore new approaches of animal biocontrol via biological control feed. Method White rats were subjected to 140 highly lytic designed phages specific against E. coli. Phages were fed via drinking water, oral injection, and vegetable capsules. Phage feeding was applied by 24 h feeding with 11d monitoring and 20d phage feeding and monitoring. Group of rats received external pathogenic E. coli and another group did not, namely groups A and B. Results Phage feeding for 20d via vegetable capsules yielded the highest reduction of fecal E. coli, 3.02 and 4.62 log, in rats group A and B respectively. Second best, feeding for 20d via drinking water with alkali yielded 2.78 and 4.08 log in rats groups A and B respectively. The peak reduction in E. coli output was 5–10 d after phage feeding. Phage control declined after 10th day of feeding. Conclusions The use of cocktail of designed phages succeeded in suppressing flora or external E. coli. The phage feed biocontrol is efficient in controlling E. coli at the pre-harvest period, precisely at the 6th-8th day of phage feeding when the lowest E. coli output found. PMID:25062829

Inhalation developmental toxicology studies: Teratology study of acetone in mice and rats: Final report

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

Mast, T.J.; Evanoff, J.J.; Rommereim, R.L.

1988-11-01

Acetone, an aliphatic ketone, is a ubiquitous industrial solvent and chemical intermediate; consequently, the opportunity for human exposure is high. The potential for acetone to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 440, 2200, or 11000 ppm, and in Swiss (CD-1) mice exposed to 0, 440, 2200, and 6600 ppm acetone vapors, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and approx.32 positively mated rats or mice. Positively mated mice were exposed on days 6-17 of gestation (dg), and rats on 6-19 dg. The day of plugmore » or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 46 refs., 6 figs., 27 tabs.« less

Initial studies using the RatCAP conscious animal PET tomograph

NASA Astrophysics Data System (ADS)

Woody, C.; Vaska, P.; Schlyer, D.; Pratte, J.-F.; Junnarkar, S.; Park, S.-J.; Stoll, S.; Purschke, M.; Southekal, S.; Kriplani, A.; Krishnamoorthy, S.; Maramraju, S.; Lee, D.; Schiffer, W.; Dewey, S.; Neill, J.; Kandasamy, A.; O'Connor, P.; Radeka, V.; Fontaine, R.; Lecomte, R.

2007-02-01

The RatCAP is a small, head-mounted PET tomograph designed to image the brain of a conscious rat without the use of anesthesia. The detector is a complete, high-performance 3D tomograph consisting of a 3.8 cm inside-diameter ring containing 12 block detectors, each of which is comprised of a 4×8 array of 2.2×2.2×5 mm 3 LSO crystals readout with a matching APD array and custom ASIC, and has a 1.8 cm axial field of view. Construction of the first working prototype detector has been completed and its performance characteristics have been measured. The results show an intrinsic spatial resolution of 2.1 mm, a time resolution of ˜14 ns FWHM, and a sensitivity of 0.7% at an energy threshold of 150 keV. First preliminary images have been obtained using 18F-FDG and 11C-methamphetamine, which show comparable image quality to those obtained from a commercial MicroPET R4 scanner. Initial studies have also been carried out to study stress levels in rats wearing the RatCAP.

Fludrocortisone: Role in Central Regulation of Fluid Balance

NASA Technical Reports Server (NTRS)

Dallman, M. F.

1996-01-01

We have performed 7 experiments in rats on the effects of systemic treatment with fludrocortisone (9a-FF) given in a variety of doses over a variety of times, in the AM and in the PM. These experiments were designed to determine the best treatment protocol to use in the head-down rat model studies which were performed at NASA-Ames Research Center during the final year. The results of the experiments in non-stressed rats have been, on the whole, disappointing in that we have so far been unable to obtain direct evidence that the 9a-FF acts as a mineralocorticoid. In the ultimate experiments using control and suspended rats, we showed mineralocorticoid and glucocorticoid effects of 9aFF. However, suspension served in our rats as a chronic stressor when they were examined 5 d after the onset of treatment.

The teratology testing of food additives.

PubMed

Barrow, Paul C; Spézia, François

2013-01-01

The developmental and reproductive toxicity testing (including teratogenicity) of new foods and food additives is performed worldwide according to the guidelines given in the FDA Redbook. These studies are not required for substances that are generally recognized as safe, according to the FDA inventory. The anticipated cumulated human exposure level above which developmental or reproduction studies are required depends on the structure-alert category. For food additives of concern, both developmental (prenatal) and reproduction (multigeneration) studies are required. The developmental studies are performed in two species, usually the rat and the rabbit. The reproduction study is generally performed in the rat. The two rat studies are preferably combined into a single experimental design, if possible. The test methods described in the FDA Redbook are similar to those specified by the OECD for the reproductive toxicity testing of chemicals.

Differential susceptibility of SD and CD rats to a novel rat theilovirus.

PubMed

Drake, Michael T; Riley, Lela K; Livingston, Robert S

2008-10-01

Antibodies to rat theilovirus (RTV) have been detected in rats for many years because of their serologic crossreactivity with strains of Theiler murine encephalomyelitis virus (TMEV) of mice. Little information exists regarding this pathogen, yet it is among the most common viruses detected in serologic surveys of rats used in research. In the study reported here, a novel isolate of RTV, designated RTV1, was cultured from the feces of infected rats. The RTV1 genome contained 8094 nucleotides and had approximately 95% identity with another rat theilovirus, NSG910, and 73% identity with TMEV strains. In addition, the genome size of RTV1 was similar to those of TMEV strains but larger than that reported for NSG910. Oral inoculation of Sprague-Dawley (SD) and CD male rats (n = 10 each group) with RTV1 revealed that SD rats were more susceptible than CD rats to RTV1 infection. At 14 d postinoculation, 100% of SD rats shed virus in the feces, and 70% were positive for RTV serum antibodies. By 56 d postinoculation 30% of SD rats continued to have detectable virus in the feces, and 90% had seroconverted. In contrast, in inoculated CD rats RTV was detected only in the feces at 14 d postinoculation, at which time 40% of CD rats were fecal positive. By 56 d postinoculation only 20% of CD rats had detectable RTV serum antibodies. Our data provide additional sequence information regarding a rat-specific Cardiovirus and indicate that SD rats are more susceptible than CD rats to RTV1 infection.

Effects of ethanol on methyl mercury toxicity in rats

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

Tamashiro, H.; Arakaki, M.; Akagi, H.

1986-01-01

This study was designed to investigate the effect of different doses of ethanol on the morbidity, mortality, and distribution of mercury in the tissues of groups of rats treated orally once daily with methyl mercury chloride (MMC: 5 mg/kg d) for 10 consecutive days. Ethanol potentiated the toxicity of methyl mercury in terms of neurological manifestations (hindleg crossings and abnormal gait) and mortality. The magnitude of effect depended on the concentration of ethanol administered. The concentration of mercury in the kidney and brain also increased with the dose of ethanol given. These findings indicate that epidemiologic studies designed to evaluatemore » methyl mercury toxicity must take into account the multiple environmental burdens that can affect the population cumulatively and simultaneously.« less

The comparison of manual and LabVIEW-based fuzzy control on mechanical ventilation.

PubMed

Guler, Hasan; Ata, Fikret

2014-09-01

The aim of this article is to develop a knowledge-based therapy for management of rats with respiratory distress. A mechanical ventilator was designed to achieve this aim. The designed ventilator is called an intelligent mechanical ventilator since fuzzy logic was used to control the pneumatic equipment according to the rat's status. LabVIEW software was used to control all equipments in the ventilator prototype and to monitor respiratory variables in the experiment. The designed ventilator can be controlled both manually and by fuzzy logic. Eight female Wistar-Albino rats were used to test the designed ventilator and to show the effectiveness of fuzzy control over manual control on pressure control ventilation mode. The anesthetized rats were first ventilated for 20 min manually. After that time, they were ventilated for 20 min by fuzzy logic. Student's t-test for p < 0.05 was applied to the measured minimum, maximum and mean peak inspiration pressures to analyze the obtained results. The results show that there is no statistical difference in the rat's lung parameters before and after the experiments. It can be said that the designed ventilator and developed knowledge-based therapy support artificial respiration of living things successfully. © IMechE 2014.

Novel pharmacokinetic studies of the Chinese formula Huang-Lian-Jie-Du-Tang in MCAO rats.

PubMed

Zhu, Huaxu; Qian, Zhilei; He, Feng; Liu, Mengzhu; Pan, Linmei; Zhang, Qichun; Tang, Yuping

2013-07-15

Our previous studies showed that after oral administration of an Huang-Lian-Jie-Du-Tang (HLJDT) decoction, there is a higher concentration of the pure components, berberine, baicalin and gardenoside in the plasma of Middle cerebral artery occlusion (MCAO) rats than in sham-operated rats, The aim of the present study was to determine whether these components could be reliably measured in MCAO rat tissues. First, the plasma concentration-time profiles of berberine, palmatine, baicalin, baicalein and gardenoside were characterised in MCAO rats after oral administration of the aqueous extract of HLJDT. Subsequently, liver, lung and kidney tissues were obtained from sudden death MCAO rats in the absorption phase (0.25 h), the distribution phase (1.0 h) and the elimination phase (8.0 h) after administration of the HLJDT aqueous extract. An HPLC method was developed and validated for the determination of the distribution characteristics of berberine, palmatine, baicalin, baicalein and gardenoside simultaneously from the above-mentioned rat tissues. The results indicated that berberine, palmatine, baicalin and baicalein distributed rapidly and accumulated at high levels in the lung, while gardenoside distributed widely in the lung and the kidney. To the best of our knowledge, this is the first report to describe the distribution of the active ingredients derived from HLJDT in MCAO rat tissues. The tissue distribution results provide a biopharmaceutical basis for the design of the clinic application of HLJDT in cerebrovascular disease. Copyright © 2012 Elsevier GmbH. All rights reserved.

Investigating the influence of chromatic aberration and optical illumination bandwidth on fundus imaging in rats

NASA Astrophysics Data System (ADS)

Li, Hao; Liu, Wenzhong; Zhang, Hao F.

2015-10-01

Rodent models are indispensable in studying various retinal diseases. Noninvasive, high-resolution retinal imaging of rodent models is highly desired for longitudinally investigating the pathogenesis and therapeutic strategies. However, due to severe aberrations, the retinal image quality in rodents can be much worse than that in humans. We numerically and experimentally investigated the influence of chromatic aberration and optical illumination bandwidth on retinal imaging. We confirmed that the rat retinal image quality decreased with increasing illumination bandwidth. We achieved the retinal image resolution of 10 μm using a 19 nm illumination bandwidth centered at 580 nm in a home-built fundus camera. Furthermore, we observed higher chromatic aberration in albino rat eyes than in pigmented rat eyes. This study provides a design guide for high-resolution fundus camera for rodents. Our method is also beneficial to dispersion compensation in multiwavelength retinal imaging applications.

A preparation for studying electrical stimulation of the retina in vivo in rat

NASA Astrophysics Data System (ADS)

Baig-Silva, M. S.; Hathcock, C. D.; Hetling, J. R.

2005-03-01

A remaining challenge to the development of electronic prostheses for vision is improving the effectiveness of retinal stimulation. Electrode design and stimulus parameters need to be optimized such that the neural output from the retina conveys information to the mind's eye that aids the patient in interpreting his or her environment. This optimization will require a detailed understanding of the response of the retina to electrical stimulation. The identity and response characteristics of the cellular targets of stimulation need to be defined and evaluated. Described here is an in vivo preparation for studying electrical stimulation of the retina in rat at the cellular level. The use of rat makes available a number of well-described models of retinal disease that motivate prosthesis development. Artificial stimulation can be investigated by adapting techniques traditionally employed to study the response of the retina to photic stimuli, such as recording at the cornea, single-cell recording, and pharmacological dissection of the response. Pilot studies include amplitude-intensity response data for subretinal and transretinal stimulation paradigms recorded in wild-type rats and a transgenic rat model of autosomal dominant retinitis pigmentosa. The ability to record single-unit ganglion cell activity in vivo is also demonstrated.

Molecular cloning of rat sperm galactosyl receptor, a C-type lectin with in vitro egg binding activity.

PubMed

Rivkin, E; Tres, L L; Kaplan-Kraicer, R; Shalgi, R; Kierszenbaum, A L

2000-07-01

Rat sperm galactosyl receptor is a member of the C-type animal lectin family showing preferential binding to N-acetylgalactosamine compared to galactose. Binding is mediated by a Ca(2+)-dependent carbohydrate-recognition domain (CRD) identical to that of the minor variant of rat hepatic lectin receptor 2/3 (RHL-2/3). The molecular organization of the genomic DNA, cDNA, and derived amino acid sequence of rat testis galactosyl receptor have been determined and in vitro fertilization studies were conducted to ascertain its role. We have determined that the rat testis galactosyl receptor gene generates two mRNA species: one species, designated liver-type, is identical to RHL-2/3; the other, designated testis-type, contains one unspliced intron (86 nt) which alters the reading frame and changes the amino acid sequence of the carboxyl terminus. As a result, the CRD (glutamine-proline-aspartic acid/QPD) and flanked Ca(2+)-binding amino acid sequences were not present in the testis-type protein. Northern and Southern blots demonstrated presence of transcripts with unspliced intron in rat sperm but not liver. Similarly, antibody, raised against a synthetic 12-amino acid peptide (p12) encoded by the unspliced intron, recognized in immunoblots a 54 kDa receptor protein in protein extracts from testis but not from liver. Immunofluorescence and immunogold electron microscopy studies demonstrated that both protein species localized on the plasma membrane surface of the head and tail of rat sperm. Furthermore, capacitated rat sperm preincubated with polyclonal antisera to RHL-2/3 or to the CRD of the liver-type galactosyl receptor showed a statistically significant decrease in the in vitro fertilization rate. We conclude that rat sperm galactosyl receptor may play a role in egg binding and that an undetermined molecular mechanism operates to generate two proteins with identical intracellular amino terminal domain but only one of them displays a CRD and associated Ca(2+)-binding sites at the carboxyl terminal extracellular domain. Copyright 2000 Wiley-Liss, Inc.

Anti-inflammatory and anti-apoptotic effects of Crataegus oxyacantha on isoproterenol-induced myocardial damage.

PubMed

Vijayan, Navin Alukkathara; Thiruchenduran, Mohana; Devaraj, Sivasitamparam Niranjali

2012-08-01

This study was designed to evaluate the anti-inflammatory and anti-apoptotic effects of the alcoholic extract of the berries of Crataegus oxyacantha (AEC), a medicinal herb, on isoproterenol-induced myocardial infarction (MI) in a rat model. Three groups of Wistar albino rats, each comprising six animals, were selected for this study. Group I rats served as control. Group II rats were given isoproterenol (85 mg/kg body weight) subcutaneously on 59th and 60th days. Group III rats were given AEC (0.5 ml/100 g body weight/day), orally on a daily basis for 60 days, and isoproterenol (85 mg/kg body weight, subcutaneously) was given on 59th and 60th days. On the 61st day, the animals were sacrificed, and marker enzymes like lactate dehydrogenase (LDH) and creatine kinase (CK) were estimated in serum. In the heart tissue sample, antioxidant status, lipid peroxidation and anti-inflammatory properties of AEC were determined. Isoproterenol significantly increased the release of LDH, CK in serum, decreased the antioxidant status in the heart along with an increase in lipid peroxidation. Nitritive stress and apoptosis were seen in isoproterenol-induced rat heart. Pre-treatment with the AEC for 60 days had a significant effect on all the above factors and maintained near normal status. The study confirms the protective effect of AEC against isoproterenol-induced inflammation and apoptosis-associated MI in rats.

Impairment of blood brain barrier is related with the neuroinflammation induced peripheral immune status in intracerebroventricular colchicine injected rats: An experimental study with mannitol.

PubMed

Sil, Susmita; Ghosh, Arijit; Ghosh, Tusharkanti

2016-09-01

The neurodegeneration in AD patients may be associated with changes of peripheral immune responses. Some peripheral immune responses are altered due to neuroinflammation in colchicine induced AD (cAD) rats. The leaky blood brain barrier (BBB) in cAD-rats may be involved in inducing peripheral inflammation, though there is no report in this regard. Therefore, the present study was designed to investigate the role of BBB in cADrats by altering the BBB in a time dependent manner with injection (i.v.) of mannitol (BBB opener). The inflammatory markers in the brain and serum along with the peripheral immune responses were measured after 30 and 60min of mannitol injection in cAD rats. The results showed higher inflammatory markers in the hippocampus and serum along with alterations in peripheral immune parameters in cAD rats. Although the hippocampal inflammatory markers did not further change after mannitol injection in cAD rats, the serum inflammatory markers and peripheral immune responses were altered and these changes were greater after 60min than that of 30min of mannitol injection. The present study shows that the peripheral immune responses in cAD rats after 30 and 60min of mannitol injection are related to magnitude of impairment of BBB in these conditions. It can be concluded from this study that impairment of BBB in cAD rats is related to the changes of peripheral immune responses observed in that condition. Copyright © 2016 Elsevier B.V. All rights reserved.

Skeletal unloading and dietary copper depletion are detrimental to bone quality of mature rats

NASA Technical Reports Server (NTRS)

Smith, Brenda J.; King, Jarrod B.; Lucas, Edralin A.; Akhter, Mohammed P.; Arjmandi, Bahram H.; Stoecker, Barbara J.

2002-01-01

This study was designed to examine the skeletal response to copper depletion and mechanical unloading in mature animals. In a 2 x 2 experimental design, 5.5-mo-old male Sprague-Dawley rats (n = 36) consumed either the control (AIN-93M) or Cu-depletion ((-)Cu) diet beginning 21 d before suspension and throughout the remainder of the study. Half of the rats in each dietary treatment group were either tail-suspended (TS) or kept ambulatory (AMB) for 28 d. Lower bone mineral densities (BMD) of 5th lumbar vertebra (L5) (P < 0.05) and femur were observed with (-)Cu and TS, but no differences were noted in the BMD of the humerus. Mechanical strength in the femur and vertebra decreased in response to TS, but were unaffected by copper depletion. Urinary deoxypyridinoline, an index of bone resorption, was significantly greater in TS rats, but unaltered by (-)Cu. No changes in serum or bone alkaline phosphatase activity, an indicator of bone formation, were observed. Our findings suggest that TS and (-)Cu decreased BMD in unloaded femur and vertebra but had no effect on normally loaded humerus. Bone loss with TS appeared to be related to accelerated bone resorption. Alterations in bone metabolism and bone mechanical properties in the mature skeleton resulting from (-)Cu warrant further investigation.

Influence of Hesperidin on the Systemic and Intestinal Rat Immune Response.

PubMed

Camps-Bossacoma, Mariona; Franch, Àngels; Pérez-Cano, Francisco J; Castell, Margarida

2017-06-06

Polyphenols, widely found in edible plants, influence the immune system. Nevertheless, the immunomodulatory properties of hesperidin, the predominant flavanone in oranges, have not been deeply studied. To establish the effect of hesperidin on in vivo immune response, two different conditions of immune system stimulations in Lewis rats were applied. In the first experimental design, rats were intraperitoneally immunized with ovalbumin (OVA) plus Bordetella pertussis toxin and alum as the adjuvants, and orally given 100 or 200 mg/kg hesperidin. In the second experimental design, rats were orally sensitized with OVA together with cholera toxin and fed a diet containing 0.5% hesperidin. In the first approach, hesperidin administration changed mesenteric lymph node lymphocyte (MLNL) composition, increasing the TCRαβ+ cell percentage and decreasing that of B lymphocytes. Furthermore, hesperidin enhanced the interferon (IFN)-γ production in stimulated MLNL. In the second approach, hesperidin intake modified the lymphocyte composition in the intestinal epithelium (TCRγδ+ cells) and the lamina propria (TCRγδ+, CD45RA+, natural killer, natural killer T, TCRαβ+CD4+, and TCRαβ+CD8+ cells). Nevertheless, hesperidin did not modify the level of serum anti-OVA antibodies in either study. In conclusion, hesperidin does possess immunoregulatory properties in the intestinal immune response, but this effect is not able to influence the synthesis of specific antibodies.

Mean girls: sex differences in the effects of mild traumatic brain injury on the social dynamics of juvenile rat play behaviour.

PubMed

Mychasiuk, R; Hehar, H; Farran, A; Esser, M J

2014-02-01

Clinical studies indicate that children who experience a traumatic brain injury (TBI) are often the victim of peer rejection, have very few mutual friends, and are at risk for long-term behavioural and social impairments. Owing to the fact that peer play is critical for healthy development, it is possible that the long-term impairments are associated not only with the TBI, but also altered play during this critical period of brain development. This study was designed to determine if social dynamics and juvenile play are altered in rats that experience a mild TBI (mTBI) early in life. Play-fighting behaviours were recorded and analyzed for young male and female Sprague Dawley rats that were given either an mTBI or a sham injury. The study found that the presence of an mTBI altered the play fighting relationship, and the nature of the alterations were dependent upon the sex of the pairing and the injury status of their peers. Sham rats were significantly less likely to initiate play with an mTBI rat, and were more likely to respond to a play initiation from an mTBI rat with an avoidant strategy. This effect was significantly more pronounced in female rats, whereby it appeared that female rats with an mTBI were particularly rejected and most often excluded from play experiences. Male rats with an mTBI learned normal play strategies from their sham peers (when housed in mixed cages), whereas female rats with an mTBI show heightened impairment in these conditions. Play therapy may need to be incorporated into treatment strategies for children with TBI. Copyright © 2013 Elsevier B.V. All rights reserved.

Acute Exacerbation of Sleep Apnea by Hyperoxia Impairs Cognitive Flexibility in Brown-Norway Rats

PubMed Central

Topchiy, Irina; Amodeo, Dionisio A.; Ragozzino, Michael E.; Waxman, Jonathan; Radulovacki, Miodrag; Carley, David W.

2014-01-01

Study Objectives: To determine whether learning deficits occur during acute exacerbation of spontaneous sleep related breathing disorder (SRBD) in rats with high (Brown Norway; BN) and low (Zucker Lean; ZL) apnea propensity. Design: Spatial acquisition (3 days) and reversal learning (3 days) in the Morris water maze (MWM) with polysomnography (12:00–08:00): (1) with acute SRBD exacerbation (by 20-h hyperoxia immediately preceding reversal learning) or (2) without SRBD exacerbation (room air throughout). Setting: Randomized, placebo-controlled, repeated-measures design. Participants: 14 BN rats; 16 ZL rats. Interventions: 20-h hyperoxia. Measurements and Results: Apneas were detected as cessation of respiration ≥ 2 sec. Swim latency in MWM, apnea indices (AI; apneas/hour of sleep) and percentages of recording time for nonrapid eye movement (NREM), rapid eye movement (REM), and total sleep were assessed. Baseline AI in BN rats was more than double that of ZL rats (22.46 ± 2.27 versus 10.7 ± 0.9, P = 0.005). Hyperoxia increased AI in both BN (34.3 ± 7.4 versus 22.46 ± 2.27) and ZL rats (15.4 ± 2.7 versus 10.7 ± 0.9) without changes in sleep stage percentages. Control (room air) BN and ZL rats exhibited equivalent acquisition and reversal learning. Acute exacerbation of AI by hyperoxia produced a reversal learning performance deficit in BN but not ZL rats. In addition, the percentage of REM sleep and REM apnea index in BN rats during hyperoxia negatively correlated with reversal learning performance. Conclusions: Acute exacerbation of sleep related breathing disorder by hyperoxia impairs reversal learning in a rat strain with high apnea propensity, but not a strain with a low apnea propensity. This suggests a non-linear threshold effect may contribute to the relationships between sleep apnea and cognitive dysfunctions, but strain-specific differences also may be important. Citation: Topchiy I, Amodeo DA, Ragozzino ME, Waxman J, Radulovacki M, Carley DW. Acute exacerbation of sleep apnea by hyperoxia impairs cognitive flexibility in brown-norway rats. SLEEP 2014;37(11):1851-1861. PMID:25364080

Treadmill exercise attenuates the severity of physical dependence, anxiety, depressive-like behavior and voluntary morphine consumption in morphine withdrawn rats receiving methadone maintenance treatment.

PubMed

Alizadeh, Maryam; Zahedi-Khorasani, Mahdi; Miladi-Gorji, Hossein

2018-05-30

This study was designed to examine whether treadmill exercise would attenuate the severity of physical dependence, methadone-induced anxiety, depression and voluntary morphine consumption in morphine withdrawn rats receiving methadone maintenance treatment (MMT). The rats were chronically treated with bi-daily doses (10 mg/kg, at 12 h intervals) of morphine for 14 days. The exercising rats receiving MMT were forced to run on a motorized treadmill for 30 days during morphine withdrawal. Then, rats were tested for the severity of morphine dependence, the elevated plus-maze (EPM), sucrose preference test (SPT) and voluntary morphine consumption using a two-bottle choice (TBC) paradigm. The results showed that naloxone- precipitated opioid withdrawal signs were decreased in exercising morphine-dependent rats receiving MMT than sedentary rats. Also, the exercising morphine-dependent rats receiving MMT exhibited an increased time on open arms, preference for sucrose and a lower morphine preference ratio than sedentary rats. We conclude that treadmill exercise decreased the severity of physical dependence, anxiety/depressive-like behaviors and also the voluntary morphine consumption in morphine withdrawn rats receiving MMT. Thus, exercise may benefit in the treatment of addicts during MMT. Copyright © 2018. Published by Elsevier B.V.

Effects of different varieties of Maca (Lepidium meyenii) on bone structure in ovariectomized rats.

PubMed

Gonzales, Carla; Cárdenas-Valencia, Isaias; Leiva-Revilla, Johanna; Anza-Ramirez, Cecilia; Rubio, Julio; Gonzales, Gustavo F

2010-01-01

This study was designed to determine the effect of different varieties of maca (Lepidium meyenii) on bone structure in ovariectomized (OVX) rats. 36 female rats were randomly divided into 6 groups: sham and OVX rats treated with vehicle, estradiol (40 microg/kg), black, yellow or red maca (63 mg/ml) for 4 weeks. At the end of the treatment, uterine weight, femoral bone and lumbar vertebra histomorphology were assessed. Ovariectomy reduced weight, diameter and width of the femoral bone. Estradiol, black and red maca treatment reduced the effect of ovariectomy on these variables. Histological analyses revealed that estradiol, black and red maca treatments reversed the effect of ovariectomy by increasing the trabecular bone area in the second lumbar vertebra. Uterine weight was reduced in OVX rats, and estradiol but neither black nor red maca increased uterine weight. Red and black maca have protective effects on bone architecture in OVX rats without showing estrogenic effects on uterine weight. 2010 S. Karger AG, Basel.

Effect of leukemia inhibitory factor and forskolin on establishment of rat embryonic stem cell lines.

PubMed

Hirabayashi, Masumi; Goto, Teppei; Tamura, Chihiro; Sanbo, Makoto; Hara, Hiromasa; Hochi, Shinichi

2014-03-07

This study was designed to investigate whether supplementation of 2i medium with leukemia inhibitory factor (LIF) and/or forskolin would support establishment of germline-competent rat embryonic stem (ES) cell lines. Due to the higher likelihood of outgrowth rates, supplementation of forskolin with or without LIF contributed to the higher establishment efficiency of ES cell lines in the WDB strain. Germline transmission competency of the chimeric rats was not influenced by the profile of ES cell lines until their establishment. When the LIF/forskolin-supplemented 2i medium was used, the rat strain used as the blastocyst donor, such as the WI strain, was a possible factor negatively influencing the establishment efficiency of ES cell lines. Once ES cell lines were established, all lines were found to be germline-competent by a progeny test in chimeric rats. In conclusion, both LIF and forskolin are not essential but can play a beneficial role in the establishment of "genuine" rat ES cell lines.

Voluntary Wheel Running Induces Exercise-Seeking Behavior in Male Rats: A Behavioral Study.

PubMed

Naghshvarian, Mojtaba; Zarrindast, Mohammad-Reza; Sajjadi, Seyedeh Fatemeh

2017-12-01

Research evidence shows that exercise is associated with positive physical and mental health. Moreover, exercise and wheel running in rats activate overlapping neural systems and reward system. The most commonly used models for the study of rewarding and aversive effects of exercise involve using treadmill and wheel running paradigms in mice or rats. The purpose of our experiment was to study the influence of continuous voluntary exercise on exercise-seeking behavior. In this experimental study, we used 24 adult male Sprague-Dawley rats weighing 275-300 g on average. Rats were divided into 3 experimental groups for 4 weeks of voluntary wheel running. Each rat ran in the cage equipped with a wheel during 24 hours. A within-subject repeated measure design was employed to evaluate the trend of running and running rates. We found that time and higher levels of exercise will increase exercise tendency. Our results also show that the interaction of exercise within 4 weeks and different levels of exercise can significantly promote rats' exercise-seeking behavior (F = 5.440; df = 2.08; P < 0.001). Our data suggest that voluntary wheel running can increase the likelihood of extreme and obsessive exercising which is a form of non-drug addiction. 2017 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The Effect of Endogenous Adenosine on Neuronal Activity in Rats: An FDG PET Study

PubMed Central

Paul, Soumen; Zhang, Dali; Mzengeza, Shadreck; Ko, Ji Hyun

2016-01-01

ABSTRACT 2–18F‐fluorodeoxy‐D‐glucose (FDG) is a glucose analog that is taken up by cells and phosphorylated. The amount of FDG accumulated by cells is a measure of the rate of glycolysis, which reflects cellular activity. As the levels and actions of the neuromodulator adenosine are dynamically regulated by neuronal activity, this study was designed to test whether endogenous adenosine affects tissue accumulation of FDG as assessed by positron emission tomography (PET) or by postmortem analysis of tissue radioactivity. Rats were given an intraperitoneal injection of the adenosine A1 receptor antagonist 8‐cyclopentyl‐1,3‐dipropyl‐xanthine (DPCPX, 3 mg/kg), the adenosine kinase inhibitor ABT‐702 (3 mg/kg), or vehicle 10 minutes prior to an intravenous injection of FDG (15.4 ± 0.7 MBq per rat). Rats were then subjected to a 15 minute static PET scan. Reconstructed images were normalized to FDG PET template for rats and standard uptake values (SUVs) were calculated. To examine the regional effect of active treatment compared to vehicle, statistical parametric mapping analysis was performed. Whole‐brain FDG uptake was not affected by drug treatment. Significant regional hypometabolism was detected, particularly in cerebellum, of DPCPX‐ and ABT‐702 treated rats, relative to vehicle‐treated rats. Thus, endogenous adenosine can affect FDG accumulation although this effect is modest in quiescent rats. PMID:27082948

Pre-treatment with puerarin affects pharmacokinetics of warfarin, but not clopidogrel, in experimental rats.

PubMed

Liu, An-Chang; Zhao, Li-Xia; Yu, Shu-Wen; Lou, Hong-Xiang

2015-04-01

The present study was designed to determine the effects of puerarin pre-treatment on the pharmacokinetics of the oral anticoagulant agent warfarin and the antiplatelet agent clopidogrel in rats. In the treatment group, rats was gavaged with warfarin or clopidogrel after repeated treatment with puerarin at intraperitoneal doses of 20, 60, or 200 mg·kg(-1) for 7 days, while rats in the control group were administrated only with the same dose warfarin or clopidogrel. Plasma samples were obtained at the prescribed times and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). The results showed that rats treated with puerarin at all the test doses of 20, 60 and 200 mg·kg(-1) were found to affect the pharmacokinetics of warfarin, but not clopidogrel, suggesting a potential herb-drug interaction between puerarin and warfarin. Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Comparison of peripheral nerve damages according to glucose control timing in experimental diabetes.

PubMed

Jin, H Y; Kang, S M; Liu, W J; Song, C H; Lee, K A; Baek, H S; Park, T S

2012-09-01

In addition to tight glucose control, early intensive therapy has been reported to be more important for the prevention of diabetic micro- and macro-vascular complications. What is not known exactly is the quantitative difference according to timing delay in glucose control and whether early period control is really better than late control in terms of diabetic peripheral neuropathy. In this study, we investigated the effect of timing differences in glucose control on the peripheral nerves in an experimental diabetic model. 5 groups (6-8 rats in each group) were comprised of normal glucose rats (designated control), rats with hyperglycemia (designated DM), rats with glucose control for the entire 28-week study period (designated DM + INS [W0-28]), rats with glucose control for the early 14-week period followed by hyperglycemia for the late 14-week period (designated DM + INS [W0-14]), and rats with hyperglycemia for the early 14-week period followed by glucose control in the late 14-week period (designated DM + INS [W15-28]). We found that the current perception threshold (CPT) was lower in the DM + INS (W0-28) and DM + INS (W15-28) groups than in the DM + INS (W0-14) or DM groups (P<0.05). The mean myelinated fiber area of the sciatic nerve was significantly greater in the DM + INS (W0-28) and DM + INS (W15-28) groups (63.5±2.32 and 60.1±2.14 um, respectively) than in the DM + INS (W0-14) or DM groups (55.5±2.81 or 51.5±2.64 um, respectively) (P<0.05), and the intraepidermal nerve fiber (IENF) density was significantly higher in the DM + INS (W0-28) and DM + INS (W15-28) groups (6.9±0.46 and 6.8±0.11, respectively) than in the DM + INS (W0-14) or DM groups (59.5±0.32 and 5.3±0.39/mm, respectively) (P<0.05). Our results indicate that continuous glucose control is necessary to alleviate peripheral nerve damage and that glycemic control during the later period may be more important than early period management. The importance of continuous glucose control, including the later period of diabetes, should therefore be emphasized in diabetic peripheral neuropathy. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Effect of Royal Jelly on spatial learning and memory in rat model of streptozotocin-induced sporadic Alzheimer's disease

PubMed Central

Zamani, Zohre; Reisi, Parham; Alaei, Hojjatallah; Pilehvarian, Ali Asghar

2012-01-01

Background: It has been recently demonstrated that Royal jelly (RJ) has a beneficial role on neural functions. Alzheimer's disease (AD) is associated with impairments of learning and memory. Therefore, the present study was designed to examine the effect of RJ on spatial learning and memory in rats after intracerebroventricular injection of streptozotocin (icv-STZ). Materials and Methods: Rats were infused bilaterally with an icv injection of STZ, while sham rats received vehicle only. The rats were feed with RJ-contained food (3% w/w) (lyophilized RJ mixed with powdered regular food) or regular food for 10 days. Then spatial learning and memory was tested in the rats by Morris water maze test. Results: Results showed that in icv-STZ group latency and path length were increased as compared to sham group, also icv-STZ rats less remembered the target quadrant that previously the platform was located; however, these were protected significantly in STZ group that received RJ-containing food. Conclusions: Our findings support the potential neuroprotective role of RJ and its helpful effects in AD. PMID:23210085

Analysis of energy expenditure in diet-induced obese rats

PubMed Central

Assaad, Houssein; Yao, Kang; Tekwe, Carmen D.; Feng, Shuo; Bazer, Fuller W.; Zhou, Lan; Carroll, Raymond J.; Meininger, Cynthia J.; Wu, Guoyao

2014-01-01

Development of obesity in animals is affected by energy intake, dietary composition, and metabolism. Useful models for studying this metabolic problem are Sprague-Dawley rats fed low-fat (LF) or high-fat (HF) diets beginning at 28 days of age. Through experimental design, their dietary intakes of energy, protein, vitamins, and minerals per kg body weight (BW) do not differ in order to eliminate confounding factors in data interpretation. The 24-h energy expenditure of rats is measured using indirect calorimetry. A regression model is constructed to accurately predict BW gain based on diet, initial BW gain, and the principal component scores of respiratory quotient and heat production. Time-course data on metabolism (including energy expenditure) are analyzed using a mixed effect model that fits both fixed and random effects. Cluster analysis is employed to classify rats as normal-weight or obese. HF-fed rats are heavier than LF-fed rats, but rates of their heat production per kg non-fat mass do not differ. We conclude that metabolic conversion of dietary lipids into body fat primarily contributes to obesity in HF-fed rats. PMID:24896330

Does inducible NOS have a protective role against hypoxia/reoxygenation injury in rat heart?

PubMed

Rus, Alma; del Moral, Maria Luisa; Molina, Francisco; Peinado, Maria Angeles

2011-01-01

The present study analyzes the role of the nitric oxide (NO) derived from inducible NO synthase (iNOS) under cardiac hypoxia/reoxygenation situations. For this, we have designed a follow-up study of different parameters of cell and tissue damage in the heart of Wistar rats submitted for 30 min to acute hypobaric hypoxia, with or without prior treatment with the selective iNOS inhibitor N-(3-(aminomethyl)benzyl) acetamidine or 1400W (10 mg/kg). The rats were studied at 0 h, 12 h, and 5 days of reoxygenation, analyzing NO production (NOx), lipid peroxidation, apoptosis, and protein nitration expression and location. This is the first time-course study which analyzes the effects of the iNOS inhibition by 1400W during hypoxia/reoxygenation in the adult rat heart. The results show that when 1400W was administered before the hypoxic episode, NOx levels fell, while both the lipid peroxidation level and the percentage of apoptotic cells rose throughout the reoxygenation period. Levels of nitrated proteins expression fell only at 12 h post-hypoxia. The inhibition of iNOS raises the peroxidative and apoptotic level in the hypoxic heart indicating that this isoform may have a protective effect on this organ against hypoxia/reoxygenation injuries, and challenging the conventional wisdom that iNOS is deleterious under these conditions. These findings could help in the design of new treatments based on NO pharmacology against hypoxia/reoxygenation dysfunctions. Copyright © 2011 Elsevier Inc. All rights reserved.

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

PubMed

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

2014-11-01

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

A ligand-based comparative molecular field analysis (CoMFA) and homology model based molecular docking studies on 3', 4'-dihydroxyflavones as rat 5-lipoxygenase inhibitors: Design of new inhibitors.

PubMed

Ahamed, T K Shameera; Muraleedharan, K

2017-12-01

In this study, ligand based comparative molecular field analysis (CoMFA) with five principal components was performed on class of 3', 4'-dihydroxyflavone derivatives for potent rat 5-LOX inhibitors. The percentage contributions in building of CoMFA model were 91.36% for steric field and 8.6% for electrostatic field. R 2 values for training and test sets were found to be 0.9320 and 0.8259, respectively. In case of LOO, LTO and LMO cross validation test, q 2 values were 0.6587, 0.6479 and 0.5547, respectively. These results indicate that the model has high statistical reliability and good predictive power. The extracted contour maps were used to identify the important regions where the modification was necessary to design a new molecule with improved activity. The study has developed a homology model for rat 5-LOX and recognized the key residues at the binding site. Docking of most active molecule to the binding site of 5-LOX confirmed the stability and rationality of CoMFA model. Based on molecular docking results and CoMFA contour plots, new inhibitors with higher activity with respect to the most active compound in data set were designed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chromium picolinate inhibits cholesterol-induced stimulation of platelet aggregation in hypercholesterolemic rats.

PubMed

Seif, A A

2015-06-01

Hypercholesterolemia indirectly increases the risk of myocardial infarction by enhancing platelet aggregation. Chromium has been shown to lower plasma lipids. This study was designed to investigate whether chromium inhibits platelet aggregation under hypercholesterolemic conditions. Albino rats were divided into four groups: control rats fed with a normolipemic diet (NLD group), chromium-supplemented rats fed with NLD (NLD + Cr group), rats fed with a high-fat diet (HF group), and chromium-supplemented rats fed with HF (HF + Cr group). After 10 weeks, blood was collected to determine adenosine diphosphate and collagen-induced platelet aggregation and plasma levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoprotein A1, apolipoprotein B, and thromboxane B2. Low-density lipoprotein cholesterol was calculated by Friedewald formula. High-fat diet animals displayed significant elevation of plasma lipids and platelet aggregation which was normalized to control levels by chromium supplementation. Chromium supplementation in normolipemic (NLD + Cr) rats did not produce significant changes in either plasma lipids or platelet activity. Chromium supplementation to hypercholesterolemic rats improves the lipid profile and returns platelet hyperaggregability to control levels. This normalization is mostly due to a reduction in plasma cholesterol level.

Characteristics of the Built Environment and the Presence of the Norway Rat in New York City: Results From a Neighborhood Rat Surveillance Program, 2008-2010.

PubMed

Johnson, Sarah; Bragdon, Caroline; Olson, Carolyn; Merlino, Mario; Bonaparte, Sancia

2016-06-01

Characteristics of an urban setting such as New York City (NYC), including readily available putrescible waste and ample underground infrastructure, make it highly attractive to the Norway rat (Rattus norvegicus). To identify property and neighborhood characteristics associated with rat presence, recent inspectional results were analyzed from over 77,000 properties in the Bronx and Manhattan. Variables capturing the location and density of factors believed to promote rat populations were tested individually and in combination in models predicting rat activity. We found that property-specific characteristics typically associated with high garbage volume, including large numbers of residential units, public ownership, and open-space designation (parks, outdoor recreation, or vacant land) were the most important factors in explaining increased rat presence across neighborhoods in NYC. Interventions that involved improved garbage management and street sanitation within a designated area reduced the likelihood of finding rats, especially in medium- and high-poverty neighborhoods. Neighborhood characteristics, such as being near a railroad or subway line, having a school nearby, the presence of numerous restaurants, or having older infrastructure, also contributed to the increased likelihood of rats. Our results support the use of built environment data to target community-level interventions and capture emerging rat infestations.

Fasting: a major limitation for resistance exercise training effects in rodents

PubMed Central

das Neves, W.; de Oliveira, L.F.; da Silva, R.P.; Alves, C.R.R.; Lancha, A.H.

2017-01-01

Protocols that mimic resistance exercise training (RET) in rodents present several limitations, one of them being the electrical stimulus, which is beyond the physiological context observed in humans. Recently, our group developed a conditioning system device that does not use electric shock to stimulate rats, but includes fasting periods before each RET session. The current study was designed to test whether cumulative fasting periods have some influence on skeletal muscle mass and function. Three sets of male Wistar rats were used in the current study. The first set of rats was submitted to a RET protocol without food restriction. However, rats were not able to perform exercise properly. The second and third sets were then randomly assigned into three experimental groups: 1) untrained control rats, 2) untrained rats submitted to fasting periods, and 3) rats submitted to RET including fasting periods before each RET session. While the second set of rats performed a short RET protocol (i.e., an adaptation protocol for 3 weeks), the third set of rats performed a longer RET protocol including overload (i.e., 8 weeks). After the short-term protocol, cumulative fasting periods promoted loss of weight (P<0.001). After the longer RET protocol, no difference was observed for body mass, extensor digitorum longus (EDL) morphology or skeletal muscle function (P>0.05 for all). Despite no effects on EDL mass, soleus muscle displayed significant atrophy in the fasting experimental groups (P<0.01). Altogether, these data indicate that fasting is a major limitation for RET in rats. PMID:29185588

Fasting: a major limitation for resistance exercise training effects in rodents.

PubMed

das Neves, W; de Oliveira, L F; da Silva, R P; Alves, C R R; Lancha, A H

2017-11-17

Protocols that mimic resistance exercise training (RET) in rodents present several limitations, one of them being the electrical stimulus, which is beyond the physiological context observed in humans. Recently, our group developed a conditioning system device that does not use electric shock to stimulate rats, but includes fasting periods before each RET session. The current study was designed to test whether cumulative fasting periods have some influence on skeletal muscle mass and function. Three sets of male Wistar rats were used in the current study. The first set of rats was submitted to a RET protocol without food restriction. However, rats were not able to perform exercise properly. The second and third sets were then randomly assigned into three experimental groups: 1) untrained control rats, 2) untrained rats submitted to fasting periods, and 3) rats submitted to RET including fasting periods before each RET session. While the second set of rats performed a short RET protocol (i.e., an adaptation protocol for 3 weeks), the third set of rats performed a longer RET protocol including overload (i.e., 8 weeks). After the short-term protocol, cumulative fasting periods promoted loss of weight (P<0.001). After the longer RET protocol, no difference was observed for body mass, extensor digitorum longus (EDL) morphology or skeletal muscle function (P>0.05 for all). Despite no effects on EDL mass, soleus muscle displayed significant atrophy in the fasting experimental groups (P<0.01). Altogether, these data indicate that fasting is a major limitation for RET in rats.

Differences in the Rate of In Situ Mammary Gland Development and Other Developmental Endpoints in Three Strains of Female Rat Commonly Used in Mammary Carcinogenesis Studies: Implications for Timing of Carcinogen Exposure

PubMed Central

Stanko, Jason P.; Kissling, Grace E.; Chappell, Vesna A.; Fenton, Suzanne E.

2016-01-01

The potential of chemicals to alter susceptibility to mammary tumor formation is often assessed using a carcinogen-induced study design in various rat strains. The rate of mammary gland development must be considered so that the timing of carcinogen administration is impactful. In this study, in situ mammary gland (MG) development was assessed in females of the Harlan Sprague Dawley (Hsd:SD), Charles River Sprague Dawley (Crl:SD), and Charles River Long Evans (Crl:LE) rat strains at postnatal day (PND) 25, 33, and 45. Development was evaluated by physical assessment of growth parameters, developmental scoring, and quantitative morphometric analysis. Though body weight was consistently lower and day of vaginal opening (VO) occurred latest in female Hsd:SD rats, they exhibited accelerated pre-and peripubertal MG development compared to other strains. Glands of Crl:SD and Crl:LE rats exhibited significantly more terminal end buds (TEBs) and TEB/mm than Hsd:SD rats around the time of VO. These data suggest a considerable difference in rate of MG development across commonly used strains, which is independent of body weight and timing of VO. In mammary tumor induction studies employing these strains, administration of the carcinogen should be timed appropriately, based on strain, to specifically target the peak of TEB occurrence. PMID:27613105

Grape seed proanthocyanidins ameliorates isoproterenol-induced myocardial injury in rats by stabilizing mitochondrial and lysosomal enzymes: an in vivo study.

PubMed

Karthikeyan, K; Sarala Bai, B R; Niranjali Devaraj, S

2007-11-30

This study was designed to examine the effects of grape seed proanthocyanidins (GSP) against myocardial injury (MI) induced by isoproterenol (ISO), in a rat model. Induction of rats with ISO (85 mg/kg body weight, subcutaneously) for 2 days resulted in a significant decrease in the activities of heart mitochondrial enzymes (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase and alpha-ketoglutarate dehydrogenase) and respiratory chain enzymes (NADH dehydrogenase and cytochrome c oxidase). The activities of lysosomal enzymes (alpha-d-glucuronidase, alpha-d-N-acetylglucosaminidase, cathepsin-D, acid phosphatases and alpha-d-galactosidase) were increased significantly in the heart and serum of ISO-induced rats. The prior administration of GSP for 6 days a week for 5 weeks significantly increased the activities of mitochondrial and respiratory chain enzymes and significantly decreased the activities of lysosomal enzymes in the heart tissues of ISO-induced rats, which proves the stress stabilizing action of GSP. Oral administration of grape seed proanthocyanidins alone (50, 100 and 150 mg/kg) to normal rats did not show any significant effect in all the parameters studied. These biochemical functional alterations were supported by the macroscopic enzyme mapping assay of ischemic myocardium. Thus, this study shows that 100 and 150 mg/kg of GSP gives protection against ISO-induced MI and demonstrates that GSP has a significant effect in the protection of heart.

Delay Discounting in Lewis and Fischer 344 Rats: Steady-state and Rapid-determination Adjusting-amount Procedures

PubMed Central

Stein, Jeffrey S; Pinkston, Jonathan W; Brewer, Adam T; Francisco, Monica T; Madden, Gregory J

2012-01-01

Lewis rats have been shown to make more impulsive choices than Fischer 344 rats in discrete-trial choice procedures that arrange fixed (i.e., nontitrating) reinforcement parameters. However, nontitrating procedures yield only gross estimates of preference, as choice measures in animal subjects are rarely graded at the level of the individual subject. The present study was designed to examine potential strain differences in delay discounting using an adjusting-amount procedure, in which distributed (rather than exclusive) choice is observed due to dynamic titration of reinforcer magnitude across trials. Using a steady-state version of the adjusting-amount procedure in which delay was manipulated between experimental conditions, steeper delay discounting was observed in Lewis rats compared to Fischer 344 rats; further, delay discounting in both strains was well described by the traditional hyperbolic discounting model. However, upon partial completion of the present study, a study published elsewhere (Wilhelm & Mitchell, 2009) demonstrated no difference in delay discounting between these strains with the use of a more rapid version of the adjusting-amount procedure (i.e., in which delay is manipulated daily). Thus, following completion of the steady-state assessment in the present study, all surviving Lewis and Fischer 344 rats completed an approximation of this rapid-determination procedure in which no strain difference in delay discounting was observed. PMID:22693360

Delay discounting in Lewis and Fischer 344 rats: steady-state and rapid-determination adjusting-amount procedures.

PubMed

Stein, Jeffrey S; Pinkston, Jonathan W; Brewer, Adam T; Francisco, Monica T; Madden, Gregory J

2012-05-01

Lewis rats have been shown to make more impulsive choices than Fischer 344 rats in discrete-trial choice procedures that arrange fixed (i.e., nontitrating) reinforcement parameters. However, nontitrating procedures yield only gross estimates of preference, as choice measures in animal subjects are rarely graded at the level of the individual subject. The present study was designed to examine potential strain differences in delay discounting using an adjusting-amount procedure, in which distributed (rather than exclusive) choice is observed due to dynamic titration of reinforcer magnitude across trials. Using a steady-state version of the adjusting-amount procedure in which delay was manipulated between experimental conditions, steeper delay discounting was observed in Lewis rats compared to Fischer 344 rats; further, delay discounting in both strains was well described by the traditional hyperbolic discounting model. However, upon partial completion of the present study, a study published elsewhere (Wilhelm & Mitchell, 2009) demonstrated no difference in delay discounting between these strains with the use of a more rapid version of the adjusting-amount procedure (i.e., in which delay is manipulated daily). Thus, following completion of the steady-state assessment in the present study, all surviving Lewis and Fischer 344 rats completed an approximation of this rapid-determination procedure in which no strain difference in delay discounting was observed.

Synergistic effect of quercetin and quinic acid by alleviating structural degeneration in the liver, kidney and pancreas tissues of STZ-induced diabetic rats: a mechanistic study.

PubMed

Arya, Aditya; Al-Obaidi, Mazen M Jamil; Shahid, Nayiar; Bin Noordin, Mohamed Ibrahim; Looi, Chung Yeng; Wong, Won Fen; Khaing, Si Lay; Mustafa, Mohd Rais

2014-09-01

The aim of this study was to investigate the synergistic effects of quercetin (QE) and quinic acid (QA) on a STZ-induced diabetic rat model to determine their potential role in alleviating diabetes and its associated complications. In our study design, diabetic rats were treated with single and combined doses of QE and QA for 45days to analyse their effects on liver, kidney and pancreas tissues. The study result showed that QE and QA treated groups down-regulated hyperglycaemia and oxidative stress by up-regulating insulin and C-peptide levels. Moreover, histological observations of the liver, kidney and pancreas of diabetic rats treated with single and combined doses of QE and QA showed a significant improvement in the structural degeneration. Interestingly, the combination dose of QE and QA (50 mg/kg) exhibited maximum inhibition of the pro-apoptotic protein Bax expression and demonstrate enhancement of the anti-apoptotic protein Bcl-2 expression in the kidney tissues, suggesting a protective role in the kidneys of diabetic rats. Taken together, these results indicates the synergistic effects of QE and QA in ameliorating hyperglycaemia, hyperlipidemia and insulin resistance in diabetic rats and therefore, open a new window of research on the combinatorial therapy of flavonoids. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of some selected blood parameters and histopathology of liver and kidney of rats fed protein-substituted mucuna flour and derived protein rich product.

PubMed

Ngatchic, Josiane Therese Metsagang; Sokeng, Selestion Dongmo; Njintang, Nicolas Yanou; Maoundombaye, Theophile; Oben, Julius; Mbofung, Carl Moses F

2013-07-01

This comparative study reports the nutritional and toxicological characteristics of Mucuna pruriens flour and a protein-rich product developed from it. The protein-rich mucuna product (PRMP) was obtained by the three steps procedure: protein solubilization, heat-coagulation and sieving. Three weeks rats (n=6 per group) were fed for 28 days on standard protein-substituted rat feed with mucuna flour or PRMP. The experimental design was a factorial design with three mucuna accessions (Velvet, Black and White) and two treatments (flour and PRMP). The protein content ranged 27.2-31.5 g/100 g for flour and 58.8-61.1% for PRMP. Processing flour into PRMP led to a significant (p<0.05) reduction of tannins (50%), total polyphenols (50%) and trypsin inhibitors (94%). The rats fed PMRP diets witnessed weight gain similar to casein, while those fed mucuna flour lost weight. The levels of total cholesterol, HDL-cholesterol and LDL-cholesterol observed in animals groups fed mucuna flour and PRMP were significantly lower (p<0.05) than the control group. In addition lymphocytes, granulocytes, red blood cells, hemoglobin and hematocrit of rats fed mucuna flour were significantly (p<0.05) lower than values in other rats groups. Kidneys glomerular sclerosis and high creatinine levels were observed in group fed mucuna flour. PRMP then represents a good alternative of using mucuna proteins for human nutrition. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Evolutionary Design and Simulation of a Tube Crawling Inspection Robot

NASA Technical Reports Server (NTRS)

Craft, Michael; Howsman, Tom; ONeil, Daniel; Howell, Joe T. (Technical Monitor)

2002-01-01

The Space Robotics Assembly Team Simulation (SpaceRATS) is an expansive concept that will hopefully lead to a space flight demonstration of a robotic team cooperatively assembling a system from its constitutive parts. A primary objective of the SpaceRATS project is to develop a generalized evolutionary design approach for multiple classes of robots. The portion of the overall SpaceRats program associated with the evolutionary design and simulation of an inspection robot's morphology is the subject of this paper. The vast majority of this effort has concentrated on the use and modification of Darwin2K, a robotic design and simulation software package, to analyze the design of a tube crawling robot. This robot is designed for carrying out inspection duties in relatively inaccessible locations within a liquid rocket engine similar to the SSME. A preliminary design of the tube crawler robot was completed, and the mechanical dynamics of the system were simulated. An evolutionary approach to optimizing a few parameters of the system was utilized, resulting in a more optimum design.

Imaging and serum biomarkers reflecting the functional efficacy of extended erythropoietin treatment in rats following infantile traumatic brain injury.

PubMed

Robinson, Shenandoah; Winer, Jesse L; Berkner, Justin; Chan, Lindsay A S; Denson, Jesse L; Maxwell, Jessie R; Yang, Yirong; Sillerud, Laurel O; Tasker, Robert C; Meehan, William P; Mannix, Rebekah; Jantzie, Lauren L

2016-06-01

OBJECTIVE Traumatic brain injury (TBI) is a leading cause of death and severe morbidity for otherwise healthy full-term infants around the world. Currently, the primary treatment for infant TBI is supportive, as no targeted therapies exist to actively promote recovery. The developing infant brain, in particular, has a unique response to injury and the potential for repair, both of which vary with maturation. Targeted interventions and objective measures of therapeutic efficacy are needed in this special population. The authors hypothesized that MRI and serum biomarkers can be used to quantify outcomes following infantile TBI in a preclinical rat model and that the potential efficacy of the neuro-reparative agent erythropoietin (EPO) in promoting recovery can be tested using these biomarkers as surrogates for functional outcomes. METHODS With institutional approval, a controlled cortical impact (CCI) was delivered to postnatal Day (P)12 rats of both sexes (76 rats). On postinjury Day (PID)1, the 49 CCI rats designated for chronic studies were randomized to EPO (3000 U/kg/dose, CCI-EPO, 24 rats) or vehicle (CCI-veh, 25 rats) administered intraperitoneally on PID1-4, 6, and 8. Acute injury (PID3) was evaluated with an immunoassay of injured cortex and serum, and chronic injury (PID13-28) was evaluated with digitized gait analyses, MRI, and serum immunoassay. The CCI-veh and CCI-EPO rats were compared with shams (49 rats) primarily using 2-way ANOVA with Bonferroni post hoc correction. RESULTS Following CCI, there was 4.8% mortality and 55% of injured rats exhibited convulsions. Of the injured rats designated for chronic analyses, 8.1% developed leptomeningeal cyst-like lesions verified with MRI and were excluded from further study. On PID3, Western blot showed that EPO receptor expression was increased in the injured cortex (p = 0.008). These Western blots also showed elevated ipsilateral cortex calpain degradation products for αII-spectrin (αII-SDPs; p < 0.001), potassium chloride cotransporter 2 (KCC2-DPs; p = 0.037), and glial fibrillary acidic protein (GFAP-DPs; p = 0.002), as well as serum GFAP (serum GFAP-DPs; p = 0.001). In injured rats multiplex electrochemiluminescence analyses on PID3 revealed elevated serum tumor necrosis factor alpha (TNFα p = 0.01) and chemokine (CXC) ligand 1 (CXCL1). Chronically, that is, in PID13-16 CCI-veh rats, as compared with sham rats, gait deficits were demonstrated (p = 0.033) but then were reversed (p = 0.022) with EPO treatment. Diffusion tensor MRI of the ipsilateral and contralateral cortex and white matter in PID16-23 CCI-veh rats showed widespread injury and significant abnormalities of functional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD); MD, AD, and RD improved after EPO treatment. Chronically, P13-P28 CCI-veh rats also had elevated serum CXCL1 levels, which normalized in CCI-EPO rats. CONCLUSIONS Efficient translation of emerging neuro-reparative interventions dictates the use of age-appropriate preclinical models with human clinical trial-compatible biomarkers. In the present study, the authors showed that CCI produced chronic gait deficits in P12 rats that resolved with EPO treatment and that chronic imaging and serum biomarkers correlated with this improvement.

Amygdala Kindling Alters Estrus Cycle and Ovarian Morphology in the Rat

PubMed Central

Pan, Juan; Zhang, Lingwu; Wang, Feng; Liu, Dan

2014-01-01

The objective of this study is to explore the effects of amygdala kindling on estrus cycle and ovarian morphology. Thirty-five female rats at the age of 8 weeks were randomly designated to electrode kindled, sham-kindled, and normal controls. Kindled rats were implanted with kindling electrodes in the left basolateral amygdala and kindled by brief suprathreshold stimulations with a bipolar electrode. Estrous cycles were daily monitored through vaginal smears. Electrographic and behavioral seizures were recorded and ovarian morphology was evaluated by light and electron microscopies. Our results showed that the kindled rats lost their ovarian periodicity displayed significant ovarian enlargement. H&E staining revealed increased number of growing follicles and total follicles, as well as polycysts in the ovaries of the kindled animals compared to sham and control animals. Ultrastructural study detected numerous apoptotic granulosa cells in growing follicles and thecal cell hyperplasia with secretary granules in the thecal cells in the kindled rats. The results suggest that amygdala kindling is a risk factor for the development of polycystic ovary syndrome. PMID:25285307

Potential Effect of Bacopa monnieri on Nitrobenzene Induced Liver Damage in Rats.

PubMed

Menon, B Rajalakshmy; Rathi, M A; Thirumoorthi, L; Gopalakrishnan, V K

2010-10-01

The study was designed to evaluate the hepatoprotective activity of ethanolic extract of Bacopa monnieri in acute experimental liver injury induced by Nitrobenzene in rats. The extract at the dose of 200 mg/kg body weight was administered orally once every day for 10 days. The increased serum marker enzymes, Aspartate transaminase, Alanine transaminase and alkaline phosphatase were restored towards normalization significantly by the extract. Significant increase in SOD, CAT and GPx was observed in extract treated liver injured experimental rats. Histopathological examination of the liver tissues supported the hepatoprotection. It is concluded that the ethanolic extract of Bacopa monieri plant possess good hepatoprotective activity.

Attenuation of Diabetic Conditions by Sida rhombifolia in Moderately Diabetic Rats and Inability to Produce Similar Effects in Severely Diabetic in Rats.

PubMed

Chaturvedi, Padmaja; Kwape, Tebogo Elvis

2015-12-01

This study was done out to evaluate the effects of Sida rhombifolia methanol extract (SRM) on diabetes in moderately diabetic (MD) and severely diabetic (SD) Sprague-Dawley rats. SRM was prepared by soaking the powdered plant material in 70% methanol and rota evaporating the methanol from the extract. Effective hypoglycemic doses were established by performing oral glucose tolerance tests (OGTTs) in normal rats. Hourly effects of SRM on glucose were observed in the MD and the SD rats. Rats were grouped, five rats to a group, into normal control 1 (NC1), MD control 1 (MDC1), MD experimental 1 (MDE1), SD control 1 (SDC1), and SD experimental 1 (SDE1) groups. All rats in the control groups were administered 1 mL of distilled water (DW). The rats in the MDE1 and the SDE1 groups were administered SRM orally at 200 and 300 mg/kg body weight (BW), respectively, dissolved in 1 mL of DW. Blood was collected initially and at intervals of 1 hour for 6 hours to measure blood glucose. A similar experimental design was followed for the 30-day long-term trial. Finally, rats were sacrificed, and blood was collected to measure blood glucose, lipid profiles, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH). OGTTs indicated that two doses (200 and 300 mg/kg BW) were effective hypoglycemic doses in normal rats. Both doses reduced glucose levels after 1 hour in the MDE1 and the SDE1 groups. A long-term trial of SRM in the MD group showed a reduced glucose level, a normal lipid profile, and normal GSH and TBARS levels. In SD rats, SRM had no statistically significant effects on these parameters. Normal weight was achieved in the MD rats, but the SD rats showed reduced BW. The study demonstrates that SRM has potential to alleviate the conditions of moderate diabetic, but not severe diabetes.

Effects of p67phox on the mitochondrial oxidative state in the kidney of Dahl salt-sensitive rats: optical fluorescence 3-D cryoimaging

PubMed Central

Salehpour, F.; Ghanian, Z.; Yang, C.; Zheleznova, N. N.; Kurth, T.; Dash, R. K.; Cowley, A. W.

2015-01-01

The goal of the present study was to quantify and correlate the contribution of the cytosolic p67phox subunit of NADPH oxidase 2 to mitochondrial oxidative stress in the kidneys of the Dahl salt-sensitive (SS) hypertensive rat. Whole kidney redox states were uniquely assessed using a custom-designed optical fluorescence three-dimensional cryoimager to acquire multichannel signals of the intrinsic fluorophores NADH and FAD. SS rats were compared with SS rats in which the cytosolic subunit p67phox was rendered functionally inactive by zinc finger nuclease mutation of the gene (SSp67phox-null rats). Kidneys of SS rats fed a 0.4% NaCl diet exhibited significantly (P = 0.023) lower tissue redox ratio (NADH/FAD; 1.42 ± 0.06, n = 5) than SSp67phox-null rats (1.64 ± 0.07, n = 5), indicating reduced levels of mitochondrial electron transport chain metabolic activity and enhanced oxidative stress in SS rats. When fed a 4.0% salt diet for 21 days, both strains exhibited significantly lower tissue redox ratios (P < 0.001; SS rats: 1.03 ± 0.05, n = 9, vs. SSp67phox-null rats: 1.46 ± 0.04, n = 7) than when fed a 0.4% salt, but the ratio was still significantly higher in SSp67phox rats at the same salt level as SS rats. These results are consistent with results from previous studies that found elevated medullary interstitial fluid concentrations of superoxide and H2O2 in the medulla of SS rats. We conclude that the p67phox subunit of NADPH oxidase 2 plays an important role in the excess production of ROS from mitochondria in the renal medulla of the SS rat. PMID:26062875

Effects of p67phox on the mitochondrial oxidative state in the kidney of Dahl salt-sensitive rats: optical fluorescence 3-D cryoimaging.

PubMed

Salehpour, F; Ghanian, Z; Yang, C; Zheleznova, N N; Kurth, T; Dash, R K; Cowley, A W; Ranji, M

2015-08-15

The goal of the present study was to quantify and correlate the contribution of the cytosolic p67(phox) subunit of NADPH oxidase 2 to mitochondrial oxidative stress in the kidneys of the Dahl salt-sensitive (SS) hypertensive rat. Whole kidney redox states were uniquely assessed using a custom-designed optical fluorescence three-dimensional cryoimager to acquire multichannel signals of the intrinsic fluorophores NADH and FAD. SS rats were compared with SS rats in which the cytosolic subunit p67(phox) was rendered functionally inactive by zinc finger nuclease mutation of the gene (SS(p67phox)-null rats). Kidneys of SS rats fed a 0.4% NaCl diet exhibited significantly (P = 0.023) lower tissue redox ratio (NADH/FAD; 1.42 ± 0.06, n = 5) than SS(p67phox)-null rats (1.64 ± 0.07, n = 5), indicating reduced levels of mitochondrial electron transport chain metabolic activity and enhanced oxidative stress in SS rats. When fed a 4.0% salt diet for 21 days, both strains exhibited significantly lower tissue redox ratios (P < 0.001; SS rats: 1.03 ± 0.05, n = 9, vs. SS(p67phox)-null rats: 1.46 ± 0.04, n = 7) than when fed a 0.4% salt, but the ratio was still significantly higher in SS(p67phox) rats at the same salt level as SS rats. These results are consistent with results from previous studies that found elevated medullary interstitial fluid concentrations of superoxide and H2O2 in the medulla of SS rats. We conclude that the p67(phox) subunit of NADPH oxidase 2 plays an important role in the excess production of ROS from mitochondria in the renal medulla of the SS rat. Copyright © 2015 the American Physiological Society.

Protective Effects of Emodin-Induced Neutrophil Apoptosis via the Ca2+-Caspase 12 Pathway against SIRS in Rats with Severe Acute Pancreatitis.

PubMed

Wang, Gui-Jun; Wang, Yue; Teng, Yong-Sheng; Sun, Fa-Lv; Xiang, Hong; Liu, Jian-Jun; Xia, Shi-Lin; Zhang, Gui-Xin; Chen, Hai-Long; Shang, Dong

2016-01-01

Severe acute pancreatitis (SAP) results in high mortality. This is partly because of early multiple organ dysfunction syndromes that are usually caused by systemic inflammatory response syndrome (SIRS). Many studies have reported the beneficial effects of emodin against SAP with SIRS. However, the exact mechanism underlying the effect of emodin remains unclear. This study was designed to explore the protective effects and underlying mechanisms of emodin against SIRS in rats with SAP. In the present study, cytosolic Ca 2+ levels, calpain 1 activity, and the expression levels of the active fragments of caspases 12 and 3 decreased in neutrophils from rats with SAP and increased after treatment with emodin. Delayed neutrophil apoptosis occurred in rats with SAP and emodin was able to reverse this delayed apoptosis and inhibit SIRS. The effect of emodin on calpain 1 activity, the expression levels of the active fragments of caspases 12 and 3, neutrophil apoptosis, and SIRS scores were attenuated by PD150606 (an inhibitor of calpain). These results suggest that emodin inhibits SIRS in rats with SAP by inducing circulating neutrophil apoptosis via the Ca 2+ -calpain 1-caspase 12-caspase 3 signaling pathway.

Protective Effects of Emodin-Induced Neutrophil Apoptosis via the Ca2+-Caspase 12 Pathway against SIRS in Rats with Severe Acute Pancreatitis

PubMed Central

Wang, Gui-Jun; Wang, Yue; Teng, Yong-Sheng; Sun, Fa-Lv; Xiang, Hong; Liu, Jian-Jun; Xia, Shi-Lin; Zhang, Gui-Xin

2016-01-01

Severe acute pancreatitis (SAP) results in high mortality. This is partly because of early multiple organ dysfunction syndromes that are usually caused by systemic inflammatory response syndrome (SIRS). Many studies have reported the beneficial effects of emodin against SAP with SIRS. However, the exact mechanism underlying the effect of emodin remains unclear. This study was designed to explore the protective effects and underlying mechanisms of emodin against SIRS in rats with SAP. In the present study, cytosolic Ca2+ levels, calpain 1 activity, and the expression levels of the active fragments of caspases 12 and 3 decreased in neutrophils from rats with SAP and increased after treatment with emodin. Delayed neutrophil apoptosis occurred in rats with SAP and emodin was able to reverse this delayed apoptosis and inhibit SIRS. The effect of emodin on calpain 1 activity, the expression levels of the active fragments of caspases 12 and 3, neutrophil apoptosis, and SIRS scores were attenuated by PD150606 (an inhibitor of calpain). These results suggest that emodin inhibits SIRS in rats with SAP by inducing circulating neutrophil apoptosis via the Ca2+-calpain 1-caspase 12-caspase 3 signaling pathway. PMID:28078280

Brain Aging and AD-Like Pathology in Streptozotocin-Induced Diabetic Rats

PubMed Central

Wang, Jian-Qin; Yin, Jie; Song, Yan-Feng; Zhang, Lang; Ren, Ying-Xiang; Wang, De-Gui; Gao, Li-Ping; Jing, Yu-Hong

2014-01-01

Objective. Numerous epidemiological studies have linked diabetes mellitus (DM) with an increased risk of developing Alzheimer's disease (AD). However, whether or not diabetic encephalopathy shows AD-like pathology remains unclear. Research Design and Methods. Forebrain and hippocampal volumes were measured using stereology in serial coronal sections of the brain in streptozotocin- (STZ-) induced rats. Neurodegeneration in the frontal cortex, hypothalamus, and hippocampus was evaluated using Fluoro-Jade C (FJC). Aβ aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA. Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin. Cognitive ability was evaluated through the Morris water maze and inhibitory avoidant box. Results. Rats are characterized by insulin deficiency accompanied with polydipsia, polyphagia, polyuria, and weight loss after STZ injection. The number of FJC-positive cells significantly increased in discrete brain regions of the diabetic rats compared with the age-matched control rats. Hippocampal atrophy, Aβ aggregation, and synapse loss were observed in the diabetic rats compared with the control rats. The learning and memory of the diabetic rats decreased compared with those of the age-matched control rats. Conclusions. Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies. PMID:25197672

Assessment of the hepatoprotective activity of the seeds of Hunteria umbellata (Hallier F.) on carbon tetrachloride (CCl4) induced liver damage in Wistar albino rats

NASA Astrophysics Data System (ADS)

Ogunlana, Olubanke Olujoke; Ogunlana, Oluseyi Ebenezer; Adelani, Isaacson Bababode; Adebayo, Angie Osariem Igbinoba; David, Opetoritse Laju; Adeleye, Oluwaseye Joseph; Udeogu, Stephanie Adaora; Adeyemi, Alaba Oladipupo; Akinyele, Julie Oluranti

2018-04-01

This study was designed to evaluate the hepatoprotective activity of the seeds of Hunteria umbellata (HU) on carbon tetrachloride (CCl4) induced rats. Rats of groups 1 (normal control), 3 and 5 were not treated with CCl4 while rats of groups 2 (negative control), 4 and 6 rats were treated with single dose of CCl4 (2 ml/kg) by intraperitoneal administration. Normal control group 1 rats were given distilled water, groups 3 and 4 rats were given 50 mg/kg of silymarin while groups 5 and 6 rats were given 500 mg/kg of HU. Treatment was administered orally for 28 days and sacrificed on the 29th day after an overnight fast. The weights of the rats were taken before and after the treatment. Blood samples were collected in heparinized tubes and biochemical analysis of liver functions and lipid profile tests were carried out on plasma. There was a significant change (p<0.05) in the levels of alanine aminotransferase, alkaline phosphatase, high density lipoprotein and triglycerides of the CCl4 induced group treated with HU compared to the CCl4 untreated group 2 animals. The results obtained showed that the ethanolic extract of HU has hepatoprotective property.

Phytase supplementation increases bone mineral density, lean body mass and voluntary physical activity in rats fed a low-zinc diet.

PubMed

Scrimgeour, Angus G; Marchitelli, Louis J; Whicker, Jered S; Song, Yang; Ho, Emily; Young, Andrew J

2010-07-01

Phytic acid forms insoluble complexes with nutritionally essential minerals, including zinc (Zn). Animal studies show that addition of microbial phytase (P) to low-Zn diets improves Zn status and bone strength. The present study determined the effects of phytase supplementation on bone mineral density (BMD), body composition and voluntary running activity of male rats fed a high phytic acid, low-Zn diet. In a factorial design, rats were assigned to ZnLO (5 mg/kg diet), ZnLO+P (ZnLO diet with 1500 U phytase/kg) or ZnAD (30 mg/kg diet) groups and were divided into voluntary exercise (EX) or sedentary (SED) groups, for 9 weeks. SED rats were significantly heavier from the second week, and no catch-up growth occurred in EX rats. Feed intakes were not different between groups throughout the study. ZnLO animals had decreased food efficiency ratios compared to both phytase-supplemented (ZnLO+P) and Zn-adequate (ZnAD) animals (P<.01 compared to ZnLO). The ZnLO+P and ZnAD rats ran 56-75 km more total distance than ZnLO rats (P<.05), with the ZnLO+P rats running more kilometers per week than the ZnLO rats by Week 6. In vivo DEXA analyses indicate that rats fed phytase-supplemented diets had higher lean body mass (LBM) than those fed ZnLO diets; and that rats fed the Zn-adequate diets had the highest LBM. Body fat (%) was significantly lower in EX rats and was both Zn- and phytase insensitive. Rats fed phytase-supplemented diets had higher bone mineral content (BMC), bone area (BA) and BMD than rats fed ZnLO diets; and in rats fed ZnAD diets these indices were the highest. The dietary effects on BMC, BA and BMD were independent of activity level. We conclude that consuming supplemental dietary phytase or dietary Zn additively enhances Zn status to increase BMD, LBM and voluntary physical activity in rats fed a low-Zn diet. While the findings confirm that bone health is vulnerable to disruption by moderate Zn deficiency in rats, this new data suggests that if dietary Zn is limiting, supplemental phytase may have beneficial effects on LBM and performance activity. (c) 2010 Elsevier Inc. All rights reserved.

Nootropic and anti-stress effects of rice bran oil in male rats.

PubMed

Mehdi, Bushra Jabeen; Tabassum, Saiqa; Haider, Saida; Perveen, Tahira; Nawaz, Amber; Haleem, Darakhshan Jabeen

2015-07-01

Rice bran oil (RBO) is an important product of rice bran. It is considered to be one of the most important nutritious oil due to its favorable fatty acid composition and unique composition of naturally occurring biologically active antioxidant compounds. This study was designed to monitor the effects of oral intake of RBO on stress response in rats. RBO was extracted using hexane. Rats were divided into Control and test (RBO-treated). RBO-treated rats were given 0.2 ml/day RBO for 6 weeks. Food intake and body weight changes were monitored weekly. After 6 weeks open field activity and Morris Water Maze (MWM) test were performed. Results showed that weekly cumulative food intake but not body weight were lower in RBO-treated rats during 1st to 5th week of treatment, which were normalized at the end of treatment. Exploratory activity of RBO-treated rats in an open field was increased. Spatial memory in Morris water maze was enhanced in RBO-treated than control rats. An episode of 2 h restraint stress decreased the 24 h food intake of both control and RBO-treated animals. Behavioral deficits were lower in RBO-treated rats. Exposure of 2 h restraint stress increased brain serotonin (5-hydroxytryptamine: 5-HT) metabolism. These increases were lower in RBO-treated restrained than their respective control animals. Serotonergic neurotransmitter mechanism is implicated in stress. The findings of the study show beneficial effects of RBO in learning and memory functions. Moreover, the study also highlights the attenuating effect of RBO on stress induced behavioral and neurochemical effects in rats.

Long-term Characterization of Retinal Degeneration in Royal College of Surgeons Rats Using Spectral-Domain Optical Coherence Tomography

PubMed Central

Ryals, Renee C.; Andrews, Michael D.; Datta, Shreya; Coyner, Aaron S.; Fischer, Cody M.; Wen, Yuquan; Pennesi, Mark E.; McGill, Trevor J.

2017-01-01

Purpose Prospective treatments for age-related macular degeneration and inherited retinal degenerations are commonly evaluated in the Royal College of Surgeons (RCS) rat before translation into clinical application. Historically, retinal thickness obtained through postmortem anatomic assessments has been a key outcome measure; however, utility of this measurement is limited because it precludes the ability to perform longitudinal studies. To overcome this limitation, the present study was designed to provide a baseline longitudinal quantification of retinal thickness in the RCS rat by using spectral-domain optical coherence tomography (SD-OCT). Methods Horizontal and vertical linear SD-OCT scans centered on the optic nerve were captured from Long-Evans control rats at P30, P60, P90 and from RCS rats between P17 and P90. Total retina (TR), outer nuclear layer+ (ONL+), inner nuclear layer (INL), and retinal pigment epithelium (RPE) thicknesses were quantified. Histologic sections of RCS retina obtained from P21 to P60 were compared to SD-OCT images. Results In RCS rats, TR and ONL+ thickness decreased significantly as compared to Long-Evans controls. Changes in INL and RPE thickness were not significantly different between control and RCS retinas. From P30 to P90 a subretinal hyperreflective layer (HRL) was observed and quantified in RCS rats. After correlation with histology, the HRL was identified as disorganized outer segments and the location of accumulated debris. Conclusions Retinal layer thickness can be quantified longitudinally throughout the course of retinal degeneration in the RCS rat by using SD-OCT. Thickness measurements obtained with SD-OCT were consistent with previous anatomic thickness assessments. This study provides baseline data for future longitudinal assessment of therapeutic agents in the RCS rat. PMID:28253400

Long-term Characterization of Retinal Degeneration in Royal College of Surgeons Rats Using Spectral-Domain Optical Coherence Tomography.

PubMed

Ryals, Renee C; Andrews, Michael D; Datta, Shreya; Coyner, Aaron S; Fischer, Cody M; Wen, Yuquan; Pennesi, Mark E; McGill, Trevor J

2017-03-01

Prospective treatments for age-related macular degeneration and inherited retinal degenerations are commonly evaluated in the Royal College of Surgeons (RCS) rat before translation into clinical application. Historically, retinal thickness obtained through postmortem anatomic assessments has been a key outcome measure; however, utility of this measurement is limited because it precludes the ability to perform longitudinal studies. To overcome this limitation, the present study was designed to provide a baseline longitudinal quantification of retinal thickness in the RCS rat by using spectral-domain optical coherence tomography (SD-OCT). Horizontal and vertical linear SD-OCT scans centered on the optic nerve were captured from Long-Evans control rats at P30, P60, P90 and from RCS rats between P17 and P90. Total retina (TR), outer nuclear layer+ (ONL+), inner nuclear layer (INL), and retinal pigment epithelium (RPE) thicknesses were quantified. Histologic sections of RCS retina obtained from P21 to P60 were compared to SD-OCT images. In RCS rats, TR and ONL+ thickness decreased significantly as compared to Long-Evans controls. Changes in INL and RPE thickness were not significantly different between control and RCS retinas. From P30 to P90 a subretinal hyperreflective layer (HRL) was observed and quantified in RCS rats. After correlation with histology, the HRL was identified as disorganized outer segments and the location of accumulated debris. Retinal layer thickness can be quantified longitudinally throughout the course of retinal degeneration in the RCS rat by using SD-OCT. Thickness measurements obtained with SD-OCT were consistent with previous anatomic thickness assessments. This study provides baseline data for future longitudinal assessment of therapeutic agents in the RCS rat.

Gliclazide inhibits diabetic neuropathy irrespective of blood glucose levels in streptozotocin-induced diabetic rats.

PubMed

Qiang, X; Satoh, J; Sagara, M; Fukuzawa, M; Masuda, T; Miyaguchi, S; Takahashi, K; Toyota, T

1998-08-01

N-acetylcysteine and pentoxifylline, free radical scavengers and inhibitors of tumor necrosis factor-alpha (TNF-alpha) production, inhibit the development of peripheral neuropathy in streptozotocin (STZ)-induced diabetic rats. This study was designed to elucidate the effect of gliclazide, an oral hypoglycemic sulfonylurea, on diabetic neuropathy, because it has been indicated to be a free radical scavenger and TNF-alpha inhibitor. Rats were fed with powder chow mixed with gliclazide or glibenclamide as a control ad libitum. Blood glucose levels and body weight were remarkably higher and lower in diabetic than in nondiabetic rats, respectively, while gliclazide and glibenclamide had no effect on these in both diabetic and nondiabetic rats throughout a 24-week experiment. Serum lipoperoxide levels and lipopolysaccharide (LPS)-induced serum TNF-alpha activities were significantly increased in diabetic rats, whereas these were significantly inhibited in gliclazide-treated rats. Motor nerve conduction velocity (MNCV) of the tibial nerve significantly slowed in diabetic rats compared with nondiabetic rats. On the other hand, the slowed MNCV was significantly inhibited in gliclazide-treated diabetic rats after 16 experimental weeks. Morphometric analysis showed that gliclazide prevented decreased myelinated fiber area (P < .05), increased fiber density (P < .001), and decreased axon/myelin ratio (P < .05) in diabetic rats. Glibenclamide treatment did not affect serum lipoperoxide, TNF-alpha, MNCV, or nerve morphology in this experiment. These results indicate that gliclazide has a beneficial effect on peripheral neuropathy in STZ-induced diabetic rats, irrespective of blood glucose levels.

Carriage of Clostridium difficile by Wild Urban Norway Rats (Rattus norvegicus) and Black Rats (Rattus rattus)

PubMed Central

Patrick, David M.; Mak, Sunny; Jardine, Claire M.; Tang, Patrick; Weese, J. Scott

2014-01-01

Clostridium difficile is an important cause of enteric infections in humans. Recently, concerns have been raised regarding whether animals could be a source of C. difficile spores. Although colonization has been identified in a number of domestic species, the ability of commensal pests to serve as a reservoir for C. difficile has not been well investigated. The objective of this study was to determine whether urban rats (Rattus spp.) from Vancouver, Canada, carry C. difficile. Clostridium difficile was isolated from the colon contents of trapped rats and was characterized using ribotyping, toxinotyping, and toxin gene identification. Generalized linear mixed models and spatial analysis were used to characterize the ecology of C. difficile in rats. Clostridium difficile was isolated from 95 of 724 (13.1%) rats, although prevalence differed from 0% to 46.7% among city blocks. The odds of being C. difficile positive decreased with increasing weight (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.53 to 0.87), suggesting that carriage is more common in younger animals. The strains isolated included 9 ribotypes that matched recognized international designations, 5 identified by our laboratory in previous studies, and 21 “novel” ribotypes. Some strains were clustered geographically; however, the majority were dispersed throughout the study area, supporting environmental sources of exposure and widespread environmental contamination with a variety of C. difficile strains. Given that urban rats are the source of a number of other pathogens responsible for human morbidity and mortality, the potential for rats to be a source of C. difficile for humans deserves further consideration. PMID:24317079

Carriage of Clostridium difficile by wild urban Norway rats (Rattus norvegicus) and black rats (Rattus rattus).

PubMed

Himsworth, Chelsea G; Patrick, David M; Mak, Sunny; Jardine, Claire M; Tang, Patrick; Weese, J Scott

2014-02-01

Clostridium difficile is an important cause of enteric infections in humans. Recently, concerns have been raised regarding whether animals could be a source of C. difficile spores. Although colonization has been identified in a number of domestic species, the ability of commensal pests to serve as a reservoir for C. difficile has not been well investigated. The objective of this study was to determine whether urban rats (Rattus spp.) from Vancouver, Canada, carry C. difficile. Clostridium difficile was isolated from the colon contents of trapped rats and was characterized using ribotyping, toxinotyping, and toxin gene identification. Generalized linear mixed models and spatial analysis were used to characterize the ecology of C. difficile in rats. Clostridium difficile was isolated from 95 of 724 (13.1%) rats, although prevalence differed from 0% to 46.7% among city blocks. The odds of being C. difficile positive decreased with increasing weight (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.53 to 0.87), suggesting that carriage is more common in younger animals. The strains isolated included 9 ribotypes that matched recognized international designations, 5 identified by our laboratory in previous studies, and 21 "novel" ribotypes. Some strains were clustered geographically; however, the majority were dispersed throughout the study area, supporting environmental sources of exposure and widespread environmental contamination with a variety of C. difficile strains. Given that urban rats are the source of a number of other pathogens responsible for human morbidity and mortality, the potential for rats to be a source of C. difficile for humans deserves further consideration.

Exercise training prevents endometrial hyperplasia and biomarkers for endometrial cancer in rat model of type 1 diabetes.

PubMed

Al-Jarrah, Muhammed; Matalka, Ismail; Aseri, Hasan Al; Mohtaseb, Alia; Smirnova, Irina V; Novikova, Lesya; Stehno-Bittel, Lisa; Alkhateeb, Ahed

2010-10-11

Endometrial cancer is one of the most common types of gynecologic cancers. The ability of exercise to reduce the risk of endometrial cancer in women with type 2 diabetes has been established, but no studies have examined this link in type 1 diabetes.A randomized, controlled animal study was designed using a standard rat model of type 1 diabetes. The goal of this study was to investigate the ability of exercise to prevent increased levels of endometrial cancer biomarkers, estrogen receptor (ERα) and p16, and endometrial hyperplasia associated with diabetes. FORTY FEMALE RATS WERE RANDOMIZED INTO FOUR GROUPS: sedentary control, exercise control, sedentary or exercised diabetic. Diabetes was induced by alloxan injection. A 4-week treadmill training program was initiated with the development of diabetes. Endometrial tissues were evaluated for hyperplasia and ERα and p16 levels and subcellular localization using microscopy. Severe diabetes lead to hyperplasia in the endometrial tissue in 70% of sedentary diabetic rats. Exercise-trained diabetic rats and the non-diabetic rats displayed no hyperplasia. The expression of ERα increased significantly (p < 0.02) while the expression level of p16 decreased significantly (p < 0.04) in the diabetic sedentary group compared to the non-diabetic groups. Exercise training led to a reversal in the percentage of p16 and ERα positive cells in diabetic rats. Severe diabetes leads to hyperplasia of the endometrial tissue and increased ERα levels and decreased p16 levels in rats, which can be prevented with aerobic exercise. Diabetes; Estrogen receptor alpha; P16; Endometrial hyperplasia; Endometrial cancer; Exercise.

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

PubMed

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

2011-09-01

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

Extract of Xylopia aethiopica (Annonaceae) protects against gamma-radiation induced testicular damage in Wistar rats.

PubMed

Adaramoye, Oluwatosin Adekunle; Adedara, Isaac Adegboyega; Popoola, Bosede; Farombi, Ebenezer Olatunde

2010-01-01

Ionizing radiation is an important environmental risk factor and, a major therapeutic agent for cancer treatment. This study was designed to evaluate the protective effect of extract of Xylopia aethiopica (XA) on gamma-radiation-induced testicular damage in rats. Vitamin C (VC) served as the reference antioxidant during the study. The study consists of 4 groups of 11 rats each. Group I received corn oil (vehicle), groups II and IV were pretreated with XA (250 mg/kg) and VC (250mg/kg) for 6 weeks before and 8 weeks after exposure to gamma-radiation; group III was exposed to a single dose of gamma-radiation (5 Gy). Biochemical analysis revealed that gamma-irradiation caused a significant increase (p < .05) in serum and testicular lipid peroxidation (LPO) levels by 217% and 221%, respectively. Irradiated rats had markedly decreased testicular catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), and reduced glutathione (GSH) levels. Irradiation resulted in 59% and 40% decreases in spermatozoa motility and live/dead sperm count, respectively, and a 161% increase in total sperm abnormalities. Histologically, testes of the irradiated rats showed extensive degenerative changes in the seminiferous tubules and defoliation of spermatocytes. Supplementation of XA and VC reversed the adverse effects of gamma-radiation on biochemical and histological indices of the rats. These findings demonstrated that Xylopia aethiopica has a protective effect by inhibiting oxidative damage in testes of irradiated rats.

Where Have I Been? Where Should I Go? Spatial Working Memory on a Radial Arm Maze in a Rat Model of Depression

PubMed Central

Richter, Sophie Helene; Zeuch, Benjamin; Lankisch, Katja; Gass, Peter; Durstewitz, Daniel; Vollmayr, Barbara

2013-01-01

Disturbances in cognitive functioning are among the most debilitating problems experienced by patients with major depression. Investigations of these deficits in animals help to extend and refine our understanding of human emotional disorder, while at the same time providing valid tools to study higher executive functions in animals. We employ the “learned helplessness” genetic rat model of depression in studying working memory using an eight arm radial maze procedure with temporal delay. This so-called delayed spatial win-shift task consists of three phases, training, delay and test, requiring rats to hold information on-line across a retention interval and making choices based on this information in the test phase. According to a 2×2 factorial design, working memory performance of thirty-one congenitally helpless (cLH) and non-helpless (cNLH) rats was tested on eighteen trials, additionally imposing two different delay durations, 30 s and 15 min, respectively. While not observing a general cognitive deficit in cLH rats, the delay length greatly influenced maze performance. Notably, performance was most impaired in cLH rats tested with the shorter 30 s delay, suggesting a stress-related disruption of attentional processes in rats that are more sensitive to stress. Our study provides direct animal homologues of clinically important measures in human research, and contributes to the non-invasive assessment of cognitive deficits associated with depression. PMID:23614050

Teratology studies in the rabbit.

PubMed

Allais, Linda; Reynaud, Lucie

2013-01-01

The rabbit is generally the non-rodent species or second species after the rat recommended by the regulatory authorities and is part of the package of regulatory reproductive studies for the detection of potential embryotoxic and/or teratogenic effects of pharmaceuticals, chemicals, food additives, and other compounds, including vaccines (see Chapters 1-7).Its availability, practicality in housing and in mating as well as its large size makes the rabbit the preferred choice as a non-rodent species. The study protocols are essentially similar to those established for the rat (Chapter 9), with some particularities. The study designs are well defined in guidelines and are relatively standardized between testing laboratories across the world.As for the rat, large litter sizes and extensive background data in the rabbit are valuable criteria for an optimal assessment of in utero development of the embryo or fetus and for the detection of potential external or internal fetal malformations.

Fludrocortisone and hydrocortisone, alone or in combination, on in vivo hemodynamics and in vitro vascular reactivity in normal and endotoxemic rats: a randomized factorial design study.

PubMed

Laviolle, Bruno; Nesseler, Nicolas; Massart, Catherine; Bellissant, Eric

2014-06-01

Hydrocortisone enhances the pressor response to catecholamines in healthy volunteers and septic shock patients. Similar data do not exist for fludrocortisone. We assessed the effects of single administrations of fludrocortisone and hydrocortisone on systolic blood pressure until 2 hours after treatments injection and on in vitro vascular contraction of mesenteric artery rings to phenylephrine at 3 hours, in normal and endotoxemic rats. Intravenous fludrocortisone (5 and 20 μg/kg) and hydrocortisone (4 and 20 mg/kg) were administered in 16 groups (8 without and 8 with lipopolysaccharide-induced endotoxemic shock) of 10 Wistar rats according to four 2 × 2-factorial designs. Fludrocortisone and hydrocortisone similarly increased systolic blood pressure (P < 0.001 for both) but more in endotoxemic than in normal animals. Fludrocortisone and hydrocortisone significantly modified contractile response to phenylephrine (P = 0.039 and P = 0.007, respectively). At dose 1, fludrocortisone had no effect and hydrocortisone decreased contraction, whereas, at dose 2, both fludrocortisone and hydrocortisone increased contraction, especially in endotoxemic rats and with additive effect. Our results show that single intravenous administrations of fludrocortisone and hydrocortisone increase blood pressure and contractile response of mesenteric arteries to phenylephrine. The magnitude of these effects depends on dose and pathophysiological conditions and is higher in endotoxemic than in normal rats.

Effects of Cage Type and NASA Rodent Food Bar in Male Sprague-Dawley Rats

NASA Technical Reports Server (NTRS)

Lau, Angela; Ramirez, J.; Pruitt, S.; Melson, E.; Zirkle-Yoshida, M.; Girten, B.; Apseloff, G.

2001-01-01

Early prototype caging for the rodent Advanced Animal Habitat (P-AAH) for the International Space Station (ISS) is currently being tested. In this five week study, effects of the wire-bottom P-AAH cages and specialized NASA rodent food bars (FB) were compared to standard vivarium cages (VIV) with corn-cob, litter-filled bottoms, and standard Purina rat chow (CH). Ninety-six male Sprague-Dawley rats were divided into four treatment groups (24 rats/treatment): Group 1) VIV+CH, Group 2) P-AAH+CH, Group 3) VIV+FB, and Group 4) P-AAH+FB. Each VIV and P-AAH cage housed three and six rats, respectively. After five weeks of treatment rats were weighed, euthanized, and blood samples were collected. Weights of liver (LIV), kidney (KID), brain (BRN), epididymal fat (EPI), and perirenal fat (PERI) were also measured. Statistical analysis to compare differences between groups was performed by standard analysis of variance procedures (ANOVA) with a significance level of pLO.05. Results indicated P-AAH housed rats had significantly lower body weights (BW), LIV weights, and LIV/BW than VIV housed rats. FB fed rats had significantly lower blood urea nitrogen (BUN) levels and LIV/BW than CH fed rats. In addition, FB fed rats had significantly higher cholesterol (CHOL) levels, EPI/BW, PERI/BW, and total fat (EPI+PERI)/BW than CH fed rats. The P-AAH+FB group had significantly lower EPI, BRN, and total fat than VIV+FB rats. VIV+FB rats had significantly higher BRN, EPI, PERI, and total fat than VIV+CH rats. Triglycerides (TG), KID, KID/BW, and BRN/BW were not significantly different among treatment groups. These findings provide valuable information regarding cage design and food bar suitability for long-term use on the ISS.

The role of estrogen G-protein coupled receptor 30 (GPR30) and sexual experience in sexual incentive motivation in male rats.

PubMed

Hawley, W R; Battista, C; Divack, S R; Morales Núñez, N B

2017-08-01

Male rats exhibit reductions in sexual motivation following systemic administration of drugs that inhibit the conversion of testosterone to estrogen, which indicates that estrogen signaling plays a role in male rat sexual motivation. Given that estrogen G-protein coupled receptor 30 (GPR30) is expressed in brain areas that are important for male sexual behaviors and endocrine function, the primary aim of the current study was to examine the role that GPR30 plays in sexual motivation in both sexually naïve and sexually experienced male rats. Following the final treatment with either a GPR30 antagonist (G-15) or vehicle control, male rats were placed into the center chamber of a larger three-chambered testing arena that was designed to assess sexual incentive motivation. A sexually receptive stimulus female rat and a stimulus male rat were individually confined to one of the two smaller chambers that were each separated by a perforated partition from the larger end chambers, which test rats had access to. Relative to vehicle treated rats, male rats treated with G-15 exhibited a reduction in the percentage of time spent in the vicinity of a sexually receptive female rat. Although G-15 reduced sexual incentive motivation independent of sexual experience, only sexually-naïve rats treated with G-15 did not exhibit a preference for the sexually receptive stimulus female rat. Collectively, these results indicate that interference with estrogen signaling at GPR30 reduces sexual motivation and that the lack of preference for a sexually receptive female rat over a male rat following G-15 treatment is abrogated by previous sexual experience. Copyright © 2017 Elsevier Inc. All rights reserved.

Blood-brain barrier disruption by continuous-wave radio frequency radiation.

PubMed

Sirav, Bahriye; Seyhan, Nesrin

2009-01-01

The increasing use of cellular phones and the increasing number of associated base stations are becoming a widespread source of non ionizing electromagnetic radiation. Some biological effects are likely to occur even at low-level EM fields. This study was designed to investigate the effects of 900 and 1,800 MHz Continuous Wave Radio Frequency Radiation (CW RFR) on the permeability of Blood Brain Barrier (BBB) of rats. Results have shown that 20 min RFR exposure of 900 and 1,800 MHz induces an effect and increases the permeability of BBB of male rats. There was no change in female rats. The scientific evidence on RFR safety or harm remains inconclusive. More studies are needed to demonstrate the effects of RFR on the permeability of BBB and the mechanisms of that breakdown.

Evaluating anesthetic protocols for functional blood flow imaging in the rat eye

NASA Astrophysics Data System (ADS)

Moult, Eric M.; Choi, WooJhon; Boas, David A.; Baumann, Bernhard; Clermont, Allen C.; Feener, Edward P.; Fujimoto, James G.

2017-01-01

The purpose of this study is to evaluate the suitability of five different anesthetic protocols (isoflurane, isoflurane-xylazine, pentobarbital, ketamine-xylazine, and ketamine-xylazine-vecuronium) for functional blood flow imaging in the rat eye. Total retinal blood flow was measured at a series of time points using an ultrahigh-speed Doppler OCT system. Additionally, each anesthetic protocol was qualitatively evaluated according to the following criteria: (1) time-stability of blood flow, (2) overall rate of blood flow, (3) ocular immobilization, and (4) simplicity. We observed that different anesthetic protocols produced markedly different blood flows. Different anesthetic protocols also varied with respect to the four evaluated criteria. These findings suggest that the choice of anesthetic protocol should be carefully considered when designing and interpreting functional blood flow studies in the rat eye.

Multidirectional approach to study peritoneal dialysis fluid biocompatibility in a chronic peritoneal dialysis model in the rat.

PubMed

Wieczorowska-Tobis, K; Polubinska, A; Wisniewska, J; Pawlaczyk, K; Kuzlan-Pawlaczyk, M; Filas, V; Breborowicz, A; Oreopoulos, D G

2001-03-01

Peritoneal dialysis causes the functional and morphological changes in the peritoneum that result from the bioincompatibility of dialysis solutions. We present a model of chronic peritoneal dialysis in the rat that can be used for testing the biocompatibility of dialysis fluids. Methods and Results. Long-term exposure of the peritoneum to dialysis solutions can be performed in rats with implanted peritoneal catheters. Sampling of the dialysate allows the evaluation of intraperitoneal inflammation by examining cell differential and dialysate cytokine levels. Peritoneal permeability can be evaluated at designed time intervals with the peritoneal equilibration test (PET). At the end of dialysis, peritoneal histology is studied with light and electron microscopy. Such a multidirectional approach is an effective way to test biocompatibility of dialysis solutions.

Age dependence of myosin heavy chain transitions induced by creatine depletion in rat skeletal muscle

NASA Technical Reports Server (NTRS)

Adams, Gregory R.; Baldwin, Kenneth M.

1995-01-01

This study was designed to test the hypothesis that myosin heavy chain (MHC) plasticity resulting from creatine depletion is an age-dependent process. At weaning (age 28 days), rat pups were placed on either standard rat chow (normal diet juvenile group) or the same chow supplemented with 1% wt/wt of the creatine analogue beta-guanidinopropionic acid (creatine depletion juvenile (CDJ) group). Two groups of adult rats (age approximately 8 wk) were placed on the same diet regimens (normal diet adult and creatine depletion adult (CDA) groups). After 40 days (CDJ and normal diet juvenile groups) and 60 days (CDA and normal diet adult groups), animals were killed and several skeletal muscles were removed for analysis of creatine content or MHC ditribution. In the CDJ group, creatine depletion (78%) was accompanied by significant shifts toward expression of slower MHC isoforms in two slow and three fast skeletal muscles. In contrast, creatine depletion in adult animals did not result in similar shifts toward slow MHC isoform expression in either muscle type. The results of this study indicate that there is a differential effect of creatine depletion on MHC tranitions that appears to be age dependent. These results strongly suggest that investigators contemplating experimental designs involving the use of the creatine analogue beta-guanidinopropionic acid should consider the age of the animals to be used.

Influence of Hesperidin on the Systemic and Intestinal Rat Immune Response

PubMed Central

Camps-Bossacoma, Mariona; Franch, Àngels; Pérez-Cano, Francisco J.; Castell, Margarida

2017-01-01

Polyphenols, widely found in edible plants, influence the immune system. Nevertheless, the immunomodulatory properties of hesperidin, the predominant flavanone in oranges, have not been deeply studied. To establish the effect of hesperidin on in vivo immune response, two different conditions of immune system stimulations in Lewis rats were applied. In the first experimental design, rats were intraperitoneally immunized with ovalbumin (OVA) plus Bordetella pertussis toxin and alum as the adjuvants, and orally given 100 or 200 mg/kg hesperidin. In the second experimental design, rats were orally sensitized with OVA together with cholera toxin and fed a diet containing 0.5% hesperidin. In the first approach, hesperidin administration changed mesenteric lymph node lymphocyte (MLNL) composition, increasing the TCRαβ+ cell percentage and decreasing that of B lymphocytes. Furthermore, hesperidin enhanced the interferon (IFN)-γ production in stimulated MLNL. In the second approach, hesperidin intake modified the lymphocyte composition in the intestinal epithelium (TCRγδ+ cells) and the lamina propria (TCRγδ+, CD45RA+, natural killer, natural killer T, TCRαβ+CD4+, and TCRαβ+CD8+ cells). Nevertheless, hesperidin did not modify the level of serum anti-OVA antibodies in either study. In conclusion, hesperidin does possess immunoregulatory properties in the intestinal immune response, but this effect is not able to influence the synthesis of specific antibodies. PMID:28587283

Joint feedback analysis modeling of nonesterified fatty acids in obese Zucker rats and normal Sprague-Dawley rats after different routes of administration of nicotinic acid.

PubMed

Tapani, Sofia; Almquist, Joachim; Leander, Jacob; Ahlström, Christine; Peletier, Lambertus A; Jirstrand, Mats; Gabrielsson, Johan

2014-08-01

Data were pooled from several studies on nicotinic acid (NiAc) intervention of fatty acid turnover in normal Sprague-Dawley and obese Zucker rats in order to perform a joint PKPD of data from more than 100 normal Sprague-Dawley and obese Zucker rats, exposed to several administration routes and rates. To describe the difference in pharmacodynamic parameters between obese and normal rats, we modified a previously published nonlinear mixed effects model describing tolerance and oscillatory rebound effects of NiAc on nonesterified fatty acids plasma concentrations. An important conclusion is that planning of experiments and dose scheduling cannot rely on pilot studies on normal animals alone. The obese rats have a less-pronounced concentration-response relationship and need higher doses to exhibit desired response. The relative level of fatty acid rebound after cessation of NiAc administration was also quantified in the two rat populations. Building joint normal-disease models with scaling parameter(s) to characterize the "degree of disease" can be a useful tool when designing informative experiments on diseased animals, particularly in the preclinical screen. Data were analyzed using nonlinear mixed effects modeling, for the optimization, we used an improved method for calculating the gradient than the usually adopted finite difference approximation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Optogenetic conditioning of paradigm and pattern discrimination in the rat somatosensory system

PubMed Central

Abe, Kenta

2017-01-01

The rodent whisker-barrel cortical system is a model for studying somatosensory discrimination at high spatiotemporal precision. Here, we applied optogenetics to produce somatosensory inputs in the whisker area using one of transgenic rat lines, W-TChR2V4, which expresses channelrhodopsin-2 (ChR2) in the mechanoreceptive nerve endings around whisker follicles. An awake W-TChR2V4 rat was head-fixed and irradiated by blue LED light on the whisker area with a paradigm conditioned with a reward. The Go task was designed so the rat is allowed to receive a reward, when it licked the nozzle within 5 s after photostimulation. The No-go task was designed so as the rat has to withhold licking for at least 5 s to obtain a reward after photostimulation. The Go-task conditioning was established within 1 hr of training with a reduction in the reaction time and increase of the success rate. To investigate the relationship between the spatiotemporal pattern of sensory inputs and the behavioral output, we designed a multi-optical fiber system that irradiates the whisker area at 9 spots in a 3×3 matrix. Although the Go-task conditioning was established using synchronous irradiation of 9 spots, the success rate was decreased with an increase of the reaction time for the asynchronous irradiation. After conditioning to the Go task, the rat responded to the blue LED flash irradiated on the barrel cortex, where many neurons also express ChR2, or photostimulation of the contralateral whisker area with a similar reaction time and success rate. Synchronous activation of the peripheral mechanoreceptive nerves is suggested to drive a neural circuit in the somatosensory cortex that efficiently couples with the decision. Our optogenetic system would enable the precise evaluation of the psychophysical values, such as the reaction time and success rate, to gain some insight into the brain mechanisms underlying conditioned behaviors. PMID:29267341

Cypermethrin induced reproductive toxicity in male Wistar rats: protective role of Tribulus terrestris.

PubMed

Sharma, Poonam; Huq, Amir Ul; Singh, Rambir

2013-09-01

The present study was designed to investigate role of ethanolic extract of Tribulus terrestris (EETT) against alpha-cypermethrin induced reproductive toxicity in male Wistar rats. 24 male Wistar rats weighing about 250-300g were divided in four groups. Group-I was control. alpha-cypermethrin (3.38 mg kg-1b.wt.) was given to group-IlI for 28 days. In Group-Ill, alpha-cypermethrin and EETT (100 mg kg -1b.wt.) were administered in combination for 28 days. Rats in group-IV were given EETT for 28 days. At the end of the experiment, rats were sacrificed, testes and epididymis were removed and sperm characteristics, sex hormones and various biochemical parameters were studied. Decrease in weight of testes and epididymis, testicular sperm head count, sperm motility, live sperm count, serum testosterone (T), follicle stimulating hormone (FSH), leutinizing hormone (LH), catalase (CAT), superoxide dismutase (SOD), glutathione S transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), total protein content and increase in sperm abnormalities and lipid peroxidation (LPO) level was observed in rats exposed to cypermethrin. In combination group-Ill, EETT treatment ameliorated alpha-cypermethrin induced damage. EETT treatment in group-IV increased testes and epididymis weight, sperm head counts, sperm motility, live sperm counts, testosterone, FSH, LH, GSH, CAT, SOD, GST, GR, GPx and total protein content. The study suggested that Tribulus terrestris plant possess reproductive system enhancement and antioxidant activity.

Combination Ointment Containing Solid Tranilast Nanoparticles and Dissolved Sericin Is Efficacious for Treating Skin Wound-Healing Deficits and Redness in Diabetic Rats.

PubMed

Nagai, Noriaki; Ogata, Fumihiko; Deguchi, Saori; Ueno, Akina; Kawasaki, Naohito; Ito, Yoshimasa

2017-01-01

We attempted to design a combination ointment containing solid tranilast nanoparticles and dissolved sericin as a wound-healing drug (TS-combination ointment), and evaluated its usefulness as therapy for wound-healing deficits in streptozotocin-induced diabetic rat (STZ rat) using kinetic analyses as an index. Solid tranilast nanoparticles were prepared by bead mill methods with low-substituted methylcellulose; the mean particle size of the tranilast nanoparticles was 70 nm. The ointment was designed to contain the tranilast nanoparticles plus sericin powder and/or Carbopol ® 934. Skin wound healing in STZ rats begins significantly later than in normal rats. Although the skin wound healing rate in STZ rats treated with an ointment containing tranilast nanoparticles was lower than in STZ rats treated with vehicle, the ointment was effective in reducing redness. An ointment containing sericin enhanced the skin-healing rate, but the preventive effect on redness was weak. On the other hand, the combination of tranilast and sericin increased both the skin healing rate and reduction in redness. In conclusion, we have adapted kinetic analyses to skin wound healing in rats, and found these analyses to be useful as an index of wound healing ability by a wound-healing drug. In addition, we show that treatment with the TS-combination ointment enhances the skin wound healing rate and reduces redness. These findings provide information significant to the search for new wound-healing therapies and for the design of wound-healing drugs.

Pressure hyperalgesia in hind limb suspended rats.

PubMed

Chowdhury, Parimal; Soulsby, Michael E; Jayroe, John; Akel, Nisreen S; Gaddy, Dana; Dobretsov, Maxim

2011-10-01

Spaceflight and simulated microgravity often associate with pain and prediabetes. Streptozotocin (STZ)-induced moderate insulinopenia rat models of prediabetes result in pressure hyperalgesia. The current study was designed to determine whether or not simulated microgravity induced by hind limb suspension (HLS) in rats lead to insulinopenia and pressure hyperalgesia. Adult male rats were divided into HLS (N = 20) and control, non-suspended (N = 16) groups, respectively. Bodyweight and hind limb pressure-pain withdrawal threshold (PPT) were measured at regular 2-5 d intervals for 7 d before and 12-13 d after HLS. Bodyweights and PPT of control and HLS animals measured on the day of suspension were not different. During the experiment, control rats gained 61 +/- 5 g, but maintained their PPT at the baseline level. Suspended rats gained 26 +/- 3 g of weight during the same time period and their PPT declined from 105 +/- 6 g to 84 +/- 6 g. Neither blood glucose nor pancreatic islet density and area were affected by HLS. However, the random plasma insulin of HLS rats was significantly lower than that of control animals (1.6 +/- 0.2 vs. 2.7 +/- 0.2 ng ml(-1)). The observed relationship between insulin and PPT levels in the HLS rats was similar to that observed in rats with STZ-induced insulinopenia. These data suggest that moderate insulinopenia may affect the rat's sensitivity to deep pressure directly, without affecting glucose homeostasis. In addition, our data suggest that HLS rats may develop peripheral neuropathy.

Sleep Deprivation and Time-on-Task Performance Decrement in the Rat Psychomotor Vigilance Task

PubMed Central

Oonk, Marcella; Davis, Christopher J.; Krueger, James M.; Wisor, Jonathan P.; Van Dongen, Hans P.A.

2015-01-01

Study Objectives: The rat psychomotor vigilance task (rPVT) was developed as a rodent analog of the human psychomotor vigilance task (hPVT). We examined whether rPVT performance displays time-on-task effects similar to those observed on the hPVT. Design: The rPVT requires rats to respond to a randomly presented light stimulus to obtain a water reward. Rats were water deprived for 22 h prior to each 30-min rPVT session to motivate performance. We analyzed rPVT performance over time on task and as a function of the response-stimulus interval, at baseline and after sleep deprivation. Setting: The study was conducted in an academic research vivarium. Participants: Male Long-Evans rats were trained to respond to a 0.5 sec stimulus light within 3 sec of stimulus onset. Complete data were available for n = 20 rats. Interventions: Rats performed the rPVT for 30 min at baseline and after 24 h total sleep deprivation by gentle handling. Measurements and Results: Compared to baseline, sleep deprived rats displayed increased performance lapses and premature responses, similar to hPVT lapses of attention and false starts. However, in contrast to hPVT performance, the time-on-task performance decrement was not significantly enhanced by sleep deprivation. Moreover, following sleep deprivation, rPVT response times were not consistently increased after short response-stimulus intervals. Conclusions: The rat psychomotor vigilance task manifests similarities to the human psychomotor vigilance task in global performance outcomes, but not in post-sleep deprivation effects of time on task and response-stimulus interval. Citation: Oonk M, Davis CJ, Krueger JM, Wisor JP, Van Dongen HPA. Sleep deprivation and time-on-task performance decrement in the rat psychomotor vigilance task. SLEEP 2015;38(3):445–451. PMID:25515099

The Labdane Ent-3-Acetoxy-Labda-8(17), 13-Dien-15-Oic Decreases Blood Pressure In Hypertensive Rats

PubMed Central

Simplicio, Janaina A.; Simão, Marilia R.; Ambrosio, Sergio R.; Tirapelli, Carlos R.

2016-01-01

Background Labdane-type diterpenes induce lower blood pressure via relaxation of vascular smooth muscle; however, there are no studies describing the effects of labdanes in hypertensive rats. Objective The present study was designed to investigate the cardiovascular actions of the labdane-type diterpene ent-3-acetoxy-labda-8(17), 13-dien-15-oic acid (labda-15-oic acid) in two-kidney 1 clip (2K-1C) renal hypertension. Methods Vascular reactivity experiments were performed in aortic rings isolated from 2K-1C and normotensive (2K) male Wistar rats. Nitrate/nitrite (NOx) measurement was performed in aortas by colorimetric assay. Blood pressure measurements were performed in conscious rats. Results Labda-15-oic acid (0.1-300 µmol/l) and forskolin (0.1 nmol/l - 1 µmol/l) relaxed endothelium-intact and endothelium-denuded aortas from both 2K-1C and 2K rats. Labda-15-oic acid was more effective at inducing relaxation in endothelium-intact aortas from 2K pre-contracted with phenylephrine when compared to the endothelium-denuded ones. Forskolin was more potent than labda-15-oic acid at inducing vascular relaxation in arteries from both 2K and 2K-1C rats. Labda-15-oic acid-induced increase in NOx levels was lower in arteries from 2K-1C rats when compared to 2K rats. Intravenous administration of labda-15-oic acid (0.3-3 mg/kg) or forskolin (0.1-1 mg/kg) induced hypotension in conscious 2K-1C and 2K rats. Conclusion The present findings show that labda-15-oic acid induces vascular relaxation and hypotension in hypertensive rats. PMID:27096521

Evidence of glycemia-lowering effect by a Cynara scolymus L. extract in normal and obese rats.

PubMed

Fantini, Noemi; Colombo, Giancarlo; Giori, Andrea; Riva, Antonella; Morazzoni, Paolo; Bombardelli, Ezio; Carai, Mauro A M

2011-03-01

Several recent preliminary clinical studies have suggested that artichoke (Cynara scolymus L., Asteraceae family) preparations may be capable of lowering post-prandial glycemia. The present study was designed to test this hypothesis in laboratory rats. To this aim, non-selected Wistar and genetically obese Zucker rats were treated acutely with a purified extract of Cynara scolymus flowering heads (500-1500 mg/kg by gavage) immediately prior to 1 h access to a fixed amount of food. Glycemia was recorded 60, 120 and 360 min after food presentation. Treatment with Cynara scolymus flowering head extract resulted in a significant decrease of post-prandial glycemia in both rat strains. The lack of any fiber content in this Cynara scolymus flowering head extract excludes the involvement of dietary fibers in glycemia reduction. The results obtained constitute the first evidence of a hypoglycemic effect of an artichoke preparation in laboratory rodents and confirm previous observations made in humans. Copyright © 2010 John Wiley & Sons, Ltd.

Onset of mandible and tibia osteoradionecrosis – a comparative pilot study in the rat

PubMed Central

Damek-Poprawa, Monika; Both, Stefan; Wright, Alexander C.; Maity, Amit; Akintoye, Sunday O.

2012-01-01

Objectives Osteoradionecrosis (ORN) is common in the jaws following radiotherapy. We hypothesized that mandible is more susceptible to ORN than tibia based on site-disparity in hypoxic-hypocellular-hypovascular tissue breakdown. Study Design Twelve rats received 50 Gy irradiation to mandible or tibia; 4 of 12 rats further received minor surgical trauma to the irradiated sites. Structural and cellular skeletal changes were assessed with computer tomography, histology and immunostaining. Results Mandible developed ORN with 70% mean bone loss 10 weeks post-irradiation (p < 0.05) while tibia was structurally and radiological intact for 20 weeks post-irradiation. Hypocellularity, hypoxia and oxidative stress were higher in irradiated mandible (p < 0.001) than tibia (p < 0.01) but vascular damage was similar at both skeletal sites. Combined effects of radiation and minor trauma promoted mandibular alveolar bone loss and tibial fracture Conclusion ORN has a more rapid onset in mandible relative to tibia in the rat PMID:23254371

Insular neural system controls decision-making in healthy and methamphetamine-treated rats

PubMed Central

Mizoguchi, Hiroyuki; Katahira, Kentaro; Inutsuka, Ayumu; Fukumoto, Kazuya; Nakamura, Akihiro; Wang, Tian; Nagai, Taku; Sato, Jun; Sawada, Makoto; Ohira, Hideki; Yamanaka, Akihiro; Yamada, Kiyofumi

2015-01-01

Patients suffering from neuropsychiatric disorders such as substance-related and addictive disorders exhibit altered decision-making patterns, which may be associated with their behavioral abnormalities. However, the neuronal mechanisms underlying such impairments are largely unknown. Using a gambling test, we demonstrated that methamphetamine (METH)-treated rats chose a high-risk/high-reward option more frequently and assigned higher value to high returns than control rats, suggestive of changes in decision-making choice strategy. Immunohistochemical analysis following the gambling test revealed aberrant activation of the insular cortex (INS) and nucleus accumbens in METH-treated animals. Pharmacological studies, together with in vivo microdialysis, showed that the insular neural system played a crucial role in decision-making. Moreover, manipulation of INS activation using designer receptor exclusively activated by designer drug technology resulted in alterations to decision-making. Our findings suggest that the INS is a critical region involved in decision-making and that insular neural dysfunction results in risk-taking behaviors associated with altered decision-making. PMID:26150496

Insular neural system controls decision-making in healthy and methamphetamine-treated rats.

PubMed

Mizoguchi, Hiroyuki; Katahira, Kentaro; Inutsuka, Ayumu; Fukumoto, Kazuya; Nakamura, Akihiro; Wang, Tian; Nagai, Taku; Sato, Jun; Sawada, Makoto; Ohira, Hideki; Yamanaka, Akihiro; Yamada, Kiyofumi

2015-07-21

Patients suffering from neuropsychiatric disorders such as substance-related and addictive disorders exhibit altered decision-making patterns, which may be associated with their behavioral abnormalities. However, the neuronal mechanisms underlying such impairments are largely unknown. Using a gambling test, we demonstrated that methamphetamine (METH)-treated rats chose a high-risk/high-reward option more frequently and assigned higher value to high returns than control rats, suggestive of changes in decision-making choice strategy. Immunohistochemical analysis following the gambling test revealed aberrant activation of the insular cortex (INS) and nucleus accumbens in METH-treated animals. Pharmacological studies, together with in vivo microdialysis, showed that the insular neural system played a crucial role in decision-making. Moreover, manipulation of INS activation using designer receptor exclusively activated by designer drug technology resulted in alterations to decision-making. Our findings suggest that the INS is a critical region involved in decision-making and that insular neural dysfunction results in risk-taking behaviors associated with altered decision-making.

Effect of tangeretin, a polymethoxylated flavone on glucose metabolism in streptozotocin-induced diabetic rats.

PubMed

Sundaram, Ramalingam; Shanthi, Palanivelu; Sachdanandam, Panchanatham

2014-05-15

The present study was designed to evaluate the antihyperglycemic potential of tangeretin on the activities of key enzymes of carbohydrate and glycogen metabolism in control and streptozotocin induced diabetic rats. The daily oral administration of tangeretin (100mg/kg body weight) to diabetic rats for 30 days resulted in a significant reduction in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and increase in the levels of insulin and hemoglobin. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase in liver of diabetic rats were significantly reverted to near normal levels by the administration of tangeretin. Further, tangeretin administration to diabetic rats improved hepatic glycogen content suggesting the antihyperglycemic potential of tangeretin in diabetic rats. The effect produced by tangeretin on various parameters was comparable to that of glibenclamide - a standard oral hypoglycemic drug. Thus, these results show that tangeretin modulates the activities of hepatic enzymes via enhanced secretion of insulin and decreases the blood glucose in streptozotocin induced diabetic rats by its antioxidant potential. Copyright © 2014 Elsevier GmbH. All rights reserved.

A new ultrasonic method for measuring minute motion activities of rats.

PubMed

Young, C W; Young, M S; Li, Y C; Lin, M T

1996-12-01

A new ultrasonic method is presented for measuring the minute motion activities of rats. A pair of low-cost 40 kHz ultrasonic transducers are used to transmit ultrasound toward a rat and receive the ultrasound reflected from the rat. The relative motion of the rat modulates the phase difference between the transmitted and received ultrasound signals. An 8-bit digital phase meter was designed to record the phase difference signal which was used to reconstruct the relative motion waveform of the rat in an 8751 single-chip microcomputer. The reconstructed data are then sent to a PC-AT microcomputer for further processing. This method employs a spectrum analysis for the reconstructed data and can measure three minute motion activities including locomotor activity (LMA), tremor and myoclonia. Finally, the method has been tested with real animal experiments. The main advantages of this new method are that it is non-invasive, non-contact, low cost and high precision. This new method could also be profitably employed for other behavioral studies and offer potential for research in basic medicine.

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

PubMed Central

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

2009-01-01

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

Differential susceptibility of rats and guinea pigs to the ototoxic effects of ethyl benzene.

PubMed

Cappaert, Natalie L M; Klis, Sjaak F L; Muijser, Hans; Kulig, Beverly M; Ravensberg, Luco C; Smoorenburg, Guido F

2002-01-01

The present study was designed to compare the ototoxic effects of volatile ethyl benzene in guinea pigs and rats. Rats showed deteriorated auditory thresholds in the mid-frequency range, based on electrocochleography, after 550-ppm ethyl benzene (8 h/day, 5 days). Outer hair cell (OHC) loss was found in the corresponding cochlear regions. In contrast, guinea pigs showed no threshold shifts and no OHC loss after exposure to much higher ethyl benzene levels (2500 ppm, 6 h/day, 5 days). Subsequently, a limited study (four rats and four guinea pigs) was performed in an attempt to understand these differences in susceptibility. Ethyl benzene concentration in blood was determined in both species after exposure to 500-ppm ethyl benzene (8 h/day, 3 days). At the end of the first day, blood of the rats contained 23.2+/-0.8-microg/ml ethyl benzene, whereas the concentration in guinea pig blood was 2.8+/-0.1 microg/ml. After 3 days, the concentration in both species decreased with respect to the first day, but the ethyl benzene concentration in rat blood was still 4.3 times higher than that in guinea pig blood. Thus, the difference in susceptibility between the species may be related to the ethyl benzene concentration in blood.

Antidiabetic Effect of Young and Old Ethanolic Leaf Extracts of Vernonia amygdalina: A Comparative Study

PubMed Central

Asante, Du-Bois; Effah-Yeboah, Emmanuel; Barnes, Precious; Abban, Heckel Amoabeng; Ameyaw, Elvis Ofori; Boampong, Johnson Nyarko; Ofori, Eric Gyamerah; Dadzie, Joseph Budu

2016-01-01

The young leaves of Vernonia amygdalina are often utilized as vegetable and for medicinal purpose compared to the old leaves. This study was designed to evaluate and compare the antidiabetic effects between ethanolic leaf extracts of old and young V. amygdalina on streptozotocin (STZ) induced diabetic rat for four weeks. Preliminary screening of both young and old ethanolic extracts revealed the presence of the same phytochemicals except flavonoids which was only present in the old V. amygdalina. Difference in antioxidant power between the young and old leaf extracts was statistically significant (p < 0.05). Both leaf extracts produced a significant (p < 0.05) antihyperglycaemic effect. Also results from treated rats revealed increasing effect in some haematological parameters. Similarly, the higher dose (300 mg/kg) of both extracts significantly (p < 0.05) reduced serum ALT, AST, and ALP levels as compared to the diabetic control rats. Results also showed significant (p < 0.05) decrease in LDL-C and VLDL-C in the extract-treated rats with a corresponding increase in HDL-C, as compared to the diabetic control rats. Moreover histopathological analysis revealed ameliorative effect of pathological insults induced by the STZ in the pancreas, liver, and spleen, most significantly the regeneration of the beta cells of the islets of Langerhans in treated rats. PMID:27294153

Beneficial effect of candesartan and lisinopril against haloperidol-induced tardive dyskinesia in rat.

PubMed

Thakur, Kuldeep Singh; Prakash, Atish; Bisht, Rohit; Bansal, Puneet Kumar

2015-12-01

Tardive dyskinesia is a serious motor disorder of the orofacial region, resulting from chronic neuroleptic treatment of schizophrenia. Candesartan (AT1 antagonist) and lisinopril (ACE inhibitor) has been reported to possess antioxidant and neuroprotective effects. The present study is designed to investigate the effect of candesartan and lisinopril on haloperidol-induced orofacial dyskinesia and oxidative damage in rats. Tardive dyskinesia was induced by administering haloperidol (1 mg/kg i.p.) and concomitantly treated with candesartan (3 and 5 mg/kg p.o.) and lisinopril (10 and 15 mg/kg p.o.) for 3 weeks in male Wistar rats. Various behavioral parameters were assessed on days 0, 7, 14 and 21 and biochemical parameters were estimated at day 22. Chronic administration of haloperidol significantly increased stereotypic behaviors in rats, which were significantly improved by administration of candesartan and lisinopril. Chronic administration of haloperidol significantly increased oxidative stress and neuro-inflammation in the striatum region of the rat's brain. Co-administration of candesartan and lisinopril significantly attenuated the oxidative damage and neuro-inflammation in the haloperidol-treated rat. The present study supports the therapeutic use of candesartan and lisinopril in the treatment of typical antipsychotic-induced orofacial dyskinesia and possible antioxidant and neuro-inflammatory mechanisms. © The Author(s) 2014.

Demonstration of Innovative Sewer System Inspection Technology: SL-RAT

EPA Science Inventory

The overall objective of this EPA-funded study was to demonstrate innovative sewer line assessment technologies that are designed for rapid deployment using portable equipment. This study focused on demonstration of technologies that are suitable for smaller diameter pipes (less ...

Hepatoprotective activity of bacoside A against N-nitrosodiethylamine-induced liver toxicity in adult rats.

PubMed

Janani, Panneerselvam; Sivakumari, Kanakarajan; Parthasarathy, Chandrakesan

2009-10-01

N-Nitrosodiethylamine (DEN) is a notorious carcinogen, present in many environmental factors. DEN induces oxidative stress and cellular injury due to enhanced generation of reactive oxygen species; free radical scavengers protect the membranes from DEN-induced damage. The present study was designed to evaluate the protective effect of bacoside A (the active principle isolated from Bacopa monniera Linn.) on carcinogen-induced damage in rat liver. Adult male albino rats were pretreated with 15 mg/kg body weight/day of bacoside A orally (for 14 days) and then intoxicated with single necrogenic dose of N-nitrosodiethylamine (200 mg/kg bodyweight, intraperitonially) and maintained for 7 days. The liver weight, lipid peroxidation (LPO), and activity of serum marker enzymes (aspartate transaminases, alanine transaminases, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transpeptidase) were markedly increased in carcinogen-administered rats, whereas the activities of marker enzymes were near normal in bacoside A-pretreated rats. Activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutatione-S-transferase, and reduced glutathione) in liver also decreased in carcinogen-administered rats, which were significantly elevated in bacoside A-pretreated rats. It is concluded that pretreatment of bacoside A prevents the elevation of LPO and activity of serum marker enzymes and maintains the antioxidant system and thus protects the rats from DEN-induced hepatotoxicity.

Exaggerated Liver Injury Induced by Renal Ischemia Reperfusion in Diabetes: Effect of Exenatide

PubMed Central

Vaghasiya, Jitendra D.; Sheth, Navin R.; Bhalodia, Yagnik S.; Jivani, Nurudin P.

2010-01-01

Background/Aim: This study was designed to investigate the possible effect of exenatide (Glucagon like Peptide-1 receptor agonist) on liver injury (distant organ) induced by renal ischemia reperfusion (IR) in diabetic rats. Materials and Methods: In vivo renal IR was performed in both type 2 diabetic and normal rats. Each protocol comprised ischemia for 30 minutes followed by reperfusion for 24 hours and a treatment period of 14 days before induction of ischemia. Results: Lipid peroxidation, xanthine oxidase activity, myeloperoxidase activity and nitric oxide level in liver tissue were significantly increased (P < 0.01, P < 0.001, P < 0.001, P < 0.05, respectively), after IR in diabetic rats compared to normal rats. Antioxidant enzymes like glutathione, superoxide dismutase, catalase and glutathione peroxidase were significantly reduced (P < 0.05, P < 0.05, P < 0.01, P < 0.05, respectively), after IR in diabetic rats compared to normal rats. Exenatide treatment significantly normalized (P < 0.01), these biochemical parameters in treated rats compared to diabetic IR rats. Serum creatinine phosphokinase activity and liver function enzymes were also significantly normalized (P < 0.001, P < 0.001, respectively), after administration of exenatide. Conclusion: Exenatide exerted protective effect on exaggerated remote organ (liver) injury induced by renal IR in diabetes. PMID:20616412

Effect of Γ-aminobutyric acid on kidney injury induced by renal ischemia-reperfusion in male and female rats: Gender-related difference.

PubMed

Vafapour, Marzieh; Nematbakhsh, Mehdi; Monajemi, Ramesh; Mazaheri, Safoora; Talebi, Ardeshir; Talebi, Nahid; Shirdavani, Soheyla

2015-01-01

The most important cause of kidney injury is renal ischemia/reperfusion injury (IRI), which is gender-related. This study was designed to investigate the protective role of Γ-aminobutyric acid (GABA (against IRI in male and female rats. Thirty-six female and male wistar rats were assigned to six experimental groups. The IRI was induced by clamping renal vessels for 45 min then was performed reperfusion for 24 h. The group sex posed to IRI were pretreated with GABA and were compared with the control groups. Serum levels of creatinine and blood urea nitrogen, kidney weight, and kidney tissue damage score increased in the IRI alone groups, (P < 0.05), while GABA decreased these parameters in female significantly (P < 0.05), but not in male rats. Uterus weight decreased significantly in female rats treated with GABA. Testis weight did not alter in male rats. Serum level of nitrite and kidney level of malondialdehyde (MDA) had no significant change in both female and male rats. Kidney level of nitrite increased significantly in female rats experienced IRI and serum level of MDA increased significantly in males that were exposed to IRI (P < 0.05). GABA could ameliorate kidney injury induced by renal IRI in a gender dependent manner.

Tracing Fasting Glucose Fluxes with Unstressed Catheter Approach in Streptozotocin Induced Diabetic Rats

PubMed Central

Wu, Hui; Xu, Xiao; Meng, Ying; Xia, Fangzhen; Zhai, Hualing; Lu, Yingli

2014-01-01

Objective. Blood glucose concentrations of type 1 diabetic rats are vulnerable, especially to stress and trauma. The present study aimed to investigate the fasting endogenous glucose production and skeletal muscle glucose uptake of Streptozotocin induced type 1 diabetic rats using an unstressed vein and artery implantation of catheters at the tails of the rats as a platform. Research Design and Methods. Streptozotocin (65 mg·kg−1) was administered to induce type 1 diabetic state. The unstressed approach of catheters of vein and artery at the tails of the rats was established before the isotope tracer injection. Dynamic measurement of fasting endogenous glucose production was assessed by continuously infusing stable isotope [6, 6-2H2] glucose, while skeletal muscle glucose uptake by bolus injecting radioactively labeled [1-14C]-2-deoxy-glucose. Results. Streptozotocin induced type 1 diabetic rats displayed polydipsia, polyphagia, and polyuria along with overt hyperglycemia and hypoinsulinemia. They also had enhanced fasting endogenous glucose production and reduced glucose uptake in skeletal muscle compared to nondiabetic rats. Conclusions. The dual catheters implantation at the tails of the rats together with isotope tracers injection is a save time, unstressed, and feasible approach to explore the glucose metabolism in animal models in vivo. PMID:24772449

Protective effects of the herbal medicine goshajinkigan in a rat model of non-alcoholic fatty liver disease.

PubMed

Hirotani, Yoshihiko; Doi, Ayae; Takahashi, Tomoki; Umezawa, Hanako; Urashima, Yoko; Myotoku, Mitiaki

2012-12-01

This study was designed to investigate the effect of an herbal medicine-goshajinkigan (GJ)-on the regulation of total body weight, as well as liver and adipose tissue weights in rats fed a highfat diet (HFD) and drinking of 30% sucrose (HFDS) (HFD; the rats received 19.6% energy from carbohydrates, 18.2% from proteins, and 62.2% from lipids; total energy, 506 kcal/100 g). Control rats were fed a standard diet (the rats received 60.5% energy from carbohydrates, 26.2% from proteins, and 13.3% from lipids; total energy, 360 kcal/100 g). Over a period of 12 weeks, rats were allowed free access to either the standard diet or HFDS containing 0, 1, or 3% GJ. In comparison with the control group, the HFDS rats showed a significant decrease in overall body weight and adipose tissue weight, and an increase in liver weight at 12 weeks. GJ treatment significantly reversed the HFDS-induced decrease in body and adipose tissue weight and reduced the elevated liver weight dose-dependently. Similarly, GJ reduced the elevated serum aspartate aminotransferase levels observed in HFDS rats. These results suggest that GJ may have the potential to alleviate damage to the liver in subjects with long-term consumption of HFDS.

The Actions of Lyophilized Apple Peel on the Electrical Activity and Organization of the Ventricular Syncytium of the Hearts of Diabetic Rats

PubMed Central

Martínez-Ladrón de Guevara, Elideth; Pérez-Hernández, Nury; Villalobos-López, Miguel Ángel; Pérez-Ishiwara, David Guillermo; Salas-Benito, Juan Santiago; Martínez Martínez, Alejandro; Hernández-García, Vicente

2016-01-01

This study was designed to examine the effects of lyophilized red delicious apple peel (RDP) on the action potentials (APs) and the input resistance-threshold current relationship. The experiments were performed on isolated papillary heart muscles from healthy male rats, healthy male rats treated with RDP, diabetic male rats, and diabetic male rats treated with RDP. The preparation was superfused with oxygenated Tyrode's solution at 37°C. The stimulation and the recording of the APs, the input resistance, and the threshold current were made using conventional electrophysiological methods. The RDP presented no significant effect in normal rats. Equivalent doses in diabetic rats reduced the APD and ARP. The relationship between input resistance and threshold current established an inverse correlation. The results indicate the following: (1) The functional structure of the cardiac ventricular syncytium in healthy rats is heterogeneous, in terms of input resistance and threshold current. Diabetes further accentuates the heterogeneity. (2) As a consequence, conduction block occurs and increases the possibility of reentrant arrhythmias. (3) These modifications in the ventricular syncytium, coupled with the increase in the ARP, are the adequate substrate so that, with diabetes, the heart becomes more arrhythmogenic. (4) RDP decreases the APD, the ARP, and most syncytium irregularity caused by diabetes. PMID:26839897

Effects of PDE4 Pathway Inhibition in Rat Experimental Stroke

PubMed Central

Yang, Fan; Sumbria, Rachita K.; Xue, Dong; Yu, Chuanhui; He, Dan; Liu, Shuo; Paganini-Hill, Annlia; Fisher, Mark J.

2015-01-01

PURPOSE The first genomewide association study indicated that variations in the phosphodiesterase 4D (PDE4D) gene confer risk for ischemic stroke. However, inconsistencies among the studies designed to replicate the findings indicated the need for further investigation to elucidate the role of the PDE4 pathway in stroke pathogenesis. Hence, we studied the effect of global inhibition of the PDE4 pathway in two rat experimental stroke models, using the PDE4 inhibitor rolipram. Further, the specific role of the PDE4D isoform in ischemic stroke pathogenesis was studied using PDE4D knockout rats in experimental stroke. METHODS Rats were subjected to either the ligation or embolic stroke model and treated with rolipram (3mg/kg; i.p.) prior to the ischemic insult. Similarly, the PDE4D knockout rats were subjected to experimental stroke using the embolic model. RESULTS Global inhibition of the PDE4 pathway using rolipram produced infarcts that were 225% (p<0.01) and 138% (p<0.05) of control in the ligation and embolic models, respectively. PDE4D knockout rats subjected to embolic stroke showed no change in infarct size compared to wild-type control. CONCLUSIONS Despite increase in infarct size after global inhibition of the PDE4 pathway with rolipram, specific inhibition of the PDE4D isoform had no effect on experimental stroke. These findings support a role for the PDE4 pathway, independent of the PDE4D isoform, in ischemic stroke pathogenesis. PMID:25224348

Effects of Rambutan Peel Extract to The Number of Erythrocytes and Haemoglobin in Rats Exposed to Cigarette Smoke

NASA Astrophysics Data System (ADS)

Lisdiana; Dewi, F. K.

2017-04-01

Cigarette smoke is one of the exogenous free radicals sources. When it is inhaled, its activity may damage the structure of erythrocyte membrane function. The impacts of free radicals can be reduced through the provision of antioxidants. Rambutan fruit peel contains the phenolic compound in the form of polyphenols that are antioxidants. The purpose of this study is to determine the effect of rambutan fruit peel extracts to the number of erythrocytes and haemoglobin in rats exposed to cigarette smoke. This design used Post Test Control Group Design. A sample of 25 rats was divided into five groups, each group consisting of 5 rats. The positive control group (K+) were given a standard food and drinking water. The negative control group (K) by three cigarettes, the treatment group (KP1, KP2, KP3) by three cigarettes and skin extract of rambutan each treatment group with a dose 15 mg/kg, 30 mg/kg and 45 mg/kg for 30 days. Data on the number of erythrocytes and haemoglobin in rat blood was analysed with LSD and to determine the optimum dosage was analysed by using regression test. Research results shown that the content of rambutan fruit peel extract may increase the number of erythrocytes and haemoglobin of blood. Conclusions from this research are the rambutan fruit peel extract at a dose of 45 mg/kg body weight can increase and maintain the number of erythrocytes and haemoglobin in the blood of rat exposed to cigarette smoke.

Characterization of SV-40 Tag rats as a model to study prostate cancer

PubMed Central

2009-01-01

Background Prostate cancer is the second most frequently diagnosed cancer in men. Animal models that closely mimic clinical disease in humans are invaluable tools in the fight against prostate cancer. Recently, a Simian Virus-40 T-antigen (SV-40 Tag) targeted probasin promoter rat model was developed. This model, however, has not been extensively characterized; hence we have investigated the ontogeny of prostate cancer and determined the role of sex steroid receptor and insulin-like growth factor-1 (IGF-1) signaling proteins in the novel SV-40 Tag rat. Methods The SV-40 Tag rat was histopathologically characterized for time to tumor development, incidence and multiplicity and in the ventral, dorsal, lateral and anterior lobes of the prostate. Immunoassay techniques were employed to measure cell proliferation, apoptosis, and sex steroid receptor and growth factor signaling-related proteins. Steroid hormone concentrations were measured via coated well enzyme linked immunosorbent assay (ELISA) kits. Results Prostatic intraepithelial neoplasia (PIN) and well-differentiated prostate cancer developed as early as 2 and 10 weeks of age, respectively in the ventral prostate (VP) followed by in the dorsolateral (DLP). At 8 weeks of age, testosterone and dihydrotestosterone (DHT) concentrations in SV-40 Tag rats were increased when compared to non-transgenic rats. High cell proliferation and apoptotic indices were found in VP and DLP of transgenic rats. Furthermore, we observed increased protein expression of androgen receptor, IGF-1, IGF-1 receptor, and extracellular signal-regulated kinases in the prostates of SV-40 Tag rats. Conclusion The rapid development of PIN and prostate cancer in conjunction with the large prostate size makes the SV-40 Tag rat a useful model for studying prostate cancer. This study provides evidence of the role of sex steroid and growth factor proteins in prostate cancer development and defines appropriate windows of opportunity for preclinical trials and aids in the rational design of chemoprevention, intervention, regression, and therapeutic studies using prostate cancer rodent models. PMID:19171036

A factorial design to identify process parameters affecting whole mechanically disrupted rat pancreata in a perfusion bioreactor.

PubMed

Sharp, Jamie; Spitters, Tim Wgm; Vermette, Patrick

2018-03-01

Few studies report whole pancreatic tissue culture, as it is a difficult task using traditional culture methods. Here, a factorial design was used to investigate the singular and combinational effects of flow, dissolved oxygen concentration (D.O.) and pulsation on whole mechanically disrupted rat pancreata in a perfusion bioreactor. Whole rat pancreata were cultured for 72 h under defined bioreactor process conditions. Secreted insulin was measured and histological (haematoxylin and eosin (H&E)) as well as immunofluorescent insulin staining were performed and quantified. The combination of flow and D.O. had the most significant effect on secreted insulin at 5 h and 24 h. The D.O. had the biggest effect on tissue histological quality, and pulsation had the biggest effect on the number of insulin-positive structures. Based on the factorial design analysis, bioreactor conditions using high flow, low D.O., and pulsation were selected to further study glucose-stimulated insulin secretion. Here, mechanically disrupted rat pancreata were cultured for 24 h under these bioreactor conditions and were then challenged with high glucose concentration for 6 h and high glucose + IBMX (an insulin secretagogue) for a further 6 h. These cultures secreted insulin in response to high glucose concentration in the first 6 h, however stimulated-insulin secretion was markedly weaker in response to high glucose concentration + IBMX thereafter. After this bioreactor culture period, higher tissue metabolic activity was found compared to that of non-bioreacted static controls. More insulin- and glucagon-positive structures, and extensive intact endothelial structures were observed compared to non-bioreacted static cultures. H&E staining revealed more intact tissue compared to static cultures. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:432-444, 2018. © 2017 American Institute of Chemical Engineers.

Human adipose tissue-derived stem cells exhibit proliferation potential and spontaneous rhythmic contraction after fusion with neonatal rat cardiomyocytes.

PubMed

Metzele, Roxana; Alt, Christopher; Bai, Xiaowen; Yan, Yasheng; Zhang, Zhi; Pan, Zhizhong; Coleman, Michael; Vykoukal, Jody; Song, Yao-Hua; Alt, Eckhard

2011-03-01

Various types of stem cells have been shown to have beneficial effects on cardiac function. It is still debated whether fusion of injected stem cells with local resident cardiomyocytes is one of the mechanisms. To better understand the role of fusion in stem cell-based myocardial regeneration, the present study was designed to investigate the fate of human adipose tissue-derived stem cells (hASCs) fused with neonatal rat cardiomyocytes in vitro. hASCs labeled with the green fluorescent probe Vybrant DiO were cocultured with neonatal rat cardiomyocytes labeled with the red fluorescent probe Vybrant DiI and then treated with fusion-inducing hemagglutinating virus of Japan (HVJ). Cells that incorporated both red and green fluorescent signals were considered to be hASCs that had fused with rat cardiomyocytes. Fusion efficiency was 19.86 ± 4.84% at 5 d after treatment with HVJ. Most fused cells displayed cardiomyocyte-like morphology and exhibited spontaneous rhythmic contraction. Both immunofluorescence staining and lentiviral vector labeling showed that fused cells contained separate rat cardiomyocyte and hASC nuclei. Immunofluorescence staining assays demonstrated that human nuclei in fused cells still expressed the proliferation marker Ki67. In addition, hASCs fused with rat cardiomyocytes were positive for troponin I. Whole-cell voltage-clamp analysis demonstrated action potentials in beating fused cells. RT-PCR analysis using rat- or human-specific myosin heavy chain primers revealed that the myosin heavy-chain expression in fused cells was derived from rat cardiomyocytes. Real-time PCR identified expression of human troponin T in fused cells and the presence of rat cardiomyocytes induced a cardiomyogenic protein expression of troponin T in human ASCs. This study illustrates that hASCs exhibit both stem cell (proliferation) and cardiomyocyte properties (action potential and spontaneous rhythmic beating) after fusion with rat cardiomyocytes, supporting the theory that fusion, even if artificially induced in our study, could indeed be a mechanism for cardiomyocyte renewal in the heart.

Effects of environmental enrichment on behavioral and spatial cognitive deficits in morphine-dependent and -withdrawn rats.

PubMed

Hammami-Abrand Abadi, Arezoo; Miladi-Gorji, Hossein

2017-02-01

This study was designed to examine the effect of environmental enrichment during morphine dependence and withdrawal on morphine-induced behavioral and spatial cognitive disorders in morphine-withdrawn rats. Adult male Wistar rats (190 ± 20 g) were injected with bi-daily doses (10 mg/kg, 12 h intervals) of morphine for 14 days. Rats were reared in SE or EE during the development of dependence on morphine and withdrawal. Then, rats were tested for spatial learning and memory (the water maze), spontaneous withdrawal signs, and grooming behavior. We found that the EE blocked chronic morphine-induced partial impairments of spatial memory retention. Moreover, the EE diminished the occurrence of spontaneous morphine withdrawal signs as mild and the self-grooming behavior. Our findings showed that EE ameliorates chronic morphine-induced partial deficits of spatial cognition, obsessive-like behavior, and the overall severity of the morphine withdrawal. Thus, environmental enrichment may be a potential therapeutic strategy for spatial memory and behavioral deficits in morphine-dependent individuals.

Potential Effect of Bacopa monnieri on Nitrobenzene Induced Liver Damage in Rats

PubMed Central

Menon, B. Rajalakshmy; Rathi, M. A.; Thirumoorthi, L.

2010-01-01

The study was designed to evaluate the hepatoprotective activity of ethanolic extract of Bacopa monnieri in acute experimental liver injury induced by Nitrobenzene in rats. The extract at the dose of 200 mg/kg body weight was administered orally once every day for 10 days. The increased serum marker enzymes, Aspartate transaminase, Alanine transaminase and alkaline phosphatase were restored towards normalization significantly by the extract. Significant increase in SOD, CAT and GPx was observed in extract treated liver injured experimental rats. Histopathological examination of the liver tissues supported the hepatoprotection. It is concluded that the ethanolic extract of Bacopa monieri plant possess good hepatoprotective activity. PMID:21966114

Effect of environmental enrichment on physical and psychological dependence signs and voluntary morphine consumption in morphine-dependent and morphine-withdrawn rats.

PubMed

Hammami-Abrand Abadi, Arezoo; Miladi-Gorji, Hossein; Bigdeli, Imanollah

2016-04-01

This study was designed to examine the effect of environmental enrichment during morphine dependency and withdrawal on the severity of naloxone-precipitated withdrawal signs, anxiety, and depressive-like behaviors and voluntary morphine consumption in morphine-dependent rats. The rats were injected with bi-daily doses (10 mg/kg, 12 h intervals) of morphine for 14 days following rearing in a standard environment (SE) or enriched environment (EE) during the development of morphine dependence and withdrawal. Then, rats were tested for withdrawal signs after naloxone injection, anxiety (the elevated plus maze) and depression-related behavior (sucrose preference test), and voluntary consumption of morphine using a two-bottle choice paradigm, in morphine-dependent and morphine-withdrawn rats. The results showed that EE decreased naloxone-precipitated withdrawal signs, but not anxiety or sucrose preference during dependence on morphine. The EE-withdrawn rats showed an increase in the elevated plus maze open arm time and entries and higher levels of sucrose preference than SE rats. Voluntary consumption of morphine was lower in the EE-withdrawn rats than in the SE groups in the second period of drug intake. Thus, exposure to EE reduced the severity of morphine dependence and voluntary consumption of morphine, alongside reductions in anxiety and depression-related behavior in morphine-withdrawn rats.

Gastroprotective effect of kefir on ulcer induced in irradiated rats.

PubMed

Fahmy, Hanan A; Ismail, Amel F M

2015-03-01

The current study was designed to investigate the protective effect of kefir milk on ethanol-induced gastric ulcers in γ-irradiated rats. The results of the present study revealed that treatment with γ-irradiation and/or ethanol showed a significant increase in ulcers number, total acidity, peptic, H(+)K(+)ATPase, MMP-2 and MMP-9 activities and MDA level, which were accompanied by a significant decrease in the mucus content, the stomach GSH level, the GSH-Px activity and DNA damage. Pre-treatment with kefir milk exert significant improvement in all the tested parameters. Kefir milk exerts comparable effect to that of the antiulcer drug ranitidine. In conclusion, the present study revealed that oral administration of kefir milk prevents ethanol-induced gastric ulcer in γ-irradiated rats that could attribute to its antioxidant, anti-apoptotic and radio-protective activities. Copyright © 2015 Elsevier B.V. All rights reserved.

Both experimental hypothyroidism and hyperthyroidism increase cardiac irisin levels in rats.

PubMed

Atici, E; Menevse, E; Baltaci, A K; Mogulkoc, R

2018-01-01

Irisin is a newly discovered myokine and adipokine that increases total body energy expenditure. The aim of this study was to determine the effect of experimental hypothyroidism and hyperthyroidism on the levels of irisin in heart tissue in rats. The study was performed on the 40 male Sprague-Dawley rats. Experimental groups were designed as; Control, Hypothyroidism, Hypothyroidism+L-Thyroxine, Hyperthyroidism and Hyperthyroidism + PTU. Following 3 weeks experimental period, irisin levels were determined in heart tissues. Hypothyroidism group values of irisin were higher than in the control group, but lower than in the hyperthyroidism group. The hyperthyroidism group had the highest levels of cardiac irisin. The results of the study showed that the experimental hypothyroidism and hyperthyroidism increased the heart irisin levels, but the increase in the hyperthyroidism group was much higher than in the hypothyroidism group. However, treatment of hypothyroidism and hyperthyroidism corrected cardiac irisin levels (Fig. 1, Ref. 28).

Toxicokinetic Model Development for the Insensitive Munitions Component 3-Nitro-1,2,4-Triazol-5-One.

PubMed

Sweeney, Lisa M; Phillips, Elizabeth A; Goodwin, Michelle R; Bannon, Desmond I

2015-01-01

3-Nitro-1,2,4-triazol-5-one (NTO) is a component of insensitive munitions that are potential replacements for conventional explosives. Toxicokinetic data can aid in the interpretation of toxicity studies and interspecies extrapolation, but only limited data on the toxicokinetics and metabolism of NTO are available. To supplement these limited data, further in vivo studies of NTO in rats were conducted and blood concentrations were measured, tissue distribution of NTO was estimated using an in silico method, and physiologically based pharmacokinetic models of the disposition of NTO in rats and macaques were developed and extrapolated to humans. The model predictions can be used to extrapolate from designated points of departure identified from rat toxicology studies to provide a scientific basis for estimates of acceptable human exposure levels for NTO. © The Author(s) 2015.

TOLERANCE AND SENSITIZATION TO WEEKLY NICOTINE EXPOSURES ON THE MOTOR ACTIVITY OF RATS.

EPA Science Inventory

Motor activity was examined in adult female Long-Evans rats in a photocell device during daily (M-F) 30-min sessions. Following adaptation to the testing routine the rats were divided into six groups of eight that were designated to receive either nothing (non-injected control),...

Safety Assessment of Food and Feed from GM Crops in Europe: Evaluating EFSA's Alternative Framework for the Rat 90-day Feeding Study.

PubMed

Hong, Bonnie; Du, Yingzhou; Mukerji, Pushkor; Roper, Jason M; Appenzeller, Laura M

2017-07-12

Regulatory-compliant rodent subchronic feeding studies are compulsory regardless of a hypothesis to test, according to recent EU legislation for the safety assessment of whole food/feed produced from genetically modified (GM) crops containing a single genetic transformation event (European Union Commission Implementing Regulation No. 503/2013). The Implementing Regulation refers to guidelines set forth by the European Food Safety Authority (EFSA) for the design, conduct, and analysis of rodent subchronic feeding studies. The set of EFSA recommendations was rigorously applied to a 90-day feeding study in Sprague-Dawley rats. After study completion, the appropriateness and applicability of these recommendations were assessed using a battery of statistical analysis approaches including both retrospective and prospective statistical power analyses as well as variance-covariance decomposition. In the interest of animal welfare considerations, alternative experimental designs were investigated and evaluated in the context of informing the health risk assessment of food/feed from GM crops.

Role of fiber dissolution in biological activity in rats.

PubMed

Eastes, W; Hadley, J G

1994-12-01

This report deals with the role of dissolution in removing long fibers from the lung and with a mathematical model that predicts chronic effects in rats following inhalation or intraperitoneal (i.p.) injection of fibers. Results of intratracheal instillation studies and inhalation studies in rats demonstrate clearly that long vitreous fibers dissolve in vivo at about the same rate measured in vitro in fluid designed to stimulate the extracellular lung fluid. For the glass, rock, and slag wool fibers tested, dissolution removed most of the fibers longer than 20 microns inhaled into the rats' lungs within 6 months after both short-term (5 days) and long-term (1 to 2 years) exposures. A mathematical model was developed that is based on fiber dissolution and allows one to predict the development of chronic lung diseases in rats. The model predicted the incidence of fibrosis and lung tumors in a series of recent inhalation studies and tumors following ip injection to within about the error of the experiments. The model suggests that all fibers, regardless of their dissolution rate in lung fluid, can produce tumors after ip injection because the dose can be unlimited by this route. After inhalation, in contrast, dissolution of many types of long vitreous fibers occurs rapidly, and disease does not ensue for these fibers.

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

PubMed

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

2017-03-01

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

Studies of (±)-3,4-methylenedioxymethamphetamine (MDMA) metabolism and disposition in rats and mice: relationship to neuroprotection and neurotoxicity profile.

PubMed

Mueller, Melanie; Maldonado-Adrian, Concepcion; Yuan, Jie; McCann, Una D; Ricaurte, George A

2013-02-01

The neurotoxicity of (±)-3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") is influenced by temperature and varies according to species. The mechanisms underlying these two features of MDMA neurotoxicity are unknown, but differences in MDMA metabolism have recently been implicated in both. The present study was designed to 1) assess the effect of hypothermia on MDMA metabolism, 2) determine whether the neuroprotective effect of hypothermia is related to inhibition of MDMA metabolism, and 3) determine if different neurotoxicity profiles in mice and rats are related to differences in MDMA metabolism and/or disposition in the two species. Rats and mice received single neurotoxic oral doses of MDMA at 25°C and 4°C, and body temperature, pharmacokinetic parameters, and serotonergic and dopaminergic neuronal markers were measured. Hypothermia did not alter MDMA metabolism in rats and only modestly inhibited MDMA metabolism in mice; however, it afforded complete neuroprotection in both species. Rats and mice metabolized MDMA in a similar pattern, with 3,4-methylenedioxyamphetamine being the major metabolite, followed by 4-hydroxy-3-methoxymethamphetamine and 3,4-dihydroxymethamphetamine, respectively. Differences between MDMA pharmacokinetics in rats and mice, including faster elimination in mice, did not account for the different profile of MDMA neurotoxicity in the two species. Taken together, the results of these studies indicate that inhibition of MDMA metabolism is not responsible for the neuroprotective effect of hypothermia in rodents, and that different neurotoxicity profiles in rats and mice are not readily explained by differences in MDMA metabolism or disposition.

Studies of (±)-3,4-Methylenedioxymethamphetamine (MDMA) Metabolism and Disposition in Rats and Mice: Relationship to Neuroprotection and Neurotoxicity Profile

PubMed Central

Mueller, Melanie; Maldonado-Adrian, Concepcion; Yuan, Jie; McCann, Una D.

2013-01-01

The neurotoxicity of (±)-3,4-methylenedioxymethamphetamine (MDMA; “Ecstasy”) is influenced by temperature and varies according to species. The mechanisms underlying these two features of MDMA neurotoxicity are unknown, but differences in MDMA metabolism have recently been implicated in both. The present study was designed to 1) assess the effect of hypothermia on MDMA metabolism, 2) determine whether the neuroprotective effect of hypothermia is related to inhibition of MDMA metabolism, and 3) determine if different neurotoxicity profiles in mice and rats are related to differences in MDMA metabolism and/or disposition in the two species. Rats and mice received single neurotoxic oral doses of MDMA at 25°C and 4°C, and body temperature, pharmacokinetic parameters, and serotonergic and dopaminergic neuronal markers were measured. Hypothermia did not alter MDMA metabolism in rats and only modestly inhibited MDMA metabolism in mice; however, it afforded complete neuroprotection in both species. Rats and mice metabolized MDMA in a similar pattern, with 3,4-methylenedioxyamphetamine being the major metabolite, followed by 4-hydroxy-3-methoxymethamphetamine and 3,4-dihydroxymethamphetamine, respectively. Differences between MDMA pharmacokinetics in rats and mice, including faster elimination in mice, did not account for the different profile of MDMA neurotoxicity in the two species. Taken together, the results of these studies indicate that inhibition of MDMA metabolism is not responsible for the neuroprotective effect of hypothermia in rodents, and that different neurotoxicity profiles in rats and mice are not readily explained by differences in MDMA metabolism or disposition. PMID:23209329

Date seed extract ameliorates β-amyloid-induced impairments in hippocampus of male rats.

PubMed

Dehghanian, Farzaneh; Kalantaripour, Taj Pari; Esmaeilpour, Khadijeh; Elyasi, Leila; Oloumi, Hakime; Pour, Fatmeh Mehdi; Asadi-Shekaari, Majid

2017-05-01

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder among the elderly. Because the existing treatments for Alzheimer's disease only offer limited symptomatic alleviation, more efficient therapeutic agents are urgently needed. Date seed is a hepatoprotective and neuroprotective agent. Date seed extract (DSE) has bioactive components like phenolics, flavonoids, and vitamins. In view of the ameliorative effects of DSE against an oxidative injury, the current study was designed to reveal whether DSE has a neuroprotective resource in the rat model of Alzheimer's disease. In the current study, 24 adult male Sprague-Dawely rats were divided into three groups (n=8) of: Sham (Distilled Water, 3μl intracerebroventricular (ICV) injection), β-Amyloid (β-amyloid, 3μl ICV injection), and DSE-treated groups (80mg/kg, Intraperitoneal (IP) injection), for 12days. Twelve days after Alzheimer induction, behavioral analysis, the Morris Water Maze (MWM), as well as western blot and histological studies were performed to reveal the neuroprotective potential of DSE in rats. Administration of DSE significantly restored memory and learning impairments induced by Aβ in the MWM test. DSE significantly decreased the caspase-3 expression level in the treated group. In addition, DSE reduced the number of degenerated neurons in the hippocampal CA1 subfield of the DSE treated rats. These results demonstrate that DSE may have beneficial effects in the prevention of Aβ-induced Alzheimer in a rat model. Date seed extract may have advantageous effects in preventing Alzheimer's disease in male rats. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

REM sleep deprivation induces endothelial dysfunction and hypertension in middle-aged rats: Roles of the eNOS/NO/cGMP pathway and supplementation with L-arginine.

PubMed

Jiang, Jiaye; Gan, Zhongyuan; Li, Yuan; Zhao, Wenqi; Li, Hanqing; Zheng, Jian-Pu; Ke, Yan

2017-01-01

Sleep loss can induce or aggravate the development of cardiovascular and cerebrovascular diseases. However, the molecular mechanism underlying this phenomenon is poorly understood. The present study was designed to investigate the effects of REM sleep deprivation on blood pressure in rats and the underlying mechanisms of these effects. After Sprague-Dawley rats were subjected to REM sleep deprivation for 5 days, their blood pressures and endothelial function were measured. In addition, one group of rats was given continuous access to L-arginine supplementation (2% in distilled water) for the 5 days before and the 5 days of REM sleep deprivation to reverse sleep deprivation-induced pathological changes. The results showed that REM sleep deprivation decreased body weight, increased blood pressure, and impaired endothelial function of the aortas in middle-aged rats but not young rats. Moreover, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) concentrations as well as endothelial NO synthase (eNOS) phosphorylation in the aorta were decreased by REM sleep deprivation. Supplementation with L-arginine could protect against REM sleep deprivation-induced hypertension, endothelial dysfunction, and damage to the eNOS/NO/cGMP signaling pathway. The results of the present study suggested that REM sleep deprivation caused endothelial dysfunction and hypertension in middle-aged rats via the eNOS/NO/cGMP pathway and that these pathological changes could be inhibited via L-arginine supplementation. The present study provides a new strategy to inhibit the signaling pathways involved in insomnia-induced or insomnia-enhanced cardiovascular diseases.

The OECD program to validate the rat Hershberger bioassay to screen compounds for in vivo and androgen and antiandrogen responses: Phase-2 dose-response studies

EPA Science Inventory

DESIGN: The Hershberger bioassay is designed to identify suspected androgens and antiandrogens based on changes in the weights of five androgen-responsive tissues (ventral prostate, paired seminal vesicles and coagulating glands, the levator ani and bulbocavernosus muscles, the g...

Design and creation of an experimental program of advanced training in reconstructive microsurgery.

PubMed

Lorenzo, Andrés R; Alvarez, Angel; Garcia-Barreiro, Juan; Centeno, Alberto; Lopez, Eduardo; Martelo, Francisco

2006-01-01

In this study, we design an experimental protocol for the purpose of enhancing performance in training in microsurgery. It is based on five free tissue transfer exercises in rat (epigastric cutaneous flap, saphenous fasciocutaneous flap, epigastric neurovascular flap, saphenous muscular flap, and hindlimb replantation), which simulate the principal clinical procedures of reconstructive microsurgery. The first part of the study consists of an anatomical review of the flaps of 5 rats and in the second part we have carried out the free transfer of flaps on 25 rats divided into 5 groups. To differentiate between them, we have created a mathematical function, referred to as difficulty in a microsurgical exercise, which has enabled us to establish a scale of progression for training, ranging form the easiest to the most difficult. As a conclusion, we believe that this protocol is a useful instrument as it allows for a more precise assessment of microsurgical capacity due to enhanced accuracy in the reproduction of global procedures and the fact that the quantification of progress in training is based on clinical monitoring after 7 days. (c) 2006 Wiley-Liss, Inc. Microsurgery, 2006.

Calcium Balance in Mature Rats Exposed to a Space Flight Model

NASA Technical Reports Server (NTRS)

Wolinsky, Ira

1996-01-01

Negative calcium balances are seen in humans during spaceflight and bed rest, an analog of space flight. Due to the infrequency and costliness of space flight and the difficulties, cost, and restraints in using invasive procedures in bed rest studies, several ground based animal models of space flight have been employed. The most useful and well developed of these models is hind limb unloading in the rat. In this model the hind limbs are non-weight bearing (unloaded) but still mobile; there is a cephalad fluid shift similar to that seen in astronauts in flight; the animals are able to feed, groom and locomote using their front limbs; the procedure is reversible; and, importantly, the model has been validated by comparison to space flight. Several laboratories have studied calcium balance using rats in hind limb unweighting. Roer and Dillaman used young male rats to study calcium balance in this model for 25 days. They found no differences in dietary calcium intake, percent calcium absorption, urinary and fecal excretion, hence indicating no differences in calcium balance between control and unloaded rats. In another study, employing 120 day old females, rats' hind limbs were unloaded for 28 days. While negative calcium balances were observed during a 25 day recovery period no balance measurements were possible during unweighting since the researchers did not employ appropriate metabolic cages. In a recent study from this laboratory, using 200 g rats in the space flight model for two weeks, we found depressed intestinal calcium absorption and increased fecal calcium excretion (indicating less positive calcium balances) and lower circulating 1,25-dihydroxyvitamin D. The above studies indicate that there remains a dearth of information on calcium balance during the hind limb unloading rat space flight model, especially in mature rats, whose use is a better model for planned manned space flight than juvenile or growing animals. With the aid of a newly designed metabolic cage developed in our laboratory it is now possible to accurately measure urinary and fecal calcium excretions in this space flight model. The purpose of this study, then, was to extend and enlarge our previous findings viz: to measure calcium balances in mature rats exposed to a space flight model.

Effects of Gelam and Acacia honey acute administration on some biochemical parameters of Sprague Dawley rats

PubMed Central

2014-01-01

Background Since ancient times, honey has been used for medicinal purposes in many cultures; it is one of the oldest and most enduring substances used in wound management. Scientific evidence for its efficacy is widely studied, but systemic safety studies are still lacking. It is essential to study the impact of consumption of honey on the health and proper development of the consumer. Therefore, the present study was designed to observe the effects of acute administration (14 days) of Gelam honey (GH), a wild harvesting honey and Acacia honey (AH), a beekeeping honey, on male and female Sprague Dawley (SD) rats. Methods An acute oral study was performed following OECD test guideline 423, with minor modifications. In the study, GH, AH and sucrose (S) were administered at 2000 mg/kg body weight. Animals were observed for the next 14 days. Gross pathology was performed at the end of the study. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Clinical biochemistry, gross pathology, relative organ weight and histopathological examination were performed. Results Rats fed with honey did not exhibit any abnormal signs or deaths. Results showed a decrease in weight gain and energy efficiency, but significantly increased in total food intake and total calories in female rats fed with GH, compared to control (p < 0.05). Nevertheless, a significant increase in body weight was observed in male rats in all honey-treated groups. Male rats fed with AH significantly decreased in total food intake, total calories and energy efficiency. Both male and female rats fed with GH displayed a significant decrease in triglycerides compared to control group. Hepatic and renal function levels were within acceptable range. The gross necropsy analysis did not reveal changes in any of the organs examined. Conclusions Our results suggest that acute consumption of GH and AH at 2000 mg/kg body weight of male and female SD rats has some discrepancy effects on biochemical parameters but in line with OECD regulation. Gelam honey may have potential in controlling weight gain and triglyceride levels in female rats compared to Acacia honey. SD rats have some effect on biochemical parameters, an exploration of which would make for intriguing analysis. PMID:24885010

Effects of Gelam and Acacia honey acute administration on some biochemical parameters of Sprague Dawley rats.

PubMed

Samat, Suhana; Nor, Nor Azmi Md; Nor Hussein, Fuzina; Ismail, Wan Iryani Wan

2014-05-04

Since ancient times, honey has been used for medicinal purposes in many cultures; it is one of the oldest and most enduring substances used in wound management. Scientific evidence for its efficacy is widely studied, but systemic safety studies are still lacking. It is essential to study the impact of consumption of honey on the health and proper development of the consumer. Therefore, the present study was designed to observe the effects of acute administration (14 days) of Gelam honey (GH), a wild harvesting honey and Acacia honey (AH), a beekeeping honey, on male and female Sprague Dawley (SD) rats. An acute oral study was performed following OECD test guideline 423, with minor modifications. In the study, GH, AH and sucrose (S) were administered at 2000 mg/kg body weight. Animals were observed for the next 14 days. Gross pathology was performed at the end of the study. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Clinical biochemistry, gross pathology, relative organ weight and histopathological examination were performed. Rats fed with honey did not exhibit any abnormal signs or deaths. Results showed a decrease in weight gain and energy efficiency, but significantly increased in total food intake and total calories in female rats fed with GH, compared to control (p<0.05). Nevertheless, a significant increase in body weight was observed in male rats in all honey-treated groups. Male rats fed with AH significantly decreased in total food intake, total calories and energy efficiency. Both male and female rats fed with GH displayed a significant decrease in triglycerides compared to control group. Hepatic and renal function levels were within acceptable range. The gross necropsy analysis did not reveal changes in any of the organs examined. Our results suggest that acute consumption of GH and AH at 2000 mg/kg body weight of male and female SD rats has some discrepancy effects on biochemical parameters but in line with OECD regulation. Gelam honey may have potential in controlling weight gain and triglyceride levels in female rats compared to Acacia honey. SD rats have some effect on biochemical parameters, an exploration of which would make for intriguing analysis.

Attenuation of Diabetic Conditions by Sida rhombifolia in Moderately Diabetic Rats and Inability to Produce Similar Effects in Severely Diabetic in Rats

PubMed Central

Chaturvedi, Padmaja; Kwape, Tebogo Elvis

2015-01-01

Objectives: This study was done out to evaluate the effects of Sida rhombifolia methanol extract (SRM) on diabetes in moderately diabetic (MD) and severely diabetic (SD) Sprague-Dawley rats. Methods: SRM was prepared by soaking the powdered plant material in 70% methanol and rota evaporating the methanol from the extract. Effective hypoglycemic doses were established by performing oral glucose tolerance tests (OGTTs) in normal rats. Hourly effects of SRM on glucose were observed in the MD and the SD rats. Rats were grouped, five rats to a group, into normal control 1 (NC1), MD control 1 (MDC1), MD experimental 1 (MDE1), SD control 1 (SDC1), and SD experimental 1 (SDE1) groups. All rats in the control groups were administered 1 mL of distilled water (DW). The rats in the MDE1 and the SDE1 groups were administered SRM orally at 200 and 300 mg/kg body weight (BW), respectively, dissolved in 1 mL of DW. Blood was collected initially and at intervals of 1 hour for 6 hours to measure blood glucose. A similar experimental design was followed for the 30-day long-term trial. Finally, rats were sacrificed, and blood was collected to measure blood glucose, lipid profiles, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH). Results: OGTTs indicated that two doses (200 and 300 mg/kg BW) were effective hypoglycemic doses in normal rats. Both doses reduced glucose levels after 1 hour in the MDE1 and the SDE1 groups. A long-term trial of SRM in the MD group showed a reduced glucose level, a normal lipid profile, and normal GSH and TBARS levels. In SD rats, SRM had no statistically significant effects on these parameters. Normal weight was achieved in the MD rats, but the SD rats showed reduced BW. Conclusion: The study demonstrates that SRM has potential to alleviate the conditions of moderate diabetic, but not severe diabetes. PMID:26998385

Hypoglycemic and hypolipidemic effects of methanol seed extract of Citrus paradisi Macfad (Rutaceae) in alloxan-induced diabetic Wistar rats.

PubMed

Adeneye, A A

2008-01-01

Alcohol decoction of Citrus paradisi Macfad (Rutaceae) seed is reputed for the local management of array of human diseases including, anemia, diabetes mellitus and obesity by some Yoruba herbalists (SouthWest, Nigeria). Despite its historic use, scientific evaluation of its folkloric use in the management of diabetes mellitus is scarce. The present study was designed at investigating the glucose and lipid lowering effects of methanol seed extract of Citrus paradisi Macfad (MECP) in alloxan-induced diabetic rats. In addition, the phytochemical analysis of the extract was also conducted using standard procedures. Young adult, male, alloxan-induced diabetic rats were randomly divided into groups I - VI with 12 rats in each group. Group I rats were the normal untreated rats while group II rats served as the diabetic untreated rats while Rats in groups III - VI served as diabetic rats treated with 100, 300 and 600 mg/kg/day MECP and 20 mg/kg/ day metformin, respectively, for 30 days. On the 15th and respectively, 31st day, blood samples from the fasted rats were obtained for fasting plasma glucose (FPG), plasma triglycerides (TG), total cholesterol (TC), high density lipoprotein- cholesterol (HDL-c), low density lipoprotein-cholesterol (LDL-c) and very low density lipoprotein-cholesterol (VLDL-c) from the sacrificed rats. Oral treatment with 100 - 600 mg/kg/day MECP, for 30 days, resulted in significant (p < 0.05, p < 0.01, p < 0.001) reductions in FPG, TG, TC, LDL-c, VLDL-c in the diabetic rats, effects which were comparable to that of metformin. The extract also caused significant (p < 0.05, p < 0.01) rise in HDL-c values in the alloxan diabetic rats. Phytochemical result showed the presence of alkaloids, flavonoids, cardiac glycosides, tannins and saponin in varying concentrations. The biological effects recorded for the extract could be due to any or a combination of these phytochemical constituents. Results of this study lend support to the traditional use of grapefruit seeds in the management of type 1 diabetic patients and may suggest a role in orthodox management of the disease.

A morphine/heroin vaccine with new hapten design attenuates behavioral effects in rats.

PubMed

Li, Qian-Qian; Luo, Yi-Xiao; Sun, Cheng-Yu; Xue, Yan-Xue; Zhu, Wei-Li; Shi, Hai-Shui; Zhai, Hai-Feng; Shi, Jie; Lu, Lin

2011-12-01

Heroin use has seriously threatened public heath in many countries, but the existing therapies continue to have many limitations. Recently, immunotherapy has shown efficacy in some clinical studies, including vaccines against nicotine and cocaine, but no opioid vaccines have been introduced in clinical studies. The development of a novel opioid antigen designed specifically for the prevention of heroin addiction is necessary. A morphine-keyhole limpet hemocyanin conjugate was prepared and administered subcutaneously in rats. Antibody titers in plasma were measured using an enzyme-linked immunosorbent assay (ELISA). Competitive ELISA was used to assess the selectivity of the antibodies. Dopamine concentrations in the nucleus accumbens in rats after vaccine administration were determined by high-performance liquid chromatography with electrochemical detection. The effects of the vaccine on the heroin-primed restatement of self-administration and locomotor sensitization were evaluated. A novel hapten, 6-glutarylmorphine, was produced, and the vaccine generated a high antibody titer response. This vaccine displayed specificity for both morphine and heroin, but the anti-morphine antibodies could not recognize dissimilar therapeutic opioid compounds, such as buprenorphine, methadone, naloxone, naltrexone, codeine, and nalorphine. The morphine antibody significantly decreased morphine-induced locomotor activity in rats after immunization. Importantly, rats immunized with this vaccine did not exhibit heroin-primed reinstatement of heroin seeking when antibody levels were sufficiently high. The vaccine reduced dopamine levels in the nucleus accumbens after morphine administration, which is consistent with its behavioral effects. These results suggest that immunization with a novel vaccine is an effective means of inducing a morphine-specific antibody response that is able to attenuate the behavioral and psychoactive effects of heroin. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

N-acetylcycsteine attenuates the deleterious effects of radiation therapy on inci-sional wound healing in rats.

PubMed

Tascilar, O; Cakmak, Gk; Emre, Au; Bakkal, H; Kandemir, N; Turkcu, Uo; Demir, Eo

2014-01-01

During preoperative radiotherapy, effective doses of ionizing radiation occasionally cause wound complications after subsequent surgery. This study was designed to determine the effects of intraperitoneally or orally administered N-acetylcysteine (NAC) on anastomotic healing of irradiated rats. Forty Wistar albino rats were randomized into four groups containing 10 rats each. A 3 cm long surgical full-thickness midline laparotomy was performed to all groups (Groups 1-4). Group 1 was designed as a control group without radiation therapy and NAC treatment. Groups 2, 3 and 4 received a single abdominal dose of 10 Gy irradiation before laparotomy and groups 3 and 4 received oral and intraperitoneal NAC, respectively. Group comparisons demonstrated that breaking strength was significantly higher in NAC treated rats. A statistically significant difference was determined in terms of superoxide dismutase (SOD), malondealdehyde (MDA) and glutation (GSH) values between groups (p<0.001). Nevertheless, advanced oxidation protein products (AOPP) levels were found to be similar between groups (p=0.163). Serum GSH and SOD levels were significantly higher in groups 3 and 4 when compared to group 2 (p < 0.05). Similarly, there was a significant increase in serum MDA concentration, predicting lipid peroxidation, in group 2 when compared to groups 1, 3 and 4 (p < 0.05). There was not a significant difference between Groups 3 and 4 regarding GSH, MDA, SOD, and AOPP levels. Histopathological analysis revealed that NAC administration, either orally or intraperitoneally, leads to a better incisional healing in terms of inflammation, granulation, collagen deposition, reepithelization and neovascularization. The present study supports the hypothesis that NAC administration alleviates the negative effects of radiotherapy on incisional wound healing by means of reducing oxidative stress markers and improving histologic parameters independent of the route of administration.

High dietary intake of sodium selenite does not affect gene mutation frequency in rat colon and liver.

PubMed

Zeng, Huawei; Uthus, Eric O; Ross, Sharon A; Davis, Cindy D

2009-10-01

Our previous studies have shown that selenium (Se) is protective against dimethylhydrazine (DMH)-induced preneoplastic colon cancer lesions, and protection against DNA damage has been hypothesized to be one mechanism for the anticancer effect of Se. The present study was designed to determine whether dietary selenite affects somatic mutation frequency in vivo. We used the Big Blue transgenic model to evaluate the in vivo mutation frequency of the cII gene in rats fed either a Se-deficient (0 microg Se/g diet) or Se-supplemented diet (0.2 or 2 microg Se/g diet; n = 3 rats/diet in experiment 1 and n = 5 rats/group in experiment 2) and injected with DMH (25 mg/kg body weight, i.p.). There were no significant differences in body weight between the Se-deficient and Se-supplemented (0.2 or 2 microg Se/g diet) rats, but the activities of liver glutathione peroxidase and thioredoxin reductase and concentration of liver Se were significantly lower (p < 0.0001) in Se-deficient rats compared to rats supplemented with Se. We found no effect of dietary Se on liver 8-hydroxy-2'-deoxyguanosine. Gene mutation frequency was significantly lower in liver (p < 0.001) than that of colon regardless of dietary Se. However, there were no differences in gene mutation frequency in DNA from colon mucosa or liver from rats fed the Se-deficient diet compared to those fed the Se-supplemented (0.2 or 2 microg Se/g diet) diet. Although gene mutations have been implicated in the etiology of cancer, our data suggest that decreasing gene mutation is not likely a key mechanism through which dietary selenite exerts its anticancer action against DMH-induced preneoplastic colon cancer lesions in a Big Blue transgenic rat model.

Reduction by the Positive Allosteric Modulator of the GABAB Receptor, GS39783, of Alcohol Self-Administration in Sardinian Alcohol-Preferring Rats Exposed to the “Sipper” Procedure

PubMed Central

Maccioni, Paola; Flore, Paolo; Carai, Mauro A. M.; Mugnaini, Claudia; Pasquini, Serena; Corelli, Federico; Gessa, Gian Luigi; Colombo, Giancarlo

2010-01-01

The present study was designed to evaluate (a) alcohol self-administration behavior of selectively bred, Sardinian alcohol-preferring (sP) rats exposed to the so-called “sipper” procedure (characterized by the temporal separation between alcohol-seeking and -taking phases), and (b) the effect of the positive allosteric modulator of the GABAB receptor, GS39783, on alcohol self-administration in sP rats exposed to this procedure. To this end, sP rats were initially trained to lever-respond under a reinforcement requirement (RR) 55 (RR55) for alcohol. Achievement of RR55 resulted in the 20-min presentation of the alcohol (15%, v/v)-containing sipper bottle. Once stable levels of lever-responding and alcohol consumption were reached, rats were treated with 0, 25, 50, and 100 mg/kg GS39783 (i.g.) 60 min before the self-administration session. Rats displayed robust alcohol-seeking (as suggested by relatively short latencies to the first lever-response and high frequencies of lever-responding) and -taking (as suggested by alcohol intakes averaging approximately 1.5 g/kg) behaviors. Pretreatment with GS39783 inhibited both alcohol-seeking (the number of rats achieving RR55 and the mean RR value were virtually halved) and -taking (the amount of self-administered alcohol was reduced by approximately 60%). The results of the present study suggest the power of the “sipper” procedure in triggering high levels of alcohol-seeking and -taking behavior in sP rats. Further, these results extend to this additional procedure of alcohol self-administration the capacity of GS39783 to reduce the motivational properties of alcohol and alcohol consumption in sP rats. PMID:21423431

Some pharmacological effects of cinnamon and ginger herbs in obese diabetic rats

PubMed Central

Shalaby, Mostafa Abbas; Saifan, Hamed Yahya

2014-01-01

Aims: The present study was designed to assess some pharmacological effects of cinnamon (CAE) and ginger (GAE) aqueous extracts in obese diabetic rats, and to elucidate the potential mechanisms. Materials and Methods: Forty-two Sprague-Dawley rats were randomized into 6 equal groups. Group 1 was a negative control and the other groups were rendered obese by feeding rats on high-fat diet for 4 weeks. The obese rats were subcutaneously injected with alloxan for 5*days to induce diabetes. Group 2 was a positive control, and Groups 3, 4, 5 and 6 were orally given CAE in doses 200 and 400 mg/kg and GAE in the same doses, respectively for 6 weeks. Blood samples were collected for serum biochemical analyses. Kidneys were dissected out to assay activity of tissue antioxidant enzymes: Superoxide dismutase, glutathione peroxidase and catalase. Results: CAE and GAE significantly reduced body weight and body fat mass; normalized serum levels of liver enzymes; improved lipid profile; decreased blood glucose and leptin and increased insulin serum levels in obese diabetic rats. Both extracts also increased activity of kidney antioxidant enzymes. Conclusion: CAE and GAE exhibit anti-obesity, hepatoprotective, hypolipidemic, antidiabetic and anti-oxidant effects in obese diabetic rats. These results confirm the previous reports on both extracts. The potential mechanisms underlying these effects are fully discussed and clarified. Our results affirm the traditional use of cinnamon and ginger for treating patients suffering from obesity and diabetes. The obese diabetic rat model used in this study is a novel animal model used in pharmacology researches. PMID:26401364

Heme-Induced Biomarkers Associated with Red Meat Promotion of colon Cancer Are Not Modulated by the Intake of Nitrite

PubMed Central

Chenni, Fatima Z; Taché, Sylviane; Naud, Nathalie; Guéraud, Françoise; Hobbs, Ditte A; Kunhle, Gunter G C; Pierre, Fabrice H; Corpet, Denis E

2013-01-01

Red and processed meat consumption is associated with the risk of colorectal cancer. Three hypotheses are proposed to explain this association, via heme/alcenal, heterocyclic amines or N-nitroso compounds. Rats have often been used to study these hypotheses, but the lack of enterosalivary cycle of nitrate in rats casts doubt on the relevance of this animal model to predict nitroso- and heme-associated human colon carcinogenesis. The present study was thus designed to clarify whether a nitrite intake that mimics the enterosalivary cycle can modulate heme-induced nitrosation and fat peroxidation. This study shows that, in contrast with the starting hypothesis, salivary nitrite did not change the effect of hemoglobin on biochemical markers linked to colon carcinogenesis, notably lipid peroxidation and cytotoxic activity in the colon of rat. However, ingested sodium nitrite increased fecal nitroso-compounds level, but their fecal concentration and their nature (iron-nitrosyl) would not be associated with an increased risk of cancer. The rat model could thus be relevant to study the effect of red meat on colon carcinogenesis in spite of the lack of nitrite recycling in rat’s saliva. PMID:23441609

The Suckling Rat as a Model for Immunonutrition Studies in Early Life

PubMed Central

Pérez-Cano, Francisco J.; Franch, Àngels; Castellote, Cristina; Castell, Margarida

2012-01-01

Diet plays a crucial role in maintaining optimal immune function. Research demonstrates the immunomodulatory properties and mechanisms of particular nutrients; however, these aspects are studied less in early life, when diet may exert an important role in the immune development of the neonate. Besides the limited data from epidemiological and human interventional trials in early life, animal models hold the key to increase the current knowledge about this interaction in this particular period. This paper reports the potential of the suckling rat as a model for immunonutrition studies in early life. In particular, it describes the main changes in the systemic and mucosal immune system development during rat suckling and allows some of these elements to be established as target biomarkers for studying the influence of particular nutrients. Different approaches to evaluate these immune effects, including the manipulation of the maternal diet during gestation and/or lactation or feeding the nutrient directly to the pups, are also described in detail. In summary, this paper provides investigators with useful tools for better designing experimental approaches focused on nutrition in early life for programming and immune development by using the suckling rat as a model. PMID:22899949

Mycophenolate mofetil prevents cerebrovascular injury in stroke-prone spontaneously hypertensive rats.

PubMed

Dhande, Isha S; Zhu, Yaming; Braun, Michael C; Hicks, M John; Wenderfer, Scott E; Doris, Peter A

2017-03-01

Stroke-prone spontaneously hypertensive rats (SHR-A3) develop strokes and progressive kidney disease as a result of naturally occurring genetic variations. We recently identified genetic variants in immune signaling pathways that contribute to end-organ injury. The present study was designed to test the hypothesis that a dysregulated immune response promotes stroke susceptibility. We salt-loaded 20 wk old male SHR-A3 rats and treated them with the immunosuppressant mycophenolate mofetil (MMF, 25 mg/kg/day po) ( n = 8) or vehicle (saline) ( n = 9) for 8 wk. Blood pressure (BP) was measured weekly by telemetry. Compared with vehicle-treated controls, MMF-treated SHR-A3 rats had improved survival and lower neurological deficit scores (1.44 vs. 0.125; P < 0.02). Gross morphology of the brain revealed cerebral edema in 8 of 9, and microbleeds and hemorrhages in 5 of 9 vehicle-treated rats. These lesions were absent in MMF-treated rats. Brain CD68 expression, indicating macrophage/microglial activation, was upregulated in vehicle-treated rats with microbleeds and hemorrhages but was undetectable in the brains of MMF-treated rats. MMF also prevented renal injury in SHR-A3 rats, evidenced by reduced proteinuria (albumin:creatinine) from 7.52 to 1.05 mg/mg ( P < 0.03) and lower tubulointerstitial injury scores (2.46 vs. 1.43; P < 0.01). Salt loading resulted in a progressive increase in BP, which was blunted in rats receiving MMF. Our findings provide evidence that abnormal immune activation predisposes to cerebrovascular and renal injury in stroke-prone SHR-A3 rats. Copyright © 2017 the American Physiological Society.

Evaluation of ameliorative potential of supranutritional selenium on enrofloxacin-induced testicular toxicity.

PubMed

Rungsung, Soya; Khan, Adil Mehraj; Sood, Naresh Kumar; Rampal, Satyavan; Singh Saini, Simrat Pal

2016-05-25

The study was designed to assess the ameliorative potential of selenium (Se) on enrofloxacin-induced testicular toxicity in rats. There was a significant decrease in body weight and non-significant decrease in mean testicular weight of enrofloxacin treated rats. In enrofloxacin treated rats, total sperm count and viability decreased where as sperm abnormalities increased. Testicular histopathology revealed dose dependent dysregulation of spermatogenesis and presence of necrotic debris in seminiferous tubules which was marginally improved with Se. Enrofloxacin also produced a dose dependent decrease in testosterone level. The activity of testicular antioxidant enzymes decreased where as lipid peroxidation increased in a dose-dependent manner. Se supplementation partially restored oxidative stress and sperm damage and did not affect the plasma concentrations of enrofloxacin or ciprofloxacain. The results indicate that enrofloxacin produces a dose-dependent testicular toxicity in rats that is moderately ameliorated with supranutritional Se. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Inhibitors of soluble epoxide hydrolase minimize ischemia-reperfusion-induced cardiac damage in normal, hypertensive, and diabetic rats.

PubMed

Islam, Oliul; Patil, Prashanth; Goswami, Sumanta K; Razdan, Rema; Inamdar, Mohammed N; Rizwan, Mohammed; Mathew, Jubin; Inceoglu, Bora; Stephen Lee, Kin S; Hwang, Sung H; Hammock, Bruce D

2017-06-01

We designed a study to evaluate the cardioprotective effect of two soluble epoxide hydrolase (sEH) inhibitors, 1-(1-propanoylpiperidin-4-yl)-3-(4-trifluoromethoxy)phenyl)urea (TPPU) and trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]cyclohexyloxy}benzoic acid (t-TUCB), in ischemia-reperfusion (IR) model. Cardioprotective effects of the sEH inhibitors were evaluated against IR-induced myocardial damage in hearts from normal, hypertensive, and diabetic rats using Langendorff's apparatus. In addition, the effect of sEH inhibitors on endothelial function was evaluated in vitro and ex vivo using isolated rat thoracic aorta. Ischemia-reperfusion (IR) increased the myocardial damage in hearts from normal rats. IR-induced myocardial damage was augmented in hearts isolated from hypertensive and diabetic rats. Myocardial damage as evident from increase in the activities of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) in heart perfusate was associated with significant decrease in the heart rate and developed tension, and increase in the resting tension in isolated heart. Both sEH inhibitors protected the heart in normal, hypertensive, and diabetic rats subjected to IR injury. The sEH inhibitor t-TUCB relaxed phenylephrine precontracted aorta from normal rats. Relaxant effect of acetylcholine (ACh) was reduced in aortas from diabetic and hypertensive rats compared to normal rats. Pretreatment of sEH inhibitors to diabetic and hypertensive rats increased relaxant effect of ACh on aortas isolated from these rats. Prophylactic treatment with sEH inhibitors decreased myocardial damage due to IR, hypertension and diabetes, and decreased endothelial dysfunction created by diabetes and hypertension. Therefore, inhibitors of sEH are useful probes to study cardiovascular pathology, and inhibition of the sEH is a potential approach in the management of IR-induced cardiac damage and endothelial dysfunction-related cardiovascular disorders. © 2017 John Wiley & Sons Ltd.

Novel effects of the cannabinoid inverse agonist AM 251 on parameters related to metabolic syndrome in obese Zucker rats.

PubMed

Merroun, Ikram; Sánchez-González, Cristina; Martínez, Rosario; López-Chaves, Carlos; Porres, Jesús M; Aranda, Pilar; Llopis, Juan; Galisteo, Milagros; Zarzuelo, Antonio; Errami, Mohammed; López-Jurado, María

2013-11-01

Recent research suggests that cannabinoid receptor CB1 antagonists can affect appetite and body weight gain, although their influence on other parameters related to metabolic syndrome is not well documented. The present study was designed to assess the effects of chronic treatment with the CB1 receptor inverse agonist AM 251 (3 mg/kg for 3 weeks) in obese and lean Zucker rats on parameters related to metabolic syndrome. Four groups of rats were used: lean Zucker rats, untreated obese Zucker rats, AM 251-treated obese Zucker rats and a pair-fed obese Zucker rat experimental group which received the same amount of food as that consumed by the animals treated with AM251. Food intake, body weight gain, energy expenditure, plasma biochemical parameters, leptin, insulin and hepatic status markers were analysed. Daily injection of AM 251 in obese Zucker rats produced a marked and sustained decrease in daily food intake and body weight and a considerable increase in energy expenditure in comparison with untreated obese Zucker rats. AM 251 administration to obese rats significantly reduced plasma levels of glucose, leptin, AST, ALT, Gamma GT, total bilirubin and LDL cholesterol whereas HDL cholesterol plasma levels increased. The results also showed a decrease in liver/weight body ratio and total fat content in the liver. The main effects of AM251 (3 mg/kg) found in this study were not observed in pair-fed obese animals, highlighting the additional beneficial effects of treatment with AM 251. The results obtained in obese rats can be interpreted as a decrease in leptin and insulin resistance, thereby improving glucose and lipid metabolism, alleviating the steatosis present in the metabolic syndrome and thus favourably modifying plasma levels of hepatic biomarkers. Our results indicate that the cannabinoid CB1 inverse agonist AM 251 represents a promising therapeutic strategy for the treatment of obesity and metabolic syndrome. © 2013.

Camel milk ameliorates hyperglycaemia and oxidative damage in type-1 diabetic experimental rats.

PubMed

Meena, Sunita; Rajput, Yudhishthir S; Pandey, Amit K; Sharma, Rajan; Singh, Raghvendar

2016-08-01

This study was designed to assess anti-diabetic potential of goat, camel, cow and buffalo milk in streptozotocin (STZ) induced type 1 diabetic albino wistar rats. A total of 48 rats were taken for the study where one group was kept as non-diabetic control group (8 rats) while others (40 rats) were made diabetic by STZ (50 mg/kg of body weight) injection. Among diabetic rats, a control group (8 rats) was kept and referred as diabetic control whereas other four groups (8 rats each) of diabetic rats were fed on 50 ml of goat or camel or cow or buffalo milk for 4 weeks. All the rats (non-diabetic and diabetic) were maintained on standard diet for four weeks. STZ administration resulted in enhancement of glucose, total cholesterol, triglyceride, low density lipoprotein, HbA1c and reduction in high density lipoprotein in plasma and lowering of antioxidative enzymes (catalase, glutathione peroxidase and superoxide dismutase) activities in pancreas, kidney, liver and RBCs, coupled with enhanced levels of TBARS and protein carbonyls in pancreas, kidney, liver and plasma. OGTT carried out at the end of 4 week milk feeding indicated that all milks helped in early maintenance of glucose level. All milks reduced atherogenic index. In camel milk fed diabetic group, insulin concentration enhanced to level noted for non-diabetic control while goat, cow and buffalo milk failed to restore insulin level. HbA1c level was also restored only in camel milk fed diabetic group. The level of antioxidative enzymes (catalase, GPx and SOD) in pancreas enhanced in all milk fed groups. Camel milk and to a reasonable extent goat milk reduced formation of TBARS and PCs in tissues and blood. It can be concluded that camel milk ameliorates hyperglycaemia and oxidative damage in type-1 diabetic experimental rats. Further, only camel milk completely ameliorated oxidative damage in pancreas and normalised insulin level.

Joint Feedback Analysis Modeling of Nonesterified Fatty Acids in Obese Zucker Rats and Normal Sprague–Dawley Rats after Different Routes of Administration of Nicotinic Acid

PubMed Central

Tapani, Sofia; Almquist, Joachim; Leander, Jacob; Ahlström, Christine; Peletier, Lambertus A; Jirstrand, Mats; Gabrielsson, Johan

2014-01-01

Data were pooled from several studies on nicotinic acid (NiAc) intervention of fatty acid turnover in normal Sprague–Dawley and obese Zucker rats in order to perform a joint PKPD of data from more than 100 normal Sprague–Dawley and obese Zucker rats, exposed to several administration routes and rates. To describe the difference in pharmacodynamic parameters between obese and normal rats, we modified a previously published nonlinear mixed effects model describing tolerance and oscillatory rebound effects of NiAc on nonesterified fatty acids plasma concentrations. An important conclusion is that planning of experiments and dose scheduling cannot rely on pilot studies on normal animals alone. The obese rats have a less-pronounced concentration–response relationship and need higher doses to exhibit desired response. The relative level of fatty acid rebound after cessation of NiAc administration was also quantified in the two rat populations. Building joint normal-disease models with scaling parameter(s) to characterize the “degree of disease” can be a useful tool when designing informative experiments on diseased animals, particularly in the preclinical screen. Data were analyzed using nonlinear mixed effects modeling, for the optimization, we used an improved method for calculating the gradient than the usually adopted finite difference approximation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2571–2584, 2014 PMID:24986056

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

Harkema, J.R.; Hotchkiss, J.A.; Griffith, W.C.

The present study was designed to examine the effects of long-term ozone exposure on nasal epithelia and intraepithelial mucosubstances (IM) throughout the nasal airways of F344/N rats. Animals were exposed to 0 (controls). 0. 12. 0.5, or 1.0 ppm ozone. 6 h/day, 5 days/wk. for 20 mo. Rats were killed 1 wk after the end of the exposure. and nasal tissues were processed for light and electron microscopy. Standard morphometric techniques were used to determine epithelial cell densities and the amounts of IM in the surface epithelium lining the nasal airways. No mucous cells or IM were present in themore » epithelia lining the nasal lateral meatus and maxillary sinus of rats exposed to 0 or 0.12 ppm ozone. In contrast, rats exposed to 0.5 or 1.0 ppm ozone had marked mucous cell metaplasia (MCM) with numerous mucous cells and conspicuous amounts of IM in the surface epithelium lining these upper airways. Ozone-induced increases in total epithelial cells (i.e., epithelial hyperplasia) were present only in rats exposed to 1.0 ppm. The results of this study indicate that rats chronically exposed to 1.0 or 0.5 ppm, but not 0. 121 ppm. ozone can develop marked MCM with significant increases in IM in both proximal and distal nasal airways. The epithelial chances observed throughout the nasal passages of ozone-exposed rats may be adaptive responses in an attempt to protect the upper and lower respiratory tract from further ozone-induced injury.« less

Preclinical Screening for Treatments for Infantile Spasms in the Multiple Hit Rat Model of Infantile Spasms: An Update.

PubMed

Galanopoulou, Aristea S; Mowrey, Wenzhu B; Liu, Wei; Li, Qianyun; Shandra, Oleksii; Moshé, Solomon L

2017-07-01

Infantile spasms are the typical seizures of West syndrome, an infantile epileptic encephalopathy with poor outcomes. There is an increasing need to identify more effective and better tolerated treatments for infantile spasms. We have optimized the rat model of infantile spasms due to structural etiology, the multiple-hit rat model, for therapy discovery. Here, we test three compounds administered after spasms induction in the multiple hit model for efficacy and tolerability. Specifically, postnatal day 3 (PN3) male Sprague-Dawley rats were induced by right intracerebral injections of doxorubicin and lipopolysaccharide. On PN5 p-chlorophenylalanine was given intraperitoneally (i.p.). Daily monitoring of weights and developmental milestones was done and rats were intermittently video monitored. A blinded, randomized, vehicle-controlled study design was followed. The caspase 1 inhibitor VX-765 (50-200 mg/kg i.p.) and the GABA B receptor inhibitor CGP35348 (12.5-100 mg/kg i.p.) each was administered in different cohorts as single intraperitoneal injections on PN4, using a dose- and time-response design with intermittent monitoring till PN5. 17β-estradiol (40 ng/g/day subcutaneously) was given daily between PN3-10 and intermittent monitoring was done till PN12. None of the treatments demonstrated acute or delayed effects on spasms, yet all were well tolerated. We discuss the implications for therapy discovery and challenges of replication trials.

GENE EXPRESSION ANALYSIS IN THE VENTRAL PROSTATE OF RATS EXPOSED TO VINCLOZOLIN OR PROCYMIDONE

EPA Science Inventory

Vinclozolin and procymidone are antiandrogens that are thought to share a common androgen receptor (AR) mediated mechanism of action. This assessment is based primarily on morphological, AR binding, and in vitro transcriptional activation studies. Studies designed to evaluate t...

Developmental Toxicity Studies with Pregabalin in Rats: Significance of Alterations in Skull Bone Morphology.

PubMed

Morse, Dennis C; Henck, Judith W; Bailey, Steven A

2016-04-01

Pregabalin was administered to pregnant Wistar rats during organogenesis to evaluate potential developmental toxicity. In an embryo-fetal development study, compared with controls, fetuses from pregabalin-treated rats exhibited increased incidence of jugal fused to maxilla (pregabalin 1250 and 2500 mg/kg) and fusion of the nasal sutures (pregabalin 2500 mg/kg). The alterations in skull development occurred in the presence of maternal toxicity (reduced body weight gain) and developmental toxicity (reduced fetal body weight and increased skeletal variations), and were initially classified as malformations. Subsequent investigative studies in pregnant rats treated with pregabalin during organogenesis confirmed the advanced jugal fused to maxilla, and fusion of the nasal sutures at cesarean section (gestation day/postmating day [PMD] 21) in pregabalin-treated groups. In a study designed to evaluate progression of skull development, advanced jugal fused to maxilla and fusion of the nasal sutures was observed on PMD 20-25 and PMD 21-23, respectively (birth occurs approximately on PMD 22). On postnatal day (PND) 21, complete jugal fused to maxilla was observed in the majority of control and 2500 mg/kg offspring. No treatment-related differences in the incidence of skull bone fusions occurred on PND 21, indicating no permanent adverse outcome. Based on the results of the investigative studies, and a review of historical data and scientific literature, the advanced skull bone fusions were reclassified as anatomic variations. Pregabalin was not teratogenic in rats under the conditions of these studies. © 2016 Wiley Periodicals, Inc.

Hyperoxic preconditioning fails to confer additional protection against ischemia-reperfusion injury in acute diabetic rat heart.

PubMed

Pourkhalili, Khalil; Hajizadeh, Sohrab; Akbari, Zahra; Dehaj, Mansour Esmaili; Akbarzadeh, Samad; Alizadeh, Alimohammad

2012-01-01

Experimental studies show that detrimental effects of ischemia-reperfusion (I/R) injury can be attenuated by hyperoxic preconditioning in normal hearts, however, there are few studies about hyperoxia effects in diseased myocardium. The present study was designed to assess the cardioprotective effects of hyperoxia pretreatment (≥ 95 % O2) in acute diabetic rat hearts. Normal and one week acute diabetic rats were either exposed to 60 (H60) and 180 (H180) min of hyperoxia or exposed to normal atmospheric air (21 % O2). Then hearts were isolated immediately and subjected to 30 min of regional ischemia followed by 120 min of reperfusion. Infarct size, cardiomyocyte apoptosis, enzymes release and ischemia induced arrhythmias were determined. Heart of diabetic control rats had less infarct size and decreased LDH and CK-MB release compared to normal hearts. 60 and 180 min of hyperoxia reduced myocardial infarct size and enzymes release in normal hearts. 180 min of hyperoxia also decreased cardiomyocytes apoptosis in normal state. On the other hand, protective values of hyperoxia were not significantly different in diabetic hearts. Moreover, hyperoxia reduced severity of ventricular arrhythmias in normal rat hearts whereas; it did not confer any additional antiarrhythmic protection in diabetic hearts. These findings suggest that diabetic hearts are less susceptible to ischemia-induced arrhythmias and infarction. Hyperoxia greatly protects rat hearts against I/R injury in normal hearts, however, it could not provide added cardioprotective effects in acute phase of diabetes.

Evaluation of 4,4'-diaminodiphenyl ether in the rat comet assay: Part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative international validation study of in vivo rat alkaline comet assay.

PubMed

Priestley, Catherine C; Walker, Joanne S; O'Donovan, Michael R; Doherty, Ann T

2015-07-01

As a part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative international validation study of the in vivo rat alkaline comet assay, 4,4'-diaminodiphenyl ether (DPE), a known rodent genotoxic carcinogen, was tested in this laboratory. Sprague Dawley rats (7-9 weeks of age) were given three oral doses of DPE, 24 and 21 h apart and liver or stomach sampled 3h after the final dose. Under the conditions of the test, no increases in DNA damage in liver and stomach were observed with DPE (up to 200 mg/kg/day). A dose-dependent decrease in DNA migration, compared to vehicle controls, was noted for DPE in rat stomach. Further analysis is required to elucidate fully whether this decrease is a consequence of the mode of action or due to the toxicity of DPE. What is perhaps surprising is the inability of the comet assay to detect a known rat genotoxic carcinogen in liver. Further investigation is needed to clarify whether this apparent lack of response results from limited tissue exposure or metabolic differences between species. This finding highlights a need for careful consideration of study design when evaluating assay performance as a measure of in vivo genotoxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Biofunctionalization of a titanium surface with a nano-sawtooth structure regulates the behavior of rat bone marrow mesenchymal stem cells

PubMed Central

Zhang, Wenjie; Li, Zihui; Liu, Yan; Ye, Dongxia; Li, Jinhua; Xu, Lianyi; Wei, Bin; Zhang, Xiuli; Liu, Xuanyong; Jiang, Xinquan

2012-01-01

Background: The topography of an implant surface can serve as a powerful signaling cue for attached cells and can enhance the quality of osseointegration. A series of improved implant surfaces functionalized with nanoscale structures have been fabricated using various methods. Methods: In this study, using an H2O2 process, we fabricated two size-controllable sawtooth-like nanostructures with different dimensions on a titanium surface. The effects of the two nano-sawtooth structures on rat bone marrow mesenchymal stem cells (BMMSCs) were evaluated without the addition of osteoinductive chemical factors. Results: These new surface modifications did not adversely affect cell viability, and rat BMMSCs demonstrated a greater increase in proliferation ability on the surfaces of the nano-sawtooth structures than on a control plate. Furthermore, upregulated expression of osteogenic-related genes and proteins indicated that the nano-sawtooth structures promote osteoblastic differentiation of rat BMMSCs. Importantly, the large nano-sawtooth structure resulted in the greatest cell responses, including increased adhesion, proliferation, and differentiation. Conclusion: The enhanced adhesion, proliferation, and osteogenic differentiation abilities of rat BMMSCs on the nano-sawtooth structures suggest the potential to induce improvements in bone-titanium integration in vivo. Our study reveals the key role played by the nano-sawtooth structures on a titanium surface for the fate of rat BMMSCs and provides insights into the study of stem cell-nanostructure relationships and the related design of improved biomedical implant surfaces. PMID:22927760

Effect of Asparagus racemosus extract on transdermal delivery of carvedilol: a mechanistic study.

PubMed

Sapra, Bharti; Jain, Subheet; Tiwary, Ashok K

2009-01-01

This study was designed for investigating the effect of Asparagus racemosus (AR) extract and chitosan (CTN) in facilitating the permeation of carvedilol (CDL) across rat epidermis. Transdermal flux of carvedilol through heat-separated rat epidermis was investigated in vitro using vertical Keshary-Chien diffusion cells. Biophysical and microscopic manifestations of epidermis treated with AR extract, CTN, and AR extract-CTN mixture were investigated by using differential scanning calorimetry, transepidermal water loss, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Biochemical estimations of cholesterol, sphingosine, and triglycerides were carried out for treated excised as well as viable rat epidermis. The antihypertensive activity of the patches in comparison with that of oral carvedilol was studied in deoxycorticosterone acetate-induced hypertensive rats. The permeation of carvedilol across excised rat epidermis was significantly higher (p < 0.05) when AR extract, CTN, or AR extract-CTN mixture was used as donor vehicle as compared to propylene glycol/ethanol (7:3) mixture. Epidermis obtained after 12 h treatment of viable rat skin with AR extract-CTN mixture showed significantly higher (p < 0.05) permeability to CDL as compared to that after treatment with AR extract or CTN alone. Further, the application of patches containing AR extract-CTN mixture resulted in sustained release of CDL which was able to control the hypertension in deoxycorticosterone acetate-induced hypertensive rats through 36 h. Estimation of micro constituents in rat epidermis revealed maximum extraction of cholesterol, sphingosine, and triglycerides after treatment with AR extract-CTN mixture. This was manifested in altered lipid and protein-specific thermotropic transitions. Further, increase in intercellular space, disordered lipid structure, and corneocyte detachment as observed in SEM and TEM suggested great potential of AR extract for use as percutaneous permeation enhancer. The developed transdermal patches of CDL containing AR extract-CTN mixture exhibited better performance as compared to oral administration in controlling hypertension in rats.

A comparison of neurodegeneration linked with neuroinflammation in different brain areas of rats after intracerebroventricular colchicine injection.

PubMed

Sil, Susmita; Ghosh, Rupsa; Sanyal, Moumita; Guha, Debjani; Ghosh, Tusharkanti

2016-01-01

Colchicine induces neurodegeneration, but the extent of neurodegeneration in different areas of the brain in relation to neuroinflammation remains unclear. Such information may be useful to allow for the development of a model to compare colchicine-induced neurodegeneration with other neurodegenerative diseases such as Alzheimer's Disease (AD). The present study was designed to investigate the extent of neurodegeneration along with neuroinflammation in different areas of the brain, e.g. frontal cortex, parietal cortex, occipital cortex, corpus striatum, amygdala and hippocampus, in rats along with memory impairment 21 days after a single intracerebroventricular (icv) injection of colchicine. Memory parameters were measured before and after icv colchicine injection in all test groups of rats (control, sham-operated, colchicine-injected [ICIR] rats). On Day 21 post-injection, rats from all groups were anesthesized and tissues from the various brain areas were collected for assessment of biomarkers of neuroinflammation (i.e. levels of ROS, nitrite and proinflammatory cytokines TNFα and IL-1β) and neurodegeneration (assessed histologically). The single injection of colchicine resulted in impaired memory and neurodegeneration (significant presence of plaques, Nissl granule chromatolysis) in various brain areas (frontal cortex, amygdala, parietal cortex, corpus striatum), with maximum severity in the hippocampus. While IL-1β, TNFα, ROS and nitrite levels were altered in different brain areas in the ICIR rats, these parameters had their greatest change in the hippocampus. This study showed that icv injection of colchicine caused strong neurodegeneration and neuroinflammation in the hippocampus of rats and the increases in neurodegeneration were corroborated with those of neuroinflammation at the site. The present study also showed that the extent of neurodegeneration and neuroinflammation in different brain areas of the colchicine-injected rats were AD-like and supported the fact that such rats might have the ability to serve as a sporadic model of AD.

The increased gastroprotective effect of pioglitazone in cholestatic rats: role of nitric oxide and tumour necrosis factor alpha.

PubMed

Moezi, Leila; Janahmadi, Zeinab; Amirghofran, Zahra; Nekooeian, Ali Akbar; Dehpour, Ahmad R

2014-02-01

The prevalence of gastric ulcers is high in cholestatic patients, but the exact mechanism of this increased frequency remains uncertain. It has been shown that pioglitazone accelerates the healing of pre-existing gastric ulcers. The present study was designed to investigate the effect of pioglitazone, on the gastric mucosal lesions in cholestatic rats. Cholestasis was induced by surgical ligation of common bile duct and sham-operated rats served as control. Different groups of sham and cholestatic animals received solvent or pioglitazone (5, 15, 30 mg/kg) for 7 days. On the day eight rats were killed after oral ethanol administration and the area of gastric lesions was measured. The serums of rats were also collected to determine serum levels of tumour necrosis factor alpha (TNF-α), IL-1β and bilirubin. The ethanol-induced gastric mucosal damage was significantly more severe in cholestatic rats than sham-operated ones. Pretreatment with pioglitazone dose-dependently attenuated gastric lesions induced by ethanol in both sham and cholestatic rats, but this effect was more prominent in cholestatic ones. The effect of pioglitazone was associated with a significant fall in serum levels of TNF-α in cholestatic rats. L-NAME, a non-selective nitric oxide synthase (NOS) inhibitor, and decreased pioglitazone-induced gastroprotective effect in cholestatic rats, while aminoguanidine, a selective inducible NOS inhibitor, potentiated pioglitazone-induced gastroprotective effect in the cholestatic rats. Chronic treatment with pioglitazone exerts an enhanced gastroprotective effect on the stomach ulcers of cholestatic rats compared to sham rats probably due to constitutive NOS induction and/or inducible NOS inhibition and attenuating release of TNF-α. © 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.

Differential modulation of the discriminative stimulus effects of methamphetamine and cocaine by alprazolam and oxazepam in male and female rats.

PubMed

Spence, A L; Guerin, G F; Goeders, N E

2016-03-01

Drug users often combine benzodiazepines with psychostimulants, such as methamphetamine. However, very little research has been conducted on this type of polydrug use, particularly in female subjects. The present study was therefore designed to examine the effects of two benzodiazepines, alprazolam and oxazepam, on the discriminative stimulus effects of methamphetamine and cocaine in both male and female rats. Rats were trained to discriminate methamphetamine (1.0 mg/kg, ip) or cocaine (10 mg/kg, ip) from saline using a two-lever operant, food-reinforced, drug discrimination design. Pretreatment with oxazepam (5, 10 and 20 mg/kg, ip) significantly attenuated methamphetamine discrimination in both male and female rats. In contrast, however, the high dose of alprazolam (4 mg/kg, ip) actually augmented the subjective effects of lower doses of methamphetamine (0.125 and 0.25 mg/kg, ip). Oxazepam produced similar effects on the subjective effects of cocaine as with methamphetamine, significantly reducing cocaine discrimination in both male and female rats. However, neither the high nor low dose of alprazolam (2 and 4 mg/kg, ip) produced any apparent effect on cocaine discrimination. Finally, while similar results were observed in both male and female rats across these experiments, methamphetamine and cocaine discrimination were more sensitive to oxazepam in female subjects. The results of these experiments suggest that alprazolam and oxazepam can differentially affect the subjective effects of methamphetamine and cocaine. These results also demonstrate that alprazolam can differentially affect the discriminative stimulus effects of methamphetamine and cocaine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of peripherally and centrally applied ghrelin on the oxidative stress induced by renin angiotensin system in a rat model of renovascular hypertension.

PubMed

Boshra, Vivian; Abbas, Amr M

2017-07-26

Renovascular hypertension (RVH) is a result of renal artery stenosis, which is commonly due to astherosclerosis. In this study, we aimed to clarify the central and peripheral effects of ghrelin on the renin-angiotensin system (RAS) in a rat model of RVH. RVH was induced in rats by partial subdiaphragmatic aortic constriction. Experiment A was designed to assess the central effect of ghrelin via the intracerebroventricular (ICV) injection of ghrelin (5 μg/kg) or losartan (0.01 mg/kg) in RVH rats. Experiment B was designed to assess the peripheral effect of ghrelin via the subcutaneous (SC) injection of ghrelin (150 μg/kg) or losartan (10 mg/kg) for 7 consecutive days. Mean arterial blood pressure (MAP), heart rate, plasma renin activity (PRA), and oxidative stress markers were measured in all rats. In addition, angiotensin II receptor type 1 (AT1R) concentration was measured in the hypothalamus of rats in Experiment B. RVH significantly increased brain AT1R, PRA, as well as the brain and plasma oxidative stress. Either SC or ICV ghrelin or losartan caused a significant decrease in MAP with no change in the heart rate. Central ghrelin or losartan caused a significant decrease in brain AT1R with significant alleviation of the brain oxidative stress. Central ghrelin caused a significant decrease in PRA, whereas central losartan caused a significant increase in PRA. SC ghrelin significantly decreased PRA and plasma oxidative stress, whereas SC losartan significantly increased PRA and decreased plasma oxidative stress. The hypotensive effect of ghrelin is mediated through the amelioration of oxidative stress, which is induced by RAS centrally and peripherally.

Application of an in vitro OAT assay in drug design and optimization of renal clearance.

PubMed

Soars, Matthew G; Barton, Patrick; Elkin, Lisa L; Mosure, Kathleen W; Sproston, Joanne L; Riley, Robert J

2014-07-01

1. Optimization of renal clearance is a complex balance between passive and active processes mediated by renal transporters. This work aimed to characterize the interaction of a series of compounds with rat and human organic anion transporters (OATs) and develop quantitative structure-activity relationships (QSARs) to optimize renal clearance. 2. In vitro inhibition assays were established for human OAT1 and rat Oat3 and rat in vivo renal clearance was obtained. Statistically significant quantitative relationships were explored between the compounds' physical properties, their affinity for OAT1 and oat3 and the inter-relationship with unbound renal clearance (URC) in rat. 3. Many of the compounds were actively secreted and in vitro analysis demonstrated that these were ligands for rat and human OAT transporters (IC50 values ranging from <1 to >100 µM). Application of resultant QSAR models reduced renal clearance in the rat from 24 to <0.1 ml/min/kg. Data analysis indicated that the properties associated with increasing affinity at OATs are the same as those associated with reducing URC but orthogonal in nature. 4. This study has demonstrated that OAT inhibition data and QSAR models can be successfully used to optimize rat renal clearance in vivo and provide confidence of translation to humans.

RatLab: an easy to use tool for place code simulations

PubMed Central

Schönfeld, Fabian; Wiskott, Laurenz

2013-01-01

In this paper we present the RatLab toolkit, a software framework designed to set up and simulate a wide range of studies targeting the encoding of space in rats. It provides open access to our modeling approach to establish place and head direction cells within unknown environments and it offers a set of parameters to allow for the easy construction of a variety of enclosures for a virtual rat as well as controlling its movement pattern over the course of experiments. Once a spatial code is formed RatLab can be used to modify aspects of the enclosure or movement pattern and plot the effect of such modifications on the spatial representation, i.e., place and head direction cell activity. The simulation is based on a hierarchical Slow Feature Analysis (SFA) network that has been shown before to establish a spatial encoding of new environments using visual input data only. RatLab encapsulates such a network, generates the visual training data, and performs all sampling automatically—with each of these stages being further configurable by the user. RatLab was written with the intention to make our SFA model more accessible to the community and to that end features a range of elements to allow for experimentation with the model without the need for specific programming skills. PMID:23908627

No long-term feeding toxicities on the health status in rats fed with cloned Korean native beef cattle (Hanwoo) meat.

PubMed

Lee, Nam-Jin; Yang, Byoung-Chul; Im, Gi-Sun; Lee, Sung-Soo; Seong, Hwan-Hoo; Park, Jin-Ki; Chang, Won-Kyong; Kang, Jong-Koo; Hwang, Seongsoo

2013-08-01

This study was designed to undertake a risk assessment to identify the health status of rats fed with somatic cell nuclear transfer (SCNT)-cloned Korean native beef cattle (Hanwoo) meat for 26 weeks. The rats were randomly divided into 5 groups, each consisting of 12 male (142.6 ± 5.23 g) and 12 female (113.7 ± 6.31 g) rats each. The animals were fed commercial pellets (control), pellets containing 5% (N-5) and 10% (N-10) of normal cattle meat, and diets containing 5% (C-5) and 10% (C-10) of cloned cattle meat. The mortality; clinical signs; body weight; food consumption; urinary, hematology, blood biochemistry, and histopathological analyses; and absolute and relative organ weights were analyzed and compared. During the 26-week test period, health status-related factors of the rats fed on cloned Hanwoo meat were found to have no test substance-related toxicities. The only difference was the increased uterus weight in female C-10 rats as compared to their counterparts counterparts (p < .05). On the basis of these health status results, it can be postulated that no food consumption risks might arise from the long-term feeding of cloned cattle meat in rats.

Mangiferin attenuates renal fibrosis through down-regulation of osteopontin in diabetic rats.

PubMed

Zhu, Xia; Cheng, Ya-Qin; Du, Lei; Li, Yu; Zhang, Fan; Guo, Hao; Liu, Yao-Wu; Yin, Xiao-Xing

2015-02-01

This study was designed to investigate the effects of mangiferin on renal fibrosis, osteopontin production, and inflammation in the kidney of diabetic rats. Diabetes was induced through the single administration of streptozotocin (55 mg/kg, i.p.). Diabetic rats were treated with mangiferin (15, 30, and 60 mg/kg/day, i.g.) for 9 weeks. The kidney was fixed in 10% formalin for glomerulus fibrosis examination using Masson trichrome staining. Kidney and blood were obtained for assays of the associated biochemical parameters. Chronic mangiferin treatment prevented renal glomerulus fibrosis evidenced by decreases in Mason-stained positive area of glomeruli, protein expression of type IV collagen, and α-smooth muscle actin in the kidney of diabetic rats, in comparison with decreases in mRNA and protein expression of osteopontin as well as protein expression of cyclooxygenase 2 and NF-кB p65 subunit in the renal cortex of diabetic rats. Moreover, mangiferin reduced the levels of interleukin 1β in both the serum and the kidney of diabetic rats. Our findings demonstrate that mangiferin prevents the renal glomerulus fibrosis of diabetic rats, which is realized through the suppression of osteopontin overproduction and inflammation likely via inactivation of NF-кB. Copyright © 2014 John Wiley & Sons, Ltd.

Impact of ethyl pyruvate on Adriamycin-induced cardiomyopathy in rats

PubMed Central

Liu, Menglin; Wang, Menglong; Liu, Jianfang; Luo, Zhen; Shi, Lei; Feng, Ying; Li, Li; Xu, Lin; Wan, Jun

2016-01-01

Ethyl pyruvate (EP), a derivative of pyruvic acid, is known to have protective effects against ischemic cardiomyopathy and other disorders. However, little is known about its role in Adriamycin (ADR)-induced cardiomyopathy. The present study was designed to investigate the impact of EP on ADR-induced cardiomyopathy in an animal model. Sixty male Sprague-Dawley (SD) rats were divided into four groups: Normal control, EP, ADR and ADR + EP groups (n=15/group). Rats in the ADR and ADR + EP groups were treated with ADR (2.5 mg/kg/week intraperitoneally) for 6 weeks. From the eighth week, rats in the EP and ADR + EP groups received EP via gastric lavage at a dose of 50 mg/kg/day for 30 days. After completing the EP treatment, cardiac function was assessed by echocardiography and then rats were sacrificed. Hearts were harvested for subsequent analysis. Compared with rats in the normal control and EP groups (without ADR treatment), rats in the ADR and ADR + EP groups showed significant impairments in terms of cardiac function, apoptosis, severe oxidative stress and fibrosis in the heart. However, these impairments were alleviated by EP treatment in the ADR + EP group. Upon EP treatment, cardiac function was significantly improved. The levels of oxidative stress, fibrosis and apoptosis in the myocardial tissues were also significantly reduced. These findings indicated that EP treatment attenuated, at least partially, ADR-induced cardiomyopathy in rats. PMID:27882138

Dietary fructans, but not cellulose, decrease triglyceride accumulation in the liver of obese Zucker fa/fa rats.

PubMed

Daubioul, Catherine; Rousseau, Nicolas; Demeure, Roger; Gallez, Bernard; Taper, Henryk; Declerck, Barbara; Delzenne, Nathalie

2002-05-01

This study was designed to compare the effects of dietary supplementation with nondigestible carbohydrates, differing in fermentability by colonic bacteria, on hepatic steatosis in growing obese Zucker rats. Male Zucker fa/fa rats were divided into three groups: a control group that received the basal diet, a fructan group that received 10 g highly fermented Synergy 1/100 g diet and a cellulose group that received 10 g poorly fermented Vivapur Microcrystalline cellulose/100 g diet. Rats consuming fructan had a lower energy intake, a lower body weight and less triacylglycerol accumulation in the liver as assessed in vivo by nuclear magnetic resonance (NMR) spectroscopy, and ex vivo by biochemical and histochemical analysis compared with the control and/or cellulose groups. The high fermentation of fructans compared with cellulose was reflected by greater cecal contents and by a twofold greater propionate concentration in the portal vein of rats fed fructan compared with those fed cellulose. By measuring the capacity of hepatocytes isolated from liver of Zucker rats to synthesize triglycerides or total lipids from different precursors, we showed that propionate, at the concentrations measured in the portal vein of rats treated with fructan, selectively decreased the incorporation of acetate into total lipids, a phenomenon that could contribute, along with the lower energy intake, to less triglyceride accumulation in the liver of obese Zucker rats fed dietary fructans.

Transplantation of Bone Marrow–Derived Mesenchymal Stem Cells Improves Diabetic Polyneuropathy in Rats

PubMed Central

Shibata, Taiga; Naruse, Keiko; Kamiya, Hideki; Kozakae, Mika; Kondo, Masaki; Yasuda, Yutaka; Nakamura, Nobuhisa; Ota, Kimiko; Tosaki, Takahiro; Matsuki, Takashi; Nakashima, Eitaro; Hamada, Yoji; Oiso, Yutaka; Nakamura, Jiro

2008-01-01

OBJECTIVE—Mesenchymal stem cells (MSCs) have been reported to secrete various cytokines that exhibit angiogenic and neurosupportive effects. This study was conducted to investigate the effects of MSC transplantation on diabetic polyneuropathy (DPN) in rats. RESEARCH DESIGN AND METHODS—MSCs were isolated from bone marrow of adult rats and transplanted into hind limb skeletal muscles of rats with an 8-week duration of streptozotocin (STZ)-induced diabetes or age-matched normal rats by unilateral intramuscular injection. Four weeks after transplantation, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) productions in transplanted sites, current perception threshold, nerve conduction velocity (NCV), sciatic nerve blood flow (SNBF), capillary number–to–muscle fiber ratio in soleus muscles, and sural nerve morphometry were evaluated. RESULTS—VEGF and bFGF mRNA expression were significantly increased in MSC-injected thigh muscles of STZ-induced diabetic rats. Furthermore, colocalization of MSCs with VEGF and bFGF in the transplanted sites was confirmed. STZ-induced diabetic rats showed hypoalgesia, delayed NCV, decreased SNBF, and decreased capillary number–to–muscle fiber ratio in soleus muscles, which were all ameliorated by MSC transplantation. Sural nerve morphometry showed decreased axonal circularity in STZ-induced diabetic rats, which was normalized by MSC transplantation. CONCLUSIONS—These results suggest that MSC transplantation could have therapeutic effects on DPN through paracrine actions of growth factors secreted by MSCs. PMID:18728233

The effect of eugenol on the cariogenic properties of Streptococcus mutans and dental caries development in rats

PubMed Central

XU, JING-SHU; LI, YAO; CAO, XUE; CUI, YUN

2013-01-01

Eugenol has been widely used in medicine due to its antibacterial, anti-inflammatory, antioxidant, anticancer and analgesic properties. The present study was designed to investigate the effects of eugenol on the cariogenic properties of Streptococcus mutans and dental caries development in rats. Eugenol demonstrated significant inhibitory effects against acid production by S. mutans. The synthesis of water-insoluble glucans by glucosyltransferases was reduced by eugenol. Eugenol also markedly suppressed the adherence of S. mutans to saliva-coated hydroxyapatite beads. Furthermore, topical application of eugenol reduced the incidence and severity of carious lesions in rats. These results suggest that the natural compound eugenol may be a useful therapeutic agent for dental caries. PMID:23837051

Genetic variation of an acid phosphatase (Acp-2) in the laboratory rat: possible homology with mouse AP-1 and human ACP2.

PubMed

Bender, K; Bissbort, S; Kuhn, A; Nagel, M; Günther, E

1986-02-01

A genetic locus controlling the electrophoretic mobility of an acid phosphatase in the rat (Rattus norvegicus) is described. The locus, designed Acp-2, is not expressed in erythrocytes but is expressed in all other tissues studied. The product of Acp-2 hydrolyzes a wide variety of phosphate monoesters and is inhibited by L(+)-tartaric acid. Inbred rat strains have fixed either allele Acp-2a or allele Acp-2b. Codominant expression is observed in the respective F1 hybrids. Backcross progenies revealed the expected 1:1 segregation ratio. Possible loose linkage was found between the Acp-2 and the Pep-3 gene loci at a recombination frequency of 0.36 +/- 0.06.

Both Central and Peripheral Auditory Systems Are Involved in Salicylate-Induced Tinnitus in Rats: A Behavioral Study

PubMed Central

Liu, Zhi; Sun, Yongzhu; Chang, Haifeng; Cui, Pengcheng

2014-01-01

Objective This study was designed to establish a low dose salicylate-induced tinnitus rat model and to investigate whether central or peripheral auditory system is involved in tinnitus. Methods Lick suppression ratio (R), lick count and lick latency of conditioned rats in salicylate group (120 mg/kg, intraperitoneally) and saline group were first compared. Bilateral auditory nerves were ablated in unconditioned rats and lick count and lick latency were compared before and after ablation. The ablation was then performed in conditioned rats and lick count and lick latency were compared between salicylate group and saline group and between ablated and unablated salicylate groups. Results Both the R value and the lick count in salicylate group were significantly higher than those in saline group and lick latency in salicylate group was significantly shorter than that in saline group. No significant changes were observed in lick count and lick latency before and after ablation. After ablation, lick count and lick latency in salicylate group were significantly higher and shorter respectively than those in saline group, but they were significantly lower and longer respectively than those in unablated salicylate group. Conclusion A low dose of salicylate (120 mg/kg) can induce tinnitus in rats and both central and peripheral auditory systems participate in the generation of salicylate-induced tinnitus. PMID:25269067

Drug gastrointestinal absorption in rat: Strain and gender differences.

PubMed

Oltra-Noguera, Davinia; Mangas-Sanjuan, Victor; González-Álvarez, Isabel; Colon-Useche, Sarin; González-Álvarez, Marta; Bermejo, Marival

2015-10-12

Predictive animal models of intestinal drug absorption are essential tools in drug development to identify compounds with promising biopharmaceutical properties. In situ perfusion absorption studies are routinely used in the preclinical setting to screen drug candidates. The objective of this work is to explore the differences in magnitude and variability on intestinal absorption associated with rat strain and gender. Metoprolol and Verapamil absorption rate coefficients were determined using the in situ closed loop perfusion model in four strains of rats and in both genders. Strains used were Sprague-Dawley, Wistar-Han, Wistar-Unilever, Long-Evans and CD∗IGS. In the case of Metoprolol only CD∗IGS and Wistar Unilever showed differences between males and females. For Verapamil, Wistar Han and Sprague-Dawley strains do not show differences between male and female rats. That means that in these strains permeability data from male and female could be combined. In male rats, which are commonly used for permeability estimation, there were differences for Metoprolol permeability between Sprague-Dawley (with lower permeability values) and the other strains, while for Verapamil Sprague-Dawley and Wistar-Han showed the lower permeability values. In conclusion, the selection of rat's strain and gender for intestinal absorption experiments is a relevant element during study design and data from different strains may not be always comparable. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparative safety testing of genetically modified foods in a 90-day rat feeding study design allowing the distinction between primary and secondary effects of the new genetic event.

PubMed

Knudsen, Ib; Poulsen, Morten

2007-10-01

This article discusses the wider experiences regarding the usefulness of the 90-day rat feeding study for the testing of whole foods from genetically modified (GM) plant based on data from a recent EU-project [Poulsen, M., Schrøder, M., Wilcks, A., Kroghsbo, S., Lindecrona, R.H., Miller, A., Frenzel, T., Danier, J., Rychlik, M., Shu, Q., Emami, K., Taylor, M., Gatehouse, A., Engel, K.-H., Knudsen, I., 2007a. Safety testing of GM-rice expressing PHA-E lectin using a new animal test design. Food Chem. Toxicol. 45, 364-377; Poulsen, M., Kroghsbo, S., Schrøder, M., Wilcks, A., Jacobsen, H., Miller, A., Frenzel, T., Danier, J., Rychlik, M., Shu, Q., Emami, K., Sudhakar, D., Gatehouse, A., Engel, K.-H., Knudsen, I., 2007b. A 90-day safety in Wistar rats fed genetically modified rice expressing snowdrop lectin Galanthus nivalis (GNA). Food Chem. Toxicol. 45, 350-363; Schrøder, M., Poulsen, M., Wilcks, A., Kroghsbo, S., Miller, A., Frenzel, T., Danier, J., Rychlik, M., Emami, K., Gatehouse, A., Shu, Q., Engel, K.-H., Knudsen, I., 2007. A 90-day safety study of genetically modified rice expressing Cry1Ab protein (Bacillus thuringiensis toxin) in Wistar rats. Food Chem. Toxicol. 45, 339-349]. The overall objective of the project has been to develop and validate the scientific methodology necessary for assessing the safety of foods from genetically modified plants in accordance with the present EU regulation. The safety assessment in the project is combining the results of the 90-day rat feeding study on the GM food with and without spiking with the pure novel gene product, with the knowledge about the identity of the genetic change, the compositional data of the GM food, the results from in-vitro/ex-vivo studies as well as the results from the preceding 28-day toxicity study with the novel gene product, before the hazard characterisation is concluded. The results demonstrated the ability of the 90-day rat feeding study to detect the biological/toxicological effects of the new gene product in the GM food. The authors consider on this basis that the 90-day, rodent feeding study with one high dose level and a dietary design based upon compositional data on the GM food and toxicity data on the gene product is sensitive and specific enough to verify the presence/absence of the biological/nutritional/toxicological effects of the novel gene insert and further by the use of spiking able to separate potentially unintended effects of the novel gene product from other unintended effects at the level of intake defined in the test and within the remit of the test. Recommendations for further work necessary in the field are given.

Evaluation of repeated exposure systemic toxicity test of PVC with new plasticizer on rats via dual parenteral routes

PubMed Central

Hou, Li; Fan, Chunguang; Liu, Chenghu; Qu, Qiujin; Wang, Chunren

2018-01-01

Abstract Systemic toxicity caused by repeated exposure to both polar and nonpolar leachables of di(2-ethylhexyl)-1,2-cyclohexane plasticized polyvinyl chloride (PVC) was evaluated with dual routes of parenteral administration method on rats in the study. Experimental group and control group were designed by researchers. Tail intravenous injection with 0.9% sodium chloride injection extracts and intraperitoneal injection with corn oil extracts were conducted to the experimental rats while tail intravenous injection with 0.9% sodium chloride Injection and intraperitoneal injection with corn oil were conducted to the control rats. After 14 days, blood specimens were collected for clinical pathology (hematology and clinical chemistry) analysis. Selected organs were weighed and a histopathological examination was conducted. As a result, compared with the control animals, there were no toxicity-related changes on the parameters above. The results show that the rats do not show obvious systemic toxicity reaction caused by repeated exposure with dual routes of parenteral administration method on rats after administration with both polar and nonpolar exacts of di(2-ethylhexyl)-1,2-cyclohexane plasticized PVC simultaneously up for 14 days. PMID:29423263

A new animal diet based on human Western diet is a robust diet-induced obesity model: comparison to high-fat and cafeteria diets in term of metabolic and gut microbiota disruption.

PubMed

Bortolin, R C; Vargas, A R; Gasparotto, J; Chaves, P R; Schnorr, C E; Martinello, Kd B; Silveira, A K; Rabelo, T K; Gelain, D P; Moreira, J C F

2018-03-01

Obesity is a metabolic disorder that predisposes patients to numerous diseases and has become a major global public-health concern. Animal models of diet-induced obesity (DIO) are frequently used to study obesity, but which DIO model most accurately reflects the pathology of human obesity remains unclear. In this study, we designed a diet based on the human Western diet (WD) and compared it with the cafeteria diet (CAF) and high-fat diet (HFD) in order to evaluate which diet most closely mirrors human obesity. Wistar rats were fed four different diets (WD, CAF, HFD and a low-fat diet) for 18 weeks. Metabolic parameters and gut microbiota changes were then characterized. Rats fed the four different diets exhibited completely different phenotypes, highlighting the importance of diet selection. This study also revealed that WD most effectively induced obesity and obesity-related disorders, and thus proved to be a robust model of human obesity. Moreover, WD-fed rats developed obesity and obesity-related comorbidities independent of major alterations in gut microbiota composition (dysbiosis), whereas CAF-fed rats developed the greatest dysbiosis independent of obesity. We also characterized gut microbiota after feeding on these four different diets and identified five genera that might be involved in the pathogenesis of obesity. These data suggest that diet, and not the obese state, was the major driving force behind gut microbiota changes. Moreover, the marked dysbiosis observed in CAF-fed rats might have resulted from the presence of several additives present in the CAF diet, or even a lack of essential vitamins and minerals. Based on our findings, we recommend the use of the prototypic WD (designed here) in DIO models. Conversely, CAF could be used to investigate the effects of excessive consumption of industrially produced and highly processed foods, which are characteristic of Western society.

Steady-State Assessment of Impulsive Choice in Lewis and Fischer 344 Rats: Between-Condition Delay Manipulations

ERIC Educational Resources Information Center

Madden, Gregory J.; Smith, Nathaniel G.; Brewer, Adam T.; Pinkston, Jonathan W.; Johnson, Patrick S.

2008-01-01

Previous research has shown that Lewis rats make more impulsive choices than Fischer 344 rats. Such strain-related differences in choice are important as they may provide an avenue for exploring genetic and neurochemical contributions to impulsive choice. The present systematic replication was designed to determine if these findings could be…

Student Preferences for Live versus Virtual Rats in a Learning Course

ERIC Educational Resources Information Center

Elcoro, Mirari; Trundle, Melissa B.

2013-01-01

We examined the preference of undergraduate students for a live or a virtual rat when learning about concepts of operant conditioning. Students were provided with the opportunity to directly compare a virtual and a live rat in a supplemental exercise for Learning courses. We argue that the design of teaching exercises should involve a systematic…

Sleep Deprivation in Pigeons and Rats Using Motion Detection

PubMed Central

Newman, Sarah M.; Paletz, Elliott M.; Obermeyer, William H.; Benca, Ruth M.

2009-01-01

Study Objectives: Forced sleep deprivation results in substantial behavioral and physiologic effects in mammals. The disk-over-water (DOW) method produces a syndrome characterized by increased energy expenditure and a robust preferentially rapid-eye-movement sleep rebound upon recovery or eventual death after several weeks of sleep deprivation. The DOW has been used successfully only in rats. This paper presents a method to enforce long-term controlled sleep deprivation across species and to compare its effects in rats and pigeons. Design and Intervention: A conveyor was substituted for the DOW disk. Behavior rather than electroencephalography was used to trigger arousal stimuli, as in gentle-handling deprivation. Rats and pigeons were deprived using this apparatus, and the were compared with each other and with published reports. Measurements and Results: The physiologic consequences and recovery sleep in rats were like those published for DOW rats. Magnitude of sleep loss and recovery patterns in pigeons were similar to those seen in rats, but expected symptoms of the sleep deprivation syndrome were absent in pigeons. The use of a motion trigger allowed us to measure and, thus, to assess the quality and impact of the procedure. Conclusion: Prolonged and controlled sleep deprivation can be enforced using automated motion detection and a conveyor-over-water system. Pigeons and rats, deprived of sleep to the same extent, showed similar patterns of recovery sleep, but pigeons did not exhibit the hyperphagia, weight loss, and debilitation seen in rats. Citation: Newman SM; Paletz EM; Obermeyer WH; Benca RM. Sleep Deprivation In Pigeons And Rats Using Motion Detection. SLEEP 2009;32(10):1299-1312. PMID:19848359

Protective effects of Labisia pumila var. alata on biochemical and histopathological alterations of cardiac muscle cells in isoproterenol-induced myocardial infarction rats.

PubMed

Dianita, Roza; Jantan, Ibrahim; Amran, Athirah Z; Jalil, Juriyati

2015-03-16

The study was designed to evaluate the cardioprotective effects of the standardized aqueous and 80% ethanol extracts of Labisia pumila var. alata (LPva) in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. The extracts were administered to Wistar rats orally for 28 days with three doses (100, 200 and 400 mg/kg of body weight) prior to ISO (85 mg/kg)-induced MI in two doses on day 29 and 30. The sera and hearts were collected for biochemical and histopathological analysis after the rats were sacrificed 48 h after the first induction. The main components of the extracts, gallic acid, alkylresorcinols and flavonoids were identified and quantitatively analyzed in the extracts by using a validated reversed phase HPLC method. The extracts showed significant protective effects as pretreated rats showed a significant dose-dependent decrease (p < 0.05) in cardiac enzyme activities, i.e., cardiac troponin I (cTnI), creatine kinase MB isoenzyme (CK-MB), lactate dehydrogenase (LDH), alanine transaminase (ALT) and aspartate transaminase (AST), when compared with ISO-control rats. There were significant rises (p < 0.05) in the activity of oxidase enzymes, i.e., glutathione peroxide (GPx), catalase (CAT) and superoxide dismutase (SOD) of the pretreated rats, when compared with ISO-control group. Histopathological examination showed an improvement in membrane cell integrity in pre-treated rats compared to untreated rats. The major components of LPva extracts can be used as their biomarkers and contributed to the cardioprotective effects against ISO-induced MI rats.

Life-span carcinogenicity studies on Sprague-Dawley rats exposed to γ-radiation: design of the project and report on the tumor occurrence after post-natal radiation exposure (6 weeks of age) delivered in a single acute exposure.

PubMed

Soffritti, Morando; Tibaldi, Eva; Bua, Luciano; Padovani, Michela; Falcioni, Laura; Lauriola, Michelina; Manservigi, Marco; Manservisi, Fabiana; Belpoggi, Fiorella

2015-01-01

Experimental long-term carcinogenicity bioassays conducted on rats and mice proved that ionizing radiation can induce a variety of tumor types. However few studies have been conducted on rats. This report deals with the effects of γ-radiation in groups of 416-1,051 6-weeks old Sprague-Dawley rats exposed to 0, 0.1, 1, or 3 Gy of γ-radiation delivered in a single acute exposure. The experiment lasted for the animals' lifespan and all were necropsied and underwent full histopathological evaluation. The results confirm the dose-related carcinogenic effects of γ-radiation for several organs and tissues. Moreover they indicate that exposure to 0.1 Gy induces a statistically significant increased incidence in Zymbal gland carcinomas and pancreas islet cell carcinomas in females. Our data show that exposure to γ-radiation induces carcinogenic effects at all tested doses. © 2014 Wiley Periodicals, Inc.

A Comparative Study on Aflatoxin B1 Metabolism in Mice and Rats

PubMed Central

Steyn, M.; Pitout, M. J.; Purchase, I. F. H.

1971-01-01

In vivo metabolic studies on rats and mice revealed a marked difference in the fluorescent compounds produced after ingestion of aflatoxin B1. The mouse converted aflatoxin B1 to three unknown fluorescent compounds, designated x1, x2 and x3 and the known aflatoxin M1, while the rat was only capable of producing aflatoxin M1. The results suggested that metabolites x1, x2, x3 and aflatoxin M1 were not part of a major metabolic pathway, but produced independently. These unknown yellowish-green fluorescent compounds did not seem to be conjugated with sulphate or glucuronic acid. In vitro incubations of various mouse liver cell fractions with aflatoxin B1 showed that metabolites x1, x2, x3 and aflatoxin M1, could only be produced by the microsomal fraction and that NADPH was needed as a co-factor. The differences in aflatoxin metabolism by mice and rats are discussed in relation to the apparent resistance of the mouse to the carcinogenic effects of this toxin. PMID:4398926

Preparation and biocompatibility study of in situ forming polymer implants in rat brains.

PubMed

Nasongkla, Norased; Boongird, Atthaporn; Hongeng, Suradej; Manaspon, Chawan; Larbcharoensub, Noppadol

2012-02-01

We describe the development of polymer implants that were designed to solidify once injected into rat brains. These implants comprised of glycofurol and copolymers of D: ,L: -lactide (LA), ε-caprolactone and poly(ethylene glycol) (PLECs). Scanning electron microscopy (SEM) and gel permeation chromatography (GPC) showed that the extent of implant degradation was increased with LA: content in copolymers. SEM analysis revealed the formation of porosity on implant surface as the degradation proceeds. PLEC with 19.3% mole of LA: was chosen to inject in rat brains at the volume of 10, 25 and 40 μl. Body weights, hematological and histopathological data of rats treated with implants were evaluated on day 3, 6, 14, 30 and 45 after the injection. Polymer solution at the injection volume of 10 μl were tolerated relatively well compared to those of 25 and 40 μl as confirmed by higher body weight and healing action (fibrosis tissue) 30 days after treatment. The results from this study suggest a possible application as drug delivery systems that can bypass the blood brain barrier.

Curcumin modulates free radical quenching in myocardial ischaemia in rats.

PubMed

Manikandan, Panchatcharam; Sumitra, Miriyala; Aishwarya, Srinivasan; Manohar, Bhakthavatsalam Murali; Lokanadam, Beema; Puvanakrishnan, Rengarajulu

2004-10-01

This study was designed to investigate the protective effect of curcumin (CUR) against isoprenaline induced myocardial ischaemia in rat myocardium. The effect of single oral dose of curcumin (15 mg kg(-1)), administered 30 min before and/or after the onset of ischaemia, was investigated by assessing oxidative stress related biochemical parameters in rat myocardium. Curcumin pre and post-treatment (PPT) was shown to decrease the levels of xanthine oxidase, superoxide anion, lipid peroxides (LPs) and myeloperoxidase while the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) activities were significantly increased after curcumin PPT. Histopathological and transmission electron microscopical studies also confirmed the severe myocardial damage occurring as a consequence of isoprenaline induced ischaemia and they also showed the significant improvement effected by curcumin PPT. These findings provided evidence that curcumin was found to protect rat myocardium against ischaemic insult and the protective effect could be attributed to its antioxidant properties as well as its inhibitory effects on xanthine dehydrogenase/xanthine oxidase (XD/XO) conversion and resultant superoxide anion production.

Effectiveness of memantine on depression-like behavior, memory deficits and brain mRNA levels of BDNF and TrkB in rats subjected to repeated unpredictable stress.

PubMed

Amidfar, Meysam; Kim, Yong-Ku; Wiborg, Ove

2018-06-01

Previous clinical and preclinical studies have indicated that the N-methyl-d-aspartate (NMDA) receptor antagonist, memantine, has neuroprotective properties as well as antidepressant effects. The present study was designed to examine behavioral and molecular effects of memantine administration in rats subjected to the repeated unpredictable stress (RUS) paradigm. Rats were split into four groups at random including control+saline, control+memantine, stressed+saline and stressed+memantine. After 10days of exposure to the RUS paradigm, rats were administered memantine (20mg/kg) intraperitoneally (ip) for 14days. Depression-like behavior and memory performance were assessed by measuring immobility time in the forced swim test and passive avoidance test, respectively. The mRNA levels of BDNF and TrkB in the prefrontal cortex and hippocampus were measured by real-time quantitative PCR. Our results demonstrated that the RUS paradigm caused depression-like behavior and impairment of memory retrieval in rats. We did not find significant changes in BDNF or TrkB mRNA levels in hippocampus, but mRNA levels of TrkB in the prefrontal cortex showed a significant downregulation. Administration of memantine reversed depression-like behavior and memory impairment and significantly increased BDNF and TrkB mRNA levels in both prefrontal cortex and hippocampus of stress exposed rats. Our study supports the hypothesis that drugs with antagonistic properties on the NMDA receptor, such as memantine, might be efficient in treatment of major depression. Our results also suggest that upregulated mRNA levels of BDNF and TrkB in the brain might be essential for antidepressant-like activity of memantine in stress exposed rats. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Chronic marijuana smoke exposure in the rhesus monkey. IV: Neurochemical effects and comparison to acute and chronic exposure to delta-9-tetrahydrocannabinol (THC) in rats.

PubMed

Ali, S F; Newport, G D; Scallet, A C; Paule, M G; Bailey, J R; Slikker, W

1991-11-01

THC is the major psychoactive constituent of marijuana and is known to produce psychopharmacological effects in humans. These studies were designed to determine whether acute or chronic exposure to marijuana smoke or THC produces in vitro or in vivo neurochemical alterations in rat or monkey brain. For the in vitro study, THC was added (1-100 nM) to membranes prepared from different regions of the rat brain and muscarinic cholinergic (MCh) receptor binding was measured. For the acute in vivo study, rats were injected IP with vehicle, 1, 3, 10, or 30 mg THC/kg and sacrificed 2 h later. For the chronic study, rats were gavaged with vehicle or 10 or 20 mg THC/kg daily, 5 days/week for 90 days and sacrificed either 24 h or 2 months later. Rhesus monkeys were exposed to the smoke of a single 2.6% THC cigarette once a day, 2 or 7 days a week for 1 year. Approximately 7 months after the last exposure, animals were sacrificed by overdose with pentobarbital for neurochemical analyses. In vitro exposure to THC produced a dose-dependent inhibition of MCh receptor binding in several brain areas. This inhibition of MCh receptor binding, however, was also observed with two other nonpsychoactive derivatives of marijuana, cannabidiol and cannabinol. In the rat in vivo study, we found no significant changes in MCh or other neurotransmitter receptor binding in hippocampus, frontal cortex or caudate nucleus after acute or chronic exposure to THC. In the monkey brain, we found no alterations in the concentration of neurotransmitters in caudate nucleus, frontal cortex, hypothalamus or brain stem.(ABSTRACT TRUNCATED AT 250 WORDS)

Overview of the Habitat Demonstration Unit Power System Integration and Operation at Desert RATS 2010

NASA Technical Reports Server (NTRS)

Colozza, Anthony J.; George, Pat; Gambrell, Ronnie; Chapman, Chris

2013-01-01

A habitat demonstration unit (HDU) was constructed at NASA Johnson Space Center (JSC) and designed by a multicenter NASA team led out of NASA Kennedy Space Center (KSC). The HDU was subsequently utilized at the 2010 Desert Research and Technology Studies (RATS) program held at the Black Point Lava Flow in Arizona. This report describes the power system design, installation and operation for the HDU. The requirements for the power system were to provide 120 VAC, 28 VDC, and 120 VDC power to the various loads within the HDU. It also needed to be capable of providing power control and real-time operational data on the load's power consumption. The power system had to be capable of operating off of a 3 phase 480 VAC generator as well as 2 solar photovoltaic (PV) power systems. The system operated well during the 2 week Desert RATS campaign and met all of the main goals of the system. The power system is being further developed to meet the future needs of the HDU and options for this further development are discussed.

Ameliorative effect of chromium-d-phenylalanine complex on indomethacin-induced inflammatory bowel disease in rats.

PubMed

Nagarjun, S; Dhadde, Shivsharan B; Veerapur, Veeresh P; Thippeswamy, B S; Chandakavathe, Baburao N

2017-05-01

Present study was designed to evaluate the effect of chromium-d-phenylalanine complex (Cr (d-phe) 3 ) on indomethacin-induced inflammatory bowel disease (IBD) in rats. Adult Wistar rats were pretreated with vehicle/Cr (d-phe) 3 (30, 60 and 90μg/kg, p.o.) for 11days. On day 8 and 9, after one h of the above mentioned treatment, indomethacin (7.5mg/kg/day,s.c.) was administered to induce IBD. On day 12, blood samples were collected from animals for lactate dehydrogenase (LDH) estimation and ileum was isolated for macroscopic scoring, biochemical estimation (lipid peroxidation, reduced glutathione and myeloperoxidase activity) and histopathological study. Administration of indomethacin significantly altered the serum LDH, macroscopic and microscopic appearance and biochemical parameters in ileum tissue. Cr (d-phe) 3 , at all the tested doses, caused a significant reversal of changes induced by indomethacin. Present study demonstrates the protective effect of Cr (d-phe) 3 against indomethacin-induced IBD in rats. The observed protective effect might be attributed to the antioxidant and anti-inflammatory properties of Cr (d-phe) 3 . Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Science Operations Development for Field Analogs: Lessons Learned from the 2010 Desert RATS Test

NASA Technical Reports Server (NTRS)

Eppler, D. B.; Ming, D. W.

2011-01-01

Desert Research and Technology Studies (Desert RATS) is a multi-year series of hardware and operations tests carried out annually in the high desert of Arizona on the San Francisco Volcanic Field. Conducted since 1997, these activities are designed to exercise planetary surface hardware and operations in conditions where long-distance, multi-day roving is achievable. Such activities not only test vehicle subsystems through extended rough-terrain driving, they also stress communications and operations systems and allow testing of science operations approaches to advance human and robotic surface capabilities.

[Specific features of 2-methyl hydroxybenzene and 3-methyl hydroxybenzene distribution in the organism of warm-blooded animals].

PubMed

Shormanov, B K; Grishenko, V K; Astashkina, A P; Elizarova, M K

2013-01-01

The present work was designed to study the specific features of 2-methyl hydroxybezene and 3-methyl hydroxybenzene distribution after intragastric administration of these toxicants to warm-blooded animals (rats). They were detected in the unmetabolized form in the internal organs and blood of the animals. The levels of 2-methyl hydroxybezene were especially high in the stomach and blood whereas the maximum content of 3-methyl hydroxybenzene was found in brain, blood, small intestines of the poisoned rats.

Comparison of Translocation and Transformation from Soil to Rice and Metabolism in Rats for Four Arsenic Species.

PubMed

Wang, Xu; Geng, Anjing; Dong, Yan; Fu, Chongyun; Li, Hanmin; Zhao, Yarong; Li, Qing X; Wang, Fuhua

2017-10-18

Arsenic (As) is ubiquitously present in the environment. The toxicity of As is related to its forms. This study was designed to compare the translocation and transformation of four As species from soil to rice, and metabolism in rats for four arsenic species. A set of 26550 data was obtained from pot experiments of rice plants grown in soil fortified with four As species, and 4050 data were obtained from rat experiments in which 81 rats were administered with the four As species. The total As in grain from the methyl arsenate fortified soil was 6.1, 4.9, and 5.2 times that from As(III), As(V), and dimethyl arsenate fortified soil, respectively. The total As in husk was 1.2-7.8 times greater than that in grain. After oral administration of each As species to rats, 83-96% was accumulatively excreted via feces and urine, while 0.1-16% was detected in blood. The translocation, transformation, and metabolism of different forms of arsenic vary greatly.

Docosahexaenoic acid Confers Neuroprotection in a Rat Model of Perinatal Hypoxia-ischemia potentiated by E. coli lipopolysaccharide-induced systemic inflammation

PubMed Central

BERMAN, Deborah R; LIU, YiQing; BARKS, John; MOZURKEWICH, Ellen

2010-01-01

Objective Lipopolysaccharide (LPS) pretreatment potentiates HI injury. We hypothesized that docosahexaenoic acid (DHA) pretreatment would improve function and reduce brain damage in this rat model of perinatal brain injury and inflammation. Study Design Seven-day-old Wistar rats were divided into 3 groups. One received intraperitoneal (IP) DHA 1 mg/kg and LPS 0.1mg/kg. The second received 25% Albumin and LPS. The third received normal saline (NS). Injections were given 2.5 hours prior to right carotid ligation, followed by 90 minutes 8% O2. Rats underwent sensorimotor testing and brain damage assessment on P14. Results DHA pretreatment improved forepaw placing compared to albumin/LPS. (Mean±SD successes/10 trials: 8.57±1.7 DHA/LPS vs 6.72±2.2 Albumin/LPS, p<.0009). There were no significant differences in brain damage among groups. Conclusions Inflammatory stimulation before HI resulted in poorer function than HI alone. Although DHA pretreatment had no impact on brain damage, it significantly improved function in neonatal rats exposed to LPS and HI. PMID:19254588

Neurotrophic peptide ACTH-(4-10) permits glucocorticoid-facilitated retention of acquired immobility response of hypophysectomized rats.

PubMed

De Kock, S; De Kloet, E R

1987-09-23

The Porsolt swimming test, which was originally designed as an experimental model to screen potential antidepressants demands that rats be forced to swim for 15 min in a narrow cylinder. Twenty four hours later they are retested for 5 min during which they stay immobile for approximately 70% of the time. The present study showed that hypophysectomized animals, 14 days after operation, were unable to retain the acquired immobility. Subcutaneous glucocorticoid administration did not restore the retention of acquired immobility in contrast to our earlier finding with adrenalectomized animals. The deficit in responsiveness to glucocorticoids was eliminated when the hypophysectomized rats received ACTH-(4-10)s.c. (20 micrograms/rat) every other day. Chronic treatment with only the peptide did not improve the impaired retention of hypophysectomized rats and a single ACTH-(4-10) injection 1 day or 1 h prior to initial testing was also ineffective. We conclude that the neurotrophic peptide ACTH-(4-10) permits the expression of the glucocorticoid effect on retention of acquired immobility in the swimming test.

Effects of Averrhoa bilimbi leaf extract on blood glucose and lipids in streptozotocin-diabetic rats.

PubMed

Pushparaj, P; Tan, C H; Tan, B K

2000-09-01

The present study was designed to investigate the hypoglycemic and hypolipidemic activities of an ethanolic extract of Averrhoa bilimbi Linn. leaves (Oxalidaceae, Common name: Bilimbi) in streptozotocin (STZ)-diabetic rats. The optimal hypoglycemic dose (125 mg kg(-1)) was determined by performing the oral glucose tolerance test (OGTT) in both normal and STZ-diabetic rats. To investigate the effect of repeated administration of an ethanolic extract of Averrhoa bilimbi (ABe) leaves, diabetic rats were treated with vehicle (distilled water), ABe (125 mg kg(-1)) or metformin (500 mg kg(-1)) twice a day for 2 weeks. Like metformin, ABe significantly lowered blood glucose by 50% and blood triglyceride by 130% when compared with the vehicle. ABe also significantly increased the HDL-cholesterol concentrations by 60% compared with the vehicle. ABe thus significantly increased the anti-atherogenic index and HDL-cholesterol/total cholesterol ratio. However, like metformin, ABe did not affect total cholesterol and LDL-cholesterol concentrations, but significantly reduced the kidney lipid peroxidation level. These data show that ABe has hypoglycemic, hypotriglyceridemic, anti-lipid peroxidative and anti-atherogenic properties in STZ-diabetic rats.

Impaired cardiac ischemic tolerance in spontaneously hypertensive rats is attenuated by adaptation to chronic and acute stress.

PubMed

Ravingerová, T; Bernátová, I; Matejíková, J; Ledvényiová, V; Nemčeková, M; Pecháňová, O; Tribulová, N; Slezák, J

2011-01-01

Chronic hypertension may have a negative impact on the myocardial response to ischemia. On the other hand, intrinsic ischemic tolerance may persist even in the pathologically altered hearts of hypertensive animals, and may be modified by short- or long-term adaptation to different stressful conditions. The effects of long-term limitation of living space (ie, crowding stress [CS]) and brief ischemia-induced stress on cardiac response to ischemia/reperfusion (I/R) injury are not yet fully characterized in hypertensive subjects. The present study was designed to test the influence of chronic and acute stress on the myocardial response to I/R in spontaneously hypertensive rats (SHR) compared with their effects in normotensive counterparts. In both groups, chronic, eight-week CS was induced by caging five rats per cage in cages designed for two rats (200 cm(2)/rat), while controls (C) were housed four to a cage in cages designed for six animals (480 cm(2)/rat). Acute stress was evoked by one cycle of I/R (5 min each, ischemic preconditioning) before sustained I/R in isolated Langendorff-perfused hearts of normotensive and SHR rats. At baseline conditions, the effects of CS were manifested only as a further increase in blood pressure in SHR, and by marked limitation of coronary perfusion in normotensive animals, while no changes in heart mechanical function were observed in any of the groups. Postischemic recovery of contractile function, severity of ventricular arrhythmias and lethal injury (infarction size) were worsened in the hypertrophied hearts of C-SHR compared with normotensive C. However, myo-cardial stunning and reperfusion-induced ventricular arrhythmias were attenuated by CS in SHR, which was different from deterioration of I/R injury in the hearts of normotensive animals. In contrast, ischemic preconditioning conferred an effective protection against I/R in both groups, although the extent of anti-infarct and anti-arrhythmic effects was lower in SHR. Both forms of stress may improve the altered response to ischemia in hypertensive subjects. In contrast to short-term preconditioning stress, chronic psychosocial stress was associated with a higher risk of lethal arrhythmias and contractile failure in normotensive animals exposed to an acute ischemic challenge.

Influence of whole-body irradiation on calcium and phosphate homeostasis in the rat

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

Pento, J.T.; Kenny, A.D.

1975-09-01

Previous irradiation studies have revealed marked alterations in calcium metabolism. Moreover, the maintenance of calcium homeostasis with parathyroid hormone or calcium salts has been reported to reduce radiation lethality. Therefore, the present study was designed to evaluate the influence of irradiation on calcium homeostasis in the rat. Nine hundred rad of whole-body irradiation produced a significant depression of both plasma calcium and phosphate at 4 days postirradiation. This effect of irradiation was observed to be dose-dependent over a range of 600 to 1200 rad, and possibly related to irradiation-induced anorexia. The physiological significance of these observations is discussed. (auth)

Topological Probes of Monoamine Oxidases A and B in Rat Liver Mitochondria: Inhibition by TEMPO-Substituted Pargyline Analogues and Inactivation by Proteolysis†

PubMed Central

Wang, Jin; Edmondson, Dale E.

2011-01-01

TEMPO-substituted pargyline analogues differentially inhibit recombinant human Monoamine Oxidase A (MAO A) and B (MAO B) in intact yeast mitochondria suggesting these membrane-bound enzymes are located on differing faces of the mitochondrial outer membrane (Upadhyay, A. and Edmondson, D.E., Biochemistry 48, 3928, 2009). This approach is extended to the recombinant rat enzymes and to rat liver mitochondria. The differential specificities exhibited for human MAO A and MAO B by the meta- and para-amido TEMPO pargylines are not as absolute with the rat enzymes. Similar patterns of reactivity are observed for rat MAO A and B in mitochondrial outer membrane preparations expressed in Pichia pastoris or isolated from rat liver. In intact yeast mitochondria, recombinant rat MAO B is inhibited by the pargyline analogue whereas MAO A activity shows no inhibition. Intact rat liver mitochondria exhibit an opposite inhibition pattern to that observed in yeast where MAO A is inhibited and MAO B activity is unaffected. Protease inactivation studies show specificity in that MAO A is sensitive to trypsin whereas MAO B is sensitive to β-chymotrypsin. In intact mitochondrial preparations, MAO A is readily inactivated in rat liver but not in yeast on trypsin treatment and MAO B is readily inactivated by β-chymotrypsin in yeast but not in rat liver. These data show MAO A is oriented on the cytosolic face and MAO B is situated on the surface facing the intermembrane space of the mitochondrial outer membrane in rat liver. The differential mitochondrial outer membrane topology of MAO A and MAO B is relevant to their inhibition by drugs designed to be cardio-protectants or neuro-protectants. PMID:21341713

Calcium and α-tocopherol suppress cured-meat promotion of chemically induced colon carcinogenesis in rats and reduce associated biomarkers in human volunteers123

PubMed Central

Martin, Océane CB; Santarelli, Raphaelle L; Taché, Sylviane; Naud, Nathalie; Guéraud, Françoise; Audebert, Marc; Dupuy, Jacques; Meunier, Nathalie; Attaix, Didier; Vendeuvre, Jean-Luc; Mirvish, Sidney S; Kuhnle, Gunter CG; Cano, Noel; Corpet, Denis E

2013-01-01

Background: Processed meat intake has been associated with increased colorectal cancer risk. We have shown that cured meat promotes carcinogen-induced preneoplastic lesions and increases specific biomarkers in the colon of rats. Objectives: We investigated whether cured meat modulates biomarkers of cancer risk in human volunteers and whether specific agents can suppress cured meat–induced preneoplastic lesions in rats and associated biomarkers in rats and humans. Design: Six additives (calcium carbonate, inulin, rutin, carnosol, α-tocopherol, and trisodium pyrophosphate) were added to cured meat given to groups of rats for 14 d, and fecal biomarkers were measured. On the basis of these results, calcium and tocopherol were kept for the following additional experiments: cured meat, with or without calcium or tocopherol, was given to dimethylhydrazine-initiated rats (47% meat diet for 100 d) and to human volunteers in a crossover study (180 g/d for 4 d). Rat colons were scored for mucin-depleted foci, putative precancer lesions. Biomarkers of nitrosation, lipoperoxidation, and cytotoxicity were measured in the urine and feces of rats and volunteers. Results: Cured meat increased nitroso compounds and lipoperoxidation in human stools (both P < 0.05). Calcium normalized both biomarkers in rats and human feces, whereas tocopherol only decreased nitro compounds in rats and lipoperoxidation in feces of volunteers (all P < 0.05). Last, calcium and tocopherol reduced the number of mucin-depleted foci per colon in rats compared with nonsupplemented cured meat (P = 0.01). Conclusion: Data suggest that the addition of calcium carbonate to the diet or α-tocopherol to cured meat may reduce colorectal cancer risk associated with cured-meat intake. This trial was registered at clinicaltrials.gov as NCT00994526. PMID:24025632

Fractal and Fourier analysis of the hepatic sinusoidal network in normal and cirrhotic rat liver

PubMed Central

Gaudio, Eugenio; Chaberek, Slawomir; Montella, Andrea; Pannarale, Luigi; Morini, Sergio; Novelli, Gilnardo; Borghese, Federica; Conte, Davide; Ostrowski, Kazimierz

2005-01-01

The organization of the hepatic microvascular network has been widely studied in recent years, especially with regard to cirrhosis. This research has enabled us to recognize the distinctive vascular patterns in the cirrhotic liver, compared with the normal liver, which may explain the cause of liver dysfunction and failure. The aim of this study was to compare normal and cirrhotic rat livers by means of a quantitative mathematical approach based on fractal and Fourier analyses performed on photomicrographs and therefore on discriminant analysis. Vascular corrosion casts of livers belonging to the following three experimental groups were studied by scanning electron microscopy: normal rats, CCl4-induced cirrhotic rats and cirrhotic rats after ligation of the bile duct. Photomicrographs were taken at a standard magnification; these images were used for the mathematical analysis. Our experimental design found that use of these different analyses reaches an efficiency of over 94%. Our analyses demonstrated a higher complexity of the normal hepatic sinusoidal network in comparison with the cirrhotic network. In particular, the morphological changes were more marked in the animals with bile duct-ligation cirrhosis compared with animals with CCl4-induced cirrhosis. The present findings based on fractal and Fourier analysis could increase our understanding of the pathophysiological alterations of the liver, and may have a diagnostic value in future clinical research. PMID:16050897

Fatal mechanical asphyxia induces changes in energy utilization in the rat brain: An (18)F-FDG-PET study.

PubMed

Ma, Suhua; You, Shengzhong; Hao, Li; Zhang, Dongchuan; Quan, Li

2015-07-01

This study was designed to evaluate changes in brain glucose metabolism in rats following ligature strangulation. Thirteen male Wistar rats were used in the present study, divided into control (n=7) and asphyxia groups (n=6, ligature strangulation). Positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) was used to evaluate brain glucose metabolism. Rats were scanned for PET-CT, and image data co-registered with a T2WI MRI template using SPM8 software. Image J was employed to draw regions of interest (ROIs) from the MRI template and acquire ROI activity information from the PET images. In the asphyxia group vs. controls, (18)F-FDG uptake (FU) was decreased in the substantia nigra (25.26%, p<0.001), rhombencephalon (pons/medulla oblongata, 13.92%, p<0.01), hypothalamus (22.06%, p<0.01), ventral tegmentum (10.12%, p<0.05) and amygdala (12.74%, p<0.05); however, FU was increased in motor (18.21%, p<0.05) and visual cortices (19.2%, p<0.05). The glucose metabolism distribution map in the asphyxiated rat brains were substantially changed versus controls. PET with (18)F-FDG can demonstrate excitement and inhibition of different brain areas even in cases of ligature strangulation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Experiment K-6-04. Trace element balance in rats during spaceflight

NASA Technical Reports Server (NTRS)

Cann, C. E.; Patterson-Buckendahl, P.; Durnova, G.; Kaplansky, A.

1990-01-01

Exposure to microgravity causes alterations in the skeletal and mineral homeostatic systems. Little is known about the effects of flight in an older skeleton; limited data suggest that bone resorption is increased after 5 days but no data are available about other metabolic effects. The response of a more slowly-growing skeleton to microgravity may be different than that of a younger animal, similar to the different responses seen in adolescents and adult humans to immobilization. This experiment was designed to investigate changes occurring in skeletal and mineral homeostatis in these older rats flown for two weeks in space. We may expect that the two portions of the rat vertebra, the vertebral body and the posterior elements, will show different responses to spaceflight. The results of the analyses from this study confirm major differences between portions of the vertebra. The posterior bone is more highly mineralized, evidenced by increased concentration (per unit weight of bone) of calcium (5 percent), phosphorus (6 percent) and osteocalcin (37 percent), similar to the differences seen between proximal and mid humerus in previous studies. The major increase in osteocalcin content indicates the presence of mature, low-turnover bone. The difference between flight and control animals were minimal in these older, slower-growing rats. Mass of whole vertebrae increased 6.2 percent in synchronous rats compared to less than 2 percent in flight rats over the 16 days when compared to basal controls, suggesting a decreased rate of bone growth in flight. Compared to young rats in which vertebral mass increased over 40 percent in 10 days in controls and 20 percent in flight rats, this may be a clear indication that even in the older skeleton bone growth will slow in microgravity.

Inflammatory factors mediate vulnerability to a social stress-induced depressive-like phenotype in passive coping rats

PubMed Central

Wood, Susan K.; Wood, Christopher S.; Lombard, Calliandra M.; Lee, Catherine S.; Zhang, Xiao-Yan; Finnell, Julie E.; Valentino, Rita J.

2014-01-01

Background Coping strategy impacts susceptibility to psychosocial stress. The locus coeruleus (LC) and dorsal raphe (DR) are monoamine nuclei that are implicated in stress-related disorders. This study was designed to identify genes in these nuclei that distinguish active and passive coping strategies in response to social stress. Methods Rats were exposed to repeated resident-intruder stress and coping strategy determined. Gene and protein expression in the LC and DR were determined by PCR array, ELISA, and compared between active and passive stress coping and unstressed rats. The effect of daily IL-1 receptor antagonist (IL-1ra, ICV) prior to stress on anhedonia was also determined. Results Rats exhibited passive or active coping strategies based on a short (SL) or longer latency (LL) to assume a defeat posture, respectively. Stress differentially regulated 19 and 26 genes in the LC and DR of SL and LL rats, respectively, many of which encoded for inflammatory factors. Notably, IL1β was increased in SL and decreased in LL rats in both the LC and DR. Protein changes were generally consistent with a proinflammatory response to stress in SL rats selectively. Stress produced anhedonia selectively in SL rats and this was prevented by IL-1ra, consistent with a role for IL1β in stress vulnerability. Conclusions This study highlighted distinctions in gene expression related to coping strategy in response to social stress. Passive coping was associated with a bias towards pro-inflammatory processes, particularly IL1β, whereas active coping and resistance to stress-related pathology was associated with suppression of inflammatory processes. PMID:25676490

Alteration in plasma corticosterone levels following long term oral administration of lead produces depression like symptoms in rats.

PubMed

Haider, Saida; Saleem, Sadia; Tabassum, Saiqa; Khaliq, Saima; Shamim, Saima; Batool, Zehra; Parveen, Tahira; Inam, Qurat-ul-ain; Haleem, Darakhshan J

2013-03-01

Lead toxicity is known to induce a broad range of physiological, biochemical and behavioral dysfunctions that may result in adverse effects on several organs, including the central nervous system. Long-term exposure to low levels of lead (Pb(2+)) has been shown to produce behavioral deficits in rodents and humans by affecting hypothalamic-pituitary-adrenal (HPA) axis. These deficits are thought to be associated with altered brain monoamine neurotransmission and due to changes in glucocorticoids levels. This study was designed to investigate the effects of Pb(2+)exposure on growth rate, locomotor activity, anxiety, depression, plasma corticosterone and brain serotonin (5-HT) levels in rats. Rats were exposed to lead in drinking water (500 ppm; lead acetate) for 5 weeks. The assessment of depression was done using the forced swimming test (FST). Estimation of brain 5-HT was determined by high-performance liquid chromatography with electrochemical detection. Plasma corticosterone was determined by spectrofluorimetric method. The present study showed that long term exposure to Pb(2+) significantly decreased the food intake followed by the decrease in growth rate in Pb(2+)exposed rats as compared to control group. No significant changes in open field activity were observed following Pb(2+)exposure while significant increase in anxiogenic effect was observed. Increased plasma corticosterone and decreased 5-HT levels were exhibited by Pb(2+)exposed rats as compared to controls. A significant increase in depressive like symptoms was exhibited by Pb(2+)exposed rats as compared to control rats. The results are discussed in the context of Pb(2+) inducing a stress-like response in rats leading to changes in plasma corticosterone and brain 5-HT levels via altering tryptophan pyrrolase activity.

Protective effect of betaine against burn-induced pulmonary injury in rats.

PubMed

Şehirli, Ahmet Özer; Satılmış, Burcu; Tetik, Şermin; Çetinel, Şule; Yeğen, Berrak; Aykaç, Aslı; Şener, Göksel

2016-09-01

This study was designed to determine possible protective effect of betaine treatment against oxidative injury in pulmonary tissue induced with thermal trauma. Under ether anesthesia, shaved dorsum of Wistar albino rats was exposed to a 90°C water bath for 10 seconds to induce burn injury. Betaine was administered orally (250 mg/kg) for a period of 21 days before burn injury, and single dose of betaine was administered after thermal injury. Control group rats were exposed to 25°C water bath for 10 seconds. Upon conclusion of experiment, rats were decapitated and blood was collected for analysis of pro-inflammatory cytokines and lactate dehydrogenase (LDH) activity. Lung tissue samples were taken to determine malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), and Na+/K+-ATPase activity, in addition to histological analysis. Burn injury caused significant increase in both cytokine levels and LDH activity. In lung samples, raised MDA levels, MPO activity, and reduced GSH levels and Na+/K+-ATPase activity were found due to burn injury. Treatment of rats with betaine significantly restored GSH level and Na+/K+-ATPase activity, and decreased MDA level and MPO activity. According to the findings of the present study, betaine significantly diminishes burn-induced damage in tissue.

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

PubMed Central

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

2017-01-01

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

A study of the effect of a single neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") on the subsequent long-term behaviour of rats in the plus maze and open field.

PubMed

Mechan, Annis O; Moran, Paula M; Elliott, MartinJ; Young, Andrew J; Joseph, Michael H; Green, RichardA

2002-01-01

Decreased 5-HT function has been shown to induce behaviour consistent with an "anxiolytic" effect. Administration of a single dose of 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy" 12.5 mg/kg IP) to rats results in prolonged damage to central serotonergic nerve terminals. Thus we wished to assess whether an MDMA-induced lesion may have longer-term behavioural consequences. The study was designed to examine the behaviour of MDMA-pretreated and control animals in the elevated plus-maze and open field at a number of time-points, up to 80 days, after the administration of a single neurotoxic dose of MDMA (12.5 mg/kg IP). MDMA-pretreated Dark Agouti rats demonstrated a statistically significant reduction in anxiety-related behaviour, compared to saline-pretreated control rats, in both the elevated plus-maze and open field when the rats were tested on day 73 (open field) and day 80 (plus maze) after MDMA administration. The behavioural consequences of a single neurotoxic dose of MDMA can be demonstrated over 2 months after administration of the compound, thereby indicating that long-term adaptive changes occur within the brain following the neurodegeneration of 5-HT neurones produced by this recreationally used drug.

Assessment of the reproductive toxicology of bromochlorodifluoromethane (BCF, halon 1211) in the rat.

PubMed Central

Wickramaratne, G A; Tinston, D J; Kinsey, D L; Doe, J E

1988-01-01

The effect of bromochlorodifluoromethane (BCF) on reproduction in the rat has been investigated in two studies. Pregnant female rats were exposed by inhalation to 1000, 10,000, or 50,000 ppm BCF for six hours a day on days six to 15 of gestation (day of mating = day 0). Exposure to 50,000 ppm BCF caused a reduction in maternal weight gain over the exposure period but there was no evidence of either teratogenicity or embryo/fetotoxicity at any concentration. In a study designed to assess the potential effect of BCF during a complete reproductive cycle male and female rats were exposed to 5000 ppm or 25,000 ppm BCF for six hours a day for five days a week for 10 weeks (males) or three weeks (females) before mating. Exposure to BCF continued during mating and up to day 20 of gestation for half the females which were subsequently allowed to litter and the development of their offspring monitored. The remaining females were removed from exposure to BCF after mating and killed on day 20 of gestation for examination of their uterine contents. There were no effects on adult fertility, pup numbers, survival, or pup development. It was concluded that BCF had no reproductive toxicity potential in the rat. PMID:3203080

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

PubMed

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

2017-03-01

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

A Judgement Bias Test to Assess Affective State and Potential Therapeutics in a Rat Model of Chemotherapy-Induced Mucositis.

PubMed

George, Rebecca P; Barker, Timothy H; Lymn, Kerry A; Bigatton, Dylan A; Howarth, Gordon S; Whittaker, Alexandra L

2018-05-29

Chemotherapy-induced mucositis is an extremely painful condition that occurs in 40-60% of patients undergoing chemotherapy. As mucositis currently has no effective treatment, and due to the self-limiting nature of the condition, the major treatment aims are to manage symptoms and limit pain with significance placed on improving patient quality of life. Rodent models are frequently used in mucositis research. These investigations typically assess pathological outcomes, yet fail to include a measure of affective state; the key therapeutic goal. Assessment of cognitive biases is a novel approach to determining the affective state of animals. Consequently, this study aimed to validate a cognitive bias test through a judgement bias paradigm to measure affective state in a rat model of chemotherapy-induced intestinal mucositis. Rats with intestinal mucositis demonstrated a negative affective state, which was partially ameliorated by analgesic administration, whilst healthy rats showed an optimistic response. This study concluded that the judgement bias test was able to evaluate the emotional state of rats with chemotherapy-induced mucositis. These findings provide a foundation for future refinement to the experimental design associated with the animal model that will expedite successful transitioning of novel therapeutics to clinical practice, and also improve humane endpoint implementation.

Rat Model of Brain Injury to Occupants of Vehicles Targeted by Land Mines: Mitigation by Elastomeric Frame Designs.

PubMed

Tchantchou, Flaubert; Puche, Adam A; Leiste, Ulrich; Fourney, William; Blanpied, Thomas A; Fiskum, Gary

2018-05-15

Many victims of blast traumatic brain injury (TBI) are occupants of vehicles targeted by land mines. A rat model of under-vehicle blast TBI was used to test the hypothesis that the ensuing neuropathology and altered behavior are mitigated by vehicle frame designs that dramatically reduce blast-induced acceleration (G force). Male rats were restrained on an aluminum platform that was accelerated vertically at up to 2850g, in response to detonation of an explosive positioned under a second platform in contact with the top via different structures. The presence of elastomeric, polyurea-coated aluminum cylinders between the platforms reduced acceleration by 80% to 550g compared with 2350g with uncoated cylinders. Moreover, 67% of rats exposed to 2850g, and 20% of those exposed to 2350g died immediately after blast, whereas all rats subjected to 550g blast survived. Assays for working memory (Y maze) and anxiety (Plus maze) were conducted for up to 28 days. Rats were euthanized at 24 h or 29 days, and their brains were used for histopathology and neurochemical measurements. Rats exposed to 2350g blasts exhibited increased cleaved caspase-3 immunoreactive neurons in the hippocampus. There was also increased vascular immunoglobulin (Ig)G effusion and F4/80 immunopositive macrophages/microglia. Blast exposure reduced hippocampal levels of synaptic proteins Bassoon and Homer-1, which were associated with impaired performance in the Y maze and the Plus maze tests. These changes observed after 2350g blasts were reduced or eliminated with the use of polyurea-coated cylinders. Such advances in vehicle designs should aid in the development of the next generation of blast-resistant vehicles.

Development of a Cyclic Strain Bioreactor for Mechanical Enhancement and Assessment of Bioengineered Myocardial Constructs

PubMed Central

Salazar, Betsy H.; Cashion, Avery T.; Dennis, Robert G.; Birla, Ravi K.

2015-01-01

Purpose The purpose of this study was to develop enabling bioreactor technologies using a novel voice coil actuator system for investigating the effects of periodic strain on cardiac patches fabricated with rat cardiomyocytes. Methods The bioengineered muscle constructs used in this study were formed by culturing rat neonatal primary cardiac cells on a fibrin gel. The physical design of the bioreactor was initially conceived using Solidworks to test clearances and perform structural strain analysis. Once the software design phase was completed the bioreactor was assembled using a combination of commercially available, custom machined, and 3-D printed parts. We utilized the bioreactor to evaluate the effect of a 4-hour stretch protocol on the contractile properties of the tissue after which immunohistological assessment of the tissue was also performed. Results An increase in contractile force was observed after the strain protocol of 10% stretch at 1Hz, with no significant increase observed in the control group. Additionally, an increase in cardiac myofibril alignment, connexin 43 expression, and collagen type I distribution were noted. Conclusion In this study we demonstrated the effectiveness of a new bioreactor design to improve contractility of engineered cardiac muscle tissue. PMID:26577484

Development of a Cyclic Strain Bioreactor for Mechanical Enhancement and Assessment of Bioengineered Myocardial Constructs.

PubMed

Salazar, Betsy H; Cashion, Avery T; Dennis, Robert G; Birla, Ravi K

2015-12-01

The purpose of this study was to develop enabling bioreactor technologies using a novel voice coil actuator system for investigating the effects of periodic strain on cardiac patches fabricated with rat cardiomyocytes. The bioengineered muscle constructs used in this study were formed by culturing rat neonatal primary cardiac cells on a fibrin gel. The physical design of the bioreactor was initially conceived using Solidworks to test clearances and perform structural strain analysis. Once the software design phase was completed the bioreactor was assembled using a combination of commercially available, custom machined, and 3-D printed parts. We utilized the bioreactor to evaluate the effect of a 4-h stretch protocol on the contractile properties of the tissue after which immunohistological assessment of the tissue was also performed. An increase in contractile force was observed after the strain protocol of 10% stretch at 1 Hz, with no significant increase observed in the control group. Additionally, an increase in cardiac myofibril alignment, connexin 43 expression, and collagen type I distribution were noted. In this study we demonstrated the effectiveness of a new bioreactor design to improve contractility of engineered cardiac muscle tissue.

Cross-site strain comparison of pharmacological deficits in the touchscreen visual discrimination test.

PubMed

Mohler, Eric G; Ding, Zhiyong; Rueter, Lynne E; Chapin, Douglas; Young, Damon; Kozak, Rouba

2015-11-01

The low rate of success for identifying effective treatments for cognitive dysfunction has prompted recent efforts to improve pharmaceutical discovery and development. In particular, investigators have emphasized improving translation from pre-clinical to clinical research. A specific area of focus has been touchscreen technology; this computer-automated behavioral testing method provides an objective assessment of performance that can be used across species. As part of a larger multi-site study with partners from the Innovative Medicines Initiative (IMI), two US sites, AbbVie and Pfizer, conducted a cross-site experiment with a common protocol for the visual discrimination (VD) task using identical testing equipment, stimuli, and rats of the same strains, sex, and age from the same supplier. As most touchscreen-based rodent experiments have used Lister-Hooded rats that are not readily available outside of Europe, a strain comparison with male Long-Evans rats was conducted as part of the study. Rats were trained for asymptotic performance, and test sessions were performed once per week in a full crossover design with cognition-impairing drugs. Drugs tested were phencyclidine and S-ketamine (N-methyl-D-aspartate (NMDA) antagonists), D-amphetamine (indirect dopamine agonist), and scopolamine (muscarinic antagonist). Satellite brain and plasma samples were taken to confirm appropriate exposures. Results indicate that both rat strains show similar patterns of impairment, although Lister-Hooded rats were more sensitive than Long-Evans rats to three out of four drugs tested. This suggests that researchers should fully explore dose-response relationships in their strain of choice and use care in the interpretation of reversal of cognitive impairment.

Electrophysiological studies of the feasibility of suprachoroidal-transretinal stimulation for artificial vision in normal and RCS rats.

PubMed

Kanda, Hiroyuki; Morimoto, Takeshi; Fujikado, Takashi; Tano, Yasuo; Fukuda, Yutaka; Sawai, Hajime

2004-02-01

Assessment of a novel method of retinal stimulation, known as suprachoroidal-transretinal stimulation (STS), which was designed to minimize insult to the retina by implantation of stimulating electrodes for artificial vision. In 17 normal hooded rats and 12 Royal College of Surgeons (RCS) rats, a small area of the retina was focally stimulated with electric currents through an anode placed on the fenestrated sclera and a cathode inserted into the vitreous chamber. Evoked potentials (EPs) in response to STS were recorded from the surface of the superior colliculus (SC) with a silver-ball electrode, and their physiological properties and localization were studied. In both normal and RCS rats, STS elicited triphasic EPs that were vastly diminished by changing polarity of stimulating electrodes and abolished by transecting the optic nerve. The threshold intensity (C) of the EP response to STS was approximately 7.2 +/- 2.8 nC in normal and 12.9 +/- 7.7 nC in RCS rats. The responses to minimal STS were localized in an area on the SC surface measuring 0.12 +/- 0.07 mm(2) in normal rats and 0.24 +/- 0.12 mm(2) in RCS rats. The responsive area corresponded retinotopically to the retinal region immediately beneath the anodic stimulating electrode. STS is less invasive in the retina than stimulation through epiretinal or subretinal implants. STS can generate focal excitation in retinal ganglion cells in normal animals and in those with degenerated photoreceptors, which suggests that this method of retinal stimulation is suitable for artificial vision.

Evaluation of Cisplatin Neurotoxicity in Cultured Rat Dorsal Root Ganglia via Cytosolic Calcium Accumulation

PubMed Central

Erol, Kevser; Yiğitaslan, Semra; Ünel, Çiğdem; Kaygısız, Bilgin; Yıldırım, Engin

2016-01-01

Background: Calcium homeostasis is considered to be important in antineoplastic as well as in neurotoxic adverse effects of cisplatin. Aims: This study aimed to investigate the role of Ca2+ in cisplatin neurotoxicity in cultured rat dorsal root ganglia (DRG) cells. Study Design: Cell culture study. Methods: DRG cells prepared from 1-day old Sprague-Dawley rats were used to determine the role of Ca2+ in the cisplatin (10–600 μM) neurotoxicity. The cells were incubated with cisplatin plus nimodipine (1–3 μM), dizocilpine (MK-801) (1–3 μM) or thapsigargin (100–300 nM). Toxicity of cisplatinon DRG cells was determined by the MTT assay. Results: The neurotoxicity of cisplatin was significant when used in high concentrations (100–600 μM). Nimodipine (1 μM) but not MK-801 or thapsigargin prevented the neurotoxic effects of 200 μM of cisplatin. Conclusion: Voltage-dependent calcium channels may play a role in cisplatin neurotoxicity. PMID:27403382

Metabonomic study of biochemical changes in the urine of Morning Glory Seed treated rat.

PubMed

Ma, Chao; Bi, Kaishun; Zhang, Ming; Su, Dan; Fan, Xinxin; Ji, Wei; Wang, Chao; Chen, Xiaohui

2010-11-02

This paper was designed to study metabonomic characters of the nephrotoxicity induced by Morning Glory Seed (MGS), a well-known traditional Chinese medicine which was used for the treatment of edema, simple obesity and lung fever. Urinary samples from control and MGS treated rats were analyzed by ultra-performance liquid chromatography/mass spectrometry (UPLC-MS) in positive ionization mode. Blood biochemistry and histopathology were examined to identify specific changes of renal damage. The results affirmatively suggested that ethanol extract of Morning Glory Seed (EMGS), instead of water extract of Morning Glory Seed (WMGS), should be responsible for the nephrotoxicity caused by this herbal medicine. The UPLC-MS analysis revealed that the levels of 8 endogenous metabolites as biomarkers were significantly changed in urine from EMGS treated rats. The underlying regulations of EMGS-perturbed metabolic pathways were discussed according to the identified metabolites. The present study proves the potential of UPLC-MS based metabonomics in mapping metabolic response for toxicology. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Animal models for treatment of unresectable liver tumours: a histopathologic and ultra-structural study of cellular toxic changes after electrochemical treatment in rat and dog liver.

PubMed

von Euler, Henrik; Olsson, Jerker M; Hultenby, Kjell; Thörne, Anders; Lagerstedt, Anne-Sofie

2003-04-01

Electrochemical treatment (EChT) has been taken under serious consideration as being one of several techniques for local treatment of malignancies. The advantage of EChT is the minimal invasive approach and the absence of serious side effects. Macroscopic, histopathological and ultra-structural findings in liver following a four-electrode configuration (dog) and a two-electrode EChT design (dog and rat) were studied. 30 female Sprague-Dawley rats and four female beagle dogs were studied with EChT using Platinum:Iridium electrodes and the delivered dose was 5, 10 or 90 C (As). After EChT, the animals were euthanized. The distribution of the lesions was predictable, irrespective of dose and electrode configuration. Destruction volumes were found to fit into a logarithmic curve (dose-response). Histopathological examination confirmed a spherical (rat) and cylindrical/ellipsoidal (dog) lesion. The type of necrosis differed due to electrode polarity. Ultra-structural analysis showed distinct features of cell damage depending on the distance from the electrode. Histopathological and ultra-structural examination demonstrated that the liver tissue close to the border of the lesion displayed a normal morphology. The in vivo dose-planning model is reliable, even in species with larger tissue mass such as dogs. A multi-electrode EChT-design could obtain predictable lesions. The cellular toxicity following EChT is clearly identified and varies with the distance from the electrode and polarity. The distinct border between the lesion and normal tissue suggests that EChT in a clinical setting for the treatment of liver tumours can give a reliable destruction margin.

Imidazopyridine derivatives as potent and selective Polo-like kinase (PLK) inhibitors.

PubMed

Sato, Yoshiyuki; Onozaki, Yu; Sugimoto, Tetsuya; Kurihara, Hideki; Kamijo, Kaori; Kadowaki, Chie; Tsujino, Toshiaki; Watanabe, Akiko; Otsuki, Sachie; Mitsuya, Morihiro; Iida, Masato; Haze, Kyosuke; Machida, Takumitsu; Nakatsuru, Yoko; Komatani, Hideya; Kotani, Hidehito; Iwasawa, Yoshikazu

2009-08-15

A novel class of imidazopyridine derivatives was designed as PLK1 inhibitors. Extensive SAR studies supported by molecular modeling afforded a highly potent and selective compound 36. Compound 36 demonstrated good antitumor efficacy in xenograft nude rat model.

EFFECTS OF CONCENTRATED AMBIENT PARTICLES AND DIESEL EMISSIONS ON RAT AIRWAYS

EPA Science Inventory

The investigators anticipate that they will successfully design and conduct  a descriptive study to evaluate the effects of two pollutants — CAPs (concentrated PM2.5) and DEE — in a rodent model of asthma.

SaRNA-mediated activation of TRPV5 reduces renal calcium oxalate deposition in rat via decreasing urinary calcium excretion.

PubMed

Zeng, Tao; Duan, Xiaolu; Zhu, Wei; Liu, Yang; Wu, Wenqi; Zeng, Guohua

2018-06-01

Hypercalciuria is a main risk factor for kidney stone  formation. TRPV5 is the gatekeeper protein for mediating calcium transport and reabsorption in the kidney. In the present study, we tested the effect of TRPV5 activation with small activating RNA (saRNA), which could induce gene expression by targeting the promoter of the gene, on ethylene glycol (EG)-induced calcium oxalate (CaOx) crystals formation in rat kidney. Five pairs of RNA activation sequences targeting the promoter of rat TRPV5 were designed and synthesized. The synthesized saRNA with the strongest activating effect was selected, and transcellular calcium transportation was tested by Fura-2 analysis. Subsequently, Sprague-Dawley rats were equally divided into three groups and fed with water, 1% EG for 28 days after injecting the negative control saRNA, 1% EG for 28 days after injecting the selected TRPV5-saRNA, respectively. The CaOx crystal formation and the 24-h urine components were assessed. In vitro study, saRNA ds-320 could significantly activate the expression of TRPV5 and transcellular calcium transportation. In vivo study, after 28 days treatment of EG, rats pre-infected with saRNA ds-320 had lower urinary calcium excretion and renal CaOx crystals formation as compared to that pre-infected with negative control saRNA. Activation of TRVP5 with saRNA ds-320 could inhibit EG-induced calcium oxalate crystals formation via promoting urine calcium reabsorption and decreasing urine calcium excretion in rats.

Beneficial effects of early hemostasis on spinal cord injury in the rat

PubMed Central

Fan, H; Chen, K; Duan, L; Wang, Y-Z; Ju, G

2016-01-01

Study design: Experimental study. Objectives: To investigate the effect of early hemostasis on spinal cord injury (SCI). Setting: Fourth Military Medical University, Xi'an, China. Methods: Sprague Dawley rats were used. Hematoxylin and eosin (HE) staining was performed to observe hemorrhage at different time points (2, 6, 12, 24 and 48 h) after SCI to determine the time window of hemostatic drug administration (n=3 per time point). Three different concentrations of Etamsylate (0.025, 0.05 and 0.1 g kg−1) were administered immediately and 5 and 10 h after SCI to evaluate the effective dosage (n=6 per group). Another 82 rats were then randomly divided into two groups, Etamsylate group (0.1 g kg−1, n=41) and glucose control group (n=41). Nissl staining was performed to observe neurons at 10 days post injury. Immunohistochemistry, western blot and quantitative real-time PCR were performed to detect tissue necrosis at 7 d.p.i., the activation of astrocytes and microglia/macrophages and lesion cavity at 10 d.p.i. Basso–Beattie–Bresnahan scoring and rump height index assay were used to examine locomotion recovery. Results: Early hemostasis reduced the lesion area and tissue necrosis, enhanced neuronal survival, alleviated the activation of microglia/macrophages and astrocytes and facilitated functional recovery after spinal cord contusion in rats. Early hemostasis decreased hemorrhage area and lesion area after spinal cord transection in rats. Conclusion: The present study demonstrated that early hemostasis has beneficial effects on SCI in the rat. It has the potential to be translated into clinical practice. PMID:27137123

Developmental toxicity evaluation of inhaled tertiary amyl methyl ether in mice and rats.

PubMed

Welsch, Frank; Elswick, Barbara; James, R Arden; Marr, Melissa C; Myers, Christina B; Tyl, Rochelle W

2003-01-01

This evaluation was part of a much more comprehensive testing program to characterize the mammalian toxicity potential of the gasoline oxygenator additive tertiary amyl methyl ether (TAME), and was initiated upon a regulatory agency mandate. A developmental toxicity hazard identification study was conducted by TAME vapor inhalation exposure in two pregnant rodent species. Timed-pregnant CD(Sprague-Dawley) rats and CD-1 mice, 25 animals per group, inhaled TAME vapors containing 0, 250, 1500 or 3500 ppm for 6 h a day on gestational days 6-16 (mice) or 6-19 (rats). The developmental toxicity hazard potential was evaluated following the study design draft guidelines and end points proposed by the United States Environmental Protection Agency. Based on maternal body weight changes during pregnancy, the no-observable-adverse-effect level (NOAEL) was 250 ppm for maternal toxicity in rats and 1500 ppm for developmental toxicity in rats using the criterion of near-term fetal body weights. In mice, more profound developmental toxicity was present than in rats, at both 1500 and 3500 ppm. At the highest concentration, mouse litters revealed more late fetal deaths, significantly reduced fetal body weights per litter and increased incidences of cleft palate (classified as an external malformation), as well as enlarged lateral ventricles of the cerebrum (a visceral variation). At 1500 ppm, mouse fetuses also exhibited an increased incidence of cleft palate and the dam body weights were reduced. Therefore, the NOAEL for the mouse maternal and developmental toxicity was 250 ppm under the conditions of this study. Copyright 2003 John Wiley & Sons, Ltd.

Age-related changes in Mastication are not improved by Tongue Exercise in a Rat Model

PubMed Central

Krekeler, Brittany N.; Connor, Nadine P.

2016-01-01

Objective Aging results in progressive changes in deglutitive functions, which may be due in part to alterations in muscle morphology and physiology. Mastication is a critical component of bolus formation and swallowing, but aging effects on masticatory function have not been well studied. Study Design The purpose of this study was to: 1) quantify the effects of aging on mastication; 2) determine the effects of tongue exercise on mastication in young adult and old rats. We hypothesized that there would be significant differences in mastication characteristics (number of bites, interval between bites, time to eat) as a function of age and that tongue exercise would resolve pre-exercise differences between age groups. Methods We expanded the established model of progressive, 8-week tongue exercise training to include a mastication measurement: acoustic recordings of vermicelli pasta biting from 17 old and 17 young adult rats, randomized into training and control groups. Results We found that: 1) mastication characteristics were impacted by age; specifically in older rats, time to eat and number of bites were increased and intervals between bites were decreased, suggesting increased oral motor processing requirements for bolus formation; 2) tongue exercise did not impact mastication behaviors in young adult or old rats. Conclusion Tongue exercise may not have been specific enough to mastication to result in behavioral changes or exercise dose may not have been sufficient. Nevertheless, results were noteworthy in expanding the established rat model of aging and have relevant clinical implications for future translation to human populations. PMID:27260802

Cellular Uptake and Localization of Polymyxins in Renal Tubular Cells Using Rationally Designed Fluorescent Probes

PubMed Central

Yun, Bo; Azad, Mohammad A. K.; Nowell, Cameron J.; Nation, Roger L.; Thompson, Philip E.; Roberts, Kade D.

2015-01-01

Polymyxins are cyclic lipopeptide antibiotics that serve as a last line of defense against Gram-negative bacterial superbugs. However, the extensive accumulation of polymyxins in renal tubular cells can lead to nephrotoxicity, which is the major dose-limiting factor in clinical use. In order to gain further insights into the mechanism of polymyxin-induced nephrotoxicity, we have rationally designed novel fluorescent polymyxin probes to examine the localization of polymyxins in rat renal tubular (NRK-52E) cells. Our design strategy focused on incorporating a dansyl fluorophore at the hydrophobic centers of the polymyxin core structure. To this end, four novel regioselectively labeled monodansylated polymyxin B probes (MIPS-9541, MIPS-9542, MIPS-9543, and MIPS-9544) were designed, synthesized, and screened for their antimicrobial activities and apoptotic effects against rat kidney proximal tubular cells. On the basis of the assessment of antimicrobial activities, cellular uptake, and apoptotic effects on renal tubular cells, incorporation of a dansyl fluorophore at either position 6 or 7 (MIPS-9543 and MIPS-9544, respectively) of the polymyxin core structure appears to be an appropriate strategy for generating representative fluorescent polymyxin probes to be utilized in intracellular imaging and mechanistic studies. Furthermore, confocal imaging experiments utilizing these probes showed evidence of partial colocalization of the polymyxins with both the endoplasmic reticulum and mitochondria in rat renal tubular cells. Our results highlight the value of these new fluorescent polymyxin probes and provide further insights into the mechanism of polymyxin-induced nephrotoxicity. PMID:26392495

Laser tissue melding: use of 1.32-μm computerized Nd:YAG laser, results of leak/burst strength studies in microsurgical procedures

NASA Astrophysics Data System (ADS)

Anderson, Dallas W.; Hsu, Tung M.; Halpern, Steven J.; Honaker, Arnold

1993-07-01

The ProClosureTM System (PCS) consists of a low power 1.32micrometers Nd:YAG laser coupled to a handheld disposable fiber optic device. The system has been designed to perform a wide range of tissue welding applications such as cosmetic skin closure,vascular surgery, and minimally invasive surgical procedures normally performed with sutures and staples. Utilizing a wavelength for tissue fusion that is least distracted by medium in the surgical field coupled with a computerized delivery system allows for a more precise application (+/- 5%) of laser energy to the tissue. The study design involved the micro-surgical anastomosis of twenty Sprague-Dawley rats (vas deferens) and twenty-one Sprague-Dawley rats (femoral arteries). Each rat is its own contralateral control. Laser repair time is approximately one-third that of conventional suturing. Postoperative dissection and burst strength testing was conducted at day 0, 1, 7, and 14. At each postoperative interval, the mean leak/burst strength for laser-assisted closure v. control, was markedly higher. The precise application of energy fluence resulting from ProClosure's computerized system yields an initial strength and a fluid static seal that is superior to conventional suture closure.

Design, formulation and optimization of valsartan transdermal gel containing iso-eucalyptol as novel permeation enhancer: preclinical assessment of pharmacokinetics in Wistar albino rats.

PubMed

Ahad, Abdul; Aqil, Mohd; Kohli, Kanchan; Sultana, Yasmin; Mujeeb, Mohd

2014-08-01

The aim of this study was to develop and optimize a transdermal gel formulation of valsartan using Box-Behnken design and to evaluate it for pharmacokinetic study. The independent variables were Carbopol 940 (X1), PEG 400 (X2) and ethanol (X3) while valsartan flux (Y1), Tlag (Y2) and gel viscosity (Y3) were the dependent variables. Iso-eucalyptol was added in all gel formulations as permeation enhancer except for control gel. It was observed that the permeation rate of valsartan significantly increased in direct proportion to the ethanol concentration, but significantly decreased in direct proportion to polymer concentration. Lag time and viscosity decreased in reverse proportion to ethanol concentration. The optimized valsartan gel formulation (VGF-OPT) yielded flux of 143.27 ± 7.11 µg/cm(2)/h and 27.55 ± 2.51 µg/cm(2)/h across rat and human cadaver skin, respectively. In vivo pharmacokinetic study of VGF-OPT-transdermal therapeutic system containing iso-eucalyptol showed a significant increase in the bioavailability (2.52 times) compared with oral formulation of valsartan by virtue of better permeation through Wistar rat skin. It was concluded that the developed transdermal gel accentuates the flux of valsartan and could be used as an antihypertensive dosage form for effective transdermal delivery of valsartan.

Aluminium chloride impairs long-term memory and downregulates cAMP-PKA-CREB signalling in rats.

PubMed

Zhang, Lifeng; Jin, Cuihong; Lu, Xiaobo; Yang, Jinghua; Wu, Shengwen; Liu, Qiufang; Chen, Rong; Bai, Chunyu; Zhang, Di; Zheng, Linlin; Du, Yanqiu; Cai, Yuan

2014-09-02

Epidemiological investigations have indicated that aluminium (Al) is an important environmental neurotoxicant that may be involved in the aetiology of the cognitive dysfunction associated with neurodegenerative diseases. Additionally, exposure to Al is known to cause neurobehavioural abnormalities in animals. Previous studies demonstrated that Al impaired early-phase long-term potentiation (E-LTP) in vivo and in vitro. Our previous research revealed that Al could impair long-term memory via the impairment of late-phase long-term potentiation (L-LTP) in vivo. However, the exact mechanism by which Al impairs long-term memory has been poorly studied thus far. This study was designed not only to observe the effects of subchronic Al treatment on long-term memory and hippocampal ultrastructure but also to explore a possible underlying mechanism (involving the cAMP-PKA-CREB signalling pathway) in the hippocampus of rats.. Pregnant Wistar rats were assigned to four groups. Neonatal rats were exposed to Al by parental lactation for 3 weeks and then fed with distilled water containing 0, 0.2%, 0.4% or 0.6% Al chloride (AlCl3) for 3 postnatal months. The levels of Al in the blood and hippocampus were quantified by atomic absorption spectrophotometry. The shuttle-box test was performed to detect long-term memory. The hippocampus was collected for ultrastructure observation, and the level of cAMP-PKA-CREB signalling was examined. The results showed that the Al concentrations in the blood and hippocampus of Al-treated rats were higher than those of the control rats. Al may impair the long-term memory of rats. Hippocampal cAMP, cPKA, pCREB, BDNF and c-jun expression decreased significantly, and the neuronal and synaptic ultrastructure exhibited pathological changes after Al treatment. These results indicated that Al may induce long-term memory damage in rats by inhibiting cAMP-PKA-CREB signalling and altering the synaptic and neuronal ultrastructure in the hippocampus. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

"Nice guys finish last": influence of mate choice on reproductive success in Long-Evans rats.

PubMed

Winland, C; Bolton, J L; Ford, B; Jampana, S; Tinker, J; Frohardt, R J; Guarraci, F A; Zewail-Foote, M

2012-02-01

The present study was designed to determine if male physiology and male reproductive behavior predict reproductive success in Long-Evans rats. Mating behavior was observed in sexually naïve, naturally cycling female rats during behavioral estrous that were given the opportunity to mate with two males simultaneously. DNA analysis of offspring born following these mating encounters was used to identify the paternity of each pup. In order to assess the effect of mate choice during these mating encounters on reproductive success, one male rat in each pair was categorized as the preferred mate if the female spent more time (>50%) with him during the mating test of the present study. Furthermore, each male in the pairs was categorized as "attractive" or "non-attractive" by computing the number of females that preferred each male across many mating tests. Similar to results reported in Lovell et al. (2007), during 76% of these mating tests the same male rat in each pair was preferred by different female rats. Overall attractiveness of individual male rats predicted reproductive success in the present study. Interestingly, "attractive" males sired significantly FEWER pups than "non-attractive" males. Neither behavioral (e.g., latency to first sexual stimulation, number of sexual stimulations) nor physiological measures (e.g., body weight, urinary testosterone levels) of male rats predicted their reproductive success. In conclusion, the present results indicate that certain features of some males are more attractive to females, but attractive males are at a reproductive disadvantage (as measured by the number of pups sired). Although basal urinary testosterone levels did not differ between males that sired the majority of pups in a litter and males that sired few or none of the pups in a litter, aggression and/or other physiological measures of fertility (e.g., penile reflexes) may differ between males that are attractive to females and those that have a reproductive advantage. Copyright © 2011 Elsevier Inc. All rights reserved.

Dose and time dependent ototoxicity of aspartame in rats.

PubMed

Ozturan, Orhan; Dogan, Remzi; Tugrul, Selahattin; Gedik, Ozge; Sjostrand, Alev Pektas; Yildirim, Yavuz Selim

2017-04-01

Low-dose administration of Aspartame (Ap) did not produce a significant ototoxic effect at the end of the 6th month. However, duration of the ototoxic effect is shortened and severity of the effect is increased as dose and duration of Ap administration is increased. While Ap toxicity has been studied in short- and long-term studies, its effects on hearing have not been investigated. This study was conducted to evaluate the effects of long-term consumption of Ap administered in various doses on hearing status of rats. The study included 54 female Wistar Albino rats. Ap was given for 6 months to the rats. The groups were assigned according to levels of Ap dosage. DPOAE and ABR tests were utilized for serial hearing evaluations. Serial hearing measurement times were designed as baseline, 1st week, 2nd week, 1st, 2nd, 3rd, and 6th months. While audiological parameters deteriorated with 100 mg/kg/day dose after the 3rd month, ABR thresholds were elevated and DPOAE values were significantly decreased in 500 mg/kg/day and 1000 mg/kg/day applications after the 2nd month. In 2000 mg/kg/day and 4000 mg/kg/day applications, deteriorations in audiological parameters were detected as early as the first and second months; respectively.

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

PubMed

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

2015-07-01

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

Comparison of the effects of three different (-)-hydroxycitric acid preparations on food intake in rats

PubMed Central

Louter-van de Haar, Johanna; Wielinga, Peter Y; Scheurink, Anton JW; Nieuwenhuizen, Arie G

2005-01-01

Background Studies on the effects of (-)-hydroxycitric acid (HCA) in humans are controversial. As differences in the HCA preparations may contribute to this apparent discrepancy, the aim of the current study is to compare different HCA-containing preparations in adult Wistar rats. Design The effects of 3 different HCA-containing preparations (Regulator, Citrin K, Super CitriMax HCA-600-SXS, all used at an effective HCA dose of 150 and 300 mg/kg, administered intragastrically) on food intake and body weight were studied in adult male Wistar rats. The efficacy was tested under 2 different experimental conditions: 1) after a single dose administration and 2) during repeated administration for 4 subsequent days. Results Regulator and Citrin K significantly reduced food intake in both experimental setups, while Super CitriMax HCA-600-SXS was less effective. When administered for 4 subsequent days Regulator and Citrin K diminished body weight gain. Conclusion Regulator and Citrin K were shown to be potent inhibitors of food intake in rats, whereas Super CitriMax HCA-600-SXS showed only small and more inconsistent effects. The striking differences in efficacy between these 3 preparations indicate that low doses of a relatively low-effective HCA preparation may have contributed to the lack of efficacy as found in several human studies. PMID:16156903

The pH dependence of silicon-iron interaction in rats.

PubMed

Jia, X; Emerick, R J; Kayongo-Male, H

1997-01-01

A 2 x 2 x 3 factorial experiment was conducted to study the pH dependence of a silicon-iron interaction in vivo. The dietary treatments used in the factorial design were the following (mg/kg of diet): silicon, 0 and 500; iron, 35 and 187; acid-base, ammonium chloride as 0.5% of total diet (acidic), sodium bicarbonate as 1.0% of total diet (basic), or no supplementation of acid or base (control). The supplementation of 500 mg silicon/kg of diet increased plasma-iron concentration in rats fed the acidic or control diets, but not in rats fed the basic diet. A high dietary-iron level suppressed copper absorption and utilization and subsequently imposed a negative effect on its own utilization. An increase in the plasma total-cholesterol concentration caused by high dietary-iron level was likely a consequence of the antagonistic effect of iron on copper absorption and utilization. The use of cupric sulfate pentahydrate as the dietary-copper source in this study resulted in plasma copper concentrations that were approximately twice those obtained in a related study using cupric carbonate. Also, a 42% coefficient of variation (C.V.) for plasma-copper concentrations of rats fed cupric sulfate in this study was greatly reduced from the C.V. = 108% previously associated with the dietary cupric carbonate.

Fluorescence probe for cervical examination during various reproductive states

NASA Astrophysics Data System (ADS)

Glassman, Wenling S.; Liao, Qin-Ping; Shi, Shao-Qing; Goodrum, Linda; Olson, Gayle; Martin, Elizabeth; Saade, George; Garfield, Robert E.

1997-05-01

These studies represent further investigations that have been done utilizing the fluorescence from pyridinoline, one of the major crosslinks of type I and III collagen, to evaluate cervical connective tissue changes during various female reproductive periods. Based on our previous studies, a prototype instrument has been constructed. The instrument was specifically designed for the purpose of vaginal examination of cervical connective tissue by measuring light induced fluorescence directly from the surface of the external os of the cervix. The studies were carried out on nonpregnant rats, rats during gestation at different periods, rats at different times during postpartum, and rats during preterm birth after being treated with antiprogesterone drugs. A study has also been done on humans during pregnancy and postpartum. The results parallel previous investigations that have used various invasive methods to analyze cervical extensibility, cervical collagen content and collagenase. In consideration of the important role of the collagen fibers and their turnover in the process of cervical function during pregnancy (softening or ripening at term), this method could be a useful tool for evaluating treatment strategies of the cervix. Moreover, the instrument could serve as a device for the non-invasive estimation of cervical status in the clinic and the diagnosis of the changes in the cervix during the preparation for labor.

A STUDY OF CHANGES IN DEFORMATION AND METABOLISM IN LEFT VENTRICLE AS A FUNCTION OF HYPERTROPHY IN SPONTANEOUS HYPERTENSIVE RATS USING MICROPET TECHNOLOGY

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

Gullberg, Grant, T; Huesman, Ronald, H; Reutter, Bryan, W

Problem: In the case of hypertrophy caused by pressure overload (hypertension) there is an increase in cardiac mass and modification cardiac metabolism. Aim: This study was designed to study the changes in glucose metabolism, ejection fraction, and deformation in the left ventricle with the progression of hypertrophy in spontaneous hypertensive rats (SHR). Methods: Dynamic PET data were acquired using the microPET II at UC Davis. Two rats were imaged at 10-week intervals for 18 months. Each time a dose of approximately 1- 1.5 mCi of F-18-FDG was injected into a normotensive Wistar Kyoto (WKY) rat and the same dose wasmore » injected into a SHR rat. Each rat was imaged using a gated dynamic acquisition for 80 minutes acquiring list mode data with cardiac gating of approximately 600-900 million total counts. For the analysis of glucose of metabolism, the list mode data were histogrammed into a dynamic sequence (42 frames over 80 mins). For each time frame, projection data of 1203 140x210 sinograms of 0.582 mm bins were formed by summing the last three gates before and one after the R-wave trigger to correspond to the diastolic phase of the cardiac cycle. Dynamic sequences of 128x128x83 matrices of 0.4x0.4x0.582 mm3 voxels in x, y, and z were reconstructed using an iterative MAP reconstruction which used a prior that penalized the high frequency components of the reconstruction using appropriate weighting between 26 nearest neighboring voxels. Time activity curves were generated from the dynamic reconstructed sequence for the blood and left ventricular tissue regions of interest which were fit to a 2-compartment model to obtain a least squares fit for the kinetic parameters. For the analysis of deformation, the list mode data were histogrammed into 8 gates of the cardiac cycle, each gate was the total sum of the later 60 mins of the 80 min acquisition. Images of 128x128x83 matrices for each gate were reconstructed using the same iterative MAP reconstruction used to reconstruct the dynamic sequence. The in-plane image dimensions were doubled to 256x256x83 in order to increase the resolution for the Warping analyses. These image data sets were then cropped to 128x128x83. The end-systolic image data sets were designated as the template images and the end-diastole image data sets were designated as the target images, thus providing an analysis of the diastolic relaxation and filling phases of the cardiac cycle. The template images were manually segmented to create surface definitions representing the epi- and endocardial surfaces. Finite element models of the left ventricles were created using the segmented surfaces and defining a transversely isotropic material with fiber angles varying from the epicardial surface to the endocardial surface. A Warping analyses was performed to obtain the LV strain tensor and fiber stretch distributions. Results: In one study, the average first principal Green-Lagrange strain, fiber stretch, ejection fraction, and metabolic rate of F-18-FDG was 0.22, 1.08, 80%, 0.1 for the WKY rat and 0.16, 1.06, 50%, 0.25 for the SHR rat, respectively. These same rats studied a year later presented with a metabolic rate of F-18-FDG of 0.11 and 0.25 for the WKY and SHR, respectively. A follow-up study the average strain (n=10) and ejection fraction (n=18) was 0.21, 72.7% for WKY and 0.17, 69.8% for the SHR, respectively. Conclusion: In the case of pressure overload there is an increased reliance on carbohydrate oxidation in an attempt to maintain contractile function.« less

Different relations between schedule-induced polydipsia and impulsive behaviour in the Spontaneously Hypertensive Rat and in high impulsive Wistar rats: questioning the role of impulsivity in adjunctive behaviour.

PubMed

Ibias, Javier; Pellón, Ricardo

2014-09-01

Rats belonging to three different strains (15 Wistar, 8 Spontaneously Hypertensive - SHR- and 8 Wistar Kyoto - WKY-) were used to evaluate the possible relationship between different levels of impulsivity and development of schedule-induced polydipsia (SIP). We first measured the rats' levels of impulsivity by means of delay-discounting and indifference-point procedures. Secondly, development of SIP was studied under a series of fixed time 15, 30, 60 and 120s food schedules, which were counterbalanced by means of a Latin-square design. Finally, we re-assessed the rats' levels of impulsivity by replicating the delay-discounting test. The findings showed that, starting from equivalent levels of impulsivity, development of SIP differed among the groups of rats. In comparison with the rest of the animals, the SHRs were observed to attain elevated drinking rates under SIP. On the other hand, the Wistar rats which had initial high impulsivity levels similar to those of the SHRs, displayed the lowest rates of induced drinking. Moreover, low levels of impulsivity in Wistar rats prior to SIP acquisition were reflected into high drinking rates. Relation of SIP and impulsivity is questioned by present results, which gives ground to the understanding of the behavioural mechanisms involved in adjunctive behaviour and its usefulness as an animal model of excessive behaviour. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of N-acetylcysteine on vascular endothelium function in aorta from oophorectomized rats.

PubMed

Delgado, J L; Landeras, J; Carbonell, L F; Parilla, J J; Abad, L; Quesada, T; Fiol, G; Hernández, I

1999-01-01

1. Experiments were performed to examine and to compare vascular endothelial function in aortic rings from oophorectomized and from ovary-intact rats and to test the effect of thiol compound as N-acetylcysteine on endothelial function. 2. In precontracted aortic rings from oophorectomized and intact rats, vascular endothelial function was evaluated by measuring changes in isometric force in response to cumulative doses of superoxide dismutase, acetylcholine and sodium nitroprusside. 3. In studies designed to assess the tone-related release of nitric oxide from aortic rings moderately precontracted with phenylephrine, superoxide dismutase produced a lower concentration-related relaxant response in aortic rings from oophorectomized rats than from ovary intact rats. 4. Acetylcholine caused a concentration- and endothelium-dependent relaxation of less magnitude in aortic rings from oophorectomized animals compared with those from ovary-intact rats. Addition of N-omega-nitro-L-arginine methyl ester eliminated the relaxation induced by both superoxide dismutase and acetylcholine. 5. No differences between groups were noticed in the concentration-relaxation curve induced by sodium nitroprusside. 6. Preincubation with N-acetylcysteine normalized the depressed vasorelaxant response to acetylcholine in the aortic rings from oophorectomized rats, whereas the concentration-response curve for acetylcholine in aortic rings from ovary-intact rats did not alter. 7. These results suggest that the absence of ovary estrogens is associated with a vascular endothelium dysfunction that can be reverted by addition of N-acetylcysteine, a thiol-containing compound with a free radical scavenger effect.

Effect of osteoporosis on fixation of osseointegrated implants in rats.

PubMed

Li, Yunfeng; He, Sheng; Hua, Yunwei; Hu, Jing

2017-11-01

The effect of osteoporosis on implant osseointegration has been widely investigated, whereas osteoporosis may also newly occur in patient with previously osseointegrated implant. This study was designed to investigate the effect of osteoporosis on implant fixation in rats after successful osseointegration had been obtained. Seventy female Sprague-Dawley rats were included, and each animal received two titanium implants in the distal metaphysis of femur bilaterally. Eight weeks later, ten rats were sacrificed to confirm the establishment of implant osseointegration. All left rats were randomly subjected to bilateral ovariectomy (OVX) or sham operation. Three, six, and twelve weeks later, implant osseointegration, peri-implant bone tissue, and biomechanical properties of implant were analyzed. Right femurs with implants were used for micro-CT and histological analysis, and left femurs with implants were used for biomechanical test. Micro-CT, histology, and biomechanical test confirmed the destructive effect of OVX on previously osseointegrated implant in rats; when compared to sham-operated rats, peri-implant bone volume, trabecular architecture, bone-to-implant contact ratio, as well as biomechanical parameters decreased progressively within 12 weeks. Results also indicated that the effect of OVX on undisturbed bone (proximal tibiae) was much stronger than that on peri-implant bone. Osteoporosis produced a progressive negative effect on previously osseointegrated implant in distal femora of rats during 12 weeks. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2426-2432, 2017. © 2016 Wiley Periodicals, Inc.

Exercise protects myelinated fibers of white matter in a rat model of depression.

PubMed

Xiao, Qian; Wang, Feifei; Luo, Yanmin; Chen, Linmu; Chao, Fenglei; Tan, Chuanxue; Gao, Yuan; Huang, Chunxia; Zhang, Lei; Liang, Xin; Tang, Jing; Qi, Yingqing; Jiang, Lin; Zhang, Yi; Zhou, Chunni; Tang, Yong

2018-02-15

The antidepressive effects of exercise have been a focus of research and are hypothesized to remodel the brain networks constructed by myelinated fibers. However, whether the antidepressant effects of exercise are dependent on changes in white matter myelination are unknown. Therefore, we chose chronic unpredictable stress (CUS) as a model of depression and designed an experiment. After a 4-week CUS period, 40 animals were tested using the sucrose preference test (SPT) and the open field test (OFT). The depressed rats then underwent 4-week running exercise. Next, electron microscopy and unbiased stereological methods were used to investigate white matter changes in the rats. After the 4-week CUS stimulation, body weight, sucrose preference and scores on the OFT were significantly lower in the depression rats than in the unstressed rats (p < .05). After undergoing a 4-week running exercise, the depression rats showed a significantly greater sucrose preference than the depression control rats without running exercise (p < .05). Furthermore, the white matter parameters of the depression rats (including the white matter volumes, the length and volumes of myelinated fibers, and the volumes and thickness of the myelin sheaths) were significantly reduced after the CUS period (p < .05). However, these white matter parameters were significantly increased after running exercise (p < .05). The present study is the first to provide evidence that running exercise has positive effects on white matter and the myelinated fibers of white matter in depressed rats, and this evidence might provide an important theoretical basis for the exercise-mediated treatment of depression. © 2017 Wiley Periodicals, Inc.

Sudden death in epileptic rats exposed to nocturnal magnetic fields that simulate the shape and the intensity of sudden changes in geomagnetic activity: an experiment in response to Schnabel, Beblo and May

NASA Astrophysics Data System (ADS)

Persinger, M. A.; McKay, B. E.; O'Donovan, C. A.; Koren, S. A.

2005-03-01

To test the hypothesis that sudden unexplained death (SUD) in some epileptic patients is related to geomagnetic activity we exposed rats in which limbic epilepsy had been induced to experimentally produced magnetic fields designed to simulate sudden storm commencements (SSCs). Prior studies with rats had shown that sudden death in groups of rats in which epilepsy had been induced months earlier was associated with the occurrence of SSCs and increased geomagnetic activity during the previous night. Schnabel et al. [(2000) Neurology 54:903 908) found no relationship between SUD in human patients and geomagnetic activity. A total of 96 rats were exposed to either 500, 50, 10 40 nT or sham (less than 10 nT) magnetic fields for 6 min every hour between midnight and 0800 hours (local time) for three successive nights. The shape of the complex, amplitude-modulated magnetic fields simulated the shape and structure of an average SSC. The rats were then seized with lithium and pilocarpine and the mortality was monitored. Whereas 10% of the rats that had been exposed to the sham field died within 24 h, 60% of the rats that had been exposed to the experimental magnetic fields simulating natural geomagnetic activity died (P<.001) during this period. These results suggest that correlational analyses between SUD in epileptic patients and increased geomagnetic activity can be simulated experimentally in epileptic rats and that potential mechanisms might be testable directly.

Effects of short-term exposure to powerline-frequency electromagnetic field on the electrical activity of the heart.

PubMed

Elmas, Onur; Comlekci, Selcuk; Koylu, Halis

2012-01-01

ABSTRACT The heart is a contractile organ that can generate its own rhythm. The contraction, or the rhythm, of the heart may be influenced by electromagnetic field (EMF) exposure, because of the heart's excitability characteristic. In previous studies, different methods have been used to study the possible effects of an extremely low frequency electromagnetic field (ELF-EMF) on the heart. But the studies' designs were not similar, and the results were also different. Recent studies have shown some evidence that short-term EMF exposure can influence the heart more than long-term exposure. This study investigated how the heart is affected in the first EMF exposure. In a simulation of the daily exposure of humans to a power frequency, Wistar albino rats were used. By utilizing the Helmholtz-coil set, we obtained a 50-Hz, 1-μT EMF and examined rat heart activity during short-term EMF exposure. No effect was observed under this exposure condition. The results obtained do not confirm a possible mechanism in the electrical activity of the rat heart model.

Supplemental dietary arginine accelerates intestinal mucosal regeneration and enhances bacterial clearance following radiation enteritis in rats.

PubMed

Gurbuz, A T; Kunzelman, J; Ratzer, E E

1998-02-01

Arginine is a dibasic amino acid with significant metabolic and immunologic, effects especially in trauma and stress situations. Arginine supplementation has been shown to promote wound healing and improve immune system. We designed a study to evaluate the effects of supplemental dietary arginine on intestinal mucosal recovery and bacterial translocation and bacterial clearance after induction of radiation injury in rats. Twenty-one male Sprague-Dawley rats were subjected to a single dose of 1100 rads of abdominal X radiation. Rats were divided into three groups; the first group received diet enriched with 2% arginine, the second group with 4% arginine, and the third group with isonitrogenous 4% glycine. Rats were sacrificed 7 days after the radiation. Blood was drawn for arginine levels and mesenteric lymph nodes were harvested for quantitative aerobic and anaerobic cultures. Segments of ileum and jejunum were evaluated for villous height, number of villi per centimeter of intestine, and the number of mucous cells per villous. Arginine is absorbed reliably from the gut following oral administration. Dietary 4% arginine supplementation enhanced bacterial clearance from mesenteric lymph nodes compared to 2% arginine and 4% glycine supplemented diet following radiation enteritis in rats. Four percent arginine resulted in clear improvement in intestinal mucosal recovery when compared to 2% arginine and 4% glycine after abdominal irradiation in rats.

Dexmedetomidine inhibits inflammatory reaction in the hippocampus of septic rats by suppressing NF-κB pathway.

PubMed

Zhang, Xiaobao; Yan, Fang; Feng, Jiying; Qian, Haitao; Cheng, Zhi; Yang, Qianqian; Wu, Yong; Zhao, Zhibin; Li, Aimin; Xiao, Hang

2018-01-01

Dexmedetomidine (DEX) is known to provide neuroprotective effect in the central nervous system. However, the detailed mechanism remains far more elusive. This study was designed to investigate the relevant mechanisms of DEX's neuroprotective effect. Sprague-Dawley (SD) rats were injected with dexmedetomidine and/or Lipopolysaccharide (LPS) intraperitoneally, and inflammatory cytokines in serum and in the hippocampus were measured by enzyme linked immunosorbent assay (ELISA). NF-κB in the brain tissue extracts was analyzed with western-blot. Then, we investigated whether NF-κB inhibitor prevents the elevation of inflammatory cytokines in rats injected with LPS. Our results indicated that compared with the control group, the rats exposed to LPS showed significant cognitive dysfunction. When compared to controls, the levels of TNF-α and IL-6 in the serum and hippocampus homogenate were increased in rats treated with LPS. DEX pretreatment inhibited the rats' TNF-α, IL-6 and NF-κB levels induced by LPS. In response to LPS, PDTC pretreatment restrains the production of proinflammatory cytokines (TNF-α and IL-6). Rats treated with PDTC and DEX alongside LPS exhibited less TNF-α and IL-6 than the LPS treated group. In combination, PDTC and DEX showed addictive effects. Our data suggest that DEX exerts a neuroprotective effect through NF-κB in part after LPS-induced cognitive dysfunction.

P-CPA pretreatment reverses the changes in sleep and behavior following acute immobilization stress rats.

PubMed

Sinha, Rakesh Kumar

2006-02-01

The effects of p-CPA (para-chlorophenylalanine) pretreatment was studied on the sleep-wake parameters and patterns of behavioral activities in an animal model of acute immobilization stress. For the experiments, young male Charles Foster rats were divided into three groups, subjected to (i) acute immobilization stress for four hours on specially designed wooden boards, (ii) a similar model of acute immobilization stress after pretreatment of p-CPA (injected through i.p. route), and (iii) control rats (p-CPA untreated and unstressed). Three channels of electrographic signals, i.e., EEG (electroencephalogram), EOG (electrooculogram), and EMG (electromyogram) were recorded continuously for four hours for all three groups of rats to analyze the changes in sleep-wake stages. The assessment of behavior was performed just after the stress on separate groups of rats in Open-Field (OF) and Elevated Plus-Maze (EPM) apparatuses. The significant changes in total sleep time (P < 0.05), total time for rapid eye movement sleep (P < 0.01), and total time in wakefulness (P < 0.01) following acute immobilization stress were found reversed in the p-CPA (a serotonin inhibitor) pretreated group of rats. Simultaneously, the results of the present work also revealed that the changes in grooming behavior (P < 0.05) in OF and the total time spent on the center of EPM (P < 0.05) were observed altered in p-CPA pretreated group of rats.

Partial sleep deprivation by environmental noise increases food intake and body weight in obesity resistant rats

PubMed Central

Mavanji, Vijayakumar; Teske, Jennifer A.; Billington, Charles J.; Kotz, Catherine M.

2012-01-01

Objective Sleep-restriction in humans increases risk for obesity, but previous rodent studies show weight loss following sleep deprivation, possibly due to stressful-methods used to prevent sleep. Obesity-resistant (OR) rats exhibit consolidated-sleep and resistance to weight-gain. We hypothesized that sleep disruption by a less-stressful method would increase body weight, and examined effect of partial sleep deprivation (PSD) on body weight in OR and Sprague-Dawley (SD) rats. Design and Methods OR and SD rats (n=12/group) were implanted with transmitters to record sleep/wake. After baseline recording, six SD and six OR rats underwent 8 h PSD during light-phase for 9 d. Sleep was reduced using recordings of random noise. Sleep/wake states were scored as wakefulness (W), slow-wave-sleep (SWS) and rapid-eye-movement-sleep (REMS). Total number of transitions between stages, SWS-delta-power, food intake and body weight were documented. Results Exposure to noise decreased SWS and REMS time, while increasing W time. Sleep-deprivation increased number of transitions between stages and SWS-delta-power. Further, PSD during the rest phase increased recovery-sleep during active phase. The PSD SD and OR rats had greater food intake and body weight compared to controls Conclusions PSD by less-stressful means increases body weight in rats. Also, PSD during rest phase increases active period sleep. PMID:23666828

Mobiloization of intracellular calcium ions in chicken and rat lymphocytes induced by T cell mitogens.

PubMed

Gerilechaogetu; Narahara, Kiyoaki; Abe, Asaki; Kondo, Yasuhiro

2009-04-01

Cytosolic Ca(2+) is known to be an important factor in intracellular signaling pathways that regulate several cellular functions. The present study was designed to measure the intracellular concentrations of Ca(2+) ([Ca(2+)](i)) in T cell mitogen-stimulated chicken lymphocytes, and to compare the results with those in rat lymphocytes. [Ca(2+)](i) was increased in the thymocytes, splenocytes and bursacytes of chickens, and in the thymocytes and splenocytes of rats following exposure to the mitogens phytohaemagglutinin (PHA) and concanavalin A (ConA). Increases were greatest in the thymocytes followed by the splenocytes and bursacytes. The PHA-induced changes in the thymocytes and splenocytes were similar in chickens and rats, but the ConA-induced increases were significantly lower in the chickens than rats. Pretreatment with EGTA before the application of PHA and ConA completely suppressed the rise in [Ca(2+)](i) in all the chicken lymphocytes, indicating that the increases that occurred in PHA- and ConA-treated chicken lymphocytes could be entirely attributed to the influx of extracellular Ca(2+). On the other hand, the PHA- and ConA-induced increase in [Ca(2+)](i) in rat lymphocytes was not completely suppressed by EGTA, indicating the recruitment of Ca(2+) from the intracellular Ca(2+) pool. The results suggest species differences in the Ca(2+)-based responses to T cell mitogens between chicken lymphocytes and rat lymphocytes.

The Role of Viscosity and Fermentability of Dietary Fibers on Satiety- and Adiposity-Related Hormones in Rats

PubMed Central

Schroeder, Natalia; Marquart, Len F.; Gallaher, Daniel D.

2013-01-01

Dietary fiber may contribute to satiety. This study examined the effect of two dietary fiber characteristics, small intestinal contents viscosity and large intestinal fermentability, on satiety-and adiposity-related hormones in rats. Diets contained fiber sources that were non-viscous, somewhat viscous, or highly viscous, and either highly fermentable or non-fermentable, in a 2 × 3 factorial design. In the fed state (2 h postprandial), rats fed non-fermentable fibers had significantly greater plasma GLP-1 concentration than fermentable fibers. In the fasted state, among non-fermentable fibers, viscosity had no effect on GLP-1 concentration. However, among fermentable fibers, greater viscosity reduced GLP-1 concentration. Plasma peptide tyrosine tyrosine (PYY) concentrations in the fasted state were not influenced by the fermentability of the fiber overall, however animals consuming a fructooligosaccharide greater PYY concentration. In both the fed and fasted states, rats fed non-fermentable fibers had a significantly lower plasma ghrelin concentration than rats fed fermentable fibers. In the fasted state, rats fed non-fermentable fibers had a significantly lower plasma leptin concentration than rats fed fermentable fibers. Thus, fermentability and viscosity of dietary fiber interacted in complex ways to influence satiety- and adiposity-related plasma hormone concentrations. However, the results suggest that highly viscous, non-fermentable fibers may limit weight gain and reduce adiposity and non-fermentable fibers, regardless of viscosity, may promote meal termination. PMID:23749206

The role of viscosity and fermentability of dietary fibers on satiety- and adiposity-related hormones in rats.

PubMed

Schroeder, Natalia; Marquart, Len F; Gallaher, Daniel D

2013-06-07

Dietary fiber may contribute to satiety. This study examined the effect of two dietary fiber characteristics, small intestinal contents viscosity and large intestinal fermentability, on satiety-and adiposity-related hormones in rats. Diets contained fiber sources that were non-viscous, somewhat viscous, or highly viscous, and either highly fermentable or non-fermentable, in a 2 × 3 factorial design. In the fed state (2 h postprandial), rats fed non-fermentable fibers had significantly greater plasma GLP-1 concentration than fermentable fibers. In the fasted state, among non-fermentable fibers, viscosity had no effect on GLP-1 concentration. However, among fermentable fibers, greater viscosity reduced GLP-1 concentration. Plasma peptide tyrosine tyrosine (PYY) concentrations in the fasted state were not influenced by the fermentability of the fiber overall, however animals consuming a fructooligosaccharide greater PYY concentration. In both the fed and fasted states, rats fed non-fermentable fibers had a significantly lower plasma ghrelin concentration than rats fed fermentable fibers. In the fasted state, rats fed non-fermentable fibers had a significantly lower plasma leptin concentration than rats fed fermentable fibers. Thus, fermentability and viscosity of dietary fiber interacted in complex ways to influence satiety- and adiposity-related plasma hormone concentrations. However, the results suggest that highly viscous, non-fermentable fibers may limit weight gain and reduce adiposity and non-fermentable fibers, regardless of viscosity, may promote meal termination.

Impulsive choice and pre-exposure to delays: iv. effects of delay- and immediacy-exposure training relative to maturational changes in impulsivity.

PubMed

Renee Renda, C; Rung, Jillian M; Hinnenkamp, Jay E; Lenzini, Stephanie N; Madden, Gregory J

2018-04-23

Impulsive choice describes preference for smaller, sooner rewards over larger, later rewards. Excessive delay discounting (i.e., rapid devaluation of delayed rewards) underlies some impulsive choices, and is observed in many maladaptive behaviors (e.g., substance abuse, gambling). Interventions designed to reduce delay discounting may provide therapeutic gains. One such intervention provides rats with extended training with delayed reinforcers. When compared to a group given extended training with immediate reinforcers, delay-exposed rats make significantly fewer impulsive choices. To what extent is this difference due to delay-exposure training shifting preference toward self-control or immediacy-exposure training (the putative control group) shifting preference toward impulsivity? The current study compared the effects of delay- and immediacy-exposure training to a no-training control group and evaluated within-subject changes in impulsive choice across 51 male Wistar rats. Delay-exposed rats made significantly fewer impulsive choices than immediacy-exposed and control rats. Between-group differences in impulsive choice were not observed in the latter two groups. While delay-exposed rats showed large, significant pre- to posttraining reductions in impulsive choice, immediacy-exposed and control rats showed small reductions in impulsive choice. These results suggest that extended training with delayed reinforcers reduces impulsive choice, and that extended training with immediate reinforcers does not increase impulsive choice. © 2018 Society for the Experimental Analysis of Behavior.

Blood-Brain Barrier Permeability Is Exacerbated in Experimental Model of Hepatic Encephalopathy via MMP-9 Activation and Downregulation of Tight Junction Proteins.

PubMed

Dhanda, Saurabh; Sandhir, Rajat

2018-05-01

The present study was designed to investigate the mechanisms involved in blood-brain barrier (BBB) permeability in bile duct ligation (BDL) model of chronic hepatic encephalopathy (HE). Four weeks after BDL surgery, a significant increase was observed in serum bilirubin levels. Masson trichrome staining revealed severe hepatic fibrosis in the BDL rats. 99m Tc-mebrofenin retention was increased in the liver of BDL rats suggesting impaired hepatobiliary transport. An increase in permeability to sodium fluorescein, Evans blue, and fluorescein isothiocyanate (FITC)-dextran along with increase in water and electrolyte content was observed in brain regions of BDL rats suggesting disrupted BBB. Increased brain water content can be attributed to increase in aquaporin-4 mRNA and protein expression in BDL rats. Matrix metalloproteinase-9 (MMP-9) mRNA and protein expression was increased in brain regions of BDL rats. Additionally, mRNA and protein expression of tissue inhibitor of matrix metalloproteinases (TIMPs) was also increased in different regions of brain. A significant decrease in mRNA expression and protein levels of tight junction proteins, viz., occludin, claudin-5, and zona occluden-1 (ZO-1) was observed in different brain regions of BDL rats. VCAM-1 mRNA and protein expression was also found to be significantly upregulated in different brain regions of BDL animals. The findings from the study suggest that increased BBB permeability in HE involves activation of MMP-9 and loss of tight junction proteins.

Observation of rat's colon polyps in real time by mini-endoscopy and raman spectroscopy

NASA Astrophysics Data System (ADS)

Andriana, Bibin Bintang; Mahardika, Anggara; Taketani, Akihiro; Sato, Hidetoshi

2018-02-01

Colorectal adenoma (CA) is a disease caused by various factors (such as genetic factors or environmental exposures). The appearance of colon polyp (CP) within colorectal might indicate the hint of CA development. Ball-lens hollow fiber Raman probe (BHRP) may has a high capability for detection of CA in living experimental animal and have already tested to rat's CP in this study, which was designed to collaborate between BHRP with mini-endoscopy to observe the biochemical alteration within normal colon tissue and rat's colon polyps in real time. BHRP and mini-endoscopy can distinguish the differences in their finger print spectra and make pictures the control and CP in the real time. At the first step, the real situation of normal colon and Rat's CP were washed by saline and observed with mini-endoscopy. BHRP was introduced to Dextran sodium sulphate (DSS)-induced Rat's CP to detect some of biochemical alteration. The main purpose of this study was to introduce mini-endoscopy to guide the BHRP for diagnosing of CP in real time and to compare it with spectra of normal colon (control group) in living rat. As the result, BHRP can provide the differences in band of control and CP group, which can inform that the biochemical of normal and CP has changed. As a major parameter to distinct normal and CP tissue were phosphatidylinositol, phosphodiester group, lipid, and collagen. Mini endoscopy and BHRP is very sensitive devices for diagnosing of CP in real time.

Maternal antioxidant supplementation prevents adiposity in the offspring of Western diet-fed rats.

PubMed

Sen, Sarbattama; Simmons, Rebecca A

2010-12-01

Obesity in pregnancy significantly increases the risk of the offspring developing obesity after birth. The aims of this study were to test the hypothesis that maternal obesity increases oxidative stress during fetal development, and to determine whether administration of an antioxidant supplement to pregnant Western diet-fed rats would prevent the development of adiposity in the offspring. Female Sprague Dawley rats were started on the designated diet at 4 weeks of age. Four groups of animals were studied: control chow (control); control + antioxidants (control+Aox); Western diet (Western); and Western diet + antioxidants (Western+Aox). The rats were mated at 12 to 14 weeks of age, and all pups were weaned onto control diet. Offspring from dams fed the Western diet had significantly increased adiposity as early as 2 weeks of age as well as impaired glucose tolerance compared with offspring of dams fed a control diet. Inflammation and oxidative stress were increased in preimplantation embryos, fetuses, and newborns of Western diet-fed rats. Gene expression of proadipogenic and lipogenic genes was altered in fat tissue of rats at 2 weeks and 2 months of age. The addition of an antioxidant supplement decreased adiposity and normalized glucose tolerance. CONCLUSIONS; Inflammation and oxidative stress appear to play a key role in the development of increased adiposity in the offspring of Western diet-fed pregnant dams. Restoration of the antioxidant balance during pregnancy in the Western diet-fed dam is associated with decreased adiposity in offspring.

Oleuropein and hydroxytyrosol protect rats' pups against bisphenol A induced hypothyroidism.

PubMed

Mahmoudi, Asma; Ghorbel, Hèla; Feki, Ines; Bouallagui, Zouhaier; Guermazi, Fadhel; Ayadi, Lobna; Sayadi, Sami

2018-04-27

Bisphenol A (BPA) can disturb the endocrine system and the organs that respond to endocrine signals in organisms, indirectly exposed during prenatal and/or early postnatal life. The present study was designed to assess the protective effect of phenolic compounds from olive leaves against BPA induced thyroid dysfunction and growth perturbation in young rats during lactation. The BPA disrupting effect on thyroid function was investigated by measuring changes in plasma levels of thyroid hormones. Free triiodothyronine (FT3) and thyroxine (FT4) were decreased in young rats breast-fed from mothers treated with bisphenol A. This effect was associated with an increase in the plasma level of thyroid-stimulating hormone (TSH). The histological and immunohistochemical study of the thyroid gland revealed a disturbance in morphological structure and thyroid cells function. Thyroid dysfunction led to a disruption in the skeletal bone growth of young rats. In fact, the infrared microspectroscopic analysis and histological examination of femoral bone showed significant changes in their histoarchitecture associated with a perturbation in the mechanism of bone tissue mineralization. The administration of oleuropein or hydroxytyrosol in BPA treated lactating mothers improved the thyroid cells function by enhancing thyroid hormone levels. Moreover, these phenolics increased the body growth characterized by an amelioration in the structure and the microstructure of femoral bone tissue. HPLC analysis of rats-breast milk indicated the presence of oleuropein and hydroxytyrosol, which could contribute to the protective effect against bisphenol A induced hypothyroidism in pups rats. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Effects of voluntary exercise on the viability, proliferation and BDNF levels of bone marrow stromal cells in rat pups born from morphine- dependent mothers during pregnancy.

PubMed

Haydari, Sakineh; Safari, Manouchehr; Zarbakhsh, Sam; Bandegi, Ahmad Reza; Miladi-Gorji, Hossein

2016-11-10

This study was designed to investigate whether free access to a running wheel during pregnancy in morphine-dependent mothers would influence the viability, proliferation and BDNF levels of bone marrow stromal cells in rat pups. Pregnant rats were made dependent by chronic administration of morphine in drinking water simultaneously with free access to a running wheel. Male pups are weaned at 21days of birth and their bones marrows were aspirated from the femurs and tibias and also the bone marrow stromal cells (BMSCs) cultured. MTT assay was used to determine cell viability and proliferation rate. The level of BDNF was measured in the supernant of BMSCs culture by ELISA. The sedentary morphine-dependent mothers' pups showed a significant increase in the percentage cell viability and proliferation rate and also a significant decrease in the BDNF protein levels in BMSCs. The rat pups borne from exercising the control and morphine-dependent mothers exhibited an increase in the percentage viability, proliferation rate and BDNF levels of the BMSCs. This study showed that maternal exercise during pregnancy in morphine-dependent and non-dependent mothers, with increasing of BDNF levels increased the proliferation and viability of BMSCs in the rat pups. Also, chronic administration of morphine during pregnancy was able to increase the proliferation and viability of BMSCs in the rat pups. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Anti-oxidative effects of curcumin on immobilization-induced oxidative stress in rat brain, liver and kidney.

PubMed

Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Farkhondeh, Tahereh; Samini, Fariborz

2017-03-01

Restraint stress has been indicated to induce oxidative damage in tissues. Several investigations have reported that curcumin (CUR) may have a protective effect against oxidative stress. The present study was designed to investigate the protective effects of CUR on restraint stress induced oxidative stress damage in the brain, liver and kidneys. For chronic restraint stress, rats were kept in the restrainers for 1h every day, for 21 consecutive days. The animals received systemic administrations of CUR daily for 21days. In order to evaluate the changes of the oxidative stress parameters following restraint stress, the levels of malondialdehyde (MDA), reduced glutathione (GSH), as well as antioxidant enzyme activities superoxide dismutase (SOD) glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) were measured in the brain, liver and kidney of rats after the end of restraint stress. The restraint stress significantly increased MDA level, but decreased the level of GSH and activists of SOD, GPx, GR, and CAT the brain, liver and kidney of rats in comparison to the normal rats (P<0.001). Intraperitoneal administration of CUR significantly attenuated oxidative stress and lipid peroxidation, prevented apoptosis, and increased antioxidant defense mechanism activity in the tissues versus the control group (P<0.05). This study shows that CUR can prevent restraint stress-induced oxidative damage in the brain, liver and kidney of rats and propose that CUR may be useful agents against oxidative stress in the tissues. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Effect of D-ribose-L-cysteine on aluminum induced testicular damage in male Sprague-Dawley rats.

PubMed

Falana, Benedict; Adeleke, Opeyemi; Orenolu, Mulikat; Osinubi, Abraham; Oyewopo, Adeoye

2017-06-01

This study investigated the effects of D-ribose and L-cysteine on aluminum-induced testicular damage in male Sprague-Dawley rats. A total number of thirty-five (35) adult male Sprague-Dawley rats were divided into four groups (AD). Group A (comprised five (5) rats) was designated the Control Group that received Physiological Saline; while groups B, C, and D (comprised ten (10) rats) were given 75 mg/kg, 150 mg/kg and 300 mg/kg of body weight of aluminum chloride respectively for 39 days. At day 40, the aluminum-treated groups were subdivided into sub-groups (B1, C1, D1) comprising of five (5) rats each, and 30 mg/kg body weight of Riboceine were administered for twenty (20) days. Groups B, C and D remained on the normal dosage of aluminum chloride for three more weeks (59 days). Andrological parameters (Sperm count, motility, morphology and testosterone) in the aluminum-treated Groups B and C showed no significant difference in their mean values when compared with their control counterparts, whereas there was a significant reduction in the andrological parameters in Group D rats when compared with the Control animals. Histoarchitecture of the testes "stain with H&E" of Group A, B and C rats appeared normal while Group D rats showed testicular damages with several abnormal seminiferous tubules with incomplete maturation of germinal cell layers and absence of spermatozoa in their lumen; Leydig cells appear hyperplastic. Group B1, C1 and D1 andrological and histological parameters appeared normal. Riboceine treatment significantly attenuates aluminum-induced testicular toxicity in male Sprague-Dawley in rats.

Synergistic effect of estradiol and fluoxetine in young adult and middle-aged female rats in two models of experimental depression.

PubMed

Récamier-Carballo, Soledad; Estrada-Camarena, Erika; Reyes, Rebeca; Fernández-Guasti, Alonso

2012-08-01

The antidepressant effect of estrogens combined with antidepressants is controversial: some preclinical data showed that estrogens facilitate the effect of antidepressants in the forced swimming test (FST) in young adult rats, while others failed to find such effect in middle-aged rats in the chronic mild stress (CMS) model. In clinics similar differences were reported and may be due to the compounds, the depression model or type of depression, the experimental design, and the age of the subjects or the women's menopause stage. The objective of this study was to analyze the antidepressant-like effect of the combination of 17β-estradiol (E(2)) and fluoxetine (FLX) in young adults (2-4 months) and middle-aged (12-14 months) ovariectomized (OVX) rats in two experimental models: FST and CMS. E(2) (5 and 10 μg/rat) and FLX (2.5 and 10 mg/kg) per se dose-dependently reduced immobility in both age groups and, in young adults both compounds increased swimming, whereas in middle-aged rats they increased swimming and climbing. Analysis of the antidepressant-like effect of the combination of suboptimal doses of FLX (1.25 mg/kg) and E(2) (2.5 μg/rat) showed a decrease in immobility and an increase in swimming in both age groups. In the CMS, chronic E(2) (2.5 μg/rat) with FLX (1.25 mg/kg) augmented relative sucrose intake, but middle-aged rats responded 2 weeks earlier than young adults. These results show that the antidepressant-like effect of the combination of E(2) and FLX in young adult and middle-aged female rats is evidenced in the two animal models of depression: FST and CMS. Copyright © 2012 Elsevier B.V. All rights reserved.

Impact of Perinatal Systemic Hypoxic–Ischemic Injury on the Brain of Male Offspring Rats: An Improved Model of Neonatal Hypoxic–Ischemic Encephalopathy in Early Preterm Newborns

PubMed Central

Xu, Hongwu; Wu, Weizhao; Lai, Xiulan; Ho, Guyu; Ma, Lian; Chen, Yunbin

2013-01-01

In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE) in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND) 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions. PMID:24324800

Purification and antimicrobial properties of three defensins from rat neutrophils.

PubMed Central

Eisenhauer, P B; Harwig, S S; Szklarek, D; Ganz, T; Selsted, M E; Lehrer, R I

1989-01-01

Three cysteine-rich cationic peptides, designated RatNP-1, RatNP-3, and RatNP-4, were purified from an acid extract of rat polymorphonuclear neutrophils, sequenced, and tested for antimicrobial activity. The peptides ranged from 29 to 32 amino acids in length (Mr, 3,252 to 3,825), and each contained all eight invariantly conserved "framework" residues that are characteristic of defensins. Each of the peptides killed Escherichia coli ML-35, Acinetobacter calcoaceticus HON-1, Staphylococcus aureus 502A, and Candida albicans 820 in vitro. RatNP-1, the most cationic rat defensin, was also the most potent. With this report, a total of 13 distinct defensins have been characterized in the polymorphonuclear leukocytes of four mammalian species. The existence of the defensin system in rats should facilitate investigations of the in vivo role of defensins in experimental infections. Images PMID:2543629

Expert panel report on a study of Splenda in male rats.

PubMed

Brusick, David; Borzelleca, Joseph F; Gallo, Michael; Williams, Gary; Kille, John; Wallace Hayes, A; Xavier Pi-Sunyer, F; Williams, Christine; Burks, Wesley

2009-10-01

A recent study in rats investigated the retail sweetener product, Granulated SPLENDA No Calorie Sweetener (Splenda) (Abou-Donia et al., 2008. Splenda alters gut microflora and increases intestinal P-glycoprotein and cytochrome P-450 in male rats. J. Toxicol. Environ. Health A, 71, 1415-1429), which is composed of (by dry weight) maltodextrin ( approximately 99%) and sucralose ( approximately 1%). The investigators reported that Splenda increased body weight, decreased beneficial intestinal bacteria, and increased the expression of certain cytochrome P450 (CYP450) enzymes and the transporter protein, P-glycoprotein (P-gp), the latter of which was considered evidence that Splenda or sucralose might interfere with the absorption of nutrients and drugs. The investigators indicated that the reported changes were attributable to the sucralose present in the product tested. An Expert Panel conducted a rigorous evaluation of this study. In arriving at its conclusions, the Expert Panel considered the design and conduct of the study, its outcomes and the outcomes reported in other data available publicly. The Expert Panel found that the study was deficient in several critical areas and that its results cannot be interpreted as evidence that either Splenda, or sucralose, produced adverse effects in male rats, including effects on gastrointestinal microflora, body weight, CYP450 and P-gp activity, and nutrient and drug absorption. The study conclusions are not consistent with published literature and not supported by the data presented.

High resolution molecular and histological analysis of renal disease progression in ZSF1 fa/faCP rats, a model of type 2 diabetic nephropathy

PubMed Central

Zhao, Shanrong; Schlerman, Franklin J.; Savary, Leigh; Campanholle, Gabriela; Johnson, Bryce G.; Xi, Li; Nguyen, Vuong; Zhan, Yutian; Lech, Matthew P.; Wang, Ju; Nie, Qing; Karsdal, Morten A.; Genovese, Federica; Boucher, Germaine; Brown, Thomas P.; Zhang, Baohong; Homer, Bruce L.; Martinez, Robert V.

2017-01-01

ZSF1 rats exhibit spontaneous nephropathy secondary to obesity, hypertension, and diabetes, and have gained interest as a model system with potentially high translational value to progressive human disease. To thoroughly characterize this model, and to better understand how closely it recapitulates human disease, we performed a high resolution longitudinal analysis of renal disease progression in ZSF1 rats spanning from early disease to end stage renal disease. Analyses included metabolic endpoints, renal histology and ultrastructure, evaluation of a urinary biomarker of fibrosis, and transcriptome analysis of glomerular-enriched tissue over the course of disease. Our findings support the translational value of the ZSF1 rat model, and are provided here to assist researchers in the determination of the model’s suitability for testing a particular mechanism of interest, the design of therapeutic intervention studies, and the identification of new targets and biomarkers for type 2 diabetic nephropathy. PMID:28746409

Comparison of the lethal effects of chemical warfare nerve agents across multiple ages.

PubMed

Wright, Linnzi K M; Lee, Robyn B; Vincelli, Nicole M; Whalley, Christopher E; Lumley, Lucille A

2016-01-22

Children may be inherently more vulnerable than adults to the lethal effects associated with chemical warfare nerve agent (CWNA) exposure because of their closer proximity to the ground, smaller body mass, higher respiratory rate, increased skin permeability and immature metabolic systems. Unfortunately, there have only been a handful of studies on the effects of CWNA in pediatric animal models, and more research is needed to confirm this hypothesis. Using a stagewise, adaptive dose design, we estimated the 24h median lethal dose for subcutaneous exposure to seven CWNA in both male and female Sprague-Dawley rats at six different developmental times. Perinatal (postnatal day [PND] 7, 14 and 21) and adult (PND 70) rats were more susceptible than pubertal (PND 28 and 42) rats to the lethal effects associated with exposure to tabun, sarin, soman and cyclosarin. Age-related differences in susceptibility were not observed in rats exposed to VM, Russian VX or VX. Published by Elsevier Ireland Ltd.

Sleep and EEG Spectra in Rats Recorded via Telemetry during Surgical Recovery

PubMed Central

Tang, Xiangdong; Yang, Linghui; Sanford, Larry D.

2007-01-01

Study Objective: To determine sleep and EEG spectra in rats during surgical recovery. Design: Sleep, activity, and EEG spectral power were examined in rats via telemetry on days 1, 2, 3, 7, 14, and 15 after implantation surgery. Results: NREM sleep and total sleep were increased on days 1 and 2 compared to later days. REM sleep was decreased on days 2 and 3 compared to days 14 and 15, and activity was decreased on days 1 and 2 compared to later days. EEG power (0.5–5 Hz for NREM and wakefulness, and 5.5–10 Hz for REM and wakefulness) was increased on days 1–3 compared to days 7, 14, and 15. Conclusion: The results are discussed in terms of their implications for post-surgery stabilization of sleep and potential relevance for sleep after injury. Citation: Tang X; Yang L; Sanford LD. Sleep and EEG spectra in rats recorded via telemetry during surgical recovery. SLEEP 2007;30(8):1057-1061. PMID:17702276

High resolution molecular and histological analysis of renal disease progression in ZSF1 fa/faCP rats, a model of type 2 diabetic nephropathy.

PubMed

Dower, Ken; Zhao, Shanrong; Schlerman, Franklin J; Savary, Leigh; Campanholle, Gabriela; Johnson, Bryce G; Xi, Li; Nguyen, Vuong; Zhan, Yutian; Lech, Matthew P; Wang, Ju; Nie, Qing; Karsdal, Morten A; Genovese, Federica; Boucher, Germaine; Brown, Thomas P; Zhang, Baohong; Homer, Bruce L; Martinez, Robert V

2017-01-01

ZSF1 rats exhibit spontaneous nephropathy secondary to obesity, hypertension, and diabetes, and have gained interest as a model system with potentially high translational value to progressive human disease. To thoroughly characterize this model, and to better understand how closely it recapitulates human disease, we performed a high resolution longitudinal analysis of renal disease progression in ZSF1 rats spanning from early disease to end stage renal disease. Analyses included metabolic endpoints, renal histology and ultrastructure, evaluation of a urinary biomarker of fibrosis, and transcriptome analysis of glomerular-enriched tissue over the course of disease. Our findings support the translational value of the ZSF1 rat model, and are provided here to assist researchers in the determination of the model's suitability for testing a particular mechanism of interest, the design of therapeutic intervention studies, and the identification of new targets and biomarkers for type 2 diabetic nephropathy.

Dosing-time-dependent variation in biliary excretion of flomoxef in rats.

PubMed

Hishikawa, Shuji; Sugimoto, Koh-ichi; Kobayashi, Eiji; Kumagai, Yuji; Fujimura, Akio

2003-05-01

We previously reported that the biliary excretion of flomoxef, an oxacephem antibiotic, was greater after dosing at 21:00 than at 09:00 h in diurnally active human subjects. The present study was undertaken to examine whether the biliary excretion of flomoxef is also dependent on its dosing time in rats. Adult male Wistar rats were housed under light on at 07:00 h and off at 19:00 h. Bile fluid was completely drained through a polyethylene catheter from conscious animals. Flomoxef (20 mg/kg) was injected into the tail vein at 09:00 or 21:00 h by a cross-over design, and drained bile fluid was collected for 8 h after each dosing. The maximum concentration of biliary flomoxef was significantly greater and its total excretion tended to be greater after dosing at 09:00 than 21:00 h. These results suggest the biliary excretion of flomoxef is enhanced after dosing at the beginning of the rest period in rats, as it is in humans.

Neuroprotective actions of the synthetic estrogen 17alpha-ethynylestradiol in the hippocampus.

PubMed

Picazo, Ofir; Becerril-Montes, Adriana; Huidobro-Perez, Delia; Garcia-Segura, Luis M

2010-07-01

17alpha-ethynylestradiol (EE2), a major constituent of many oral contraceptives, is similar in structure to 17beta-estradiol, which has neuroprotective properties in several animal models. This study explored the potential neuroprotective actions of EE2 against kainic and quinolinic acid toxicity in the hippocampus of adult ovariectomized Wistar rats. A decrease in the number of Nissl-stained neurons and the induction of vimentin immunoreactivity in astrocytes was observed in the hilus of the dentate gyrus of the hippocampus after the administration of either kainic acid or quinolinic acid. EE2 prevented the neuronal loss and the induction of vimentin immunoreactivity induced by kainic acid at low (1 microg/rat) and high (10-100 microg/rat) doses and exerted a protection against quinolinic acid toxicity at a low dose (1 microg/rat) only. These observations demonstrate that EE2 exerts neuroprotective actions against excitotoxic insults. This finding is relevant for the design of new neuroprotective estrogenic compounds.

Using Castration Surgery in Male Rats to Demonstrate the Physiological Effects of Testosterone on Seminal Vesicle Anatomy in an Undergraduate Laboratory Setting

ERIC Educational Resources Information Center

Belanger, Rachelle M.; Conant, Stephanie B.; Grabowski, Gregory M.

2013-01-01

Rats can be used as a model organism to teach physiological concepts in a laboratory setting. This article describes a two-part laboratory that introduces students to hypothesis testing, experimental design, the appropriate use of controls and surgical techniques. Students perform both a castration and sham-control surgery on male rats and test…

Flow Cytometric Analysis of Hepatocytes from Normal, PFDA, and PH/DEN/ PB-Treated Rats

DTIC Science & Technology

1989-12-31

SUB-GROUP’ Perfluorodecanoic acid ( PFDA ); hepatocarcinogenesis; preneoplastic lesions; flow cytometry; imunotoxicitYyc3 1%&STRACT (Continue on...effects of perfluorodecanoic acid ( PFDA ). Flow cytometric evaluation of hepatocytes from PEDA-treated rats revealed an increase in size and granularity...was designed to generate preliminary information regarding the toxic and potential carcinogenic effects of perfluorodecanoic acid ( PFDA ) on rat

Prefrontal cortex, caloric restriction and stress during aging: studies on dopamine and acetylcholine release, BDNF and working memory.

PubMed

Del Arco, Alberto; Segovia, Gregorio; de Blas, Marta; Garrido, Pedro; Acuña-Castroviejo, Dario; Pamplona, Reinald; Mora, Francisco

2011-01-01

This study was designed to investigate whether long-term caloric restriction during the life span of the rat changes the effects of an acute mild stress on the release of dopamine and acetylcholine in the prefrontal cortex (PFC) and on working memory performance. Spontaneous motor activity was also monitored and levels of BDNF measured in the prefrontal cortex, amygdala and hippocampus. Male Wistar rats (3 months of age) were housed during 3, 12, 21 and 27 months (6, 15, 24 and 30 months of age at the end of housing) in caloric restriction (CR; 40% food intake restriction) or control conditions. After behavioural testing, animals were further subdivided into two other groups. In one of the groups BDNF protein levels were determined. In the other group rats were implanted with guide cannulas into the PFC to perform microdialysis experiments. In CR rats the release of dopamine produced by handling stress did not differ from the response found in control rats of 6, 15 and 24 months of age. The release of acetylcholine was not changed at the ages of 6 and 15 months but reduced at the age of 24 months. Stress did not change dopamine or acetylcholine release in CR and control rats of 30 months of age. BDNF levels were increased in the hippocampus and amygdala, but not in the PFC, of 6 and 15 months CR rats. Spontaneous motor activity was increased in all groups of CR rats. Age, however, decreased motor activity in CR and control rats. Both experimental groups showed similar working memory performance in a delayed alternation task in basal conditions and after a situation of acute stress. These results suggest that CR does not modify the function of the PFC in response to an acute stress nor the changes found as a result of the normal process of aging. Copyright © 2010 Elsevier B.V. All rights reserved.

Effect of troxerutin on insulin signaling molecules in the gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic adult male rat.

PubMed

Sampath, Sathish; Karundevi, Balasubramanian

2014-10-01

Troxerutin is a trihydroxyethylated derivative of the flavonoid, rutin. It has been reported to possess the hepatoprotective, nephroprotective, antioxidant, anti-inflammatory, and antihyperlipidemic activities. Troxerutin treatment reduced the blood glucose and glycosylated hemoglobin levels in high-cholesterol-induced insulin-resistant mice and in type-2 diabetic patients. However, the mechanism by which it exhibits antidiabetic property was unknown. Therefore, the present study was designed to evaluate the effect of troxerutin on insulin signaling molecules in gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic rats. Wistar male albino rats were selected and divided into five groups. Group I: Control. Group II: High fat and sucrose-induced type-2 diabetic rats. Group III: Type-2 diabetic rats treated with troxerutin (150 mg/kg body weight/day orally). Group IV: Type-2 diabetic rats treated with metformin (50 mg/kg body weight/day orally). Group V: Normal rats treated with troxerutin (150 mg/kg body weight/day orally). After 30 days of treatment, fasting blood glucose, oral glucose tolerance, serum lipid profile, and the levels of insulin signaling molecules, glycogen, glucose uptake, and oxidation in gastrocnemius muscle were assessed. Diabetic rats showed impairment in insulin signaling molecules (IR, p-IRS-1(Tyr632), p-Akt(Ser473), β-arrestin-2, c-Src, p-AS160(Thr642), and GLUT4 proteins), glycogen concentration, glucose uptake, and oxidation. Oral administration of troxerutin showed near normal levels of blood glucose, serum insulin, lipid profile, and insulin signaling molecules as well as GLUT4 proteins in type-2 diabetic rats. It is concluded from the present study that troxerutin may play a significant role in the management of type-2 diabetes mellitus, by improving the insulin signaling molecules and glucose utilization in the skeletal muscle.

TRIMETHYLTIN EFFECTS ON AUDITORY FUNCTION AND COCHLEAR MORPHOLOGY

EPA Science Inventory

TMT is neurotoxicant known to alter auditory function. he present study was designed to compare TNT-induced auditory dysfunction using behavioral, electrophysiological, and anatomical techniques. dult male long Evans hooded rats (n=9-l2/group) were acutely exposed to saline, 3, 5...

Renovascular hypertension in spontaneous hypertensive rats: an experimental model of renal artery stenosis superimposed on essential hypertension.

PubMed

Rosenthal, T; Bass, A; Grossman, E; Shani, M; Griffel, B; Adar, R

1987-09-01

Renovascular hypertension superimposed on essential hypertension, a condition encountered in the elderly, was studied. An experimental animal model consisting of a two-kidney one-clip Goldblatt preparation in the spontaneous hypertensive (SHR) rat, that would simulate this condition, was designed. A 0.25 mm silver clip was placed on the left renal artery of SHR male rats. The same procedure performed on WKY rats served as control. All experiments were performed on low, normal, and rich sodium diet. Systolic blood pressure (BP) was measured by tail-cuff method. Plasma renin concentration (PRC) was determined before and after clipping of the renal artery. Results were as follows: Mean systolic BP increased significantly in clipped rats fed with normal and rich sodium diets. SHR showed an increase from 144 +/- 3 (mean + s.e.m.) to 168 +/- 3 mmHg, and WKY rats showed an increase from 120 +/- 2 to 139 +/- 5 mmHg. There was a two- to threefold rise in PRC. A low-salt diet given prior to clipping prevented the appearance of renovascular hypertension despite a significant rise in PRC. We concluded that renal artery narrowing plays a significant role in the rise of BP in the basically essential type of hypertension.

Antibacterial effect of royal jelly for preservation of implant-related spinal infection in rat.

PubMed

Gunaldi, Omur; Daglioglu, Yusuf Kenan; Tugcu, Bekir; Kizilyildirim, Suna; Postalci, Lutfi; Ofluoglu, Ender; Koksal, Fatih

2014-01-01

Implant-related infections are still a significant problem in spinal surgical procedures. Many drugs and methods have been tried to prevent implant-related infections. Our objective in this study was to evaluate whether royal jelly, which was found to hinder the growth of MRSA, has any preventive role in the prognosis of an infection in rats in an implant-related infection model. Rats were divided into 3 groups of eight rats. Group-1 consisted of rats that underwent only a spinal implant, group-2 included those rats that were inoculated bacteria together with a spinal implant and group-3 was administered royal jelly in addition to a spinal implant and infection. The amount of bacteria that grew in vertebral columns and implants was more in Group-2 than in Group-3, which meant that the number of bacteria colonies that grew was more quantitatively. This difference was found to be statistically significant in vertebral columns, but not in implants. Royal jelly could not fully prevent the MRSA infection in this model, but decreased the severity of infection noticeably. More objective and promising results may be obtained if royal jelly can be used at regular intervals in a different model to be designed with respect to implant-related infections.

Expression of brain-derived neurotrophic factors, neurotrophin-3, and neurotrophin-4 in the nucleus accumbens during heroin dependency and withdrawal.

PubMed

Li, Yixin; Xia, Baijuan; Li, Rongrong; Yin, Dan; Wang, Yanlin; Liang, Wenmei

2017-08-02

Neurotrophins, brain-derived neurotrophic factors (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), have been implicated in the modulation of heroin dependency. This study was designed to explore the expression alterations of BDNF, NT-3, and NT-4 in the context of heroin dependence and withdrawal in the rat nucleus accumbens (NAc). Heroin dependence was induced by a progressive intraperitoneal treatment of heroin. The results showed that the expression levels of BDNF and NT-4 were significantly decreased in the NAc of rats with heroin addiction in comparison with the control group, whereas there was a significant increase in BDNF and NT-4 expressions in the groups of rats with both naloxone-induced and spontaneous withdrawal. Moreover, NT-3 expression was markedly increased in the NAc of rats with heroin addiction and spontaneous withdrawal in comparison with the control group, but decreased in the NAc of rats with naloxone-induced withdrawal. These results indicated that chronic administration of heroin results in the alterations of BDNF, NT-3, and NT-4 expressions in the rat NAc. BDNF, NT-3, and NT-4 may play a critical role in the development of heroin dependency and withdrawal.

Expression of brain-derived neurotrophic factors, neurotrophin-3, and neurotrophin-4 in the nucleus accumbens during heroin dependency and withdrawal

PubMed Central

Li, Yixin; Xia, Baijuan; Li, Rongrong; Yin, Dan; Wang, Yanlin

2017-01-01

Neurotrophins, brain-derived neurotrophic factors (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), have been implicated in the modulation of heroin dependency. This study was designed to explore the expression alterations of BDNF, NT-3, and NT-4 in the context of heroin dependence and withdrawal in the rat nucleus accumbens (NAc). Heroin dependence was induced by a progressive intraperitoneal treatment of heroin. The results showed that the expression levels of BDNF and NT-4 were significantly decreased in the NAc of rats with heroin addiction in comparison with the control group, whereas there was a significant increase in BDNF and NT-4 expressions in the groups of rats with both naloxone-induced and spontaneous withdrawal. Moreover, NT-3 expression was markedly increased in the NAc of rats with heroin addiction and spontaneous withdrawal in comparison with the control group, but decreased in the NAc of rats with naloxone-induced withdrawal. These results indicated that chronic administration of heroin results in the alterations of BDNF, NT-3, and NT-4 expressions in the rat NAc. BDNF, NT-3, and NT-4 may play a critical role in the development of heroin dependency and withdrawal. PMID:28538519

A comparative study of the effect of diet and soda carbonated drinks on the histology of the cerebellum of adult female albino Wistar rats.

PubMed

Eluwa, M A; Inyangmme, I I; Akpantah, A O; Ekanem, T B; Ekong, M B; Asuquo, O R; Nwakanma, A A

2013-09-01

Carbonated drinks are widely consumed because of their taste and their ability to refresh and quench thirst. These carbonated drinks also exist in the form of diet drinks, for example Diet Coke®, Pepsi®, extra. A comparative effect of the diet and regular soda carbonated drinks on the histology of the cerebellum of female albino Wistar rats was investigated. Fifteen adult female Wistar rats weighing between 180-200 g were divided into 3 groups; designated as groups A, B and C, and each group consisted of five rats. Group A was the Control group and received distilled water, while groups B and C were the experimental groups. Group B was administered 50 ml of regular soda (RS), and group C was administered 50 ml of diet soda (DS) each per day for 21 days, and the rats were sacrificed on Day 22, and their cerebellums excised and preserved. Histological result of the sections of the cerebellum showed shrunken and degenerated Purkinje cells with hypertrophied dendrites, especially in the DS group, which was less in the RS group compared to the control group. These results suggest that diet soda has adverse effect on the cerebellum of adult female albino Wistar rats.

Upregulation of GLUT-4 in right ventricle of rats with monocrotaline-induced pulmonary hypertension.

PubMed

Broderick, Tom L; King, Tiffany M

2008-12-01

Pulmonary hypertension is characterized by abnormal vascular remodeling leading to occlusion of pulmonary arteries and increased stress placed on the right ventricle (RV). This causes the RV to hypertrophy and eventually to failure. This study was designed to examine the effects of pulmonary hypertension in rats on right ventricular remodeling and glucose transporter protein (GLUT4) content in right (RV) and left ventricle (LV). Pulmonary hypertension was induced in male Sprague-Dawley rat by a single subcutaneous injection of monocrotaline (MCT) at the concentration of 60 mg/kg. Forty-six days following the injection of MCT, animals were sacrificed. MCT-treated rats displayed significant increases in lung weight and RV weight. Marked RV hypertrophy was evident as the ratio of the RV to LV plus septum weight was nearly 40% higher in MCT-treated rats compared to control rats. Total GLUT4 content from whole homogenates from the RV was increased by approximately 28% in MCT-treated hearts compared to control hearts. No differences, however, in the LV content between groups were observed. Our findings indicate that the structural remodeling of the RV in MCT-induced pulmonary hypertension results in the upregulation of glucose transporters. This increase in RV GLUT4 levels may potentially result in alterations in substrate energy metabolism.

Design, optimization, and biological evaluation of novel keto-benzimidazoles as potent and selective inhibitors of phosphodiesterase 10A (PDE10A).

PubMed

Hu, Essa; Kunz, Roxanne K; Chen, Ning; Rumfelt, Shannon; Siegmund, Aaron; Andrews, Kristin; Chmait, Samer; Zhao, Sharon; Davis, Carl; Chen, Hang; Lester-Zeiner, Dianna; Ma, Ji; Biorn, Christopher; Shi, Jianxia; Porter, Amy; Treanor, James; Allen, Jennifer R

2013-11-14

Our development of PDE10A inhibitors began with an HTS screening hit (1) that exhibited both high p-glycoprotein (P-gp) efflux ratios in rat and human and poor metabolic stability. On the basis of cocrystal structure of 1 in human PDE10A enzyme, we designed a novel keto-benzimidazole 26 with comparable PDE10A potency devoid of efflux liabilities. On target in vivo coverage of PDE10A in rat brain was assessed using our previously reported LC-MS/MS receptor occupancy (RO) technology. Compound 26 achieved 55% RO of PDE10A at 30 mg/kg po and covered PDE10A receptors in rat brain in a dose-dependent manner. Cocrystal structure of 26 in PDE10A confirmed the binding mode of the novel scaffold. Further optimization resulted in the identification of keto-benzimidazole 34, which showed an increased in vivo efficacy of 57% RO in rats at 10 mg/kg po and an improved in vivo rat clearance and oral bioavailability.

A Probablistic Diagram to Guide Chemical Design with Reduced Potency to Incur Cytotoxicity

EPA Science Inventory

Toxicity is a concern with many chemicals currently in commerce, and with new chemicals that are introduced each year. The standard approach to testing chemicals is to run studies in laboratory animals (e.g. rats, mice, dogs), but because of the expense of these studies and conce...

D-optimal experimental approach for designing topical microemulsion of itraconazole: Characterization and evaluation of antifungal efficacy against a standardized Tinea pedis infection model in Wistar rats.

PubMed

Kumar, Neeraj; Shishu

2015-01-25

The study aims to statistically develop a microemulsion system of an antifungal agent, itraconazole for overcoming the shortcomings and adverse effects of currently used therapies. Following preformulation studies like solubility determination, component selection and pseudoternary phase diagram construction, a 3-factor D-optimal mixture design was used for optimizing a microemulsion having desirable formulation characteristics. The factors studied for sixteen experimental trials were percent contents (w/w) of water, oil and surfactant, whereas the responses investigated were globule size, transmittance, drug skin retention and drug skin permeation in 6h. Optimized microemulsion (OPT-ME) was incorporated in Carbopol based hydrogel to improve topical applicability. Physical characterization of the formulations was performed using particle size analysis, transmission electron microscopy, texture analysis and rheology behavior. Ex vivo studies carried out in Wistar rat skin depicted that the optimized formulation enhanced drug skin retention and permeation in 6h in comparison to conventional cream and Capmul 908P oil solution of itraconazole. The in vivo evaluation of optimized formulation was performed using a standardized Tinea pedis model in Wistar rats and the results of the pharmacodynamic study, obtained in terms of physical manifestations, fungal-burden score, histopathological profiles and oxidative stress. Rapid remission of Tinea pedis from rats treated with OPT-ME formulation was observed in comparison to commercially available therapies (ketoconazole cream and oral itraconazole solution), thereby indicating the superiority of microemulsion hydrogel formulation over conventional approaches for treating superficial fungal infections. The formulation was stable for a period of twelve months under refrigeration and ambient temperature conditions. All results, therefore, suggest that the OPT-ME can prove to be a promising and rapid alternative to conventional antifungal therapies against superficial fungal infections. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of Clozapine and Alprazolam on Cognitive Deficits and Anxiety-Like Behaviors in a Ketamine-Induced Rat Model of Schizophrenia

DTIC Science & Technology

2005-01-01

xii LIST OF TABLES Table 1. DSM-IV-TR Criteria for Schizophrenia (abbreviated) Table 2. Experimental Design Table 3. Experiment #1... Experimental Timeline Table 4. Experiment #2: Experimental Timeline Table 5. Experiment #1: Results of MANOVAs for Prepulse Inhibition Variables...rats. Please see Table 2 for a description of treatments and cell sizes for each experiment . Table 2. Experimental Design Ketamine (mg/kg

Biomarkers for Pulmonary Injury Following Deployment

DTIC Science & Technology

2013-02-01

Department of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No...methods, please refer to the 2012 Annual Report for this contract. Rat BALF samples were denatured, digested, and desalted prior to liquid chromatography...that were part of the dust instillation studies designed by USACHER and carried out by a team at NIOSH. These samples were obtained both from a first

A comparative histological study of alginate beads as a promising controlled release delivery for mefenamic acid.

PubMed

Sevgi, Ferhan; Kaynarsoy, Buket; Ozyazici, Mine; Pekcetin, Cetin; Ozyurt, Dogan

2008-01-01

The new mefenamic acid-alginate bead formulation prepared by ionotropic gelation method using 3 x 2(2) factorial design has shown adequate controlled release properties in vitro. In the present study, the irritation effects of mefenamic acid (MA), a prominent non-steroidal anti-inflammatory (NSAI) drug, were evaluated on rat gastric and duodenal mucosa when suspended in 0.5% (w/v) sodiumcarboxymethylcellulose (NaCMC) solution and loaded in alginate beads. Wistar albino rats weighing 200 +/- 50 g were used during in vivo animal studies. In this work, biodegradable controlled release MA beads and free MA were evaluated according to the degree of gastric or duodenal damage following oral administration in rats. The gastric and duodenal mucosa was examined for any haemorrhagic changes. Formulation code A10 showing both Case II transport and zero order drug release and t(50) % value of 5.22 h was chosen for in vivo animal studies. For in vivo trials, free MA (100 mgkg(-1)), blank and MA (100 mgkg(-1)) loaded alginate beads (formulation code A10) were suspended in 0.5% (w/v) NaCMC solution and each group was given to six rats orally by gavage. NaCMC solution was used as a control in experimental studies. In vivo data showed that the administration of MA in alginate beads prevented the gastric lesions.

Continuous-wave optical stimulation of the rat prostate nerves using an all-single-mode 1455 nm diode laser and fiber system

NASA Astrophysics Data System (ADS)

Tozburun, Serhat; Lagoda, Gwen A.; Burnett, Arthur L.; Fried, Nathaniel M.

2011-03-01

Optical nerve stimulation (ONS) has recently been reported as a potential alternative to electrical nerve stimulation. Continuous-wave (CW) laser stimulation of the prostate cavernous nerves (CN) in a rat model, in vivo, has also been demonstrated in our previous studies. The objective of this study is to present a new all-single-mode-fiber configuration for ONS with the laser operating in CW mode for potential diagnostic applications. An infrared pigtailed single-mode diode laser (λ = 1455 nm) was used in this study for noncontact ONS. This new all-fiber approach introduces several advantages including: (1) a less expensive and more compact ONS system, (2) elimination of alignment of optical components, and (3) an improved spatial beam profile. Successful optical stimulation of the rat CN using this new design was observed after the CN reached a threshold temperature of ~ 41 °C with response times as short as 3 s. Upon further study, this configuration may be useful for identification and preservation of the cavernous nerves during prostate cancer surgery.

Development and optimisation of atorvastatin calcium loaded self-nanoemulsifying drug delivery system (SNEDDS) for enhancing oral bioavailability: in vitro and in vivo evaluation.

PubMed

Kassem, Abdulsalam M; Ibrahim, Hany M; Samy, Ahmed M

2017-05-01

The objective of this study was to develop and optimise self-nanoemulsifying drug delivery system (SNEDDS) of atorvastatin calcium (ATC) for improving dissolution rate and eventually oral bioavailability. Ternary phase diagrams were constructed on basis of solubility and emulsification studies. The composition of ATC-SNEDDS was optimised using the Box-Behnken optimisation design. Optimised ATC-SNEDDS was characterised for various physicochemical properties. Pharmacokinetic, pharmacodynamic and histological findings were performed in rats. Optimised ATC-SNEDDS resulted in droplets size of 5.66 nm, zeta potential of -19.52 mV, t 90 of 5.43 min and completely released ATC within 30 min irrespective of pH of the medium. Area under the curve of optimised ATC-SNEDDS in rats was 2.34-folds higher than ATC suspension. Pharmacodynamic studies revealed significant reduction in serum lipids of rats with fatty liver. Photomicrographs showed improvement in hepatocytes structure. In this study, we confirmed that ATC-SNEDDS would be a promising approach for improving oral bioavailability of ATC.

N-acetylcycsteine attenuates the deleterious effects of radiation therapy on inci-sional wound healing in rats

PubMed Central

Tascilar, O; Çakmak, GK; Emre, AU; Bakkal, H; Kandemir, N; Turkcu, UO; Demir, EO

2014-01-01

Background: During preoperative radiotherapy, effective doses of ionizing radiation occasionally cause wound complications after subsequent surgery. This study was designed to determine the effects of intraperitoneally or orally administered N-acetylcysteine (NAC) on anastomotic healing of irradiated rats. Material & Methods: Forty Wistar albino rats were randomized into four groups containing 10 rats each. A 3 cm long surgical full-thickness midline laparotomy was performed to all groups (Groups 1-4). Group 1 was designed as a control group without radiation therapy and NAC treatment. Groups 2, 3 and 4 received a single abdominal dose of 10 Gy irradiation before laparotomy and groups 3 and 4 received oral and intraperitoneal NAC, respectively. Results: Group comparisons demonstrated that breaking strength was significantly higher in NAC treated rats. A statistically significant difference was determined in terms of superoxide dismutase (SOD), malondealdehyde (MDA) and glutation (GSH) values between groups (p<0.001). Nevertheless, advanced oxidation protein products (AOPP) levels were found to be similar between groups (p=0.163). Serum GSH and SOD levels were significantly higher in groups 3 and 4 when compared to group 2 (p < 0.05). Similarly, there was a significant increase in serum MDA concentration, predicting lipid peroxidation, in group 2 when compared to groups 1, 3 and 4 (p < 0.05). There was not a significant difference between Groups 3 and 4 regarding GSH, MDA, SOD, and AOPP levels. Histopathological analysis revealed that NAC administration, either orally or intraperitoneally, leads to a better incisional healing in terms of inflammation, granulation, collagen deposition, reepithelization and neovascularization. Conclusion: The present study supports the hypothesis that NAC administration alleviates the negative effects of radiotherapy on incisional wound healing by means of reducing oxidative stress markers and improving histologic parameters independent of the route of administration. PMID:25125946

Exposure setup to study potential adverse effects at GSM 1800 and UMTS frequencies on the auditory systems of rats.

PubMed

Lopresto, V; Pinto, R; De Vita, A; Mancini, S; Galloni, P; Marino, C; Ravazzani, P; Lovisolo, G A

2007-01-01

To investigate possible biological effects of exposure to electromagnetic (EM) fields at the frequencies of global system for mobile communication (GSM) 1800 system and universal mobile telecommunication system (UMTS) on the auditory system of rats, an exposure setup for in vivo experiments is presented. The study was carried out in the framework of two European research projects. The target of the investigation was the cochlea. A dosimetric study was performed, both numerically and through direct measurements, to assess the interaction of the radiated fields and the dose distribution in the biological target. For the local exposure of rats, a loop antenna operating at the frequency bands of interest was designed, realised and characterised through numerical and experimental dosimetric procedures. Moreover, an exposure apparatus was set up, consisting of three arrays of four loop antennas, placed on three levels, thus allowing simultaneous exposure of 12 rats to give statistical power to the experiments. To isolate the exposure arrays, the setup was assembled by a wooden rack with EM field absorbing panels, inserted among the levels and at the four sides of the rack. Isolation was verified by direct measurements. Two exposure arrays were simultaneously supplied, whereas the third one was used for sham exposure. Blind exposure was achieved through a black box, hiding physical connections to the microwave power supply. During exposure sessions, rats were restrained in special plastic jigs for repeatable positioning, thus assuring the fixed level of dose in the target.

Rats and rabbits as pharmacokinetic screening tools for long acting intramuscular depots: case study with paliperidone palmitate suspension.

PubMed

Patel, Harilal; Patel, Prakash; Modi, Nirav; Patel, Pinakin; Wagh, Yogesh; George, Alex; Desai, Nirmal; Srinivas, Nuggehally R

2018-05-08

Development of prodrug of 9-hydroxyrisperidone (paliperidone) long-acting intramuscular injection has enabled delivery over four-week time period with improved compliance. The key aim of this work was to establish a reliable preclinical model which may potentially serve as a screening tool for judging the pharmacokinetics of paliperidone formulation(s) prior to human clinical work. Sparse sampling composite study was used in rats, (Wistar/Sprague-Dawley (SD; n = 10)) and a serial blood sampling study design was used in rabbits (n = 4). Animals received intramuscular injection of paliperidone palmitate in the thigh muscle at dose of 16 (rats) and 4.5 mg/kg (rabbits). Samples were drawn in rats (retro-orbital sinus) and rabbits (central ear artery) and were analysed for paliperidone using liquid chromatography-mass spectrometry/ mass spectrometry (LC-MS/MS) assay. The plasma data was subjected to pharmacokinetic analysis. Following intramuscular injection of depot formulation in Wistar/SD rats and rabbits, absorption of paliperidone was slow and gradual with median value of time to reach maximum concentration (T max ) occurring on day 7. The exposures (i.e. area under the curve (AUC; 0-28) days) were 18,597, 21,865 and 18,120 ng.h/mL, in Wistar, SD and rabbits, respectively. The clearance was slow and supported long half-life (8-10 days). Either one of the two models can serve as a research tool for establishing pharmacokinetics of paliperidone formulation(s).

Gamma-aminobutyric acid aggravates nephrotoxicity induced by cisplatin in female rats.

PubMed

Peysepar, Elham; Soltani, Nepton; Nematbakhsh, Mehdi; Eshraghi-Jazi, Fatemeh; Talebi, Ardeshir

2016-01-01

Cisplatin (CP) is a major antineoplastic drug for treatment of solid tumors. CP-induced nephrotoxicity may be gender-related. This is while gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the central nervous system that has renoprotective impacts on acute renal injury. This study was designed to investigate the protective role of GABA against CP-induced nephrotoxicity in male and female rats. Sixty Wistar male and female rats were used in eight experimental groups. Both genders received GABA (50 μg/kg/day; i. p.) for 14 days and CP (2.5 mg/kg/day; i. p.) was added from day 8 to the end of the study, and they were compared with the control groups. At the end of the study, all animals were sacrificed and the serum levels of blood urea nitrogen (BUN), creatinine (Cr), nitrite, malondialdehyde (MDA), and magnesium (Mg) were measured. The kidney tissue damage was also determined via staining. CP significantly increased the serum levels of Cr and BUN, kidney weight, and kidney tissue damage score in both genders (P<0.05). GABA did not attenuate these markers in males; even these biomarkers were intensified in females. Serum level of Mg, and testis and uterus weights did not alter in the groups. However, the groups were significantly different in terms of nitrite and MDA levels. It seems that GABA did not improve nephrotoxicity induced by CP-treated rats, and it exacerbated renal damage in female rats.

Long term effects of PCBs (Phenoclor DP5) on rat microsomal enzymes, liver, and blood lipids after peri- and postnatal exposure

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

Poul, J.M.

1992-02-01

It was shown that activities of some hepatic drug metabolizing enzymes and parameters of lipid metabolism were modified in adult rats (PND100), after exposure to PCBs (Phenoclor DP5) during lactation. Perinatal or early postnatal treatment with inducers, like phenobarbital and phenytoin, seems to induce permanent effects on hepatic microsomal enzymes in adults though the drugs have completely disappeared from the body. Time course evolution of induction-related parameters and tissue residues of DP5, from weaning to PND100, have been studied the effects observed in adult rats at PND100 could be residual aspects of the important changes induced before weaning by acutemore » exposure via milk or consequences of the relative high concentrations of PCBs still present in tissues. The present study was designed to investigate the effects of DP5, administered peri- and postnatally, on microsomal enzyme activities and in vitro genotoxic activation of 2-aminofluorene and on liver and blood lipids, in adult rats at PND180 and PND300. Tissue residues of Phenoclor DP5 were measured in liver, fat and brain at the same periods.« less

Effects of Aging on Thyroarytenoid Muscle Regeneration

PubMed Central

Lee, Kyungah; Kletzien, Heidi; Connor, Nadine P.; Schultz, Edward; Chamberlain, Connie S.; Bless, Diane M.

2012-01-01

Objectives/hypotheses Regenerative properties of age-associated changes in the intrinsic laryngeal muscles following injury are unclear. The purpose of this study was to investigate the regenerative properties of the thyroarytenoid muscle (TA) in an aging rat model. The hypothesis was that, following myotoxic injury, old animals would exhibit a decrease in mitotic activities of muscle satellite cells when compared with younger rats, suggesting reduced regenerative potential in the aging rat TA. Study Design Animal group comparison. Method Regeneration responses following injury to the TA were examined in 18 young adult, middle-aged, and old Fischer 344/Brown Norway rats. TA muscle fiber cross sectional area (CSA), satellite cell mitosis (number/fiber), and regeneration index (CSA injured side/CSA non-injured side) were measured and compared across age groups. Results Young animals had a significantly higher regeneration index than the middle-aged and old groups. Within the lateral region of the TA (LTA), the regeneration index was significantly higher in the young animals than in the middle-aged and old animals. The regeneration index of the medial TA (MTA) was significantly higher than the LTA across all age groups. Conclusions The regenerative capacity of the TA muscle is impaired with increasing age. Evidence N/A PMID:22965923

Antidiabetic, Lipid Normalizing, and Nephroprotective Actions of the Strawberry: A Potent Supplementary Fruit

PubMed Central

Mandave, Pallavi; Khadke, Suresh; Karandikar, Manjiri; Pandit, Vijaya; Ranjekar, Prabhakar; Kuvalekar, Aniket; Mantri, Nitin

2017-01-01

The study was designed to assess the effect of different strawberry extracts on glucose levels, lipid profiles, and oxidative stress in nicotinamide-streptozotocin (NIC-STZ) induced diabetic rats. The associated changes were evaluated through biochemical, molecular, and histological assays. Diabetes was induced by intraperitoneal injection of STZ to albino Wistar rats after treatment with nicotinamide. Aqueous, hydroalcoholic, and alcoholic strawberry extracts were administrated orally to diabetic rats. Treatment of strawberry extracts improved lipid profile, liver function, and serum creatinine and led to a significant increase in antioxidant status in diabetic rats. Real-time PCR expression analysis of genes from the liver of animals treated with strawberry extracts exhibited downregulation of several fatty acid synthesis genes, transcription factors, such as Sterol regulatory Element Binding Transcription factor (SREBP) and Nuclear Factor-κβ (NF-κβ), and inflammatory markers, like Interleukin 6 (IL6) and Tumor Necrosis Factor-α (TNF-α). Strawberry extracts also upregulated liver Peroxisome Proliferator Activated Receptor-γ (PPAR-γ). Histological examination confirmed the nephroprotective and β-cell regeneration/protection effects of strawberry extracts. The present study demonstrates several beneficial effects of strawberry extracts along with its probable mechanism of action. PMID:28085064

Oestrous phase cyclicity influences judgment biasing in rats.

PubMed

Barker, Timothy Hugh; Kind, Karen Lee; Groves, Peta Danielle; Howarth, Gordon Stanley; Whittaker, Alexandra Louise

2018-04-10

The identification of cognitive bias has become an important measure of animal welfare. Negative cognitive biases develop from a tendency for animals to process novel information pessimistically. Judgment-bias testing is the commonplace methodology to detect cognitive biases. However, concerns with these methods have been frequently-reported; one of which being the discrepancy between male and female cognitive expression. The current study assessed the factors of social status and oestrus, to investigate whether oestrous cycle rotation, or subordination stress encouraged an increase in pessimistic responses. Female Sprague-Dawley rats (n = 24) were trained on an active-choice judgment bias paradigm. Responses to the ambiguous probe were recorded as optimistic or pessimistic. Oestrous phase was determined by assessing vaginal cytology in stained vaginal cell smears. Rats in the dioestrous phase and those rats considered to be subordinate demonstrated an increased percentage of pessimistic responses. However, no interaction between these factors was observed. This suggests that oestrous cyclicity can influence the judgment biases of female animals; a previously unreported finding. On this basis, researchers should be encouraged to account for both oestrous phase cyclicity and social status as an additional fixed effect in study design. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Acute Toxicological Responses of Fischer Rats to Naturally Occurring Asbestos from theUnited States and Canada

EPA Science Inventory

This study was designed to provide understanding of the toxicity of naturally occurring asbestos (NOA) including Libby amphibole (LA), Sumas Mountain chrysotile (SM), EI Dorado Hills tremolite (ED) and Ontario actinolite/ferroactinolite cleavage fragments (ON). Ratrespirable fra...

EFFECTS OF DOPAMINERGIC DRUGS ON WORKING AND REFERENCE MEMORY IN RATS

EPA Science Inventory

Occupational exposure to styrene monomer has been associated with cognitive dysfunction in humans, and changes in dopaminergic function have been suggested to underly effects of repeated exposure to styrene monomer in animals. his study was designed to determine whether styrene a...

EFFECTS OF TRANSPLACENTAL EXPOSURE TO CHLORINATED PHENOLS

EPA Science Inventory

Female rats were exposed to 0,5,50 or 500 ppm of 2-Chlorophenol (2CP) or pentachlorophenol (PCP). The study was designed to produce progeny which were exposed to the chlorophenolic compounds both prenatally and postnatally. Percent conception, litter size, birth weight, and numbe...

METHOXYCHLOR ACCELERATES EMBRYO TRANSPORT THROUGH THE RAT REPRODUCTIVE TRACT

EPA Science Inventory

The estrogenic pesticide methoxychlor (MXC) is known to reduce implantation, and, in our previous work, this reduction has been attributed to a direct effect on uterine function. The present study was designed to investigate the effect of MXC on embryo transport rate, another phe...

Repeated administration of an acetylcholinesterase inhibitor attenuates nicotine taking in rats and smoking behavior in human smokers

PubMed Central

Ashare, R L; Kimmey, B A; Rupprecht, L E; Bowers, M E; Hayes, M R; Schmidt, H D

2016-01-01

Tobacco smoking remains the leading cause of preventable death worldwide and current smoking cessation medications have limited efficacy. Thus, there is a clear need for translational research focused on identifying novel pharmacotherapies for nicotine addiction. Our previous studies demonstrated that acute administration of an acetylcholinesterase inhibitor (AChEI) attenuates nicotine taking and seeking in rats and suggest that AChEIs could be repurposed for smoking cessation. Here, we expand upon these findings with experiments designed to determine the effects of repeated AChEI administration on voluntary nicotine taking in rats as well as smoking behavior in human smokers. Rats were trained to self-administer intravenous infusions of nicotine (0.03 mg kg−1 per 0.59 ml) on a fixed-ratio-5 schedule of reinforcement. Once rats maintained stable nicotine taking, galantamine or donepezil was administered before 10 consecutive daily nicotine self-administration sessions. Repeated administration of 5.0 mg kg−1 galantamine and 3.0 mg kg−1 donepezil attenuated nicotine self-administration in rats. These effects were reinforcer-specific and not due to adverse malaise-like effects of drug treatment as repeated galantamine and donepezil administration had no effects on sucrose self-administration, ad libitum food intake and pica. The effects of repeated galantamine (versus placebo) on cigarette smoking were also tested in human treatment-seeking smokers. Two weeks of daily galantamine treatment (8.0 mg (week 1) and 16.0 mg (week 2)) significantly reduced smoking rate as well as smoking satisfaction and reward compared with placebo. This translational study indicates that repeated AChEI administration reduces nicotine reinforcement in rats and smoking behavior in humans at doses not associated with tolerance and/or adverse effects. PMID:26784967

Hepaprotective Effect of Standardized Ecklonia stolonifera Formulation on CCl4-Induced Liver Injury in Sprague-Dawley Rats.

PubMed

Byun, Jae-Hyuk; Kim, Jun; Choung, Se-Young

2018-03-01

The liver is an essential organ for the detoxification of exogenous xenobiotics, drugs and toxic substances. The incidence rate of non-alcoholic liver injury increases due to dietary habit change and drug use increase. Our previous study demonstrated that Ecklonia stolonifera (ES) formulation has hepatoprotective effect against alcohol-induced liver injury in rat and tacrine-induced hepatotoxicity in HepG2 cells. This present study was designated to elucidate hepatoprotective effects of ES formulation against carbon tetrachloride (CCl 4 )-induced liver injury in Sprague Dawley rat. Sixty rats were randomly divided into six groups. The rats were treated orally with ES formulation and silymarin (served as positive control, only 100 mg/kg/day) at a dose of 50, 100, or 200 mg/kg/day for 21 days. Seven days after treatment, liver injury was induced by intraperitoneal injection of CCl 4 (1.5 ml/kg, twice a week for 14 days). The administration of CCl 4 exhibited significant elevation of hepatic enzymes (like AST and ALT), and decrease of antioxidant related enzymes (superoxide dismutase, glutathione peroxidase and catalase) and glutathione. Then, it leaded to DNA damages (8-oxo-2'-deoxyguanosine) and lipid peroxidation (malondialdehyde). Administration of ES formulation inhibited imbalance of above factors compared to CCl 4 induced rat in a dose dependent manner. Real time PCR analysis indicates that CYP2E1 was upregulated in CCl 4 induced rat. However, increased gene expression was compromised by ES formulation treatment. These findings suggests that ES formulation could protect hepatotoxicity caused by CCl 4 via two pathways: elevation of antioxidant enzymes and normalization of CYP2E1 enzyme.

Oxidative stress induced by cadmium in the plasma, erythrocytes and lymphocytes of rats: Attenuation by grape seed proanthocyanidins.

PubMed

Nazima, B; Manoharan, V; Miltonprabu, S

2016-04-01

The present study has been designed to investigate the ameliorative effect of grape seed proanthocyanidins (GSP) on cadmium (Cd)-induced oxidative damage in rat erythrocytes. Twenty four male Wistar rats were divided into four groups: control, GSP-treated group (100 mg kg(-1) body weight (BW)), Cd-treated group (cadmium chloride, 5 mg kg(-1) BW), and GSP + Cd-treated group in which GSP was orally pre-administered 90 min before Cd intoxication for 4 weeks. At the end of the experimental period, blood samples were collected by cardiac puncture and were processed for various biochemical estimations. The extent of oxidative damage in isolated rat erythrocyte membrane was assessed by measuring lipid peroxidation, enzymatic and non-enzymatic content, calcium ion (Ca(2+))/magnesium ion (Mg(2+))-ATPase and sodium ion (Na(+))/potassium ion (K(+))-ATPase activities, free iron, calcium, hydrogen peroxide (H2O2) concentration, and osmotic fragility. Our results unveiled that Cd intoxication significantly increased the erythrocyte lipid peroxidation markers and decreased the activity of enzymatic and non-enzymatic markers in erythrocytes. Conversely, GSP pretreatment significantly prevented the decrease in the activities of antioxidant enzymes and membrane-bound ATPases. GSP also restored the levels of iron, calcium, and H2O2 in Cd-treated rats. Conformational changes in erythrocytes of various groups were also determined using morphological and ultrastructural electron microscopic analysis. The findings of our study clearly revealed that GSP affords superior protection against Cd-induced reactive oxygen species generation, lipid peroxidation, and free radical generation in Cd-treated rats, which presumably reflects the ability of this flavonoid to protect erythrocytes and lymphocytes of rats from the toxic effects of Cd. © The Author(s) 2015.

Electroencephalographic patterns of lithium poisoning: a study of the effect/concentration relationships in the rat.

PubMed

Hanak, Anne-Sophie; Malissin, Isabelle; Poupon, Joël; Risède, Patricia; Chevillard, Lucie; Mégarbane, Bruno

2017-03-01

Lithium overdose may result in encephalopathy and electroencephalographic abnormalities. Three poisoning patterns have been identified based on the ingested dose, previous treatment duration and renal function. Whether the severity of lithium-induced encephalopathy depends on the poisoning pattern has not been established. We designed a rat study to investigate lithium-induced encephalopathy and correlate its severity to plasma, erythrocyte, cerebrospinal fluid and brain lithium concentrations previously determined in rat models mimicking human poisoning patterns. Lithium-induced encephalopathy was assessed and scored using continuous electroencephalography. We demonstrated that lithium overdose was consistently responsible for encephalopathy, the severity of which depended on the poisoning pattern. Acutely poisoned rats developed rapid-onset encephalopathy which reached a maximal grade of 2/5 at 6 h and disappeared at 24 h post-injection. Acute-on-chronically poisoned rats developed persistent and slightly fluctuating encephalopathy which reached a maximal grade of 3/5. Chronically poisoned rats developed rapid-onset but gradually increasing life-threatening encephalopathy which reached a maximal grade of 4/5. None of the acutely, 20% of the acute-on-chronically and 57% of the chronically lithium-poisoned rats developed seizures. The relationships between encephalopathy severity and lithium concentrations fitted a sigmoidal E max model based on cerebrospinal fluid concentrations in acute poisoning and brain concentrations in acute-on-chronic poisoning. In chronic poisoning, worsening of encephalopathy paralleled the increase in plasma lithium concentrations. The severity of lithium-induced encephalopathy is dependent on the poisoning pattern, which was previously shown to determine lithium accumulation in the brain. Our data support the proposition that electroencephalography is a sensitive tool for scoring lithium-related neurotoxicity. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Restoration of a healthy intestinal microbiota normalizes portal hypertension in a rat model of nonalcoholic steatohepatitis.

PubMed

García-Lezana, Teresa; Raurell, Imma; Bravo, Miren; Torres-Arauz, Manuel; Salcedo, María Teresa; Santiago, Alba; Schoenenberger, Andreu; Manichanh, Chaysavanh; Genescà, Joan; Martell, María; Augustin, Salvador

2018-04-01

Portal hypertension (PH) drives most of the clinical complications in chronic liver diseases. However, its progression in nonalcoholic steatohepatitis (NASH) and its association with the intestinal microbiota (IM) have been scarcely studied. Our aim was to investigate the role of the IM in the mechanisms leading to PH in early NASH. The experimental design was divided in two stages. In stage 1, Sprague-Dawley rats were fed for 8 weeks a high-fat, high-glucose/fructose diet (HFGFD) or a control diet/water (CD). Representative rats were selected as IM donors for stage 2. In stage 2, additional HFGFD and CD rats underwent intestinal decontamination, followed by IM transplantation with feces from opposite-diet donors (heterologous transplant) or autologous fecal transplant (as controls), generating four groups: CD-autotransplanted, CD-transplanted, HFGFD-autotransplanted, HFGFD-transplanted. After IM transplantation, the original diet was maintained for 12-14 days until death. HFGFD rats developed obesity, insulin resistance, NASH without fibrosis but with PH, intrahepatic endothelial dysfunction, and IM dysbiosis. In HFGFD rats, transplantation with feces from CD donors caused a significant reduction of PH to levels comparable to CD without significant changes in NASH histology. The reduction in PH was due to a 31% decrease of intrahepatic vascular resistance compared to the HFGFD-autotransplanted group (P < 0.05). This effect occurs through restoration of the sensitivity to insulin of the hepatic protein kinase B-dependent endothelial nitric oxide synthase signaling pathway. The IM exerts a direct influence in the development of PH in rats with diet-induced NASH and dysbiosis; PH, insulin resistance, and endothelial dysfunction revert when a healthy IM is restored. (Hepatology 2018;67:1485-1498). © 2017 by the American Association for the Study of Liver Diseases.

On the association between nandrolone-mediated testosterone reduction during alcohol intoxication and attenuated voluntary alcohol intake in rats.

PubMed

Etelälahti, T J; Eriksson, C J P

2013-11-01

Human studies have indicated that the use of anabolic androgenic steroids may be associated with the abuse of alcohol and other drugs. Also, experimental animal research has indicated that chronic nandrolone administration subsequently increases voluntary alcohol drinking. The aim of our study was to test our hypothesis that alcohol-induced testosterone elevation, especially associated with stress conditions derived by nandrolone treatment, could be the underlying factor in causing increased alcohol drinking. Male alcohol-preferring AA and low drinking Wistar rats were randomly divided into control and nandrolone decanoate treated (15 mg/kg for 14 days) groups. Basal serum testosterone and corticosterone were determined before the first nandrolone treatment, after 7 days of treatment, and after an additional (7-day) washout period, during which also the acute effect of alcohol (1.5 g/kg) on steroid hormones was determined. Hereafter followed a (5-week) voluntary alcohol consumption period, during the last 2 weeks of which the rats were treated again with nandrolone. Both normal and reversed dark- vs. light-cycle experimental designs were used. Contrary to our hypothesis, nandrolone treatment decreased voluntary alcohol consumption in both AA and Wistar rats. Also, instead of stress causation, elevated basal testosterone and lowered basal corticosterone levels were observed after nandrolone treatment in both AA rats and Wistars. During acute alcohol intoxication the frequency of testosterone decreases was higher in the nandrolone-treated groups compared with control AA and Wistar rats. Present data support the hypothesis that nandrolone-treatment mediated attenuation of alcohol intake in both AA and Wistar rats may be the result of negative reinforcement caused by alcohol-mediated testosterone reduction. © 2013.

Estradiol and Progesterone Modulate Spontaneous Sleep Patterns and Recovery from Sleep Deprivation in Ovariectomized Rats

PubMed Central

Deurveilher, Samüel; Rusak, Benjamin; Semba, Kazue

2009-01-01

Study Objectives: Women undergo hormonal changes both naturally during their lives and as a result of sex hormone treatments. The objective of this study was to gain more knowledge about how these hormones affect sleep and responses to sleep loss. Design: Rats were ovariectomized and implanted subcutaneously with Silastic capsules containing oil vehicle, 17β-estradiol and/or progesterone. After 2 weeks, sleep/wake states were recorded during a 24-h baseline period, 6 h of total sleep deprivation induced by gentle handling during the light phase, and an 18-h recovery period. Measurements and Results: At baseline and particularly in the dark phase, ovariectomized rats treated with estradiol or estradiol plus progesterone spent more time awake at the expense of non-rapid eye movement sleep (NREMS) and/or REMS, whereas those given progesterone alone spent less time in REMS than ovariectomized rats receiving no hormones. Following sleep deprivation, all rats showed rebound increases in NREMS and REMS, but the relative increase in REMS was larger in females receiving hormones, especially high estradiol. In contrast, the normal increase in NREMS EEG delta power (an index of NREMS intensity) during recovery was attenuated by all hormone treatments. Conclusions: Estradiol promotes arousal in the active phase in sleep-satiated rats, but after sleep loss, both estradiol and progesterone selectively facilitate REMS rebound while reducing NREMS intensity. These results indicate that effects of ovarian hormones on recovery sleep differ from those on spontaneous sleep. The hormonal modulation of recovery sleep architecture may affect recovery of sleep related functions after sleep loss. Citation: Deurveilher S; Rusak B; Semba K. Estradiol and progesterone modulate spontaneous sleep patterns and recovery from sleep deprivation in ovariectomized rats. SLEEP 2009;32(7):865-877. PMID:19639749

Impulsive choice behavior in four strains of rats: Evaluation of possible models of Attention Deficit/Hyperactivity Disorder

PubMed Central

Garcia, Ana; Kirkpatrick, Kimberly

2012-01-01

Several studies have examined impulsive choice behavior in spontaneously hypertensive rats (SHRs) as a possible pre-clinical model for Attention-Deficit/Hyperactivity Disorder (ADHD). However, this strain was not specifically selected for the traits of ADHD and as a result their appropriateness as a model has been questioned. The present study investigated whether SHRs would exhibit impulsive behavior in comparison to their control strain, Wistar Kyoto (WKY) rats. In addition, we evaluated a strain that has previously shown high levels of impulsive choice, the Lewis (LEW) rats and compared them with their source strain, Wistar (WIS) rats. In the first phase, rats could choose between a Smaller-sooner (SS) reward of 1 pellet after 10 s and a Larger-later (LL) reward of 2 pellets after 30 s. Subsequently, the rats were exposed to increases in LL reward magnitude and SS delay. These manipulations were designed to assess sensitivity to magnitude and delay within the choice task to parse out possible differences in using the strains as models of specific deficits associated with ADHD. The SHR and WKY strains did not differ in their choice behavior under either delay or magnitude manipulations. In comparison to WIS, LEW showed deficits in choice behavior in the delay manipulation, and to a lesser extent in the magnitude manipulation. An examination of individual differences indicated that the SHR strain may not be sufficiently homogeneous in their impulsive choice behavior to be considered as a viable model for impulse control disorders such as ADHD. The LEW strain may be worthy of further consideration for their suitability as an animal model. PMID:23085479

Anticancer benefits of early versus late use of rapamycin in a rat model of urothelial carcinoma.

PubMed

Chang, C-H; Fu, Y-C; Li, J-R; Shu, K-H; Ho, H-C; Shiu, Y-N; Wu, M-J

2014-05-01

We previously reported both in vivo and in vitro effects of rapamycin on urothelial carcinoma. Clinically, the use of rapamycin could not completely prevent the recurrence of urothelial carcinoma. Therefore, we designed this study to compare the difference of efficacy between early and late use of rapamycin in a rat model of urothelial carcinoma. The rat model of urothelial carcinoma was induced by adding 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) to the drinking water for up to 20 weeks in male Fisher-344 rats. Rapamycin was fed orally from the 1st day, 5th week, 9th week, 13th week, and 17th week. The antitumor effects of different periods of rapamycin treatment were assessed grossly and microscopically. Papillary tumors of urinary bladder were successfully induced in the BBN group. Simultaneous use of rapamycin and BBN from the 1st day of treatment significantly reduced the tumor growth in urinary bladder: 80% of the rats had no tumor and 20% had low-grade tumors. Adding rapamycin from the 5th week was associated with more tumor growth: 20% of the rats had no tumors, 20% had low-grade tumors, and 60% had high-grade tumors. Moreover, in the groups with rapamycin treatment from the 9th week, 13th week, and 17th week, all rats developed high-grade papillary tumors in urinary bladder, as did the control group that received no rapamycin. The study results suggest that the anticancer effect of rapamycin on urothelial carcinoma is stage dependent. Early use of rapamycin provides better anticancer effect, whereas late use of rapamycin fails to inhibit the cancer growth. Copyright © 2014 Elsevier Inc. All rights reserved.

New designer drug p-methoxymethamphetamine: studies on its metabolism and toxicological detection in urine using gas chromatography-mass spectrometry.

PubMed

Staack, Roland F; Fehn, Josef; Maurer, Hans H

2003-06-05

Studies are described on the metabolism and the toxicological analysis of the new designer drug rac-p-methoxymethamphetamine (PMMA) in rat urine using gas chromatography-mass spectrometry (GC-MS). The identified metabolites indicated that PMMA was extensively metabolized mainly by O-demethylation to pholedrine and to a minor extent to p-methoxyamphetamine (PMA), 1-hydroxypholedrine diastereomers (one being oxilofrine), 4'-hydroxy-3'-methoxymethamphetamine and 4'-hydroxy-3'-methoxyamphetamine. The authors' systematic toxicological analysis (STA) procedure using full-scan GC-MS after acid hydrolysis, liquid-liquid extraction and microwave-assisted acetylation allowed the detection of the main metabolites of PMMA in rat urine after a dose corresponding to that of drug users. Therefore, this procedure should be suitable for detection of PMMA intake in human urine via its metabolites. However, it must be considered that pholedrine and oxilofrine are also in therapeutic use. Differentiation of PMMA, PMA and/or pholedrine intake is discussed.

Dendritic branching angles of pyramidal cells across layers of the juvenile rat somatosensory cortex.

PubMed

Leguey, Ignacio; Bielza, Concha; Larrañaga, Pedro; Kastanauskaite, Asta; Rojo, Concepción; Benavides-Piccione, Ruth; DeFelipe, Javier

2016-09-01

The characterization of the structural design of cortical microcircuits is essential for understanding how they contribute to function in both health and disease. Since pyramidal neurons represent the most abundant neuronal type and their dendritic spines constitute the major postsynaptic elements of cortical excitatory synapses, our understanding of the synaptic organization of the neocortex largely depends on the available knowledge regarding the structure of pyramidal cells. Previous studies have identified several apparently common rules in dendritic geometry. We study the dendritic branching angles of pyramidal cells across layers to further shed light on the principles that determine the geometric shapes of these cells. We find that the dendritic branching angles of pyramidal cells from layers II-VI of the juvenile rat somatosensory cortex suggest common design principles, despite the particular morphological and functional features that are characteristic of pyramidal cells in each cortical layer. J. Comp. Neurol. 524:2567-2576, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Attenuation of cadmium-induced decline in spatial, habituation and recognition memory by long-term administration of almond and walnut supplementation: Role of cholinergic function.

PubMed

Batool, Zehra; Agha, Faiza; Ahmad, Saara; Liaquat, Laraib; Tabassum, Saiqa; Khaliq, Saima; Anis, Lubna; Sajid, Irfan; Emad, Shaista; Perveen, Tahira; Haider, Saida

2017-01-01

Excessive exposure of cadmium which is regarded as a neurotoxin can stimulate aging process by inducing abnormality in neuronal function. It has been reported that supplementation of almond and walnut attenuate age-related memory loss. Present study was designed to investigate the weekly administration of cadmium for one month on learning and memory function with relation to cholinergic activity. Cadmium was administered at the dose of 50 mg/kg/week. Whereas, almond and walnut was supplemented at the dose of 400 mg/kg/day along with cadmium administration to separate set of rats. At the end of experiment, memory function was assessed by Morris water maze, open field test and novel object recognition test. Results of the present study showed that cadmium administration significantly reduced memory retention. Reduced acetylcholine levels and elevated acetyl cholinesterase activity were also observed in frontal cortex and hippocampus of cadmium treated rats. Malondialdehyde levels were also significantly increased following the administration of cadmium. Daily supplementation of almond and walnut for 28 days significantly attenuated cadmium-induced memory impairment in rats. Results of the present study are discussed in term of cholinergic activity in cadmium-induced memory loss and its attenuation by nuts supplementation in rats.

Agmatine improves renal function in gentamicin-induced nephrotoxicity in rats.

PubMed

El-Kashef, Dalia H; El-Kenawi, Asmaa E; Abdel Rahim, Mona; Suddek, Ghada M; Salem, Hatem A

2016-03-01

The present study was designed to explore the possible protective effects of agmatine, a known nitric oxide (NO) synthase inhibitor, against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of agmatine on gentamicin-induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was evaluated. Twenty-four male Wistar albino rats were randomly divided into 3 groups, namely control, gentamicin (100 mg/kg, i.p.), and gentamicin plus agmatine (40 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood and urine samples and kidneys were taken. Administration of agmatine significantly decreased kidney/body mass ratio, serum creatinine, lactate dehydrogenase (LDH), renal malondialdehyde (MDA), myeloperoxidase (MPO), NO, and tumor necrosis factor-alpha (TNF-α) while it significantly increased creatinine clearance and renal superoxide dismutase (SOD) activity when compared with the gentamicin-treated group. Additionally, agmatine ameliorated tissue morphology as evidenced by histological evaluation and reduced the responses of isolated bladder rings to ACh. Our study indicates that agmatine administration with gentamicin attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation, restoring NO level and inhibiting inflammatory mediators such as TNF-α.

Environmental and Risk Factors of Leptospirosis: A Spatial Analysis in Semarang City

NASA Astrophysics Data System (ADS)

Nur Fajriyah, Silviana; Udiyono, Ari; Saraswati, Lintang Dian

2017-02-01

Leptospirosis is zoonotic potentially epidemic with clinical manifestations from mild to severe and can cause death. The incidence of leptospirosis in Indonesia tends to increase by the year. The case fatality rate in Semarang was greater than the national’s (9.38%). The purpose of this study was to describe the environmental risk factors of leptospirosis in Semarang spatially. The study design was descriptive observational with cross sectional approach. The population and samples in this study were confirmed leptospirosis in Semarang from January 2014 until May 2015, 88 respondents in 61 villages of 15 sub-districts in Semarang. The variables were environmental conditions, the presence of rats, wastewater disposal, waste disposal facilities, the presence of pets, the presence of rivers, flood’s profile, tidal inundation profile, vegetation, contact with rats, and Protected Personal Equipment/PPE utilization. Based on the spatial analysis, variables that found in the big half area of Semarang are environmental conditions, the presence of rats, wastewater disposal, waste disposal facilities, contact with rats, and PPE utilization. The presence of pets at risk, the presence of rivers, flood’s profile, inundation profile, and vegetation were found only in small half of Semarang area. People are expected to maintain their personal and environmental hygiene to prevent the transmission.

Discovery of a fluorinated 4-oxo-quinoline derivative as a potential positron emission tomography radiotracer for imaging cannabinoid receptor type 2.

PubMed

Slavik, Roger; Müller Herde, Adrienne; Haider, Ahmed; Krämer, Stefanie D; Weber, Markus; Schibli, Roger; Ametamey, Simon M; Mu, Linjing

2016-09-01

The cannabinoid receptor type 2 (CB2) is part of the endocannabinoid system and has gained growing attention in recent years because of its important role in neuroinflammatory/neurodegenerative diseases. Recently, we reported on a carbon-11 labeled 4-oxo-quinoline derivative, designated RS-016, as a promising radiotracer for imaging CB2 using PET. In this study, three novel fluorinated analogs of RS-016 were designed, synthesized, and pharmacologically evaluated. The results of our efforts led to the identification of N-(1-adamantyl)-1-(2-(2-fluoroethoxy)ethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxamide (RS-126) as the most potent candidate for evaluation as a CB2 PET ligand. [(18) F]RS-126 was obtained in ≥ 99% radiochemical purity with an average specific radioactivity of 98 GBq/μmol at the end of the radiosynthesis. [(18) F]RS-126 showed a logD7.4 value of 1.99 and is stable in vitro in rat and human plasma over 120 min, whereas 55% intact parent compound was found in vivo in rat blood plasma at 10 min post injection. In vitro autoradiographic studies with CB2-positive rat spleen tissue revealed high and blockable binding which was confirmed in in vivo displacement experiments with rats by dynamic PET imaging. Ex vivo biodistribution studies confirmed accumulation of [(18) F]RS-126 in rat spleen with a specificity of 79% under blocking conditions. The moderate elevated CB2 levels in LPS-treated mice brain did not permit the detection of CB2 by [(18) F]RS-126 using PET imaging. In summary, [(18) F]RS-126 demonstrated high specificity toward CB2 receptor in vitro and in vivo and is a promising radioligand for imaging CB2 receptor expression. Cannabinoid receptor type 2 (CB2) is an interesting target for PET imaging. Specific binding of [(18) F]RS-126 in CB2-positive spleen tissue (white arrow head) was confirmed in in vivo displacement experiments with rats. Time activity curve of [(18) F]RS-126 in the spleen after the addition of GW405833 (CB2 specific ligand, green) demonstrates faster radiotracer elimination (blue) compared to the tracer only (red). © 2016 International Society for Neurochemistry.

Protective Effect of Thalidomide on Liver Injury in Rats with Acute Pancreatitis via Inhibition of Oxidative Stress.

PubMed

Lv, Peng; Fan, Li-Juan; Li, Hong-Yun; Meng, Qing-Shun; Liu, Jie

2015-01-01

This study was designed to investigate the preventive effect of thalidomide on acute pancreatitis-associated liver injury in the rat and analyze its relationship with oxidative stress. The acute pancreatitis of rats was induced by the retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. Thalidomide (100 mg/kg) was given daily via the intragastric route for 8 days before this injection. The levels of oxidative stress parameters including superoxide dismutase (SOD), glutathione peroxidase (GSHpx), and malondialdehyde (MDA) in the liver were detected by biochemical assay. Nuclear factor-κB p65 (NF-κBp65), tumor necrosis factor α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) protein and mRNA levels in the liver were detected using western blots and reverse transcriptase polymerase chain reaction, respectively. Compared with the untreated model group, liver histopathology, SOD, GSHpx, MDA levels, NF-κBp65, TNF-α, ICAM-1 protein, and mRNA levels in the liver of rats given thalidomide were improved significantly. Results demonstrate that thalidomide may exert its effects on oxidative stress to attenuate the progression of acute pancreatitis-associated liver injury in rats. © 2015 by the Association of Clinical Scientists, Inc.

Comparison of cardiovascular protective effects of tropical seaweeds, Kappaphycus alvarezii, Caulerpa lentillifera, and Sargassum polycystum, on high-cholesterol/high-fat diet in rats.

PubMed

Matanjun, Patricia; Mohamed, Suhaila; Muhammad, Kharidah; Mustapha, Noordin Mohamed

2010-08-01

This study was designed to investigate the comparative in vivo cardiovascular protective effects of red, green, and brown tropical seaweeds, namely, Kappaphycus alvarezii (or Eucheuma cottonii), Caulerpa lentillifera, and Sargassum polycystum, in rats fed on high-cholesterol/high-fat (HCF) diets. Male Sprague-Dawley rats (weighing 260-300 g) on the HCF diet had significantly increased body weight, plasma total cholesterol (TC), plasma low-density lipoprotein cholesterol (LDL-C), plasma triglycerides (TG), lipid peroxidation, and erythrocyte glutathione peroxidase (GSH-Px) and superoxide dismutase levels after 16 weeks. Supplementing 5% seaweeds to HCF diet significantly reduced plasma TC (-11.4% to -18.5%), LDL-C (-22% to -49.3%), and TG (-33.7% to -36.1%) levels and significantly increased HDL-C levels (16.3-55%). Among the seaweeds, S. polycystum showed the best anti-obesity and blood GSH-Px properties, K. alvarezii showed the best antihyperlipemic and in vivo antioxidation effects, and C. lentillifera was most effective at reducing plasma TC. All seaweeds significantly reduced body weight gain, erythrocyte GSH-Px, and plasma lipid peroxidation of HCF diet rats towards the values of normal rats.

Adrenal hormones in rats before and after stress-experience: effects of ipsapirone.

PubMed

Korte, S M; Bouws, G A; Bohus, B

1992-06-01

The present study was designed to investigate the effects of the anxiolytic 5-HT1A receptor agonist ipsapirone on the hormonal responses in rats under nonstress and stress conditions by means of repeated blood sampling through an intracardiac catheter. Ipsapirone was given in doses of 2.5, 5, 10, and 20 mg/kg (IP) under nonstress conditions in the home cages of the rats. Plasma corticosterone levels increased in a dose-dependent way in the dose range of 5 to 20 mg/kg, whereas the plasma catecholamines were only significantly increased with the highest dose of the drug. The effect of ipsapirone in control and in stressed rats was studied with the selected dose of 5 mg/kg. Conditioned fear of inescapable electric footshock (0.6 mA, AC for 3 s) given one day earlier was used as stressor. Surprisingly, ipsapirone potentiated the magnitude of the neuroendocrine responses. Rats receiving an inescapable footshock 1 day earlier showed a further elevated corticosterone response to the 5-HT1A receptor agonist ipsapirone even before exposing them to the conditioned stress situation. The present findings suggest that if an animal has no possibilities to escape or avoid a noxious event, functional hypersensitivity will develop in the serotonergic neuronal system, which is reflected in the increased responsiveness of the HPA axis to a 5-HT1A agonist challenge.

Edaravone protects rats against oxidative stress and apoptosis in experimentally induced myocardial infarction: Biochemical and ultrastructural evidence.

PubMed

Hassan, Md Quamrul; Akhtar, Md Sayeed; Akhtar, M; Ali, Javed; Haque, Syed Ehtaishamul; Najmi, Abul Kalam

2015-01-01

The present study was designed to evaluate the cardioprotective potential of edaravone on oxidative stress, anti-apoptotic, anti-inflammatory and ultrastructure findings in isoproterenol (ISO) induced myocardial infarction (MI) in rats. Rats were pretreated with edaravone (1, 3, 10 mg/kg body weight-1 day-1) intraperitoneally. MI was induced by subcutaneous administration of ISO (85 mg/kg body weight-1) at two doses with 24h interval. ISO treated rats showed significant increase in the levels of thiobarbituric acid reactive substances (TBARS) and decreased levels of reduced glutathione, glutathione perdoxidase, glutathione reductase and glutathione-S- transferase in the cardiac tissues. Moreover, significant increase in the levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), C--reactive protein and caspase-3 activity was observed in ISO treated group. Pretreatment of ISO intoxicated rats with edaravone showed significant decrease in the level of TBARS, increased activities of antioxidant enzymes and significantly decreased levels of LDH and CK-MB. Moreover, results also showed decreased C-reactive protein level, caspase-3 activity and maintained ultrastructure of the myocardial cells. Our study suggests that edaravone possess strong cardioprotective potential. Edaravone may have exhibited cardioprotective effects by restoring antioxidant defense mechanism, maintaining integrity of myocardial cell membrane, reducing apoptosis and inflammation against ISO induced MI and associated oxidative stress.

Inhalation of water electrolysis-derived hydrogen ameliorates cerebral ischemia-reperfusion injury in rats - A possible new hydrogen resource for clinical use.

PubMed

Cui, Jin; Chen, Xiao; Zhai, Xiao; Shi, Dongchen; Zhang, Rongjia; Zhi, Xin; Li, Xiaoqun; Gu, Zhengrong; Cao, Liehu; Weng, Weizong; Zhang, Jun; Wang, Liping; Sun, Xuejun; Ji, Fang; Hou, Jiong; Su, Jiacan

2016-10-29

Hydrogen is a kind of noble gas with the character to selectively neutralize reactive oxygen species. Former researches proved that low-concentration of hydrogen can be used to ameliorating cerebral ischemia/reperfusion injury. Hydrogen electrolyzed from water has a hydrogen concentration of 66.7%, which is much higher than that used in previous studies. And water electrolysis is a potential new hydrogen resource for regular clinical use. This study was designed and carried out for the determination of safety and neuroprotective effects of water electrolysis-derived hydrogen. Sprague-Dawley rats were used as experimental animals, and middle cerebral artery occlusion was used to make cerebral ischemia/reperfusion model. Pathologically, tissues from rats in hydrogen inhalation group showed no significant difference compared with the control group in HE staining pictures. The blood biochemical findings matched the HE staining result. TTC, Nissl, and TUNEL staining showed the significant improvement of infarction volume, neuron morphology, and neuron apoptosis in rat with hydrogen treatment. Biochemically, hydrogen inhalation decreased brain caspase-3, 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine-positive cells and inflammation factors concentration. Water electrolysis-derived hydrogen inhalation had neuroprotective effects on cerebral ischemia/reperfusion injury in rats with the effect of suppressing oxidative stress and inflammation, and it is a possible new hydrogen resource to electrolyze water at the bedside clinically. Copyright © 2016. Published by Elsevier Ltd.

The effect of phloretin on synaptic proteins and adult hippocampal neurogenesis in Aβ (1-42)-injected male Wistar rats.

PubMed

Ghumatkar, Priya; Peshattiwar, Vaibhavi; Patil, Sachin; Muke, Suraj; Whitfield, David; Howlett, David; Francis, Paul; Sathaye, Sadhana

2018-04-23

Considering the deleterious effect of Aβ1-42, a study was designed to evaluate the effect of phloretin on altered synaptic proteins and adult hippocampal neurogenesis in Aβ1-42-injected Wistar rats. The rats were pretreated with 5 mg/kg p.o dose of phloretin and donepezil (positive control) for 28 days, followed by intrahippocampal injections of aggregated Aβ1-42. After termination, perfused brains were isolated and subjected to Western blot and immunohistochemistry (IHC) analysis. The Western blot revealed that Aβ1-42-injected rats had significantly low levels of synaptophysin as compared to sham control. Phloretin pretreatment significantly protected the presynaptic protein synaptophysin against the effects of Aβ1-42. There were no significant changes in the levels of PSD95 between different groups. The IHC findings showed that Aβ1-42 significantly reduced the Ki67 and DCX in the dentate gyrus as compared to sham control. However, phloretin significantly improved the number of Ki67- and DCX-positive neurons in the dentate gyrus region as compared to Aβ1-42 group. This study demonstrated the protective effect of phloretin on synaptophysin and adult neuronal proliferating cells in Aβ1-42-injected rats. The encouraging findings highlight the potential of phloretin as a dietary supplement targeting key therapeutic mechanisms in neurodegenerative disorders such as AD. © 2018 Royal Pharmaceutical Society.

Preconditioning of intravenous parecoxib attenuates focal cerebral ischemia/reperfusion injury in rats.

PubMed

Wang, Na; Guo, Qu-lian; Ye, Zhi; Xia, Ping-ping; Wang, E; Yuan, Ya-jing

2011-07-05

Several studies suggest that cyclooxygenase-2 (COX-2) contributes to the delayed progression of ischemic brain damage. This study was designed to investigate whether COX-2 inhibition with parecoxib reduces focal cerebral ischemia/reperfusion injury in rats. Ninety male Sprague-Dawley rats were randomly assigned to three groups: the sham group, ischemia/reperfusion (I/R) group and parecoxib group. The parecoxib group received 4 mg/kg of parecoxib intravenously via the vena dorsalis penis 15 minutes before ischemia and again at 12 hours after ischemia. The neurological deficit scores (NDSs) were evaluated at 24 and 72 hours after reperfusion. The rats then were euthanized. Brains were removed and processed for hematoxylin and eosin staining, Nissl staining, and measurements of high mobility group Box 1 protein (HMGB1) and tumor necrosis factor-α (TNF-α) levels. Infarct volume was assessed with 2,3,5-triphenyltetrazolium chloride (TTC) staining. The rats in the I/R group had lower NDSs (P < 0.05), larger infarct volume (P < 0.05), lower HMGB1 levels (P < 0.05), and higher TNF-α levels (P < 0.05) compared with those in the sham group. Parecoxib administration significantly improved NDSs, reduced infarct volume, and decreased HMGB1 and TNF-α levels (P < 0.05). Pretreatment with intravenous parecoxib was neuroprotective. Its effects may be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory mediators.

Isoquercetin ameliorates hyperglycemia and regulates key enzymes of glucose metabolism via insulin signaling pathway in streptozotocin-induced diabetic rats.

PubMed

Jayachandran, Muthukumaran; Zhang, Tongze; Ganesan, Kumar; Xu, Baojun; Chung, Stephen Sum Man

2018-06-15

Among the foremost common flavonoids within the human diet, quercetin glycosides possess neuroprotective, cardioprotective, anti-oxidative, chemopreventive, and anti-allergic properties. Isoquercetin is one such promising candidate with anti-diabetic potential. However, complete studies of its molecular action on insulin signaling pathway and carbohydrate metabolizing enzymes remain unclear. Hence, we have designed this study to accumulate the experimental evidence in support of anti-diabetic effects of isoquercetin. Male albino Wistar rats were divided into seven groups. Rats (Groups 3-7) were administered a single intraperitoneal injection of streptozotocin (STZ; 40 mg/kg b.w) to induce diabetes mellitus. As an extension, STZ rats received isoquercetin at three different doses (20, 40 and 80 mg/kg b.w), and Group 7 rats received glibenclamide (standard drug) (600 μg/kg b.w). The results showed that STZ exaggerated blood sugar, decreased insulin, altered metabolizing enzymes, and impaired the mRNA expression of insulin signaling genes and carbohydrate metabolizing enzyme genes. Supplementation with isoquercetin significantly normalized blood sugar levels, insulin and regulated the mRNA expression of insulin signaling genes and carbohydrate metabolizing enzyme genes. The results achieved with isoquercetin are similar to that of standard drug glibenclamide. The findings suggest isoquercetin could be a possible therapeutic agent for treating diabetes mellitus in the near future. Copyright © 2018 Elsevier B.V. All rights reserved.

Beneficial Effect of Ocimum sanctum (Linn) against Monocrotaline-Induced Pulmonary Hypertension in Rats.

PubMed

Meghwani, Himanshu; Prabhakar, Pankaj; Mohammed, Soheb A; Dua, Pamila; Seth, Sandeep; Hote, Milind P; Banerjee, Sanjay K; Arava, Sudheer; Ray, Ruma; Maulik, Subir Kumar

2018-04-17

The study was designed to explore any beneficial effect of Ocimum sanctum (Linn) (OS) in experimental pulmonary hypertension (PH) in rats. OS is commonly known as “holy basil” and “Tulsi” and is used in the Indian System of Medicine as antidiabetic, antioxidant, hepatoprotective, adaptogenic, and cardioprotective. Monocrotaline (MCT) administration caused development of PH in rats after 28 days and rats were observed for 42 days. Treatments (sildenafil; 175 µg/kg, OS; 200 mg/kg) were started from day 29 after the development of PH and continued for 14 days. Parameters to assess the disease development and effectiveness of interventions were echocardiography, right and left ventricular systolic pressures, and right ventricular end diastolic pressure, percentage medial wall thickness (%MWT) of pulmonary artery, oxidative stress markers in lung tissue, NADPH oxidase (Nox-1) protein expression in lung, and mRNA expression of Bcl2 and Bax in right ventricular tissue. OS (200 mg/kg) treatment ameliorated increased lung weight to body weight ratio, right ventricular hypertrophy, increased RVSP, and RVoTD/AoD ratio. Moreover, OS treatment decreases Nox-1 expression and increases expression of Bcl2/Bax ratio caused by MCT. The present study demonstrates that OS has therapeutic ability against MCT-induced PH in rat which are attributed to its antioxidant effect. The effect of OS was comparable with sildenafil.

Protective Effects of a Rhodiola Crenulata Extract and Salidroside on Hippocampal Neurogenesis against Streptozotocin-Induced Neural Injury in the Rat

PubMed Central

Qu, Ze-qiang; Zhou, Yan; Zeng, Yuan-shan; Lin, Yu-kun; Li, Yan; Zhong, Zhi-qiang; Chan, Wood Yee

2012-01-01

Previously we have demonstrated that a Rhodiola crenulata extract (RCE), containing a potent antioxidant salidroside, promotes neurogenesis in the hippocampus of depressive rats. The current study was designed to further investigate the protective effect of the RCE on neurogenesis in a rat model of Alzheimer's disease (AD) induced by an intracerebroventricular injection of streptozotocin (STZ), and to determine whether this neuroprotective effect is induced by the antioxidative activity of salidroside. Our results showed that pretreatment with the RCE significantly improved the impaired neurogenesis and simultaneously reduced the oxidative stress in the hippocampus of AD rats. In vitro studies revealed that (1) exposure of neural stem cells (NSCs) from the hippocampus to STZ strikingly increased intracellular reactive oxygen species (ROS) levels, induced cell death and perturbed cell proliferation and differentiation, (2) hydrogen peroxide induced similar cellular activities as STZ, (3) pre-incubation of STZ-treated NSCs with catalase, an antioxidant, suppressed all these cellular activities induced by STZ, and (4) likewise, pre-incubation of STZ-treated NSCs with salidroside, also an antioxidant, suppressed all these activities as catalase: reduction of ROS levels and NSC death with simultaneous increases in proliferation and differentiation. Our findings indicated that the RCE improved the impaired hippocampal neurogenesis in the rat model of AD through protecting NSCs by its main ingredient salidroside which scavenged intracellular ROS. PMID:22235318

Vibrational bone characteristics versus bone density for the assessment of osteoporosis in ovariectomized rats.

PubMed

Anastassopoulos, G; Panteliou, S; Christopoulou, G; Stavropoulou, A; Panagiotopoulos, E; Lyritis, G; Khaldi, Lubna; Varakis, J; Karamanos, N

2010-01-01

Our previous research findings suggested this integrated study in order to monitor changes of bone properties and assess bone integrity using vibrational characteristics in osteoporosis. The method is based on measurement of the bone dynamic characteristic modal damping factor (MDF). The experimental animal model is ovariectomized rat followed by alendronate treatment. According to the experimental design, adult female Wistar rats are ovariectomized and 60 days later, with confirmed osteoporosis, the population is divided into two groups. One is administered alendronate and the second is given no treatment. Furthermore, established techniques such as pQCT and histomorphometry are applied at all time points, in order to compare and correlate to MDF. The results indicate induction of osteoporosis due to ovariectomy and render MDF capable of monitoring changes in bone material properties and architecture, with high sensitivity and repeatability.

[Effects of space-flight factors on cytochemical characteristics of the motor analyzer neurons].

PubMed

Gorbunova, A V

2010-01-01

The work was designed to study metabolism of motoneurons in anterior horns of the spinal cord and sensorimotor cortex of Wistar rats after flights on Earth's satellites for 22.5 days (Kosmos-605), 19.5 days (Kosmos-782), and 18.5 days (Kosmos-936). Control rats underwent simulated space-flight factors under laboratory conditions excepting weightlessness. Rats placed in Kosmos-936 were subjected to artificial gravity (AG). They showed complete recovery of motoneuronal metabolism 25 days after landing unlike animals that had experienced weightlessness in which enhanced functional activity of the genetic apparatus was manifest as increased RNA level, protein content, and nuclei size. These finding may reflect differences of neuronal metabolism in animals experiencing weightlessness and AG. We believe they may be due to reduced static load on the locomotor system during the space flight.

Acute withdrawal but not long-term withdrawal from methamphetamine affects sexual behavior in female rats.

PubMed

Thibodeau, Rachel B; Ornelas, Laura C; Romero, Jordan; Memos, Nicoletta; Scheible, Matthew; Avila, Alfred; Schumacher, Abby; Navarro, April; Zimmermann, Karen; Cuenod, Bethany A; Frohardt, Russell J; Guarraci, Fay A

2013-02-01

The present study was designed to investigate the long-term effects of repeated methamphetamine (MA) exposure on sexual motivation in female rats tested after a period of drug abstinence. In Experiment 1, female subjects received three injections of MA (1.0mg/kg/day, every other day) or saline and were tested for paced mating behavior (where females could control the receipt of sexual stimulation from one male rat) 21 days after their last injection. In Experiment 2, female subjects received 12 consecutive injections of MA (1.0mg/kg/day) or saline and were tested for mate choice (where females could control the receipt of sexual stimulation from two male rats simultaneously) 6 days after their last injection. Experiment 3 was identical to Experiment 2 except that female subjects received no baseline mating test and were tested for mate choice 24h and 6 days after their last injection. Open field tests were conducted in each experiment to measure locomotor activity after repeated exposure to MA. Although repeated MA exposure increased locomotor activity, mating behavior was not facilitated after either a short (6 days) or long (21 days) period of drug abstinence. Nevertheless, sexual behavior was disrupted during the 24h acute withdrawal period. Therefore, although the present study found no evidence of cross-sensitization between female sexual behavior and MA after either a short or a long period of drug abstinence, sexual behavior in sexually naïve female rats is sensitive to the depressive state associated with acute withdrawal from MA. In conclusion, the results of the present study suggest that MA acts differently from other psychomotor stimulants, and that the effects of MA withdrawal on sexual behavior differ between male and female rats. Copyright © 2012 Elsevier Inc. All rights reserved.

Penile enhancement using a porcine small intestinal submucosa graft in a rat model.

PubMed

Leungwattanakij, S; Pummangura, N; Ratana-Olarn, K

2006-01-01

Several biodegradable materials have been experimented for penile enhancement, but none show the potential for clinical use. This study was designed to use porcine small intestinal submucosa (SIS) augmenting the normal tunica albuginea to increase the functional girth of the rat penis. In all, 20 adult male Sprague-Dawley rats constituted the study population. The animals were divided into two groups: group 1 consisted of the control (n=10) and group 2 (n=10) consisted of rats that underwent penile enhancement by a longitudinal I-shaped incision of the tunica albuginea on both sides, and the dissection of the plane between tunica albuginea and cavernosal tissue was carried out (n=10). The incision was then patched with a 3 x 10 mm2 piece of SIS, using a 6/0 nylon suture material. The penile length and mid-circumference were then measured using a Vernier Caliper before and 2 months after surgery. All rat penises underwent histological examination using Masson's trichome and Verhoff's van Giesen's stain for collagen and elastic fibers. The penile length, mid-circumference and degree of fibrosis score were expressed as mean+/-s.e. (standard error) and analyzed using a Wilcoxon rank-sum test. A statistical significance was accepted at P-value < or =0.05. Our results showed similar preoperative penile length and circumference in both groups. However, 2 months after the surgery, the mean penile circumference of the SIS group has grown significantly larger than the control group, while the mean penile length remained unchanged. The histological study of the rat penises revealed minimal amounts of fibrosis under the graft, and the elastic fibers of the graft showed orientation in a circular manner. In conclusion, SIS appears promising for material use in a penile enhancement.

Tannoid principles of Emblica officinalis renovate cognitive deficits and attenuate amyloid pathologies against aluminum chloride induced rat model of Alzheimer's disease.

PubMed

Justin Thenmozhi, Arokiasamy; Dhivyabharathi, Mathiyazahan; William Raja, Tharsius Raja; Manivasagam, Thamilarasan; Essa, Musthafa Mohamed

2016-07-01

Emblica officinalis is mentioned as a maharasayana in many Ayurvedic texts and promotes intelligence, memory, freedom from disease, longevity, and strength of the senses. The present study has been designed to explore the memory-enhancing effect of the tannoid principles of E. officinalis (EoT) at the biochemical, anatomical, behavioral, and molecular levels against aluminum chloride (AlCl3) induced Alzheimer's disease (AD) in rats. Aluminum is reported to have an important role in the etiology, pathogenesis, and development of AD. Male Wistar rats were divided into control, AlCl3 treated, AlCl3 and EoT (50, 100, and 200 mg/kg bw) co-treated, and EoT (200 mg/kg bw) alone treated groups. In control and experimental rats, behavior tests including water maze and open field test, estimation of aluminum, assay of acetylcholinesterase (AChE) activity, and expression of amyloidogenic proteins were performed. Intraperitonial injection of AlCl3 (100 mg/kg bw) for 60 days significantly elevated the concentration of aluminum (Al), activity of AChE and protein expressions of amyloid precursor protein, A-beta1-42, beta-, and gamma-secretases as compared to control group in hippocampus and cortex. Co-administration of EoT orally to AlCl3 rats for 60 days significantly revert back the Al concentration, AChE activity, and A-beta synthesis-related molecules in the studied brain regions. The spatial learning, memory, and locomotor impairments observed in AlCl3 treated rats were significantly attenuated by EoT. Therefore, EoT may be a promising therapy in ameliorating neurotoxicity of aluminum, however further studies are warranted to elucidate the exact mechanism of action of EoT.

The Influence of Chitosan Cross-linking on the Properties of Alginate Microparticles with Metformin Hydrochloride-In Vitro and In Vivo Evaluation.

PubMed

Szekalska, Marta; Sosnowska, Katarzyna; Zakrzeska, Agnieszka; Kasacka, Irena; Lewandowska, Alicja; Winnicka, Katarzyna

2017-01-22

Sodium alginate is a polymer with unique ability to gel with different cross-linking agents in result of ionic and electrostatic interactions. Chitosan cross-linked alginate provides improvement of swelling and mucoadhesive properties and might be used to design sustained release dosage forms. Therefore, the aim of this research was to develop and evaluate possibility of preparing chitosan cross-linked alginate microparticles containing metformin hydrochloride by the spray-drying method. In addition, influence of cross-linking agent on the properties of microparticles was evaluated. Formulation of microparticles prepared by the spray drying of 2% alginate solution cross-linked by 0.1% chitosan was characterized by good mucoadhesive properties, high drug loading and prolonged metformin hydrochloride release. It was shown that designed microparticles reduced rat glucose blood level, delayed absorption of metformin hydrochloride and provided stable plasma drug concentration. Additionally, histopathological studies of pancreas, liver and kidneys indicated that all prepared microparticles improved degenerative changes in organs of diabetic rats. Moreover, no toxicity effect and no changes in rats behavior after oral administration of chitosan cross-linked alginate microparticles were noted.

Effect of chronic usage of tramadol on motor cerebral cortex and testicular tissues of adult male albino rats and the effect of its withdrawal: histological, immunohistochemical and biochemical study.

PubMed

Ghoneim, Fatma M; Khalaf, Hanaa A; Elsamanoudy, Ayman Z; Helaly, Ahmed N

2014-01-01

This study was designed to demonstrate the histopathological and biochemical changes in rat cerebral cortex and testicles due to chronic usage of tramadol and the effect of withdrawal. Thirty adult male rats weighing 180-200 gm were classified into three groups; group I (control group) group II (10 rats received 50 mg/kg/day of tramadol intraperitoneally for 4 weeks) and group III (10 rats received the same dose as group II then kept 4 weeks later to study the effect of withdrawal). Histological and immunohistochemical examination of cerebral cortex and testicular specimens for Bax (apoptotic marker) were carried out. Testicular specimens were examined by electron microscopy. RT-PCR after RNA extraction from both specimens was done for the genes of some antioxidant enzymes .Also, malondialdehyde (MDA) was measured colourimetrically in tissues homogenizate. The results of this study demonstrated histological changes in testicular and brain tissues in group II compared to group I with increased apoptotic index proved by increased Bax expression. Moreover in this group increased MDA level with decreased gene expression of the antioxidant enzymes revealed oxidative stress. Group III showed signs of improvement but not returned completely normal. It could be concluded that administration of tramadol have histological abnormalities on both cerebral cortex and testicular tissues associated with oxidative stress in these organs. Also, there is increased apoptosis in both organs which regresses with withdrawal. These findings may provide a possible explanation for delayed fertility and psychological changes associated with tramadol abuse.

Assessment in rats of the reproductive toxicity of gasoline from a gasoline vapor recovery unit.

PubMed

McKee, R H; Trimmer, G W; Whitman, F T; Nessel, C S; Mackerer, C R; Hagemann, R; Priston, R A; Riley, A J; Cruzan, G; Simpson, B J; Urbanus, J H

2000-01-01

Gasoline (CAS 86290-81-5) is one of the world's largest volume commercial products. Although numerous toxicology studies have been conducted, the potential for reproductive toxicity has not been directly assessed. Accordingly, a two-generation reproductive toxicity study in rats was conducted to provide base data for hazard assessment and risk characterization. The test material, vapor recovery unit gasoline (68514-15-8), is the volatile fraction of formulated gasoline and the material with which humans are most likely to come in contact. The study was of standard design. Exposures were by inhalation at target concentrations of 5000, 10 000, and 20 000 mg/m(3). The highest exposure concentration was approximately 50% of the lower explosive limit and several orders of magnitude above anticipated exposure during refueling. There were no treatment-related clinical or systemic effects in the parental animals, and no microscopic changes other than hyaline droplet nephropathy in the kidneys of the male rats. None of the reproductive parameters were affected, and there were no deleterious effects on offspring survival and growth. The potential for endocrine modulation was also assessed by analysis of sperm count and quality as well as time to onset of developmental landmarks. No toxicologically important differences were found. Therefore, the NOAEL for reproductive toxicity in this study was > or =20 000 mg/m(3). The only systemic effects, in the kidneys of the male rats, were consistent with an alpha-2 u-globulin-mediated process. This is a male rat-specific effect and not relevant to human health risk assessment.

Oral treatment with Euterpe oleracea Mart. (açaí) extract improves cardiac dysfunction and exercise intolerance in rats subjected to myocardial infarction.

PubMed

Zapata-Sudo, Gisele; da Silva, Jaqueline S; Pereira, Sharlene L; Souza, Pergentino J C; de Moura, Roberto S; Sudo, Roberto Takashi

2014-07-08

This study was designed to evaluate the cardioprotective effects of Euterpe oleracea Mart., popularly known as "açaí", on rats subjected to myocardial infarction (MI). Hydroalcoholic extracts of açaí were obtained from a decoction of the seeds. Two male Wistar rat groups were delineated: 1) the sham-operated group (control, n = 6), with no surgical amendment, and 2) the MI group (n = 12), in which the anterior descendent coronary artery was occluded during surgery. MI group was divided into two subgroups, in which rats were either treated with hydroalcoholic extract of Euterpe oleracea seeds (100 mg/kg/day p.o.) or received no treatment. Treatment began on the day of surgery, and lasted 4 weeks. Subsequently, rats were subject to an exercise test protocol, hemodynamic evaluation, and histological analysis of the left ventricle. Groups were compared using one-way analysis of variance (ANOVA), followed by Dunnett's test. The total running distance of sham rats was 1339.0 ± 276.6 m, MI rats was 177.6 ± 15.8 m (P < 0.05), and MI-açaí rats was 969.9 ± 362.2 m. Systolic arterial pressure was significantly decreased in MI rats (86.88 ± 4.62 mmHg) compared to sham rats (115.30 ± 7.24 mmHg; P < 0.05). Açaí treatment prevented a reduction in systolic arterial pressure (130.00 ± 8.16 mmHg) compared to MI rats (P < 0.05). Left ventricular (LV) end-diastolic pressure was significantly augmented in MI rats (17.62 ± 1.21 mmHg) compared to sham rats (4.15 ± 1.60 mmHg; P < 0.05), but was 3.69 ± 2.69 mmHg in açaí-treated rats (P < 0.05 vs. MI). The LV relaxation rate (-dp/dt) was reduced in MI rats compared to the sham group, whereas açaí treatment prevented this reduction. Açaí treatment prevented cardiac hypertrophy and LV fibrosis in MI rats. Euterpe oleracea treatment of MI rats prevented the development of exercise intolerance, cardiac hypertrophy, fibrosis, and dysfunction.

Metabolic Disposition of Osimertinib in Rats, Dogs, and Humans: Insights into a Drug Designed to Bind Covalently to a Cysteine Residue of Epidermal Growth Factor Receptor.

PubMed

Dickinson, Paul A; Cantarini, Mireille V; Collier, Jo; Frewer, Paul; Martin, Scott; Pickup, Kathryn; Ballard, Peter

2016-08-01

Preclinical and clinical studies were conducted to determine the metabolism and pharmacokinetics of osimertinib and key metabolites AZ5104 and AZ7550. Osimertinib was designed to covalently bind to epidermal growth factor receptors, allowing it to achieve nanomolar cellular potency (Finlay et al., 2014). Covalent binding was observed in incubations of radiolabeled osimertinib with human and rat hepatocytes, human and rat plasma, and human serum albumin. Osimertinib, AZ5104, and AZ7550 were predominantly metabolized by CYP3A. Seven metabolites were detected in human hepatocytes, also observed in rat or dog hepatocytes at similar or higher levels. After oral administration of radiolabeled osimertinib to rats, drug-related material was widely distributed, with the highest radioactivity concentrations measured at 6 hours postdose in most tissues; radioactivity was detectable in 42% of tissues 60 days postdose. Concentrations of [(14)C]-radioactivity in blood were lower than in most tissues. After the administration of a single oral dose of 20 mg of radiolabeled osimertinib to healthy male volunteers, ∼19% of the dose was recovered by 3 days postdose. At 84 days postdose, mean total radioactivity recovery was 14.2% and 67.8% of the dose in urine and feces. The most abundant metabolite identified in feces was AZ5104 (∼6% of dose). Osimertinib accounted for ∼1% of total radioactivity in the plasma of non-small cell lung cancer patients after 22 days of 80-mg osimertinib once-daily treatment; the most abundant circulatory metabolites were AZ7550 and AZ5104 (<10% of total osimertinib-related material). Osimertinib is extensively distributed and metabolized in humans and is eliminated primarily via the fecal route. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Age-related declines in exploratory behavior and markers of hippocampal plasticity are attenuated by prenatal choline supplementation in rats

PubMed Central

Glenn, Melissa J.; Kirby, Elizabeth D.; Gibson, Erin M.; Wong-Goodrich, Sarah; Mellott, Tiffany J.; Blusztajn, Jan K.; Williams, Christina L.

2008-01-01

Supplemental choline in the maternal diet produces a lasting enhancement in memory in offspring that resists age-related decline and is accompanied by neuroanatomical, neurophysiological and neurochemical changes in the hippocampus. The present study was designed to examine: 1) if prenatal choline supplementation alters behaviors that contribute to risk or resilience in cognitive aging, and 2) whether, at old age (25 months), prenatally choline supplemented rats show evidence of preserved hippocampal plasticity. A longitudinal design was used to look at exploration of an open field, with and without objects, at 1 and 24 months of age in male and female rats whose mothers were fed a diet supplemented with choline (SUP; 5 mg/kg choline chloride) or not supplemented (CON; 1.1 mg/kg choline chloride) on embryonic days 12–17. Aging caused a significant decline in open field exploration that was more pronounced in males but interest in novel objects was maintained in both sexes. Prenatal choline supplementation attenuated, but did not prevent age-related decline in exploration in males and increased object exploration in young females. Following behavioral assessment, rats were euthanized to assess markers of hippocampal plasticity. Aged SUP males and females had more newly proliferated cells in the hippocampal dentate gyrus and protein levels of vascular-endothelial growth factor (VEGF) and neurotrophin-3 (NT-3) were significantly elevated in female SUP rats in comparison to all other groups. Taken together, these findings provide the first evidence that prenatal cholinesupplementation causes changes in exploratory behaviors over the lifespan and preserves some features of hippocampal plasticity that can be seen even at 2 years of age. PMID:18786518

Protective effect of the daming capsule on impaired baroreflexes in STZ-induced diabetic rats with hyperlipoidemia.

PubMed

Ai, Jing; Wang, Li-Hong; Zhang, Rong; Qiao, Guo-Fen; Wang, Ning; Sun, Li-Hua; Lu, Guan-Yi; Sun, Chao; Yang, Bao-Feng

2010-12-22

The Daming capsule (DMC) is a traditional Chinese medicine used to treat hyperlipoidemia. Both clinic trials and studies on animal models have demonstrated that DMC is beneficial against diabetic symptoms. Impairment of the baroreflex can cause life-threatening arrhythmias and sudden cardiac death in patients with diabetes mellitus (DM). This study was designed to elucidate the effects of DMC on baroreflexes in streptozocin (STZ)-induced diabetic rats with hyperlipoidemia. Wistar rats were randomly divided into three groups: untreated controls, rats pretreated STZ and high lipids (a diabetes model or DM rats), and DM rats treated with DMC. The baroreflex sensitivity was examined during intravenous injection of phenylephrine (PE) or sodium nitroprusside (SNP) and quantified by the change in heart rate over the change in mean arterial blood pressure (ΔHR/ΔMABP). Morphological remodeling of baroreceptors was analyzed by transmission electron microscopy (TEM). The mRNA levels and expression of GluR2 and a GABAA receptor subunit were measured by quantitative RT-PCR and Western blotting. Compared to untreated DM rats, DMC significantly elevated the ratio of ΔHR/ΔMABP by enhancing the compensatory reduction in HR (-ΔHR) in response to PE-induced hypertension (+ΔMABP) (P < 0.05). In the presence of SNP, DMC increased the ΔMABP (P < 0.05). In addition, DMC markedly shortened the duration of blood pressure changes elicited by PE or SNP in DM rats compared to the untreated DM group (P < 0.05). Electron microscopy revealed disrupted myelin sheaths, swollen ER, and lysed mitochondria in the nucleus ambiguous (NAm) DM rats. These signs of neuropathology were largely prevented by treatment with DMC for 30 days. Treatment with DMC elevated both mRNA and protein level of GluR2 in the NAm of DM rats, but had no effect on GABAA receptor expression. The Daming capsule partially reversed the parasympathetic baroreflex impairment observed in STZ-induced diabetic rats with hyperlipoidemia. Treatment with DMC also prevented the degeneration of neurons and myelinated axons in the brain stem NAm and reversed the down-regulation of GluR2 mRNA. Rescue of NAm function may contribute to the medicinal properties of DMC in diabetic rats.

Centrally administered urocortin 2 decreases gorging on high-fat diet in in both diet induced obesity-prone and -resistant rats

PubMed Central

Cottone, Pietro; Sabino, Valentina; Nagy, Tim R.; Coscina, Donald V.; Levin, Barry E.; Zorrilla, Eric P.

2013-01-01

Objective Obesity is a costly, deadly public health problem for which new treatments are needed. Individual differences in meal pattern have been proposed to play a role in obesity risk. The present study tested the hypothesis that i) the microstructure of chronic high-fat diet intake differs between genetically selected Diet-Induced Obesity (DIO) and Diet Resistant (DR) rats, and ii) central administration of urocortin 2 (Ucn 2), a corticotropin-releasing factor type 2 (CRF2) agonist, decreases high-fat diet intake not only in lean DR rats, but also in obese DIO rats. Design Male, selectively bred DIO and DR rats (n=10/genotype) were chronically fed a high-fat diet. Food and water intake as well as ingestion microstructure were then compared under baseline conditions and following third intracerebroventricular injection of Ucn 2 (0, 0.1, 0.3, 1, 3 µg). Results Irrespective of genotype, Ucn 2 reduced nocturnal food intake with a minimum effective dose of 0.3 µg, suppressing high-fat diet intake by ~40% at the 3 µg dose. Ucn 2 also made rats of both genotypes eat smaller and briefer meals, including at doses that did not reduce drinking. Obese DIO rats ate fewer but larger meals than DR rats, which they ate more quickly and consumed with 2/3rd less water. Conclusions Unlike leptin and insulin, Ucn 2 retains its full central anorectic efficacy to reduce high-fat diet intake even in obese, genetically-prone DIO rats, which otherwise show a “gorging” meal pattern. These results open new opportunities of investigation towards treating some forms of diet-induced obesity. PMID:23478425

Postural control during quiet bipedal standing in rats

PubMed Central

Sato, Yota; Fujiki, Soichiro; Sato, Yamato; Aoi, Shinya; Tsuchiya, Kazuo; Yanagihara, Dai

2017-01-01

The control of bipedal posture in humans is subject to non-ideal conditions such as delayed sensation and heartbeat noise. However, the controller achieves a high level of functionality by utilizing body dynamics dexterously. In order to elucidate the neural mechanism responsible for postural control, the present study made use of an experimental setup involving rats because they have more accessible neural structures. The experimental design requires rats to stand bipedally in order to obtain a water reward placed in a water supplier above them. Their motions can be measured in detail using a motion capture system and a force plate. Rats have the ability to stand bipedally for long durations (over 200 s), allowing for the construction of an experimental environment in which the steady standing motion of rats could be measured. The characteristics of the measured motion were evaluated based on aspects of the rats’ intersegmental coordination and power spectrum density (PSD). These characteristics were compared with those of the human bipedal posture. The intersegmental coordination of the standing rats included two components that were similar to that of standing humans: center of mass and trunk motion. The rats’ PSD showed a peak at approximately 1.8 Hz and the pattern of the PSD under the peak frequency was similar to that of the human PSD. However, the frequencies were five times higher in rats than in humans. Based on the analysis of the rats’ bipedal standing motion, there were some common characteristics between rat and human standing motions. Thus, using standing rats is expected to be a powerful tool to reveal the neural basis of postural control. PMID:29244818

Behavioral predictors of alcohol drinking in a neurodevelopmental rat model of schizophrenia and co-occurring alcohol use disorder.

PubMed

Khokhar, Jibran Y; Todd, Travis P

2018-04-01

Alcohol use disorder commonly occurs in patients with schizophrenia and contributes greatly to its morbidity. Unfortunately, the neural and behavioral underpinnings of alcohol drinking in these patients are not well understood. In order to begin to understand the cognitive and reward-related changes that may contribute to alcohol drinking, this study was designed to address: 1) latent inhibition; 2) conditioning; and 3) extinction of autoshaping in a neurodevelopmental rat model with relevance to co-occurring schizophrenia and alcohol use disorders, the neonatal ventral hippocampal lesioned (NVHL) rat. NVHL lesions (or sham surgeries) were performed on post-natal day 7 (PND7) and animals were given brief exposure to alcohol during adolescent (PND 28-42). Latent inhibition of autoshaping, conditioning and extinction were assessed between PND 72-90. On PND90 animals were given alcohol again and allowed to establish stable drinking. Latent inhibition of autoshaping was found to be prolonged in the NVHL rats; the NVHL rats pre-exposed to the lever stimulus were slower to acquire autoshaping than sham pre-exposed rats. NVHL rats that were not pre-exposed to the lever stimulus did not differ during conditioning, but were slower to extinguish conditioned responding compared to sham controls. Finally, the NVHL rats from both groups drank significantly more alcohol than sham rats, and the extent of latent inhibition predicted future alcohol intake in the pre-exposed animals. These findings suggest that the latent inhibition of autoshaping procedure can be used to model cognitive- and reward-related dysfunctions in schizophrenia, and these dysfunctions may contribute to the development of co-occurring alcohol use. Copyright © 2017 Elsevier B.V. All rights reserved.

The effects of pyridostigmine bromide and permethrin, alone or in combination, on response acquisition in male and female rats.

PubMed

Van Haaren, F; Cody, B; Hoy, J B; Karlix, J L; Schmidt, C J; Tebbett, I R; Wielbo, D

2000-08-01

It has been hypothesized that concurrent exposure to pyridostigmine bromide and permethrin may have contributed to the development of neurocognitive symptoms in Gulf War veterans. The present experiment was designed to investigate the effects of pyridostigmine bromide and permethrin alone, or in combination, on the acquisition of a novel response, one measure of normal cognitive functioning. Male and female Sprague-Dawley rats were treated with pyridostigmine bromide (1.5 mg/kg/day, by gavage in a volume of 5 ml/kg) or its vehicle for 7 consecutive days. They then also received an intraperitoneal injection of permethrin (0, 15, or 60 mg/kg) before they were exposed to an experimental session during which they could earn food by pressing a lever in an operant chamber. Serum permethrin levels increased as a function of its dose, and were higher in rats treated with pyridostigmine bromide. Sex differences were observed as permethrin levels were higher in female rats than in male rats following the highest dose. Pyridostigmine bromide delayed response acquisition in male and female rats, and resulted in higher response rates on the inactive lever in female rats than in male rats. Although permethrin levels were higher in subjects treated with pyridostigmine bromide than in those treated with vehicle, there were no differences in the behavioral effects of permethrin. Whether or not these behavioral effects of pyridostigmine bromide are of central or peripheral origin will need to be determined in future studies, as its effects on motor activity and/or gastro-intestinal motility may have affected response acquisition.

Green tea, phytic acid, and inositol in combination reduced the incidence of azoxymethane-induced colon tumors in Fisher 344 male rats.

PubMed

Khatiwada, Janak; Verghese, Martha; Davis, Shurrita; Williams, Leonard L

2011-11-01

Experimental as well as epidemiologic studies in human populations provide evidence that consumption of phytochemicals reduces the incidence of degenerative diseases. Green tea (GT) catechins are known for their antioxidative potential. Phytic acid (PA) also acts as a natural antioxidant and may have numerous health benefits. This experiment was designed to investigate the inhibitory effects of combinations of 1% and 2% GT, PA, and inositol (I) in reducing the incidence of azoxymethane-induced colon tumors in Fisher 344 male rats. After an acclimatization period of 1 week, nine groups of rats (15 rats per group) were initially assigned to consume AIN 93 G diet and later AIN 93 M diet after 20 weeks of age. Treatments were given in drinking water. All rats received azoxymethane injections (16 mg/kg of body weight) subcutaneously at 7 and 8 weeks of age. Rats were killed at 45 weeks of age by CO(2) euthanasia. Tumor incidence (93.76%) and the number of tumors per tumor-bearing rat ratio (2.25) were significantly (P<.05) higher in the control group compared with treatment groups. Glutathione S-transferase activity was significantly (P<.05) higher in rats fed combinations of 2% GT+PA+I and GT+PA (33.25 ± 1.23 and 29.83 ± 1.10 μmol/mL, respectively) compared with other groups. These findings suggest that the synergistic effect of the 2% level of GT, PA, and I may reduce the incidence of colon tumors and therefore have potential as a chemopreventive agent.

Housing conditions affect rat responses to two types of ambiguity in a reward–reward discrimination cognitive bias task

PubMed Central

Parker, Richard M.A.; Paul, Elizabeth S.; Burman, Oliver H.P.; Browne, William J.; Mendl, Michael

2014-01-01

Decision-making under ambiguity in cognitive bias tasks is a promising new indicator of affective valence in animals. Rat studies support the hypothesis that animals in a negative affective state evaluate ambiguous cues negatively. Prior automated operant go/go judgement bias tasks have involved training rats that an auditory cue of one frequency predicts a Reward and a cue of a different frequency predicts a Punisher (RP task), and then measuring whether ambiguous cues of intermediate frequency are judged as predicting reward (‘optimism’) or punishment (‘pessimism’). We investigated whether an automated Reward–Reward (RR) task yielded similar results to, and was faster to train than, RP tasks. We also introduced a new ambiguity test (simultaneous presentation of the two training cues) alongside the standard single ambiguous cue test. Half of the rats experienced an unpredictable housing treatment (UHT) designed to induce a negative state. Control rats were relatively ‘pessimistic’, whilst UHT rats were quicker, but no less accurate, in their responses in the RR test, and showed less anxiety-like behaviour in independent tests. A possible reason for these findings is that rats adapted to and were stimulated by UHT, whilst control rats in a predictable environment were more sensitive to novelty and change. Responses in the new ambiguity test correlated positively with those in single ambiguous cue tests, and may provide a measure of attention bias. The RR task was quicker to train than previous automated RP tasks. Together, they could be used to disentangle how reward and punishment processes underpin affect-induced cognitive biases. PMID:25106739

Long-term feeding of red algae (Gelidium amansii) ameliorates glucose and lipid metabolism in a high fructose diet-impaired glucose tolerance rat model.

PubMed

Liu, Hshuan-Chen; Chang, Chun-Ju; Yang, Tsung-Han; Chiang, Meng-Tsan

2017-07-01

This study was designed to investigate the effect of Gelidium amansii (GA) on carbohydrate and lipid metabolism in rats with high fructose (HF) diet (57.1% w/w). Five-week-old male Sprague-Dawley rats were fed a HF diet to induce glucose intolerance and hyperlipidemia. The experiment was divided into three groups: (1) control diet group (Con); (2) HF diet group (HF); and (3) HF with GA diet group (HF + 5% GA). The rats were fed the experimental diets and drinking water ad libitum for 23 weeks. The results showed that GA significantly decreased retroperitoneal fat mass weight of HF diet-fed rats. Supplementation of GA caused a decrease in plasma glucose, insulin, tumor necrosis factor-α, and leptin. HF diet increased hepatic lipid content. However, intake of GA reduced the accumulation of hepatic lipids including total cholesterol (TC) and triglyceride contents. GA elevated the excretion of fecal lipids and bile acid in HF diet-fed rats. Furthermore, GA significantly decreased plasma TC, triglyceride, low density lipoprotein plus very low density lipoprotein cholesterol, and TC/high density lipoprotein cholesterol ratio in HF diet-fed rats. HF diet induced an in plasma glucose and an impaired glucose tolerance, but GA supplementation decreased homeostasis model assessment equation-insulin resistance and improved impairment of glucose tolerance. Taken together, these results indicate that supplementation of GA can improve the impairment of glucose and lipid metabolism in an HF diet-fed rat model. Copyright © 2016. Published by Elsevier B.V.

Renoprotective effect of aged garlic extract in streptozotocin-induced diabetic rats

PubMed Central

Shiju, T. M.; Rajesh, N. G.; Viswanathan, Pragasam

2013-01-01

Objective: Aged garlic extract (AGE) has been proven to exhibit antioxidant, hypolipidemic, hypoglycemic and antidiabetic properties. However, its effect on diabetic nephropathy was unexplored. Therefore, the present study was designed to investigate the renoprotective effect of AGE in streptozotocin-induced diabetic rats. Materials and Methods: Albino Wistar rats were induced with diabetes by a single intraperitoneal injection of 45 mg/kg b.w. of streptozotocin. Commercially available AGE was supplemented orally at a dose of 500 mg/kg body weight/day. Aminoguanidine, which has been proven to be an anti-glycation agent was used as positive control and was supplemented at a dose of 1 g/L in drinking water. The serum and urinary biochemical parameters were analyzed in all the groups and at the end of 12 weeks follow up, the renal histological examination were performed using H & E and PAS staining. Results: The diabetic rats showed a significant change in the urine (P < 0.001) and serum (P < 0.01) constituents such as albumin, creatinine, urea nitrogen and glycated hemoglobin. In addition, the serum lipid profile of the diabetic rats were altered significantly (P < 0.05) compared to that of the control rats. However, the diabetic rats supplemented with aged garlic extract restored all these biochemical changes. The efficacy of the extract was substantiated by the histopathological changes in the kidney. Conclusion: From our results, we conclude that aged garlic extract has the ability to ameliorate kidney damage in diabetic rats and the renoprotective effect of AGE may be attributed to its anti-glycation and hypolipidemic activities. PMID:23543654

Variation in the form of Pavlovian conditioned approach behavior among outbred male Sprague-Dawley rats from different vendors and colonies: sign-tracking vs. goal-tracking.

PubMed

Fitzpatrick, Christopher J; Gopalakrishnan, Shyam; Cogan, Elizabeth S; Yager, Lindsay M; Meyer, Paul J; Lovic, Vedran; Saunders, Benjamin T; Parker, Clarissa C; Gonzales, Natalia M; Aryee, Emmanuel; Flagel, Shelly B; Palmer, Abraham A; Robinson, Terry E; Morrow, Jonathan D

2013-01-01

Even when trained under exactly the same conditions outbred male Sprague-Dawley (SD) rats vary in the form of the Pavlovian conditioned approach response (CR) they acquire. The form of the CR (i.e. sign-tracking vs. goal-tracking) predicts to what degree individuals attribute incentive salience to cues associated with food or drugs. However, we have noticed variation in the incidence of these two phenotypes in rats obtained from different vendors. In this study, we quantified sign- and goal-tracking behavior in a reasonably large sample of SD rats obtained from two vendors (Harlan or Charles River), as well as from individual colonies operated by both vendors. Our sample of rats acquired from Harlan had, on average, more sign-trackers than goal-trackers, and vice versa for our sample of rats acquired from Charles River. Furthermore, there were significant differences among colonies of the same vendor. Although it is impossible to rule out environmental variables, SD rats at different vendors and barriers may have reduced phenotypic heterogeneity as a result of genetic variables, such as random genetic drift or population bottlenecks. Consistent with this hypothesis, we identified marked population structure among colonies from Harlan. Therefore, despite sharing the same name, investigators should be aware that important genetic and phenotypic differences exist among SD rats from different vendors or even from different colonies of the same vendor. If used judiciously this can be an asset to experimental design, but it can also be a pitfall for those unaware of the issue.

The effects of amphetamine exposure on outcome-selective Pavlovian-instrumental transfer in rats

PubMed Central

Shiflett, Michael W.

2012-01-01

Rationale Repeated exposure to psychostimulants alters behavioral responses to reward-related cues; however, the motivational underpinnings of this effect have not been fully characterized. Objectives The following study was designed to examine how amphetamine sensitization affects performance in rats on a series of Pavlovian and operant tasks that distinguish between general-incentive and outcome-selective forms of conditioned responses. Methods Adult male rats underwent Pavlovian and instrumental training for food pellet rewards. Following training, rats were sensitized to d-amphetamine (2 mg/kg for 7 days). Rats were subsequently tested on an outcome-selective Pavlovian-instrumental transfer (PIT) task, an outcome-reinstatement task, and an outcome devaluation task. Additionally, in a separate experiment PIT was assessed in amphetamine-sensitized and control rats using a Pavlovian backward-conditioned stimulus. Results Repeated amphetamine exposure sensitized locomotor activity to acute amphetamine challenge. Amphetamine altered responses to CS presentations by increasing conditioned approach. During tests of PIT amphetamine-treated rats showed no outcome-selectivity in their responding, responding to a CS whether or not it shared a common outcome with the instrumental response. No effect of amphetamine sensitization was observed on tests of outcome-selective reinstatement by outcome delivery, or action selection based on outcome value. Amphetamine-sensitized rats showed impaired outcome-selective PIT to a backward CS but were unaltered in conditioned approach. Conclusions Amphetamine sensitization prevents outcome-selective responding during PIT, which is dissociable from amphetamine’s effects on conditioned approach. These data suggest fundamental alterations in how stimuli motivate action in addiction. PMID:22562522

A novel nutritional supplement containing chromium picolinate, phosphatidylserine, docosahexaenoic acid, and boron activates the antioxidant pathway Nrf2/HO-1 and protects the brain against oxidative stress in high-fat-fed rats.

PubMed

Sahin, Nurhan; Akdemir, Fatih; Orhan, Cemal; Aslan, Abdullah; Agca, Can A; Gencoglu, Hasan; Ulas, Mustafa; Tuzcu, Mehmet; Viyaja, Juturu; Komorowskı, James R; Sahin, Kazim

2012-09-01

A novel nutritional supplement complex (N21 #125) composed of four well-known compounds (chromium picolinate, phosphatidylserine, docosahexaenoic acid, and boron) was designed to improve memory function and maintain brain health. The present study evaluated the complex's potential mechanism of action and its role in reducing oxidative stress in the brain of obese rats fed a high-fat diet (HFD). Male Wistar rats (n = 40, 8-week-old) were divided into four groups. Group I was fed a standard diet; Group II was fed a standard diet and supplemented with N21 } Group III was fed an HFD; and Group IV was fed an HFD and supplemented with N21 #125 for 12 weeks. Rats fed HFD had greater serum C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-α) and brain malondialdehyde (MDA) concentrations than rats fed the control diet. Supplementation of N21 #125 decreased CRP, TNF-α, and MDA concentration in rats fed HFD. The levels of brain nuclear factor-E2-related factor-2 (Nrf2), heme oxygenase, extracellular signal-regulated kinases and protein kinase B were lower in rats fed the control diet than for rats fed the HFD. These parameters were increased by supplementation of N21 #125. The data indicate that N21 #125 protected the brain from oxidative damage and inflammation induced by the HFD. This effect may be through up-regulation of the transcription factor Nrf2 expression.

Beneficial effect of zinc chloride and zinc ionophore pyrithione on attenuated cardioprotective potential of preconditioning phenomenon in STZ-induced diabetic rat heart.

PubMed

Jamwal, Sumit; Kumar, Kushal; Reddy, B V Krishna

2016-05-01

Ischemic preconditioning (IPC) is well demonstrated to produce cardioprotection by phosphorylation and subsequent inactivation of glycogen synthase kinase-3β (GSk-3β) in the normal rat heart, but its effect is attenuated in the diabetic rat heart. This study was designed to investigate the effect of zinc chloride and zinc ionophore pyrithione (ZIP) on the attenuated cardioprotective potential of IPC in the diabetic rat heart. Diabetes mellitus (DM) was induced by a single intraperitoneal administration of streptozotocin (STZ) (50 mg/kg; i.p). The isolated perfused rat heart was subjected to 30 minutes of ischemia followed by 120 minutes of reperfusion. Myocardial infarct size was estimated by triphenyltetrazolium chloride (TTC) staining and cardiac injury was measured by estimating lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) in the coronary effluent. Also, GSK-3β was measured and neutrophil accumulation was measured by estimating myeloperoxidase (MPO) levels. IPC significantly decreased the myocardial infarct size, the release of LDH and CK-MB, the GSK-3β levels and the MPO levels in the normal rat heart. Pre- and post-ischemic treatment with zinc chloride and zinc ionophore pyrithione (ZIP) in the normal and diabetic rat hearts significantly decreased the myocardial infarct size, the level of CK-MB and LDH in the coronary effluent and GSK-3β and MPO levels. Our results suggest that pharmacological preconditioning with zinc chloride and ZIP significantly restored the attenuated cardioprotective potential of IPC in the diabetic rat heart. © The Author(s) 2015.

Cellular Uptake and Localization of Polymyxins in Renal Tubular Cells Using Rationally Designed Fluorescent Probes.

PubMed

Yun, Bo; Azad, Mohammad A K; Nowell, Cameron J; Nation, Roger L; Thompson, Philip E; Roberts, Kade D; Velkov, Tony; Li, Jian

2015-12-01

Polymyxins are cyclic lipopeptide antibiotics that serve as a last line of defense against Gram-negative bacterial superbugs. However, the extensive accumulation of polymyxins in renal tubular cells can lead to nephrotoxicity, which is the major dose-limiting factor in clinical use. In order to gain further insights into the mechanism of polymyxin-induced nephrotoxicity, we have rationally designed novel fluorescent polymyxin probes to examine the localization of polymyxins in rat renal tubular (NRK-52E) cells. Our design strategy focused on incorporating a dansyl fluorophore at the hydrophobic centers of the polymyxin core structure. To this end, four novel regioselectively labeled monodansylated polymyxin B probes (MIPS-9541, MIPS-9542, MIPS-9543, and MIPS-9544) were designed, synthesized, and screened for their antimicrobial activities and apoptotic effects against rat kidney proximal tubular cells. On the basis of the assessment of antimicrobial activities, cellular uptake, and apoptotic effects on renal tubular cells, incorporation of a dansyl fluorophore at either position 6 or 7 (MIPS-9543 and MIPS-9544, respectively) of the polymyxin core structure appears to be an appropriate strategy for generating representative fluorescent polymyxin probes to be utilized in intracellular imaging and mechanistic studies. Furthermore, confocal imaging experiments utilizing these probes showed evidence of partial colocalization of the polymyxins with both the endoplasmic reticulum and mitochondria in rat renal tubular cells. Our results highlight the value of these new fluorescent polymyxin probes and provide further insights into the mechanism of polymyxin-induced nephrotoxicity. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Effects of prenatal stress on differentiation of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of the rat brain.

PubMed

Anderson, D K; Rhees, R W; Fleming, D E

1985-04-15

The present study was designed to determine the effects of prenatal malnutrition or environmental stress on the development of the sexually dimorphic nucleus of the preoptic area (SDN-POA). Pregnant rats were divided into a control group and two treatment groups (immobilization-illumination-heat or environmental stress, and nutritional stress). The two forms of stress were administered during the third trimester of gestation (days 14-20). Male and female offspring were sacrificed at birth, 20, and 60 days postnatally. The cross-sectional area of the SDN-POA was identified under light microscopy and was measured. The data confirm previous studies by showing a significant sex difference in the SDN-POA between control male and female rats. Prenatally stressed males sacrificed 20 and 60 days after birth showed SDN-POA areas 50% smaller than the nuclear areas of control males. The size of the SDN-POA of female offspring, however, was not significantly altered by prenatal treatments.

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...

Possible mechanism of protective effect of thalidomide in STZ-induced-neuropathic pain behavior in rats.

PubMed

Taliyan, Rajeev; Sharma, Pyare Lal

2012-04-01

Diabetes-induced neuropathic pain is recognized as one of the most difficult type of pain to treat and conventional analgesics are well known to be partially effective or associated with potential toxicity. Recently, it has been demonstrated that thalidomide, besides its teratogenic potential, reduced chronic pain in an SNL experimental pain model. The present study was designed to investigate the effect of thalidomide on streptozotocin (STZ)-induced neuropathic pain in rats. Streptozotocin (20 mg/kg, i.p, daily × 4 days) was administered to induce diabetes in the rats. Nociceptive latency was measured using tail-flick and paw-withdrawal test. Thermal hyperalgesia and mechanical allodynia were measured using planter test and dynamic aesthesiometer (Ugo-Basile, Italy), respectively. Urinary and serum nitrite concentration was estimated using Greiss reagent method. Spleen homogenate supernatant was prepared from spleen of 28th day diabetic rats and administered to normal rats (400 ul, i.v) daily for 28 days. Pain threshold progressively decreased in STZ-treated rats, as compared with control rats. 3 weeks after induction of diabetes, the rat exhibited thermal hyperalgesia and mechanical allodynia. The analgesic effect of morphine (8 mg/kg, s.c.) was significantly decreased in both diabetic and in SHS-treated non-diabetic rats. Administration of thalidomide (25 and 50 mg/kg, i.p), a TNF-α inhibitor, significantly prevented hyperglycemia-induced thermal hyperalgesia and mechanical allodynia and also attenuated the increase in serum and urinary nitrite concentration, as compared with untreated diabetic rats. Also, thalidomide (25 and 50 mg/kg, i.p) 1 h before or concurrently with morphine significantly restored the analgesic effect of morphine in diabetic rats. It may be concluded that thalidomide has a beneficial effect in neuropathic pain by decreasing cytokines (TNF-α) and nitric oxide level and may provide a novel promising therapeutic approach for managing painful diabetic neuropathy.

Repeated Sleep Restriction in Adolescent Rats Altered Sleep Patterns and Impaired Spatial Learning/Memory Ability

PubMed Central

Yang, Su-Rong; Sun, Hui; Huang, Zhi-Li; Yao, Ming-Hui; Qu, Wei-Min

2012-01-01

Study Objectives: To investigate possible differences in the effect of repeated sleep restriction (RSR) during adolescence and adulthood on sleep homeostasis and spatial learning and memory ability. Design: The authors examined electroencephalograms of rats as they were subjected to 4-h daily sleep deprivation that continued for 7 consecutive days and assessed the spatial learning and memory by Morris water maze test (WMT). Participants: Adolescent and adult rats. Measurements and Results: Adolescent rats exhibited a similar amount of rapid eye movement (REM) and nonrapid eye movement (NREM) sleep with higher slow wave activity (SWA, 0.5-4 Hz) and fewer episodes and conversions with prolonged durations, indicating they have better sleep quality than adult rats. After RSR, adult rats showed strong rebound of REM sleep by 31% on sleep deprivation day 1; this value was 37% on sleep deprivation day 7 in adolescents compared with 20-h baseline level. On sleep deprivation day 7, SWA in adult and adolescent rats increased by 47% and 33%, and such elevation lasted for 5 h and 7 h, respectively. Furthermore, the authors investigated the effects of 4-h daily sleep deprivation immediately after the water maze training sessions on spatial cognitive performance. Adolescent rats sleep-restricted for 7 days traveled a longer distance to find the hidden platform during the acquisition training and had fewer numbers of platform crossings in the probe trial than those in the control group, something that did not occur in the sleep-deprived adult rats. Conclusions: Repeated sleep restriction (RSR) altered sleep profiles and mildly impaired spatial learning and memory capability in adolescent rats. Citation: Yang SR; Sun H; Huang ZL; Yao MH; Qu WM. Repeated sleep restriction in adolescent rats altered sleep patterns and impaired spatial learning/memory ability. SLEEP 2012;35(6):849-859. PMID:22654204

Testing the efficacy of antimicrobial peptides in the topical treatment of induced osteomyelitis in rats.

PubMed

Melicherčík, Pavel; Čeřovský, Václav; Nešuta, Ondřej; Jahoda, David; Landor, Ivan; Ballay, Rastislav; Fulín, Petr

2018-01-01

Joint replacement infections and osteomyelitis are among the most serious complications in orthopaedics and traumatology. The risk factors for these infections are often bacterial resistance to antimicrobials. One of the few solutions available to control bacterial resistance involves antimicrobials, which have a different mechanism of action from traditional antibiotics. Antimicrobial peptides (AMP) appear to be highly promising candidates in the treatment of resistant infections. We have identified several AMP in the venom of various wild bees and designed analogues that show potent antimicrobial activity and low toxicity against eukaryotic cells. The aim of the present study was to test the efficacy of one of those synthetic peptide analogues for the treatment of acute osteomyelitis invoked in laboratory rats. Femoral cavities of 20 laboratory Wistar rats were infected with Staphylococcus aureus. After 1 week, eight rats received an injectable calcium phosphate carrier alone, another eight rats were treated with a calcium phosphate mixed with AMP, and four rats were left without any further treatment. After another week, all rats were euthanized and radiographs were made of both the operated and healthy limbs. The animals with the carrier alone exhibited more severe acute osteomyelitis on radiographs in comparison to the recipients of the calcium phosphate carrier loaded AMP and untreated infected individuals. Based on the results of the above mentioned experiment, it was concluded that when injected directly into the site of femoral acute osteomyelitis, the calcium phosphate carrier mixed with AMP reduced osteomyelitis signs visible on radiographs.

Haloperidol and Rimonabant Increase Delay Discounting in Rats Fed High-Fat and Standard-Chow Diets

PubMed Central

Boomhower, Steven R.; Rasmussen, Erin B.

2016-01-01

The dopamine and endocannabinoid neurotransmitter systems have been implicated in delay discounting, a measure of impulsive choice, and obesity. The current study was designed to determine the extent to which haloperidol and rimonabant affected delay discounting in rats fed standard-chow and high-fat diets. Sprague-Dawley rats were allowed to free-feed under a high-fat diet (4.73 kcal/g) or a standard-chow diet (3.0 kcal/g) for three months. Then, operant sessions began in which rats (n = 9 standard chow; n = 10 high-fat) chose between one sucrose pellet delivered immediately vs. three sucrose pellets after a series of delays. In another condition, carrot-flavored pellets replaced sucrose pellets. After behavior stabilized, acute injections of rimonabant (0.3-10 mg/kg) and haloperidol (0.003-0.1 mg/kg) were administered i.p. before some choice sessions in both pellet conditions. Haloperidol and rimonabant increased discounting in both groups of rats by decreasing percent choice for the larger reinforcer and area-under-the-curve (AUC) values. Rats in the high-fat diet condition demonstrated increased sensitivity to haloperidol compared to chow-fed controls: haloperidol increased discounting in both dietary groups in the sucrose condition,, but only in the high-fat-fed rats in the carrot-pellet condition. These findings indicate that blocking D2 and CB1 receptors results in increased delay discounting, and that a high-fat diet may alter sensitivity to dopaminergic compounds using the delay-discounting task. PMID:25000488

Behavioral and Neural Discrimination of Speech Sounds After Moderate or Intense Noise Exposure in Rats

PubMed Central

Reed, Amanda C.; Centanni, Tracy M.; Borland, Michael S.; Matney, Chanel J.; Engineer, Crystal T.; Kilgard, Michael P.

2015-01-01

Objectives Hearing loss is a commonly experienced disability in a variety of populations including veterans and the elderly and can often cause significant impairment in the ability to understand spoken language. In this study, we tested the hypothesis that neural and behavioral responses to speech will be differentially impaired in an animal model after two forms of hearing loss. Design Sixteen female Sprague–Dawley rats were exposed to one of two types of broadband noise which was either moderate or intense. In nine of these rats, auditory cortex recordings were taken 4 weeks after noise exposure (NE). The other seven were pretrained on a speech sound discrimination task prior to NE and were then tested on the same task after hearing loss. Results Following intense NE, rats had few neural responses to speech stimuli. These rats were able to detect speech sounds but were no longer able to discriminate between speech sounds. Following moderate NE, rats had reorganized cortical maps and altered neural responses to speech stimuli but were still able to accurately discriminate between similar speech sounds during behavioral testing. Conclusions These results suggest that rats are able to adjust to the neural changes after moderate NE and discriminate speech sounds, but they are not able to recover behavioral abilities after intense NE. Animal models could help clarify the adaptive and pathological neural changes that contribute to speech processing in hearing-impaired populations and could be used to test potential behavioral and pharmacological therapies. PMID:25072238

Attenuation of the cyproterone acetate-induced testicular hypofunction by a novel nutraceutical lycopene: a genomic approach.

PubMed

Tripathy, A; Ghosh, A; Dey, A; Pakhira, B P; Ghosh, D

2017-10-01

This study was designed to explore the cyproterone acetate (CPA)-induced andrological hypofunction and its correction by oral administration of lycopene. In this concern, spermatogenic, biochemical, histological and genomic profiles were studied. Cyproterone acetate administration for 1 month helped to develop infertile model rats. A significant recovery was noted in sperm motility, sperm count, sperm viability, hypo-osmotic swelling tail-coiled spermatozoa; activities of testicular ∆ 5 , 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD, catalase (CAT) and superoxide dismutase (SOD); and levels of conjugated diene (CD), malondialdehyde (MDA), testicular cholesterol and serum testosterone after the administration of lycopene at 1.5 mg/0.5 ml Tween-80/100 g body weight/day for last 1 month to infertile model rats. Simultaneously, qRT-PCR study of Bax, Bcl-2, caspase-3, ∆ 5 , 3β-HSD and 17β-HSD genes in testicular tissue showed a significant rectification towards the control in CPA-pre-treated cum CPA-lycopene-cotreated rats. Side-by-side histological and histometric studies showed a significant correction in qualitative analysis of spermatogenesis and seminiferous tubular diameter (STD) in CPA-pre-treated cum CPA-lycopene-cotreated rats. Lycopene showed outstanding efficacy in the management of CPA-induced testicular hypofunction with special reference to correction in oxidative stress-induced testicular apoptosis at genomic level. © 2016 Blackwell Verlag GmbH.

Sexual odor preference and dopamine release in the nucleus accumbens by estrous olfactory cues in sexually naïve and experienced male rats.

PubMed

Fujiwara, Masaya; Chiba, Atsuhiko

2018-03-01

Sexual behavior is a natural reward that activates mesolimbic dopaminergic system. Microdialysis studies have shown that extracellular level of dopamine (DA) in the nucleus accumbens (NAcc) significantly increases during copulation in male rats. The NAcc DA level is also known to be increased during the presentation of a sexually receptive female before mating. This rise in DA was probably associated with sexual motivation elicited by incentive stimuli from the receptive female. These microdialysis studies, however, did not thoroughly investigated if olfactory stimuli from estrous females could significantly increase the extracellular DA in the NAcc of male rats. The present study was designed to examine systematically the relationship between the expression of preference for the olfactory stimuli from estrous females and the effects of these stimuli on the extracellular DA levels in the NAcc measured by in vivo microdialysis in male Long-Evans (LE) rats. We used two types of olfactory stimuli, either airborne odors (volatile stimuli) or soiled bedding (volatile plus nonvolatile stimuli). The sexually experienced male rats, which experienced six ejaculations, significantly preferred both of these olfactory stimuli from estrous females as opposed to males. Exposure to these female olfactory stimuli gradually increased extracellular DA in the NAcc, which reached significantly higher level above baseline during the period following the removal of the stimuli although not during the 15-min stimulus presentation period. The sexually naïve male rats, on the other hand, showed neither preference for olfactory stimuli from estrous females nor increase in the NAcc DA after exposure to these stimuli. These data suggest that in male LE rats olfactory stimuli from estrous females in and of themselves can be conditional cues that induce both incentive motivation and a significant increase in the NAcc DA probably as a result of being associated with sexual reward through copulatory experience. Copyright © 2017. Published by Elsevier Inc.

N-acetylcysteine with apocynin prevents hyperoxaluria-induced mitochondrial protein perturbations in nephrolithiasis.

PubMed

Sharma, Minu; Sud, Amit; Kaur, Tanzeer; Tandon, Chanderdeep; Singla, S K

2016-09-01

Diminished mitochondrial activities were deemed to play an imperative role in surged oxidative damage perceived in hyperoxaluric renal tissue. Proteomics is particularly valuable to delineate the damaging effects of oxidative stress on mitochondrial proteins. The present study was designed to apply large-scale proteomics to describe systematically how mitochondrial proteins/pathways govern the renal damage and calcium oxalate crystal adhesion in hyperoxaluria. Furthermore, the potential beneficial effects of combinatorial therapy with N-acetylcysteine (NAC) and apocynin were studied to establish its credibility in the modulation of hyperoxaluria-induced alterations in mitochondrial proteins. In an experimental setup with male Wistar rats, five groups were designed for 9 d. At the end of the experiment, 24-h urine was collected and rats were euthanized. Urinary samples were analyzed for kidney injury marker and creatinine clearance. Transmission electron microscopy revealed distorted renal mitochondria in hyperoxaluria but combinatorial therapy restored the normal mitochondrial architecture. Mitochondria were isolated from renal tissue of experimental rats, and mitochondrial membrane potential was analyzed. The two-dimensional electrophoresis (2-DE) based comparative proteomic analysis was performed on proteins isolated from renal mitochondria. The results revealed eight differentially expressed mitochondrial proteins in hyperoxaluric rats, which were identified by Matrix-assisted laser desorption/ionization time of flight/time of flight (MALDI-TOF/TOF) analysis. Identified proteins including those involved in important mitochondrial processes, e.g. antioxidant defense, energy metabolism, and electron transport chain. Therapeutic administration of NAC with apocynin significantly expunged hyperoxaluria-induced discrepancy in the renal mitochondrial proteins, bringing them closer to the controls. The results provide insights to further understand the underlying mechanisms in the development of hyperoxaluria-induced nephrolithiasis and the therapeutic relevance of the combinatorial therapy.

Contraction of Abdominal Wall Muscles Influences Incisional Hernia Occurrence and Size

PubMed Central

Lien, Samuel C.; Hu, Yaxi; Wollstein, Adi; Franz, Michael G.; Patel, Shaun P.; Kuzon, William M.; Urbanchek, Melanie G.

2015-01-01

Background Incisional hernias are a complication in 10% of all open abdominal operations and can result in significant morbidity. The purpose of this study is to determine if inhibiting abdominal muscle contraction influences incisional hernia formation during laparotomy healing. We hypothesize that reducing abdominal musculature deformation reduces incisional hernia occurrence and size. Study Design Using an established rat model for incisional hernia, a laparotomy through the linea alba was closed with one mid-incision, fast-absorbing suture. Three groups were compared: a SHAM group (SHAM; n = 6) received no laparotomies while the Saline Hernia (SH; n = 6) and Botox Hernia (BH; n = 6) groups were treated once with equal volume saline or Botulinum Toxin (Botox®, Allergan) before the incomplete laparotomy closure. On post-operative day 14, the abdominal wall was examined for herniation and adhesions and contractile forces were measured for abdominal wall muscles. Results No hernias developed in SHAM rats. Rostral hernias developed in all SH and BH rats. Caudal hernias developed in all SH rats, but in only 50% of the BH rats. Rostral hernias in the BH group were 35% shorter and 43% narrower compared to those in the SH group (p < 0.05). The BH group had weaker abdominal muscles compared to the SHAM and SH groups (p < 0.05). Conclusions In our rat model, partial paralysis of abdominal muscles reduces the number and size of incisional hernias. These results confirm abdominal wall muscle contractions play a significant role in the pathophysiology of incisional hernia formation. PMID:25817097

Glutamine reduces myocardial cell apoptosis in a rat model of sepsis by promoting expression of heat shock protein 90.

PubMed

Li, Wanxia; Tao, Shaoyu; Wu, Qinghua; Wu, Tao; Tao, Ran; Fan, Jun

2017-12-01

Myocardial cell injury and cardiac myocyte apoptosis are associated with sepsis. Glutamine (Gln) has been reported to repair myocardial cell injury. The aim of this study was to explore the role of Gln on cardiac myocytes in a cecal ligation and puncture (CLP) model of sepsis in Wistar rats. Following induction of sepsis in a CLP rat model, viral encoding heat shock protein 90 (Hsp90) gene and Hsp90dsDNA were designed to express and knockdown Hsp90, respectively. Rat cardiac tissues were examined histologically, and apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein, Hsp90, p53 upregulated modulator of apoptosis, and p53 was measured by western blotting and real-time polymerase chain reaction. Caspase-3, caspase-8, and caspase-9 were detected by enzyme-linked immunosorbent assay. Rat cardiac myocyte damage induced by CLP was reduced by Gln treatment and Hsp90 overexpression, and these changes were reversed by Hsp90 knockdown. Bcl-2 expression, Bcl-2-associated X protein, p53, p53 upregulated modulator of apoptosis, caspase-8, caspase-9, and caspase-3 activities were significantly upregulated in the CLP model, which were reduced by Gln treatment and Hsp90 overexpression. Gln reduced apoptosis of cardiac myocytes in a rat model of sepsis, by promoting Hsp90 expression. Further studies are needed to determine the possible therapeutic action of Gln in sepsis in human tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

Helichrysum and Grapefruit Extracts Boost Weight Loss in Overweight Rats Reducing Inflammation.

PubMed

de la Garza, Ana Laura; Etxeberria, Usune; Haslberger, Alexander; Aumueller, Eva; Martínez, J Alfredo; Milagro, Fermín I

2015-08-01

Obesity is characterized by an increased production of inflammatory markers. High levels of circulating free fatty acids and chronic inflammation lead to increased oxidative stress, contributing to the development of insulin resistance (IR). Recent studies have focused on the potential use of flavonoids for obesity management due to their antioxidant and anti-inflammatory properties. This study was designed to investigate the antioxidant and anti-inflammatory effects of helichrysum and grapefruit extracts in overweight insulin-resistant rats. Thirty-eight male Wistar rats were randomly distributed in two groups: control group (n=8) and high-fat sucrose (HFS) group (n=30). After 22 days of ad libitum water and food access, the rats fed HFS diet changed to standard diet and were reassigned into three groups (n=10 each group): nonsupplemented, helichrysum extract (2 g/kg bw), and grapefruit extract (1 g/kg bw) administered for 5 weeks. Rats supplemented with both extracts gained less body weight during the 5-week period of treatment, showed lower serum insulin levels and liver TBARS levels. Leptin/adiponectin ratio, as an indicator of IR, was lower in both extract-administered groups. These results were accompanied by a reduction in TNFα gene expression in epididymal adipose tissue and intestinal mucosa, and TLR2 expression in intestinal mucosa. Helichrysum and grapefruit extracts might be used as complement hypocaloric diets in weight loss treatment. Both extracts helped to reduce weight gain, hyperinsulinemia, and IR, improved inflammation markers, and decreased the HFS diet-induced oxidative stress in insulin-resistant rats.

Translational Neuromodulation: Approximating Human Transcranial Magnetic Stimulation Protocols In Rats

PubMed Central

Vahabzadeh-Hagh, Andrew M.; Muller, Paul A.; Gersner, Roman; Zangen, Abraham; Rotenberg, Alexander

2015-01-01

Objective Transcranial magnetic stimulation (TMS) is a well-established clinical protocol with numerous potential therapeutic and diagnostic applications. Yet, much work remains in the elucidation of TMS mechanisms, optimization of protocols, and in development of novel therapeutic applications. As with many technologies, the key to these issues lies in the proper experimentation and translation of TMS methods to animal models, among which rat models have proven popular. A significant increase in the number of rat TMS publications has necessitated analysis of their relevance to human work. We therefore review the essential principles necessary for the approximation of human TMS protocols in rats as well as specific methods that addressed these issues in published studies. Materials and Methods We performed an English language literature search combined with our own experience and data. We address issues that we see as important in the translation of human TMS methods to rat models and provide a summary of key accomplishments in these areas. Results An extensive literature review illustrated the growth of rodent TMS studies in recent years. Current advances in the translation of single, paired-pulse, and repetitive stimulation paradigms to rodent models are presented. The importance of TMS in the generation of data for preclinical trials is also highlighted. Conclusions Rat TMS has several limitations when considering parallels between animal and human stimulation. However, it has proven to be a useful tool in the field of translational brain stimulation and will likely continue to aid in the design and implementation of stimulation protocols for therapeutic and diagnostic applications. PMID:22780329

Specific multi-nutrient enriched diet enhances hippocampal cholinergic transmission in aged rats.

PubMed

Cansev, Mehmet; van Wijk, Nick; Turkyilmaz, Mesut; Orhan, Fulya; Sijben, John W C; Broersen, Laus M

2015-01-01

Fortasyn Connect (FC) is a specific nutrient combination designed to target synaptic dysfunction in Alzheimer's disease by providing neuronal membrane precursors and other supportive nutrients. The aim of the present study was to investigate the effects of FC on hippocampal cholinergic neurotransmission in association with its effects on synaptic membrane formation in aged rats. Eighteen-month-old male Wistar rats were randomized to receive a control diet for 4 weeks or an FC-enriched diet for 4 or 6 weeks. At the end of the dietary treatments, acetylcholine (ACh) release was investigated by in vivo microdialysis in the right hippocampi. On completion of microdialysis studies, the rats were sacrificed, and the left hippocampi were obtained to determine the levels of choline, ACh, membrane phospholipids, synaptic proteins, and choline acetyltransferase. Our results revealed that supplementation with FC diet for 4 or 6 weeks, significantly enhanced basal and stimulated hippocampal ACh release and ACh tissue levels, along with levels of phospholipids. Feeding rats the FC diet for 6 weeks significantly increased the levels of choline acetyltransferase, the presynaptic marker Synapsin-1, and the postsynaptic marker PSD-95, but decreased levels of Nogo-A, a neurite outgrowth inhibitor. These data show that the FC diet enhances hippocampal cholinergic neurotransmission in aged rats and suggest that this effect is mediated by enhanced synaptic membrane formation. These data provide further insight into cellular and molecular mechanisms by which FC may support memory processes in Alzheimer's disease. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

High dose infusion of activated protein C (rhAPC) fails to improve neuronal damage and cognitive deficit after global cerebral ischemia in rats.

PubMed

Brückner, Melanie; Lasarzik, Irina; Jahn-Eimermacher, Antje; Peetz, Dirk; Werner, Christian; Engelhard, Kristin; Thal, Serge C

2013-09-13

Recent studies demonstrated anticoagulatory, antiinflammatory, antiapoptotic, and neuroprotective properties of activated protein C (APC) in rodent models of acute neurodegenerative diseases, suggesting APC as promising broad acting therapeutic agent. Unfortunately, continuous infusion of recombinant human APC (rhAPC) failed to improve brain damage following cardiac arrest in rats. The present study was designed to investigate the neuroprotective effect after global cerebral ischemia (GI) with an optimized infusion protocol. Rats were subjected to bilateral clip occlusion of the common carotid arteries (BCAO) and controlled hemorrhagic hypotension to 40 mm Hg for 14 min and a subsequent 5h-infusion of rhAPC (2mg/kg bolus+6 mg/kg/h continuous IV) or vehicle (0.9% NaCl). The dosage was calculated to maintain plasma hAPC activity at 150%. Cerebral inflammation, apoptosis and neuronal survival was determined at day 10. rhAPC infusion did not influence cortical cerebral perfusion during reperfusion and failed to reduce neuronal cell loss, microglia activation, and caspase 3 activity. Even an optimized rhAPC infusion protocol designed to maintain a high level of APC plasma activity failed to improve the sequels following GI. Despite positive reports about protective effects of APC following, e.g., ischemic stroke, the present study supports the notion that infusion of APC during the early reperfusion phase does not result in sustained neuroprotection and fails to improve outcome after global cerebral ischemia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Enhancement of the bioavailability of an antihypertensive drug by transdermal protransfersomal system: formulation and in vivo study.

PubMed

Morsi, Nadia M; Aboelwafa, Ahmed A; Dawoud, Marwa H S

2018-06-01

Timolol Maleate (TiM), a nonselective β-adrenergic blocker, is a potent highly effective agent for management of hypertension. The drug suffers from poor oral bioavailability (50%) due to its first pass effect and a short elimination half-life of 4 h; resulting in its frequent administration. Transdermal formulation may circumvent these problems in the form of protransfersomes. The aim of this study is to develop and optimize transdermal protransfersomal system of Timolol Maleate by film deposition on carrier method where protransfersomes were converted to transfersomes upon skin hydration following transdermal application under occlusive conditions. Two 2 3 full factorial designs were employed to investigate the influence of three formulation variables which were; phosphatidyl choline: surfactant molar ratio, carrier: mixture and the type of SAA each on particle size, drug entrapment efficiency and release rate. The optimized formulation was evaluated regarding permeation through hairless rat skin and compared with oral administration of aqueous solution on male Wistar rats. Optimized protransfersomal system had excellent permeation rate through shaved rat skin (780.69 μg/cm 2 /h) and showed six times increase in relative bioavailability with prolonged plasma profile up to 72 h. A potential protransfresomal transdermal system was successfully developed and factorial design was found to be a smart tool in its optimization.

[Effects of penetration enhancers on curcumin transdermal drug delivery].

PubMed

Gao, Zhen-Shen; Wang, Lan; Zhang, Mei

2012-01-01

To study the effects of penetration enhancers and their combinations on the curcumine transdermal drug delivery (CUR-TDDS). The penetration rate of curcumin through rat skin in vitro was measured using Valia-Chien diffusion cells, and orthogonal design method was set up for experimental design. The optimum penetration enhancers were: 3% hydroxypropyl beta cyclodextrins (HP-beta-CD), 9% borneol and 3% peppermint oil. The HP-beta-CD has the most potent enhancing effect.

NASA's Habitat Demonstration Unit (HDU) Pressurized Excursion Module (PEM) In-Field Demonstration at Desert RATS 2010

NASA Technical Reports Server (NTRS)

Tri, Terry O.; Kennedy, Kriss J.; Toups, Larry; Gill, Tracy R.; Howe, A. Scott

2011-01-01

This paper describes the construction, assembly, subsystem integration, transportation, and field testing operations associated with the Habitat Demonstration Unit (HDU) Pressurized Excursion Module (PEM) and discusses lessons learned. In a one-year period beginning summer 2009, a tightly scheduled design-develop-build process was utilized by a small NASA "tiger team" to produce the functional HDU-PEM prototype in time to participate in the 2010 Desert Research and Technology Studies (Desert RATS) field campaign. The process required the coordination of multiple teams, subcontractors, facility management and safety staff. It also required a well-choreographed material handling and transportation process to deliver the finished product from the NASA-Johnson Space Center facilities to the remote Arizona desert locations of the field test. Significant findings of this paper include the team s greater understanding of the HDU-PEM s many integration issues and the in-field training the team acquired which will enable the implementation of the next-generation of improvements and development of high-fidelity field operations in a harsh environment. The Desert RATS analog environment is being promoted by NASA as an efficient means to design, build, and integrate multiple technologies in a mission architecture context, with the eventual goal of evolving the technologies into robust flight hardware systems. The HDU-PEM in-field demonstration at Desert RATS 2010 provided a validation process for the integration team, which has already begun to retool for the 2011 field tests that require an adapted architecture.

A Target-Specific Oral Formulation of Doxorubicin-Protein Nanoparticles: Efficacy and Safety in Hepatocellular Cancer

PubMed Central

Golla, Kishore; Bhaskar, Cherukuvada; Ahmed, Farhan; Kondapi, Anand K.

2013-01-01

Background/Aims: Hepatocellular carcinoma (HCC) also known as malignant hepatoma is a most common liver cancer. Doxorubicin (Doxo) is an anti-cancer drug having activity against a wide spectrum of cancer types. Clinical Utility of doxo has been limited due to its poor bioavailability and toxicity to heart and spleen. Furthermore, cancer chemotherapeutics have limited oral absorption. Transferrin family proteins are highly abundant and plays important role in transport and storage of iron in cells and tissues. Since apotransferrin and lactoferrin receptors are highly expressed on the surface of metabolically active cancer cells, the principal objective of present study is to evaluate efficacy of doxorubicin loaded apotransferrin and lactoferrin nanoparticles (apodoxonano or lactodoxonano) in oral treatment of HCC in rats. Study Design: HCC was induced in rats by supplementing 100 mg/L of diethylnitrosamine (DENA) in drinking water for 8 weeks. A week after the last day of DENA administration, rats were divided into four groups, each group comprising of five animals. Each group was administered with one of the drug viz., saline, doxorubicin (doxo), apodoxonano and lactodoxonano (4 mg/ kg equivalent of drug). In each case, they received 8 doses of the drug orally with six day interval. One week after the last dose, anticancer activity was evaluated by counting the liver nodules, H & E analysis of tissue sections and expression levels of angiogenic and antitumor markers. Results: In rats treated with apodoxonano and lactodoxonano, the number of neoplastic nodules was significantly lower than that of rats administered with saline or with doxo. Apodoxonano and lactodoxonano did not exhibit decrease in mean body weight, which was markedly reduced by 22% in the case of doxo administered rats. In rats treated with nanoformulations, the number of liver nodules was found reduced by >93%. Both nanoformulations showed significantly high localization in liver compared to doxo. Conclusions: Apodoxonano and lactodoxonano showed improved efficacy, bioavailability and safety compared to doxo for treatment of HCC in rats when administered orally. PMID:24155776

Role of the median preoptic nucleus in the chronic hypotensive effect of losartan in sodium-replete normal rats.

PubMed

Ployngam, Trasida; Katz, Stephen S; Collister, John P

2010-01-01

1. We have shown previously that the chronic hypotensive effect of the angiotensin II AT1 receptor antagonist losartan is mediated, in part, by the subfornical organ (SFO). However, the neural pathway(s) mediating this central effect of losartan downstream from the SFO has not been completely elucidated. 2. The present study was designed to test the hypothesis that the median preoptic nucleus (MnPO) is a crucial part of the neural pathway necessary for the chronic hypotensive effect of losartan. To test this hypothesis, male Sprague-Dawley rats were subjected to either Sham or electrolytic lesion of the MnPO (MnPOx). Rats were instrumented with radiotelemetric transducers and aortic flow probes for the continuous measurement of mean arterial pressure (MAP) and heart rate and cardiac output (CO), respectively. Total peripheral resistance (TPR) was calculated as MAP/CO. After 3 days of baseline measurements, rats were infused intraperitoneally with losartan (10 mg/kg per day) via an osmotic minipump at a rate of 5 microL/min. 3. The data revealed that, by Day 9 of losartan treatment, MAP had decreased 34 +/- 2 mmHg in MnPOx rats (n = 9), whereas the MAP of Sham-lesioned rats (n = 8) had only decreased 24 +/- 3 mmHg. These findings were accompanied by a greater decrease in TPR in MnPOx compared with Sham rats (-0.464 vs-0.237 mmHg/mL per min, respectively), whereas CO remained unchanged throughout the study protocol. 4. These results do not support the hypothesis that an intact MnPO is necessary to mediate the full chronic hypotensive effect of losartan in normal rats. Instead, they appear to suggest that the MnPO may play an important role in buffering the profound hypotension induced by losartan.

Angiotensin converting enzyme (ACE) gene expression in experimentally induced liver cirrhosis in rats.

PubMed

Shahid, Syed Muhammad; Fatima, Syeda Nuzhat; Mahboob, Tabassum

2013-09-01

Angiotensin converting enzyme (ACE) is a key player of Renin Angiotensin System (RAS), involved in conversion of active product, angiotensin-II. Alterations in RAS have been implicated in the pathophysiology of various diseases involving heart, kidney, lung and liver. This study is designed to investigate the association of ACE gene expression in induction of liver cirrhosis in rats. Total 12 male albino Wistar rats were selected and divided in two groups. Control group received 0.9% NaCl, where as Test group received thioacidamide (TAA), dissolved in 0.9%NaCl, injected intraperitoneally at a dosage of 200mg/Kg of body weight, twice a week for 12 weeks. The rats were decapitated and blood sample was collected at the end of experimental period and used for liver functions, enzyme activity, antioxidant enzymes and lipid peroxidation estimations. Genomic DNA was isolated from excised tissue determine the ACE genotypes using specific primers. The ACE gene expression in liver tissue was assessed using the quantitative RT-PCR method. The activity of ALT, total and direct bilirubin, SOD and CAT levels were significantly high (p<0.05) and level of MDA was significantly low (p<0.05) in TAA treated rats as compared to control rats. The ACE gene expression after 12 weeks TAA treatment in cirrhotic rats was significantly increased (p<0.05) in comparison to controls. This study describes the importance of RAS in the development of hepatic fibrosis and the benefits of modulation of this system ACE gene expression. The finding of major up-regulation of ACE in the experimental rat liver provides further insight into the complexities of the RAS and its regulation in liver injury. The development of specific modulators of ACE activity and function, in future, will help determine the role of ACE and its genetic variants in the pathophysiology of liver disease.

Peroral Estradiol Is Sufficient to Induce Carcinogen-Induced Mammary Tumorigenesis in Ovariectomized Rats without Progesterone

PubMed Central

Stires, Hillary; Saboya, Mariana; Globerman, Samantha P.; Cohick, Wendie S.

2016-01-01

A role for estrogens in breast cancer is widely accepted, however, recent evidence highlights that timing and exposure levels are important in determining whether they elicit harmful versus beneficial effects. The rat chemical carcinogen model has been widely used to study the effects of estrogens but conclusions on the levels that lead to tumor development and an absolute requirement for progesterone (P4) are lacking. A newer method of hormone administration mixes hormones with nut butter for peroral consumption allowing for a less stressful method of long-term administration with lower spikes in serum estradiol (E2) levels. The present study was designed to determine if estrogens alone at a physiological dose can drive carcinogen-induced tumors in ovariectomized (OVX) rats or if P4 is also required using this method of hormone administration. Short-term studies were conducted to determine the dose of estrogen (E) that would lead to increased uterine weight following OVX. Subsequently, rats were OVX on postnatal day (PND) 40 then treated daily with E (600 μg/kg/day), P4 (15 mg/kg/day), or the combination. On PND 50, all rats were injected with nitrosomethylurea to induce mammary tumors. Uterine weights, body weights, and serum E2 levels were measured to demonstrate the efficacy of the method for increasing E2 levels during long-term treatment. After 26 weeks, tumor incidence was similar in Sham, E, and E + P4 animals indicating that E was sufficient to induce tumorigenesis when hormone levels were normalized by this method. This study demonstrates peroral administration can be used in long-term studies to elucidate relationships between different types and levels of steroid hormones. PMID:27611094

Electromagnetic pulse reduces free radical generation in rat liver mitochondria in vitro.

PubMed

Wang, C; Zhou, H; Peng, R; Wang, L; Su, Z; Chen, P; Wang, S; Wang, S; Liu, Y; Cong, J; Wu, K; Hu, X; Fan, E

2013-04-01

Non-ionizing radiation electromagnetic pulse (EMP) is generally recorded to induce the generation of free radicals in vivo. Though mitochondria are the primary site to produce free radicals, a rare report is designed to directly investigate the EMP effects on free radical generation at mitochondrial level. Thus the present work was designed to study how EMP induces free radical generation in rat liver mitochondria in vitro using electron paramagnetic resonance technique. Surprisingly, our data suggest that EMP prevents free radical generation by activating antioxidant enzyme activity and reducing oxygen consumption and therefore free radical generation. Electron spin resonance measurements clearly demonstrate that disordering of mitochondrial lipid fluidity and membrane proteins mobility are the underlying contributors to this decreased oxygen consumption. Therefore, our results suggest that EMP might hold the potentiality to be developed as a non-invasive means to benefit certain diseases.

Evaluation of Epidemiology and Animal Data for Risk Assessment: Chlorpyrifos Developmental Neurobehavioral Outcomes

PubMed Central

Li, Abby A.; Lowe, Kimberly A.; McIntosh, Laura J.; Mink, Pamela J.

2012-01-01

Developmental neurobehavioral outcomes attributed to exposure to chlorpyrifos (CPF) obtained from epidemiologic and animal studies published before June 2010 were reviewed for risk assessment purposes. For epidemiological studies, this review considered (1) overall strength of study design, (2) specificity of CPF exposure biomarkers, (3) potential for bias, and (4) Hill guidelines for causal inference. In the case of animal studies, this review focused on evaluating the consistency of outcomes for developmental neurobehavioral endpoints from in vivo mammalian studies that exposed dams and/or offspring to CPF prior to weaning. Developmental neuropharmacologic and neuropathologic outcomes were also evaluated. Experimental design and methods were examined as part of the weight of evidence. There was insufficient evidence that human developmental exposures to CPF produce adverse neurobehavioral effects in infants and children across different cohort studies that may be relevant to CPF exposure. In animals, few behavioral parameters were affected following gestational exposures to 1 mg/kg-d but were not consistently reported by different laboratories. For postnatal exposures, behavioral effects found in more than one study at 1 mg/kg-d were decreased errors on a radial arm maze in female rats and increased errors in males dosed subcutaneously from postnatal day (PND) 1 to 4. A similar finding was seen in rats exposed orally from PND 1 to 21 with incremental dose levels of 1, 2, and 4 mg/kg-d, but not in rats dosed with constant dose level of 1 mg/kg-d. Neurodevelopmental behavioral, pharmacological, and morphologic effects occurred at doses that produced significant brain or red blood cell acetylcholinesterase inhibition in dams or offspring. PMID:22401178

An Efficient and Reproducible Protocol for Distraction Osteogenesis in a Rat Model Leading to a Functional Regenerated Femur.

PubMed

Pithioux, Martine; Roseren, Flavy; Jalain, Christian; Launay, Franck; Charpiot, Philippe; Chabrand, Patrick; Roffino, Sandrine; Lamy, Edouard

2017-10-23

This protocol describes the use of a newly developed external fixator for distraction osteogenesis in a rat femoral model. Distraction osteogenesis (DO) is a surgical technique leading to bone regeneration after an osteotomy. The osteotomized extremities are moved away from each other by gradual distraction to reach the desired elongation. This procedure is widely used in humans for lower and upper limb lengthening, treatment after a bone nonunion, or the regeneration of a bone defect following surgery for bone tumor excision, as well as in maxillofacial reconstruction. Only a few studies clearly demonstrate the efficiency of their protocol in obtaining a functional regenerated bone, i.e., bone that will support physiological weight-bearing without fracture after removal of the external fixator. Moreover, protocols for DO vary and reproducibility is limited by lack of information, making comparison between studies difficult. The aim of this study was to develop a reproducible protocol comprising an appropriate external fixator design for rat limb lengthening, with a detailed surgical technique that permits physiological weight-bearing by the animal after removal of the external fixator.

Lithium-ion Battery Demonstration for the 2007 NASA Desert Research and Technology Studies (Desert RATS) Program

NASA Technical Reports Server (NTRS)

Bennett, William; Baldwin, Richard

2007-01-01

The NASA Glenn Research Center (GRC) Electrochemistry Branch designed and produced five lithium-ion battery packs for demonstration in a portable life support system (PLSS) on spacesuit simulators. The experimental batteries incorporated advanced, NASA-developed electrolytes and included internal protection against over-current, over-discharge and over-temperature. The 500-gram batteries were designed to deliver a constant power of 38 watts over 103 minutes of discharge time (130 Wh/kg). Battery design details are described and field and laboratory test results are summarized.

Effect of vagal stimulation on gastric mucosal barrier in albino rats.

PubMed

Somasundaram, K; Ganguly, A K

1987-01-01

To study the influence of vagus nerves on gastric mucosal barrier in albino rats, gastric adherent mucus and mucosal epithelial neutral glycoproteins were quantitatively assessed after vagal stimulation at the cardio-esophageal region by a specially designed circular electrode. Gastric adherent mucus and epithelial mucus were studied from oxyntic and pyloric gland areas by Alcian blue binding and periodic acid Schiff's (PAS) staining method respectively. The results when compared with sham operated control animals showed increase in the visible mucus concurrent with decrease in PAS positive materials. The stimulation at the cardio-esophageal region of vagotomized animals did not produce these effects. This study indicates that in an acute condition, increased vagal influence is important in increasing mucus secretion and strengthening the first line of defence of the mucosal barrier.

Learned helplessness in the rat: effect of response topography in a within-subject design.

PubMed

dos Santos, Cristiano Valerio; Gehm, Tauane; Hunziker, Maria Helena Leite

2011-02-01

Three experiments investigated learned helplessness in rats manipulating response topography within-subject and different intervals between treatment and tests among groups. In Experiment 1, rats previously exposed to inescapable shocks were tested under an escape contingency where either jumping or nose poking was required to terminate shocks; tests were run either 1, 14 or 28 days after treatment. Most rats failed to jump, as expected, but learned to nose poke, regardless of the interval between treatment and tests and order of testing. The same results were observed in male and female rats from a different laboratory (Experiment 2) and despite increased exposure to the escape contingencies using a within-subject design (Experiment 3). Furthermore, no evidence of helplessness reversal was observed, since animals failed to jump even after having learned to nose-poke in a previous test session. These results are not consistent with a learned helplessness hypothesis, which claims that shock (un)controllability is the key variable responsible for the effect. They are nonetheless consistent with the view that inescapable shocks enhance control by irrelevant features of the relationship between the environment and behavior. Copyright © 2010 Elsevier B.V. All rights reserved.

Effect of exposure and withdrawal of 900-MHz-electromagnetic waves on brain, kidney and liver oxidative stress and some biochemical parameters in male rats.

PubMed

Ragy, Merhan Mamdouh

2015-01-01

Increasing use of mobile phones in daily life with increasing adverse effects of electromagnetic radiation (EMR), emitted from mobile on some physiological processes, cause many concerns about their effects on human health. Therefore, this work was designed to study the effects of exposure to mobile phone emits 900-MHz EMR on the brain, liver and kidney of male albino rats. Thirty male adult rats were randomly divided into four groups (10 each) as follows: control group (rats without exposure to EMR), exposure group (exposed to 900-MHz EMR for 1 h/d for 60 d) and withdrawal group (exposed to 900-MHz electromagnetic wave for 1 h/d for 60 d then left for 30 d without exposure). EMR emitted from mobile phone led to a significant increase in malondialdehyde (MDA) levels and significant decrease total antioxidant capacity (TAC) levels in brain, liver and kidneys tissues. The sera activity of alanine transaminase (ALT), aspartate aminotransferase (AST), urea, creatinine and corticosterone were significantly increased (p < 0.05), while serum catecholamines were insignificantly higher in the exposed rats. These alterations were corrected by withdrawal. In conclusion, electromagnetic field emitting from mobile phone might produce impairments in some biochemicals changes and oxidative stress in brain, liver and renal tissue of albino rats. These alterations were corrected by withdrawal.

Reduction of Acute Rejection by Bone Marrow Mesenchymal Stem Cells during Rat Small Bowel Transplantation

PubMed Central

Zhang, Wen; Wu, Ben-Juan; Fu, Nan-Nan; Zheng, Wei-Ping; Don, Chong; Shen, Zhong-Yang

2014-01-01

Background Bone marrow mesenchymal stem cells (BMMSCs) have shown immunosuppressive activity in transplantation. This study was designed to determine whether BMMSCs could improve outcomes of small bowel transplantation in rats. Methods Heterotopic small bowel transplantation was performed from Brown Norway to Lewis rats, followed by infusion of BMMSCs through the superficial dorsal veins of the penis. Controls included rats infused with normal saline (allogeneic control), isogeneically transplanted rats (BN-BN) and nontransplanted animals. The animals were sacrificed after 1, 5, 7 or 10 days. Small bowel histology and apoptosis, cytokine concentrations in serum and intestinal grafts, and numbers of T regulatory (Treg) cells were assessed at each time point. Results Acute cellular rejection occurred soon after transplantation and became aggravated over time in the allogeneic control rats, with increase in apoptosis, inflammatory response, and T helper (Th)1/Th2 and Th17/Treg-related cytokines. BMMSCs significantly attenuated acute cellular rejection, reduced apoptosis and suppressed the concentrations of interleukin (IL)-2, IL-6, IL-17, IL-23, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ while upregulating IL-10 and transforming growth factor (TGF)-β expression and increasing Treg levels. Conclusion BMMSCs improve the outcomes of allogeneic small bowel transplantation by attenuating the inflammatory response and acute cellular rejection. Treatment with BMMSCs may overcome acute cellular rejection in small bowel transplantation. PMID:25500836

Effects of unripe Citrus hassaku fruits extract and its flavanone glycosides on blood fluidity.

PubMed

Itoh, Kimihisa; Masuda, Megumi; Naruto, Shunsuke; Murata, Kazuya; Matsuda, Hideaki

2010-01-01

The enhancement of blood fluidity may lead to improvements in skin problems resulting from unsmooth circulation or blood stagnation. Since a 50% ethanolic extract (CH-ext) obtained from unripe Citrus hassaku fruits may be a useful ingredient in skin-whitening cosmetics, the present study was designed to examine the effect of CH-ext on blood fluidity. CH-ext concentration-dependently inhibited in vitro collagen-induced rabbit platelet aggregation and in vitro polybrene-induced rat erythrocyte aggregation. The CH-ext showed in vitro fibrinolysis activity in fibrin plate assay. Activity-guided fractionation of the CH-ext using antiplatelet activity, inhibitory activity of erythrocyte aggregation, and fibrinolysis activity revealed that these activities of CH-ext were attributable to naringenin-7-glycoside (prunin). Successive oral administration of CH-ext to rats inhibited the lipopolysaccharide (LPS)-induced decrease of blood platelets and fibrinogen, and LPS-induced increase of fibrin degradation products (FDP) in LPS-induced disseminated intravascular coagulation (DIC) model rats. Effects of CH-ext on blood fluidity were analyzed by a micro channel array flow analyzer (MC-FAN). Preventive oral administration of CH-ext to rats showed dose-dependent reduction of the passage time of whole blood flow of the DIC model rats in comparison with that of the vehicle control rats. These results imply that CH-ext may have effects which improve effects on blood fluidity.

High dosage of cannabidiol (CBD) alleviates pentylenetetrazole-induced epilepsy in rats by exerting an anticonvulsive effect

PubMed Central

Mao, Ke; You, Chao; Lei, Ding; Zhang, Heng

2015-01-01

The study was designed to investigate the effect of various concentrations of cannabidiol (CBD) in rats with chronic epilepsy. The chronic epilepsy rat model was prepared by intraperitoneally injecting pentylenetetrazole to the rats pre-treated with CBD (10, 20 and 50 mg/kg) for 28 consecutive days. Behavioral measurements of convulsion following pentylenetetrazole treatment and morphological changes of the hippocampal neurons with hematoxylin and eosin staining were used to observe the epileptic behaviour. Immunohistochemistry was used to detect the expression levels of glial fibrillary acidic protein and inducible nitric oxide synthase (iNOS) in the hippocampus. The mRNA expression of N-methyl-D-aspartic acid (NMDA) receptor subunits (NR1 and NR2B) was detected by reverse transcription polymerase chain reaction. The results revealed a significant decrease in the daily average grade of epileptic seizures on treatment with CBD (50 mg/kg). The neuronal loss and astrocyte hyperplasia in the hippocampal area were also decreased. CBD treatment did not affect the expression of iNOS in the hippocampus; however, the expression of NR1 was decreased significantly. Thus, CBD administration inhibited the effect of pentylenetetrazole in rats, decreased the astrocytic hyperplasia, decreased neuronal damage in the hippocampus caused by seizures and selectively reduced the expression of the NR1 subunit of NMDA. Therefore, CBD exhibits an anticonvulsive effect in the rats with chronic epilepsy. PMID:26309534

Effects of Xylopia aethiopica (Annonaceae) fruit methanol extract on gamma-radiation-induced oxidative stress in brain of adult male Wistar rats.

PubMed

Adaramoye, O A; Popoola, Bosede O; Farombi, E O

2010-09-01

Xylopia aethiopica (XA) (Annonaceae) possesses great nutritional and medicinal values. This study was designed to investigate the effects of XA fruit methanol extract on oxidative stress in brain of rats exposed to whole body gamma-radiation (5 Gy). Vitamin C (VC) served as standard antioxidant. Forty-four rats were divided into 4 groups of 11 rats each. One group served as control, two different groups were treated with XA and VC (250 mg/kg), 6 weeks before and 8 weeks after irradiation, and fourth group was only irradiated. Rats were sacrificed 1 and 8 weeks after irradiation. The antioxidant status, viz. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST) and glutathione (GSH) were estimated. Results indicate a significant increase (p < 0.05) in levels of brain LPO after irradiation. LPO increased by 90% and 151%, after 1 and 8 weeks of irradiation, respectively. Irradiation caused significant (p < 0.05) decreases in levels of GSH and GST by 61% and 43% after 1 week and, 75% and 73%, respectively, after 8 weeks of exposure. CAT and SOD levels were decreased by 62% and 68%, respectively, after 8 weeks of irradiation. Treatment with XA and VC ameliorated the radiation-induced decreases in antioxidant status of the animals. These suggest that XA could have beneficial effect by inhibiting oxidative damage in brain of exposed rats.

High dosage of cannabidiol (CBD) alleviates pentylenetetrazole-induced epilepsy in rats by exerting an anticonvulsive effect.

PubMed

Mao, Ke; You, Chao; Lei, Ding; Zhang, Heng

2015-01-01

The study was designed to investigate the effect of various concentrations of cannabidiol (CBD) in rats with chronic epilepsy. The chronic epilepsy rat model was prepared by intraperitoneally injecting pentylenetetrazole to the rats pre-treated with CBD (10, 20 and 50 mg/kg) for 28 consecutive days. Behavioral measurements of convulsion following pentylenetetrazole treatment and morphological changes of the hippocampal neurons with hematoxylin and eosin staining were used to observe the epileptic behaviour. Immunohistochemistry was used to detect the expression levels of glial fibrillary acidic protein and inducible nitric oxide synthase (iNOS) in the hippocampus. The mRNA expression of N-methyl-D-aspartic acid (NMDA) receptor subunits (NR1 and NR2B) was detected by reverse transcription polymerase chain reaction. The results revealed a significant decrease in the daily average grade of epileptic seizures on treatment with CBD (50 mg/kg). The neuronal loss and astrocyte hyperplasia in the hippocampal area were also decreased. CBD treatment did not affect the expression of iNOS in the hippocampus; however, the expression of NR1 was decreased significantly. Thus, CBD administration inhibited the effect of pentylenetetrazole in rats, decreased the astrocytic hyperplasia, decreased neuronal damage in the hippocampus caused by seizures and selectively reduced the expression of the NR1 subunit of NMDA. Therefore, CBD exhibits an anticonvulsive effect in the rats with chronic epilepsy.

Analgesic Effect of Intra-Articular Injection of Temperature-Responsive Hydrogel Containing Bupivacaine on Osteoarthritic Pain in Rats

PubMed Central

Kim, Taemin; Seol, Dong Rim; Hahm, Suk-Chan; Ko, Cheolwoong; Kim, Eun-Hye; Chun, Keyoungjin; Kim, Junesun; Lim, Tae-Hong

2015-01-01

The present study examined the analgesic effects of slow-releasing bupivacaine from hydrogel on chronic arthritic pain in rats. Osteoarthritis (OA) was induced by monosodium iodoacetate (MIA) injection into the right knee joint. Hydrogel (HG: 20, 30, and 50 μL) and temperature-sensitive hydrogel containing bupivacaine (T-gel: 20, 30, and 50 μL) were injected intra-articularly 14 days after MIA injection. Behavioral tests were conducted. The rats showed a significant decrease in weight load and paw withdrawal threshold (PWT). Intra-articular 0.5% bupivacaine (10 and 20 μL) significantly reversed MIA-induced decreased PWT, with no effect on weight load. In normal rats, hydrogel did not produce significant changes in PWT but at 30 and 50 μL slightly decreased weight bearing; T-gel did not cause any changes in both the weight load and PWT. In OA rats, T-gel at 20 μL had a significant analgesic effect for 2 days, even though T-gel at 50 μL further reduced the weight load, demonstrating that intra-articular T-gel (20 μL) has long-lasting analgesic effects in OA rats. Thus, T-gel designed to deliver analgesics into the joint cavity could be an effective therapeutic tool in the clinical setting. PMID:26881207

Carbonated soft drinks alter hepatic cytochrome P450 isoform expression in Wistar rats.

PubMed

Alkhedaide, Adel; Soliman, Mohamed Mohamed; Ibrahim, Zein Shaban

2016-11-01

The aim of the current study was to examine the effects of chronic consumption of soft drinks (SDs) on hepatic oxidative stress and cytochrome P450 enzymes (CYPs) expression in the livers of Wistar rats. For 3 consecutive months, the rats had free access to three different soft drinks, Coca-Cola, Pepsi-Cola and 7-UP. The rats were subsequently compared with control group rats that had consumed water. Blood and hepatic tissue samples were assayed for the changes in antioxidants, liver function biomarkers and hepatic gene expression for different isoforms of hepatic CYP. The results indicated that SD consumption (SDC) decreased serum antioxidant levels and increased malondialdehyde secretion, and increased liver biomarkers (glutamate pyruvate transaminase and glutamate oxaloacetate). SD induced alterations in mRNA expression of hepatic antioxidants and cytochrome isoforms. The expression of peroxidase, catalase, CYP1A2, CYP3A2 and CYP2C11 in the liver were upregulated following SDC. By contrast, CYP2B1 was downregulated after 3 months of SDC in liver tissue samples. Thus, the present findings indicate that SDs induced oxidative stress in the liver of Wistar rats and for the first time, to the best of our knowledge, indicate that SDC disrupts hepatic CYP enzymes that may affect drug metabolism. Therefore, drug-dosing programs should be carefully designed to take these novel findings into consideration for the treatment of diseases.

Maternal swimming exercise during pregnancy attenuates anxiety/depressive-like behaviors and voluntary morphine consumption in the pubertal male and female rat offspring born from morphine dependent mothers.

PubMed

Torabi, Masoumeh; Pooriamehr, Alireza; Bigdeli, Imanollah; Miladi-Gorji, Hossein

2017-10-17

This study was designed to examine whether maternal swimming exercise during pregnancy would attenuate prenatally morphine-induced anxiety, depression and voluntary consumption of morphine in the pubertal male and female rat offspring. Pregnant rats during the development of morphine dependence were allowed to swim (30-45min/d, 3days per a week) on gestational days 11-18. Then, the pubertal male and female rat offspring were tested for the elevated plus-maze (EPM), sucrose preference test (SPT) and voluntary morphine consumption using a two-bottle choice (TBC) paradigm. The results showed that male and female rat offspring born of the swimmer morphine-dependent mothers exhibited an increase in EPM open arm time and entries, higher levels of sucrose preference than their sedentary control mothers. Voluntary consumption of morphine was less in the male and female rat offspring born of the swimmer morphine-dependent mothers as compared with their sedentary control mothers during three periods of the intake of drug. Thus, swimming exercise in pregnant morphine dependent mothers decreased anxiety, depressive-like behavior and also the voluntary morphine consumption in the pubertal male and female offspring, which may prevent prenatally morphine-induced behavioral sensitization in offspring. Copyright © 2017 Elsevier B.V. All rights reserved.

Differential expression of the phthalate syndrome in male Sprague-Dawley and Wistar rats after in utero DEHP exposure

EPA Science Inventory

Exposure to phthalate esters during sexual differentiation disrupts testosterone and insulin-like three hormones resulting in malformations of androgen- and insulin-like three-dependent tissues. The current study was designed to test the hypothesis that gubernacular lesions would...

Impact of Chemical Proportions on the Acute Neurotoxicity of a Mixture of Seven Carbamates in Preweanling and Adult Rats

EPA Science Inventory

Statistical design and environmental relevance are important aspects of studies of chemical mixtures, such as pesticides. We used a dose-additivity model to test experimentally the default assumptions of dose-additivity for two mixtures of seven N-methylcarbamates (carbaryl, carb...

Toxicological Responses of Fischer Rats to Naturally Occurring Asbestos Samples from the United States and Canada

EPA Science Inventory

To support risk assessment efforts, a comparative study was designed to provide understanding of the toxicity of different types of fibers encountered in EPA clean-up efforts. Physico-chemical properties, and consequentially toxicity, are likely to be different among various fib...

Sumas Mountain chrysotile induces greater lung fibrosis in Fischer 344 rats than Libby amphibole, El Dorado tremolite, and Ontario ferroactinolite

EPA Science Inventory

The physical properties of different types of asbestos may strongly affect health outcomes in exposed individuals. This study was designed to provide understanding of the comparative toxicity of naturally occurring asbestos (NOA) fibers including Libby amphibole (LA), Sumas Moun...

Regional heterogeneity for the intracranial self-administration of ethanol within the ventral tegmental area of female Wistar rats.

PubMed

Rodd-Henricks, Z A; McKinzie, D L; Crile, R S; Murphy, J M; McBride, W J

2000-04-01

Because current findings indicate that the selectively bred alcohol-preferring P line of rats self-administers 50-200 mg% ethanol (EtOH) directly into the ventral tegmental area (VTA), whereas the alcohol-nonpreferring NP line does not, it is important to determine whether unselected, common stock rats would self-administer EtOH directly into the VTA. In addition, because neuroanatomical and self-administration studies indicate that the VTA may be functionally heterogeneous, the present study was designed to determine whether there were subregional differences within the VTA for the intracranial self-administration (ICSA) of EtOH. The objective of this study was to employ the ICSA technique to determine whether adult female Wistar rats would self-administer EtOH directly into the VTA, and whether regional heterogeneity existed for EtOH self-infusion within the VTA. Following surgery to implant guide cannulae aimed at either the posterior or anterior VTA, subjects were placed in standard experimental chambers equipped with an 'active lever' [fixed ratio (FR)1 schedule of reinforcement], which caused the delivery of the infusate, and an 'inactive lever', which had no programmed consequence. Subjects were assigned to groups that self-administered either artificial cerebrospinal fluid (aCSF) throughout, or 100-400 mg% EtOH for the first four sessions (acquisition), aCSF in sessions 5 and 6 (extinction), and EtOH again during session 7 (reinstatement). During the four acquisition sessions, rats with posterior VTA placements readily self-administered 200 mg% and 250 mg% EtOH and discriminated between the active and inactive levers. These subjects also demonstrated extinction, when aCSF was substituted for EtOH, and reinstatement when EtOH was reintroduced. Rats with posterior VTA placements self-infused 300 mg% and 400 mg% EtOH, and demonstrated lever discrimination only during the initial acquisition sessions. In contrast, rats with anterior VTA placements did not self-administer EtOH. The findings suggest that EtOH is reinforcing within the posterior VTA of Wistar rats, and the VTA is a functionally heterogeneous structure with regard to EtOH reinforcement.

A Basic Robotic Excavator (the Glenn Digger): Description, Design, and Initial Operation

NASA Technical Reports Server (NTRS)

Bauman, Steve; Newman, Paul; Izadnegahdar, Alain; Johnson, Kyle; Abel, Phillip

2016-01-01

This paper describes the design, commercial part selections, fabrication, assembly, installation, and initial operation of a two degree of freedom robotic excavator. Colloquially referred to as "the NASA Glenn Digger," it was designed specifically to be mounted onto, and to operate with, the then newly developed Centaur 2 robotic mobility base. The excavator, when mounted to Centaur 2, is designed to scoop loose regolith from the terrain, raise its loaded bucket up and dump the load into a hopper of at least a 1-m-height. The hopper represents the input to a machine that would process the raw material, such as to produce oxygen from lunar regolith as would be required for long-term lunar habitation. This equipment debuted at the annual Research and Technology Studies ("Desert RATS", Ref. 1) event held north of Flagstaff, Arizona, in September of 2010, when the Digger was successfully joined to Centaur 2 and the shoveling articulation was demonstrated. During 2011, the hardware was modified for added strength, strain gauges were added to measure loads, and the controls were improved in preparation for the 2011 Desert RATS event, where additional "field operations" experience was gained.

Fructo-oligosaccharides reduce energy intake but do not affect adiposity in rats fed a low-fat diet but increase energy intake and reduce fat mass in rats fed a high-fat diet.

PubMed

Hadri, Zouheyr; Rasoamanana, Rojo; Fromentin, Gilles; Azzout-Marniche, Dalila; Even, Patrick C; Gaudichon, Claire; Darcel, Nicolas; Bouras, Abdelkader Dilmi; Tomé, Daniel; Chaumontet, Catherine

2017-12-01

The ingestion of low or high lipid diets enriched with fructo-oligosaccharide (FOS) affects energy homeostasis. Ingesting protein diets also induces a depression of energy intake and decreases body weight. The goal of this study was to investigate the ability of FOS, combined or not with a high level of protein (P), to affect energy intake and body composition when included in diets containing different levels of lipids (L). We performed two studies of similar design over a period of 5weeks. During the first experiment (exp1), after a 3-week period of adaptation to a normal protein-low fat diet, the rats received one of the following four diets for 5weeks (6 rats per group): (i) normal protein (14% P/E (Energy) low fat (10% L/E) diet, (ii) normal protein, low fat diet supplemented with 10% FOS, (iii) high protein (55%P/E) low fat diet, and (iv) high protein, low fat diet supplemented with 10% FOS. In a second experiment (exp2) after the 3-week period of adaptation to a normal protein-high fat diet, the rats received one of the following 4 diets for 5weeks (6 rats per group): (i) normal protein, high fat diet (35% of fat), (ii) normal protein, high fat diet supplemented with 10% FOS, (iii) high protein high fat diet and (iv) high protein high fat diet supplemented with 10% FOS. In low-fat fed rats, FOS did not affect lean body mass (LBM) and fat mass but the protein level reduced fat mass and tended to reduce adiposity. In high-fat fed rats, FOS did not affect LBM but reduced fat mass and adiposity. No additive or antagonistic effects between FOS and the protein level were observed. FOS reduced energy intake in low-fat fed rats, did not affect energy intake in normal-protein high-fat fed rats but surprisingly, and significantly, increased energy intake in high-protein high-fat fed rats. The results thus showed that FOS added to a high-fat diet reduced body fat and body adiposity. Published by Elsevier Inc.

Data in support of qPCR primer design and verification in a Pink1 -/- rat model of Parkinson disease.

PubMed

Kelm-Nelson, Cynthia A; Stevenson, Sharon A; Ciucci, Michelle R

2016-09-01

Datasets provided in this article represent the Rattus norvegicus primer design and verification used in Pink1 -/- and wildtype Long Evans brain tissue. Accessible tables include relevant information, accession numbers, sequences, temperatures and product length, describing primer design specific to the transcript amplification use. Additionally, results of Sanger sequencing of qPCR reaction products (FASTA aligned sequences) are presented for genes of interest. Results and further interpretation and discussion can be found in the original research article "Atp13a2 expression in the periaqueductal gray is decreased in the Pink1 -/- rat model of Parkinson disease" [1].

Precolumn derivatization followed by liquid chromatographic separation and determination of tramiprosate in rat plasma by fluorescence detector: application to pharmacokinetics.

PubMed

Rao, R Nageswara; Maurya, Pawan K; Shinde, Dhananjay D; Khalid, Sara

2011-05-15

Alzheimer disease (AD) is characterized pathologically by extracellular amyloid deposits composed of amyloid β (Aβ) protein. A simple and rapid method using HPLC with fluorescence detector was developed and validated for determination of tramiprosate in rat plasma. Pre-column derivatization of the deproteinized rat plasma was carried out using o-phthaldialdehyde (OPA) as a fluorescent reagent in presence of 3-mercaptopropionic acid. The liquid chromatographic separation was achieved on a Kromasil C18 column using methanol:acetonitrile: 20 mM phosphate buffer pH 7.5 (8.0:17.5:74.5 v/v/v) as a mobile phase in an isocratic elution mode. The eluents were monitored by a fluorescence detector set at 330 and 450 nm of excitation and emission wavelength respectively. Vigabatrin was used as an internal standard. The method was linear within the range 30.0-1000.0 ng/mL. Design of experiments (DOE) was used to evaluate the robustness of the method. The developed method was applied to study the pharmacokinetics of tramiprosate in rats. Copyright © 2011. Published by Elsevier B.V.

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

PubMed

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

2015-03-01

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

Treatment with docosahexaenoic acid after hypoxia–ischemia improves forepaw placing in a rat model of perinatal hypoxia-ischemia

PubMed Central

Berman, Deborah R; Liu, YiQing; Barks, John; Mozurkewich, Ellen

2010-01-01

Objective Docosahexaenoic acid (DHA) is a dietary fatty acid with neuroprotective properties. We hypothesized that DHA treatment after hypoxia-ischemia (HI) would improve function and reduce brain volume loss in a perinatal rat model. Study design Seven-day-old Wistar rat pups from 7 litters (N=84) underwent right carotid ligation, followed by 8% O2 for 90 minutes. Fifteen minutes after HI, pups were divided into 3 treatment groups (intraperitoneal injections of DHA 1, 2.5 or 5 mg/kg) and 2 control groups (25% albumin or saline). At 14 days, rats underwent vibrissae-stimulated forepaw placing testing, and bilateral regional volumes were calculated for cortex, striatum, hippocampus, and hemisphere. Results Post HI treatment with DHA significantly improved vibrissae forepaw placing (complete responses: 8.5±2 treatment vs. 7.4±2 controls; normal=10; p = 0.032, t-test). Post injury DHA treatment did not attenuate brain volume loss in any region. Conclusion Post-hypoxia-ischemia DHA treatment significantly improves functional outcome. PMID:20691409

Hindlimb unloading has a greater effect on cortical compared with cancellous bone in mature female rats

NASA Technical Reports Server (NTRS)

Allen, Matthew R.; Bloomfield, Susan A.

2003-01-01

This study was designed to determine the effects of 28 days of hindlimb unloading (HU) on the mature female rat skeleton. In vivo proximal tibia bone mineral density and geometry of HU and cage control (CC) rats were measured with peripheral quantitative computed tomography (pQCT) on days 0 and 28. Postmortem pQCT, histomorphometry, and mechanical testing were performed on tibiae and femora. After 28 days, HU animals had significantly higher daily food consumption (+39%) and lower serum estradiol levels (-49%, P = 0.079) compared with CC. Proximal tibia bone mineral content and cortical bone area significantly declined over 28 days in HU animals (-4.0 and 4.8%, respectively), whereas total and cancellous bone mineral densities were unchanged. HU animals had lower cortical bone formation rates and mineralizing surface at tibial midshaft, whereas differences in similar properties were not detected in cancellous bone of the distal femur. These results suggest that cortical bone, rather than cancellous bone, is more prominently affected by unloading in skeletally mature retired breeder female rats.

The effects of tramadol on hepatic ischemia/reperfusion injury in rats

PubMed Central

Mahmoud, Mona F.; Gamal, Samar; Shaheen, Mohamed A.; El-Fayoumi, Hassan M.

2016-01-01

Objectives: Tramadol is a centrally acting synthetic analgesic. It has a cardioprotective effect against myocardial ischemia-reperfusion (I/R) injury in isolated rat heart. We hypothesized that tramadol may exert a similar protective effect on hepatic I/R injury. Hence, the current investigation was designed to study the possible protective effects of tramadol on experimentally-induced hepatic I/R injury in rats. Materials and Methods: Tramadol was administered 30 min before ischemia following which the rats were subjected to 45 min of ischemia followed by 1 h of reperfusion. Results: Tramadol attenuated hepatic injury induced by I/R as evidenced by the reduction of transaminases, structural changes, and apoptotic cell death. It decreased the level of inflammatory markers such as tumor necrosis factor-alpha (TNF-α), TNF-α/interleukin-10 (IL-10) ratio, and nuclear factor-κB gene expression. It also increased the anti-inflammatory cytokine, IL-10 levels in hepatic tissues. Furthermore, it reduced oxidative stress parameters except manganese superoxide dismutase activity. Conclusion: The results suggest that tramadol has hepatoprotective effects against hepatic I/R injury via anti-inflammatory, antiapoptotic, and antioxidant effects. PMID:27298497

The effects of tramadol on hepatic ischemia/reperfusion injury in rats.

PubMed

Mahmoud, Mona F; Gamal, Samar; Shaheen, Mohamed A; El-Fayoumi, Hassan M

2016-01-01

Tramadol is a centrally acting synthetic analgesic. It has a cardioprotective effect against myocardial ischemia-reperfusion (I/R) injury in isolated rat heart. We hypothesized that tramadol may exert a similar protective effect on hepatic I/R injury. Hence, the current investigation was designed to study the possible protective effects of tramadol on experimentally-induced hepatic I/R injury in rats. Tramadol was administered 30 min before ischemia following which the rats were subjected to 45 min of ischemia followed by 1 h of reperfusion. Tramadol attenuated hepatic injury induced by I/R as evidenced by the reduction of transaminases, structural changes, and apoptotic cell death. It decreased the level of inflammatory markers such as tumor necrosis factor-alpha (TNF-α), TNF-α/interleukin-10 (IL-10) ratio, and nuclear factor-κB gene expression. It also increased the anti-inflammatory cytokine, IL-10 levels in hepatic tissues. Furthermore, it reduced oxidative stress parameters except manganese superoxide dismutase activity. The results suggest that tramadol has hepatoprotective effects against hepatic I/R injury via anti-inflammatory, antiapoptotic, and antioxidant effects.

Study of molecular mechanisms of learning and memory impairment in neonatal rats post intrauterine distress via the pathway of Tau protein hyperphosphorylation.

PubMed

Wang, X-S; Huang, H

2018-05-01

To explore the reversion of the excitatory amino acid receptor antagonists against the impairment of learning-memory and the hyperphosphorylation of protein Tau induced by fetal intrauterine distress in neonatal rats. The analysis of variance of factorial design set up two intervention factors, fetal intrauterine distress (two levels: no fetal intrauterine distress and a course of fetal intrauterine distress) and the excitatory amino acid receptor antagonists (three levels: Saline; NMDA receptor antagonist MK-801; astragalosides). Forty-eight pregnant rats were randomly divided into six experimental groups (n=8, in each group). After the end of the fetal intrauterine distress, the pregnant rats continued until the birth of newborn rats. When the neonatal rats grow to 12W, the Morris water maze test started in order to evaluate learning-memory. The hippocampus was removed from newborn rats within 1 day after the Morris water maze test finished. The content of glutamate in the hippocampus of rats was detected by high performance liquid chromatography. Besides, the content of protein Tau including Tau5 (total protein Tau), p-PHF1Ser396/404, p-AT8Ser199/202, p-12E8Ser262 in the hippocampus of rats, was examined with the method of immunohistochemistry (IHC) staining (SP). Fetal intrauterine distress and the glutamate ionic receptor blockers could induce the impairment of learning-memory in neonatal rats, extending the evasive latency time and shorten the space exploration time. Both influences present subtract effect. Fetal intrauterine distress could significantly up-regulate the content of glutamate in the hippocampus of neonatal rats, which was not affected by the glutamate ionic receptor blockers. Fetal intrauterine distress and the glutamate ionic receptor blockers did not affect the total protein Tau in the hippocampus of rats. Moreover, fetal intrauterine distress could increase the hyperphosphorylation of protein Tau in the hippocampus of neonatal rats, which were reduced by the glutamate ionic receptor blockers. Both influences presented subtract effect. We showed that fetal intrauterine distress upregulates the content of glutamate in the hippocampus of neonatal rats, up-regulating the hyperphosphorylation of protein Tau and inducing the impairment of learning-memory in neonatal rats.

Indomethacin can downregulate the levels of inflammatory mediators in the hippocampus of rats submitted to pilocarpine-induced status epilepticus

PubMed Central

Vieira, Michele Juliane; Perosa, Sandra Regina; Argañaraz, Gustavo Adolfo; Silva, José Antônio; Cavalheiro, Esper Abrão; da Graça Naffah-Mazzacoratti, Maria

2014-01-01

OBJECTIVE: Refractory status epilepticus is one of the most life-threatening neurological emergencies and is characterized by high morbidity and mortality. Additionally, the use of anti-inflammatory drugs during this period is very controversial. Thus, this study has been designed to analyze the effect of a low dose of indomethacin (a COX inhibitor) on the expression of inflammatory molecules. METHOD: The hippocampus of rats submitted to pilocarpine-induced long-lasting status epilepticus was analyzed to determine the expression of inflammatory molecules with RT-PCR and immunohistochemistry. RESULTS: Compared with controls, reduced levels of the kinin B2 receptors IL1β and TNFα were found in the hippocampus of rats submitted to long-lasting status epilepticus and treated with indomethacin. CONCLUSIONS: These data show that low doses of indomethacin could be employed to minimize inflammation during long-lasting status epilepticus. PMID:25318094

Behavioral Effects of Acclimatization To Restraint Protocol Used for Awake Animal Imaging

PubMed Central

Reed, Michael D.; Pira, Ashley S.; Febo, Marcelo

2013-01-01

Functional MRI of awake rats involves acclimatization to restraint to minimize motion. We designed a study to examine the effects of an acclimatization protocol (5 days of restraint, 60 minutes per day) on the emission of 22-kHz ultrasonic vocalizations and performance on a forced swim test (FST). Our results show that USV calls are reduced significantly by day 3, 4 and 5 of acclimatization. Although rats show less climbing activity (and more immobility) in FST on day 5 compared to the 1st day of restraint acclimatization, the difference is gone once animals are given a 2 week hiatus. Overall, we show that animals adapt to the restraint over the five day period, however, restraint may introduce confounding behavioral outcomes that may hinder the interpretation of results derived from awake rat imaging. The present data warrant further testing of the effects of MRI restraint on behavior. PMID:23562621

Histopathology and pathogenesis of caerulein-, duct ligation-, and arginine-induced acute pancreatitis in Sprague-Dawley rats and C57BL6 mice.

PubMed

Zhang, Jun; Rouse, Rodney L

2014-09-01

Three classical rodent models of acute pancreatitis were created in an effort to identify potential pre-clinical models of drug-induced pancreatitis (DIP) and candidate non-invasive biomarkers for improved detection of DIP. Study objectives included designing a lexicon to minimize bias by capturing normal variation and spontaneous and injury-induced changes while maintaining the ability to statistically differentiate degrees of change, defining morphologic anchors for novel pancreatic injury biomarkers, and improved understanding of mechanisms responsible for pancreatitis. Models were created in male Sprague-Dawley rats and C57BL6 mice through: 1) administration of the cholecystokinin analog, caerulein; 2) administration of arginine; 3) surgical ligation of the pancreatic duct. Nine morphologically detectable processes were used in the lexicon; acinar cell hypertrophy; acinar cell autophagy; acinar cell apoptosis; acinar cell necrosis; vascular injury; interstitial edema, inflammation and hemorrhage; fat necrosis; ductal changes; acinar cell atrophy. Criteria were defined for scoring levels (0 = absent, 1 = mild, 2 = moderate, 3 = severe) for each lexicon component. Consistent with previous studies, histopathology scores were significant greater in rats compared to mice at baseline and after treatment. The histopathology scores in caerulein and ligation-treated rats and mice were significantly greater than those of arginine-treated rats and mice. The present study supports a multifaceted pathogenesis for acute pancreatitis in which intra-acinar trypsinogen activation, damage to acinar cells, fat cells, and vascular cells as well as activation/degranulation of mast cells and activated macrophages all contribute to the initiation and/or progression of acute inflammation of the exocrine pancreas.

Common variations in the pretest environment influence genotypic comparisons in models of anxiety.

PubMed

Izídio, G S; Lopes, D M; Spricigo, L; Ramos, A

2005-10-01

The behavioral characterization of rodent strains in different studies and laboratories can provide unreplicable results even when genotypes are kept constant and environmental control is maximized. In the present study, the influence of common laboratory environmental variables and their interaction with genotype on the results of behavioral tests of anxiety/emotionality were investigated. To this end, the inbred rat strains Lewis (LEW) and spontaneously hypertensive rats (SHR), which are known to differ for numerous emotionality-related behaviors, were tested in the open field (OF), elevated plus maze (EPM) and black/white box (BWB), while three environmental factors were systematically controlled and analyzed: (1) the experimenter handling the animal (familiar or unfamiliar); (2) the position of the home cage (top or bottom shelf of the rack) and (3) the behavioral state of the animal immediately before the test (arousal or rest). Experimenter familiarity did not alter the behavior of rats in the OF. Cage position, on the other hand, influenced the behavior in the OF and BWB, with rats housed in top cages appearing less anxious than those housed in the bottom. In the BWB (but not in the OF), these effects were genotype dependent. Finally, the behavioral state of the animals prior to testing altered the results of the EPM in a strain-dependent manner, with some anxiety-related genotypic differences being found only among rats that were aroused in their home cages. This study showed that common variations in the laboratory environment interact with genotype in behavioral tests of anxiety/emotionality. Recognizing and understanding such variations can help in the design of more effective experiments.

Effects of acupuncturing Pishu combined with Ginsenoside Rg3 on the immune function of rats with chronic fatigue.

PubMed

Zhang, Wenjing; Zhang, Yue; Ma, Xiande; Chen, Yiguo

2015-01-01

This study was designed to investigate the effects of acupuncturing Pishu combined with Ginsenoside Rg3 on the immune function of rats with chronic fatigue. Forty male SD rats were equally randomized into control group, chronic fatigue system group (CFS), Ginsenoside Rg3 (Rg3) group, acupuncture group and acupuncture combined with Ginsenoside Rg3 (A+Rg3) group. Rats with chronic fatigue were established by bounding and forced swimming in cold water once daily for 21 days except control group, then the rats in the acupuncture and A+Rg3 group were treated by manual acupuncture stimulation of bilateral "Pishu" once daily for 7 days. Ginsenoside Rg3 was administered by intravenous to the rats of the A+Rg3 and Rg3 group for 7 days in dosages of 2 mg/kg body weight, and two markers of physical fatigue were evaluated: body weight and blood lactic acid (LA). The percentages of CD3(+) lymphocytes, CD4(+) lymphocytes, and CD8(+) lymphocytes in the spleens of the rats were evaluated using flow cytometric analysis. Serum IFN-gamma (IFN-γ) and IL-4 contents were detected by ELISA. Increased body weight and reduced blood LA concentrations were found in the rat of Rg3 group and A+Rg3 group than that in CFS group. The rat of Rg3 group and A+Rg3 group also showed a significant increase in the percentage of CD4(+) lymphocytes and a significant decrease in the percentage of CD8(+) lymphocytes and correct CD4(+)/CD8(+) ratio. Compared with the CFS group, the level of IFN-γ in the Rg3, acupuncture and A+Rg3 groups was reduced and IL-4 was increased. Acupuncture and Rg3 can improve the immune system activity of CFS rats and acupuncturing Pishu combined with Rg3 was significantly superior compared with Rg3 and acupuncture, respectively.

Nicotine intake and problem solving strategies are modified during a cognitively demanding water maze task in rats.

PubMed

Nesil, Tanseli; Kanit, Lutfiye; Pogun, Sakire

2015-11-01

Nicotine is the major addictive component in tobacco, and despite well-established adverse health effects of tobacco addiction, some smokers have difficulty quitting. The acute cognitive enhancement and/or the amelioration of the cognitive disruption during withdrawal that some smokers experience after smoking are among important factors that hinder quit attempts. The animal model presented in the current study is comparable to the human smoking condition although nicotine intake routes are different. Rats were exposed to a free choice of oral nicotine starting at adolescence, and given a water maze (WM) task as adults. This design allowed us to see if rats alter their nicotine intake during the WM task and if nicotine preference and intake modify abilities and strategies rats use for problem solving. Male and female rats were exposed to a free choice of oral nicotine/water for 24weeks, starting at five weeks of age. After this period, they were selected based on their nicotine intake and, together with control animals that received only water, were subjected to a place-learning task in the WM. Free-choice nicotine exposure continued during WM testing. Following acquisition, the probe trial presented the rats with a choice between using two different strategies for problem solving. Nicotine supported acquisition and rats increased their nicotine intake during WM testing; this effect was more pronounced in male rats with minimum nicotine preference and intake. Furthermore, nicotine modified the "female type" strategy in solving the place-learning task and nicotine treated female rats, unlike control females, behaved like males. The increase in nicotine intake during mental engagement, and the sexually dimorphic effect of nicotine on problem solving strategies that we have observed in rats, may suggest that implementing sex-specific smoking cessation approaches, especially under stressful and cognitively demanding conditions, may be useful in helping smokers quit. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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

2017-08-01

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

Beaming into the Rat World: Enabling Real-Time Interaction between Rat and Human Each at Their Own Scale

PubMed Central

Normand, Jean-Marie; Sanchez-Vives, Maria V.; Waechter, Christian; Giannopoulos, Elias; Grosswindhager, Bernhard; Spanlang, Bernhard; Guger, Christoph; Klinker, Gudrun; Srinivasan, Mandayam A.; Slater, Mel

2012-01-01

Immersive virtual reality (IVR) typically generates the illusion in participants that they are in the displayed virtual scene where they can experience and interact in events as if they were really happening. Teleoperator (TO) systems place people at a remote physical destination embodied as a robotic device, and where typically participants have the sensation of being at the destination, with the ability to interact with entities there. In this paper, we show how to combine IVR and TO to allow a new class of application. The participant in the IVR is represented in the destination by a physical robot (TO) and simultaneously the remote place and entities within it are represented to the participant in the IVR. Hence, the IVR participant has a normal virtual reality experience, but where his or her actions and behaviour control the remote robot and can therefore have physical consequences. Here, we show how such a system can be deployed to allow a human and a rat to operate together, but the human interacting with the rat on a human scale, and the rat interacting with the human on the rat scale. The human is represented in a rat arena by a small robot that is slaved to the human’s movements, whereas the tracked rat is represented to the human in the virtual reality by a humanoid avatar. We describe the system and also a study that was designed to test whether humans can successfully play a game with the rat. The results show that the system functioned well and that the humans were able to interact with the rat to fulfil the tasks of the game. This system opens up the possibility of new applications in the life sciences involving participant observation of and interaction with animals but at human scale. PMID:23118987

Beaming into the rat world: enabling real-time interaction between rat and human each at their own scale.

PubMed

Normand, Jean-Marie; Sanchez-Vives, Maria V; Waechter, Christian; Giannopoulos, Elias; Grosswindhager, Bernhard; Spanlang, Bernhard; Guger, Christoph; Klinker, Gudrun; Srinivasan, Mandayam A; Slater, Mel

2012-01-01

Immersive virtual reality (IVR) typically generates the illusion in participants that they are in the displayed virtual scene where they can experience and interact in events as if they were really happening. Teleoperator (TO) systems place people at a remote physical destination embodied as a robotic device, and where typically participants have the sensation of being at the destination, with the ability to interact with entities there. In this paper, we show how to combine IVR and TO to allow a new class of application. The participant in the IVR is represented in the destination by a physical robot (TO) and simultaneously the remote place and entities within it are represented to the participant in the IVR. Hence, the IVR participant has a normal virtual reality experience, but where his or her actions and behaviour control the remote robot and can therefore have physical consequences. Here, we show how such a system can be deployed to allow a human and a rat to operate together, but the human interacting with the rat on a human scale, and the rat interacting with the human on the rat scale. The human is represented in a rat arena by a small robot that is slaved to the human's movements, whereas the tracked rat is represented to the human in the virtual reality by a humanoid avatar. We describe the system and also a study that was designed to test whether humans can successfully play a game with the rat. The results show that the system functioned well and that the humans were able to interact with the rat to fulfil the tasks of the game. This system opens up the possibility of new applications in the life sciences involving participant observation of and interaction with animals but at human scale.

Desert Rats 2010 Operations Tests: Insights from the Geology Crew Members

NASA Technical Reports Server (NTRS)

Bleacher, J. E.; Hurtado, J. M., Jr.; Young, K. E.; Rice, J.; Garry, W. B.; Eppler, D.

2011-01-01

Desert Research and Technology Studies (Desert RATS) is a multi-year series of tests of NASA hardware and operations deployed in the high desert of Arizona. Conducted annually since 1997, these activities exercise planetary surface hardware and operations in relatively harsh conditions where long-distance, multi-day roving is achievable. Such activities not only test vehicle subsystems, they also stress communications and operations systems and enable testing of science operations approaches that advance human and robotic surface exploration capabilities. Desert RATS 2010 tested two crewed rovers designed as first-generation prototypes of small pressurized vehicles, consistent with exploration architecture designs. Each rover provided the internal volume necessary for crewmembers to live and work for periods up to 14 days, as well as allowing for extravehicular activities (EVAs) through the use of rear-mounted suit ports. The 2010 test was designed to simulate geologic science traverses over a 14-day period through a volcanic field that is analogous to volcanic terrains observed throughout the Solar System. The test was conducted between 31 August and 13 September 2010. Two crewmembers lived in and operated each rover for a week with a "shift change" on day 7, resulting in a total of eight test subjects for the two-week period. Each crew consisted of an engineer/commander and an experienced field geologist. Three of the engineer/commanders were experienced astronauts with at least one Space Shuttle flight. The field geologists were drawn from the scientific community, based on funded and published field expertise.

Role of aqueous extract of Cynodon dactylon in prevention of carbofuran- induced oxidative stress and acetylcholinesterase inhibition in rat brain.

PubMed

Rai, D K; Sharma, R K; Rai, P K; Watal, G; Sharma, B

2011-02-12

The present study was designed to investigate the ameliorating effect of aqueous extract of C. dactylon on carbofuran induced oxidative stress (OS) and alterations in the activity of acetylcholinesterase (AChE) in the brain of rats. Vitamin C was used as a positive control. Wistar rats were administered with single sub-acute oral dose (1.6 mgkg-1 b.wt.) of carbofuran for 24 h. The OS parameters such as lipid peroxidation (LPO) and the activities of antioxidant enzymes including super oxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST), and that of AChE were studied in brain. Carbofuran treatment significantly increased the activities of SOD and CAT by 75 and 60%, respectively. It also induced the level of LPO by 113%. In contrast, the activities of GST and AChE were recorded to be diminished by 25 and 33%, respectively. Pretreatment of the rats with aqueous extract of C. dactylon (oral; 500mgkg-1) restored SOD activity completely but CAT activity only partially (7%). Carbofuran induced LPO was moderated by 95% in the brain of C. dactylon treated rats. The observed changes in OS parameters in C. dactylon treated group were comparable to that observed in vitamin C (200 mg-kg-1 b. wt.) treated group. Surprisingly, C. dactylon treatment significantly recovered the activity of AChE to a similar level as observed in the brain of control group. In contrast vitamin C treatment did not cause significant change in the activity of AChE in carbofuran treated group. There were no noticeable changes in the aforementioned study parameters in the brain of rats receiving C. dactylon and vitamin C, only. The results suggest that the study is extremely important in the context of development of new anticholinestesterase and antioxidant antidotes against carbofuran from C. dactylon.

Investigation of mitigating effect of colon-specific prodrugs of boswellic acid on 2,4,6-trinitrobenzene sulfonic acid-induced colitis in Wistar rats: Design, kinetics and biological evaluation

PubMed Central

Sarkate, Ajinkya; Dhaneshwar, Suneela S

2017-01-01

AIM To develop a colon-targeting bioreversible delivery system for β-boswellic acid (BBA) and explore utility of its prodrugs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. METHODS Synthesis of 4 co-drugs of BBA with essential amino acids was achieved by CDI coupling, followed by their spectral characterization. In vitro kinetics were studied by HPLC in aqueous buffers, homogenates of gastrointestinal tract and fecal matter. In vivo kinetic studies were performed in Wistar rat plasma, urine and feces. The prodrugs were screened in TNBS-induced colitis modeled Wistar rats. Statistical significance was assumed at P < 0.05, P < 0.01, P < 0.001 when compared with disease controls using one-way and two-way ANOVAs. RESULTS Prodrugs were stable in 0.05 mol/L HCl buffer (pH 1.2) and stomach homogenates. Negligible hydrolysis was observed in phosphate buffer and intestinal homogenates. Substantial release (55%-72% and 68%-86%) of BBA was achieved in rat fecal matter and homogenates of colon. In vivo studies of BBA with L-tryptophan (BT) authenticated colon-specific release of BBA. But, surprisingly substantial concentration of BBA was seen to reach the systemic circulation due to probable absorption through colonic mucosa. Site-specifically enhanced bioavailability of BBA could be achieved in colon, which resulted in demonstration of significant mitigating effect on TNBS-induced colitis in rats without inducing any adverse effects on stomach, liver and pancreas. Prodrug of BT was found to be 1.7% (P < 0.001) superior than sulfasalazine in reducing the inflammation to colon among all prodrugs tested. CONCLUSION The outcome of this study strongly suggests that these prodrugs might have dual applicability to inflammatory bowel disease and chronotherapy of rheumatoid arthritis. PMID:28275295

Individual Differences in Spatial Pattern Separation Performance Associated with Healthy Aging in Humans

ERIC Educational Resources Information Center

Stark, Shauna M.; Yassa, Michael A.; Stark, Craig E. L.

2010-01-01

Rodent studies have suggested that "pattern separation," the ability to distinguish among similar experiences, is diminished in a subset of aged rats. We extended these findings to the human using a task designed to assess spatial pattern separation behavior (determining at time of test whether pairs of pictures shown during the study were in the…

Comparative Analgesic Efficacy of Pregabalin Administered According to Either a Prevention Protocol or an Intervention Protocol in Rats with Cisplatin-induced Peripheral Neuropathy.

PubMed

Han, F Y; Kuo, A; Nicholson, J R; Corradinni, L; Smith, M T

2018-05-21

Chemotherapy-induced peripheral neuropathy (CIPN) is a type of peripheral neuropathic pain that may be dose-limiting in patients administered potentially curative cancer chemotherapy dosing regimens. In cancer survivors, persistent CIPN adversely affects patient quality of life and so adjuvant drugs (anticonvulsants e.g. pregabalin or antidepressants e.g. amitriptyline) are recommended for the relief of CIPN. However, most studies in rodent models of CIPN involve administration of single bolus doses of adjuvant drugs to assess pain-relieving efficacy. Hence this study was designed to assess the efficacy of pregabalin administered to CIPN-rats according to either a prevention or an intervention protocol. Groups of male Sprague-Dawley rats received four single intraperitoneal bolus doses of cisplatin at 3 mg/kg at once-weekly intervals to induce CIPN. For the prevention protocol, oral pregabalin (or vehicle) was administered to CIPN-rats once-daily for 21 consecutive days from day 0 to day 20 inclusive. For the intervention protocol, oral pregabalin was administered once-daily for 21 consecutive days from day 28 to day 48 inclusive. Mechanical allodynia and mechanical hyperalgesia in the bilateral hindpaws were assessed just prior to each dose of cisplatin and at least once-weekly until study completion (day 27, prevention protocol; or day 48, intervention protocol). Mechanical allodynia and mechanical hyperalgesia were also determined at the time of peak effect at ~2 h post- pregabalin/vehicle administration once-weekly until study completion. For the prevention protocol in CIPN-rats, pregabalin alleviated mechanical hyperalgesia but not mechanical allodynia. For the intervention protocol, pregabalin alleviated both mechanical allodynia and mechanical hyperalgesia in the hindpaws. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Neonatal Colonic Inflammation Increases Spinal Transmission and Cystathionine β-Synthetase Expression in Spinal Dorsal Horn of Rats with Visceral Hypersensitivity

PubMed Central

Zhao, Liting; Xiao, Ying; Weng, Rui-Xia; Liu, Xuelian; Zhang, Ping-An; Hu, Chuang-Ying; Yu, Shan P.; Xu, Guang-Yin

2017-01-01

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal pain and alteration of bowel movements. The pathogenesis of visceral hypersensitivity in IBS patients remains largely unknown. Hydrogen sulfide (H2S) is reported to play an important role in development of visceral hyperalgesia. However, the role of H2S at spinal dorsal horn level remains elusive in visceral hypersensitivity. The aim of this study is designed to investigate how H2S takes part in visceral hypersensitivity of adult rats with neonatal colonic inflammation (NCI). Visceral hypersensitivity was induced by neonatal colonic injection of diluted acetic acid. Expression of an endogenous H2S synthesizing enzyme cystathionine β-synthetase (CBS) was determined by Western blot. Excitability and synaptic transmission of neurons in the substantia gelatinosa (SG) of spinal cord was recorded by patch clamping. Here, we showed that expression of CBS in the spinal dorsal horn was significantly upregulated in NCI rats. The frequency of glutamatergic synaptic activities in SG was markedly enhanced in NCI rats when compared with control rats. Application of NaHS increased the frequency of both spontaneous and miniature excitatory post-synaptic currents of SG neurons in control rats through a presynaptic mechanism. In contrast, application of AOAA, an inhibitor of CBS, dramatically suppressed the frequency of glutamatergic synaptic activities of SG neurons of NCI rats. Importantly, intrathecal injection of AOAA remarkably attenuated visceral hypersensitivity of NCI rats. These results suggest that H2S modulates pain signaling likely through a presynaptic mechanism in SG of spinal dorsal horn, thus providing a potential therapeutic strategy for treatment for chronic visceral pain in patients with IBS. PMID:29046639

The role of trigeminal nucleus caudalis orexin 1 receptors in orofacial pain transmission and in orofacial pain-induced learning and memory impairment in rats.

PubMed

Kooshki, Razieh; Abbasnejad, Mehdi; Esmaeili-Mahani, Saeed; Raoof, Maryam

2016-04-01

It is widely accepted that the spinal trigeminal nuclear complex, especially the subnucleus caudalis (Vc), receives input from orofacial structures. The neuropeptides orexin-A and -B are expressed in multiple neuronal systems. Orexin signaling has been implicated in pain-modulating system as well as learning and memory processes. Orexin 1 receptor (OX1R) has been reported in trigeminal nucleus caudalis. However, its roles in trigeminal pain modulation have not been elucidated so far. This study was designed to investigate the role of Vc OX1R in the modulation of orofacial pain as well as pain-induced learning and memory deficits. Orofacial pain was induced by subcutaneous injection of capsaicin in the right upper lip of the rats. OX1R agonist (orexin-A) and antagonist (SB-334867-A) were microinjected into Vc prior capsaicin administration. After recording nociceptive times, learning and memory was investigated using Morris water maze (MWM) test. The results indicated that, orexin-A (150 pM/rat) significantly reduced the nociceptive times, while SB334867-A (80 nM/rat) exaggerated nociceptive behavior in response to capsaicin injection. In MWM test, capsaicin-treated rats showed a significant learning and memory impairment. Moreover, SB-334867-A (80 nM/rat) significantly exaggerated learning and memory impairment in capsaicin-treated rats. However, administration of orexin-A (100 pM/rat) prevented learning and memory deficits. Taken together, these results indicate that Vc OX1R was at least in part involved in orofacial pain transmission and orexin-A has also a beneficial inhibitory effect on orofacial pain-induced deficits in abilities of spatial learning and memory. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of long-term administration of aspartame on biochemical indices, lipid profile and redox status of cellular system of male rats.

PubMed

Adaramoye, Oluwatosin A; Akanni, Olubukola O

2016-01-01

Aspartame (N-L-α-aspartyl-L-phenylalanine-1-methyl ester) (ASP) is a synthetic sweetener used in foods and its safety remains controversial. The study was designed to investigate the effects of long-term administration of aspartame on redox status, lipid profile and biochemical indices in tissues of male Wistar rats. Rats were assigned into four groups and given distilled water (control), aspartame at doses of 15 mg/kg (ASP 1), 35 mg/kg (ASP 2) and 70 mg/kg (ASP 3) daily by oral gavage for consecutive 9 weeks. Administration of ASP 2 and ASP 3 significantly increased the weight of liver and brain, and relative weight of liver of rats. Lipid peroxidation products significantly increased in the kidney, liver and brain of rats at all doses of ASP with concomitant depletion of antioxidant parameters, viz. glutathione-s-transferase, glutathione peroxidase, superoxide dismutase, catalase and reduced glutathione. Furthermore, ASP 2 and ASP 3 significantly increased the levels of gamma glutamyl transferase by 70% and 85%; alanine aminotransferase by 66% and 117%; aspartate aminotransferase by 21% and 48%; urea by 72% and 58% and conjugated bilirubin by 63% and 64%, respectively. Also, ASP 2 and ASP 3 significantly increased the levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol in the rats. Histological findings showed that ASP 2 and ASP 3 caused cyto-architectural changes such as degeneration, monocytes infiltration and necrotic lesions in brain, kidney and liver of rats. Aspartame may induce redox and lipid imbalance in rats via mechanism that involves oxidative stress and depletion of glutathione-dependent system.

Sipa1l1 is an early biomarker of liver fibrosis in CCl4-treated rats

PubMed Central

Marfà, Santiago; Morales-Ruiz, Manuel; Oró, Denise; Ribera, Jordi; Fernández-Varo, Guillermo; Jiménez, Wladimiro

2016-01-01

ABSTRACT At present, several procedures are used for staging liver fibrosis. However, these methods may involve clinical complications and/or present diagnostic uncertainty mainly in the early stages of the disease. Thus, this study was designed to unveil new non-invasive biomarkers of liver fibrosis in an in vivo model of fibrosis/cirrhosis induction by CCl4 inhalation by using a label-free quantitative LC-MS/MS approach. We analyzed 94 serum samples from adult Wistar rats with different degrees of liver fibrosis and 36 control rats. Firstly, serum samples from 18 CCl4-treated rats were clustered into three different groups according to the severity of hepatic and the serum proteome was characterized by label-free LC-MS/MS. Furthermore, three different pooled serum samples obtained from 16 control Wistar rats were also analyzed. Based on the proteomic data obtained, we performed a multivariate analysis which displayed three main cell signaling pathways altered in fibrosis. In cirrhosis, more biological imbalances were detected as well as multi-organ alterations. In addition, hemopexin and signal-induced proliferation-associated 1 like 1 (SIPA1L1) were selected as potential serum markers of liver fibrogenesis among all the analyzed proteins. The results were validated by ELISA in an independent group of 76 fibrotic/cirrhotic rats and 20 controls which confirmed SIPA1L1 as a potential non-invasive biomarker of liver fibrosis. In particular, SIPA1L1 showed a clear diminution in serum samples from fibrotic/cirrhotic rats and a great accuracy at identifying early fibrotic stages. In conclusion, the proteomic analysis of serum samples from CCl4-treated rats has enabled the identification of SIPA1L1 as a non-invasive marker of early liver fibrosis. PMID:27230648

Species differences in the localization and number of CNS beta adrenergic receptors: Rat versus guinea pig

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

Booze, R.M.; Crisostomo, E.A.; Davis, J.N.

1989-06-01

The localization and number of beta adrenergic receptors were directly compared in the brains of rats and guinea pigs. The time course of association and saturability of (125I)cyanopindolol (CYP) binding to slide-mounted tissue sections was similar in rats (Kd = 17 pM) and guinea pigs (Kd = 20 pM). The beta-1 and beta-2 receptor subtypes were examined through the use of highly selective unlabeled receptor antagonists, ICI 118,551 (50 nM) and ICI 89,406 (70 nM). Dramatic species differences between rats and guinea pigs were observed in the neuroanatomical regional localization of the beta adrenergic receptor subtypes. For example, in themore » thalamus prominent beta-1 and beta-2 receptor populations were identified in the rat; however, the entire thalamus of the guinea pig had few, if any, beta adrenergic receptors of either subtype. Hippocampal area CA1 had high levels of beta-2 adrenergic receptors in both rats and guinea pigs but was accompanied by a widespread distribution of beta-2 adrenergic receptors only in rats. Quantitative autoradiographic analyses of 25 selected neuroanatomical regions (1) confirmed the qualitative differences in CNS beta adrenergic receptor localization, (2) determined that guinea pigs had significantly lower levels of beta adrenergic receptors than rats and (3) indicated a differential pattern of receptor subtypes between the two species. Knowledge of species differences in receptor patterns may be useful in designing effective experiments as well as in exploring the relationships between receptor and innervation patterns. Collectively, these data suggest caution be used in extrapolation of the relationships of neurotransmitters and receptors from studies of a single species.« less

Recovery of skeletal muscle mass after extensive injury: positive effects of increased contractile activity.

PubMed

Richard-Bulteau, Hélène; Serrurier, Bernard; Crassous, Brigitte; Banzet, Sébastien; Peinnequin, André; Bigard, Xavier; Koulmann, Nathalie

2008-02-01

The present study was designed to test the hypothesis that increasing physical activity by running exercise could favor the recovery of muscle mass after extensive injury and to determine the main molecular mechanisms involved. Left soleus muscles of female Wistar rats were degenerated by notexin injection before animals were assigned to either a sedentary group or an exercised group. Both regenerating and contralateral intact muscles from active and sedentary rats were removed 5, 7, 14, 21, 28 and 42 days after injury (n = 8 rats/group). Increasing contractile activity through running exercise during muscle regeneration ensured the full recovery of muscle mass and muscle cross-sectional area as soon as 21 days after injury, whereas muscle weight remained lower even 42 days postinjury in sedentary rats. Proliferator cell nuclear antigen and MyoD protein expression went on longer in active rats than in sedentary rats. Myogenin protein expression was higher in active animals than in sedentary animals 21 days postinjury. The Akt-mammalian target of rapamycin (mTOR) pathway was activated early during the regeneration process, with further increases of mTOR phosphorylation and its downstream effectors, eukaryotic initiation factor-4E-binding protein-1 and p70(s6k), in active rats compared with sedentary rats (days 7-14). The exercise-induced increase in mTOR phosphorylation, independently of Akt, was associated with decreased levels of phosphorylated AMP-activated protein kinase. Taken together, these results provided evidence that increasing contractile activity during muscle regeneration ensured early and full recovery of muscle mass and suggested that these beneficial effects may be due to a longer proliferative step of myogenic cells and activation of mTOR signaling, independently of Akt, during the maturation step of muscle regeneration.

Effect of palatable hyperlipidic diet on lipid metabolism of sedentary and exercised rats.

PubMed

Estadella, Debora; Oyama, Lila M; Dâmaso, Ana R; Ribeiro, Eliane B; Oller Do Nascimento, Claudia M

2004-02-01

The present study was designed to examine 1) whether continuous feeding with a palatable hyperlipidic diet and cycling this diet with chow diet would affect lipid and carbohydrate metabolism in a similar way; and 2) whether the effect of chronic exercise on lipid and carbohydrate metabolism would be modified by these diet regimens. Male 25-d-old Wistar rats were assigned to one of six groups: sedentary rats fed with chow diet; exercised (swimming 90 min/d, 5 d/wk) rats fed with chow diet; sedentary rats fed with a palatable hyperlipidic diet; exercised rats fed with the palatable hyperlipidic diet; sedentary rats fed with food cycles (four cycles alternating the chow and hyperlipidic diets weekly); and exercised rats fed with food cycles. After 8 wk of treatment, the animals were killed 24 h after the last exercise session. The hyperlipidic diet and food cycles schedules caused similar increases in body weight gain, carcass lipogenesis rate and adiposity, lipid content of the liver and gastrocnemius muscle, and serum total lipid, triacylglycerol, insulin, and leptin levels. The exercise attenuated body weight gain, adipose tissue mass, and serum triacylglycerol, insulin, and leptin levels similarly in the hyperlipidic and food cycles groups. Carcass lipogenesis rate was not affected by exercise in any of the three groups. The data showed that the continuous intake of a hyperlipidic palatable diet for 8 wk and the alternation of the high-fat intake with periods of chow intake cause obesity and affected lipid metabolism in a similar way. Chronic exercise attenuated body weight gain and adiposity and improved serum lipid concentrations in both high-fat feeding regimens.

A grape polyphenol extract modulates muscle membrane fatty acid composition and lipid metabolism in high-fat--high-sucrose diet-fed rats.

PubMed

Aoun, Manar; Michel, Francoise; Fouret, Gilles; Schlernitzauer, Audrey; Ollendorff, Vincent; Wrutniak-Cabello, Chantal; Cristol, Jean-Paul; Carbonneau, Marie-Annette; Coudray, Charles; Feillet-Coudray, Christine

2011-08-01

Accumulation of muscle TAG content and modification of muscle phospholipid fatty acid pattern may have an impact on lipid metabolism, increasing the risk of developing diabetes. Some polyphenols have been reported to modulate lipid metabolism, in particular those issued from red grapes. The present study was designed to determine whether a grape polyphenol extract (PPE) modulates skeletal muscle TAG content and phospholipid fatty acid composition in high-fat-high-sucrose (HFHS) diet-fed rats. Muscle plasmalemmal and mitochondrial fatty acid transporters, GLUT4 and lipid metabolism pathways were also explored. The PPE decreased muscle TAG content in HFHS/PPE diet-fed rats compared with HFHS diet-fed rats and induced higher proportions of n-3 PUFA in phospholipids. The PPE significantly up-regulated GLUT4 mRNA expression. Gene and protein expression of muscle fatty acid transporter cluster of differentiation 36 (CD36) was increased in HFHS diet-fed rats but returned to control values in HFHS/PPE diet-fed rats. Carnitine palmitoyltransferase 1 protein expression was decreased with the PPE. Mitochondrial β-hydroxyacyl CoA dehydrogenase was increased in HFHS diet-fed rats and returned to control values with PPE supplementation. Lipogenesis, mitochondrial biogenesis and mitochondrial activity were not affected by the PPE. In conclusion, the PPE modulated membrane phospholipid fatty acid composition and decreased muscle TAG content in HFHS diet-fed rats. The PPE lowered CD36 gene and protein expression, probably decreasing fatty acid transport and lipid accumulation within skeletal muscle, and increased muscle GLUT4 expression. These effects of the PPE are in favour of a better insulin sensibility.

Effects of melatonin on lipid peroxidation and anti-oxidant enzyme activity in rats with experimentally induced hyperthyroidism.

PubMed

Baydas, Burhanettin; Meral, Ismail

2005-07-01

1. The present study was designed to investigate the effects of high-dose melatonin on lipid peroxidation and anti-oxidant enzyme activity in rats with experimentally induced hyperthyroidism. 2. Twenty-four albino male rats, weighing 240-260 g, were randomly allotted into one of three experimental groups (control, hyperthyroid and hyperthyroid + melatonin treatment), with each group containing eight animals. Hyperthyroidism was induced by a daily with i.p. injection of 200 microg l-thyroxine for 30 days. In addition to l-thyroxin treatment, rats in the hyperthyroid + melatonin treatment group were also given daily i.p. injections of 10 mg/kg melatonin on the last 10 days of l-thyroxine treatment. Control animals received injections of an equivalent volume of saline solution. Rats received the last injection 24 h before being killed. 3. At the end of the experiment, rats in all three groups were fasted for 12 h and killed by cardiac puncture under ether anaesthesia. Blood samples were taken for the determination of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) levels and concentrations of tri-iodothyronine (T(3)) and thyroxine (T(4)). 4. It was found that MDA and SOD levels and concentrations of T(3) and T(4) were higher and the GSH level was lower in rats with hyperthyroidism compared with controls. Melatonin treatment decreased the elevated MDA and SOD levels and increased the lowered GSH level to control levels in rats with hyperthyroidism, but did not ameliorate the concentrations of T(3) and T(4). 5. It was concluded that high-dose melatonin treatment may decrease the hyperthyroidism-induced disturbances of lipid peroxidation and anti-oxidant enzyme activity and oxidative damage.

Nephroprotective effects of b-carotene on ACE gene expression, oxidative stress and antioxidant status in thioacetamide induced renal toxicity in rats.

PubMed

Fazal, Yumna; Fatima, Syeda Nuzhat; Shahid, Syed Muhammad; Mahboob, Tabassum

2016-07-01

β -carotene is one of carotenoid natural pigments, which are produced by plants and are accountable for the bright colors of various fruits and vegetables. These pigments have been widely studied for their ability to prevent chronic diseases and toxicities. This study was designed to evaluate the effects of β-carotene on angiotensin converting enzyme (ACE) gene expression, oxidative stress and antioxidant status in thioacetamide induced renal toxicity. Total 24 albino wistar rats of male sex (200-250gm) were divided into 6 groups as Group-1: The control remained untreated; Group-2: Received thioacetamide (200mg/kg b.w; i.p) for 12 weeks; Group-3: Received β-carotene orally (200mg/kg b.w), for 24 weeks; and Group-4: Received thioacetamide (200mg/kg b.w; i.p) for 12 weeks + received β-carotene orally (200mg/kg b.w), for further 12 weeks. The expression of ACE gene in thioacetamide induced renal toxicity in rats as well as supplemented with β-carotene was investigated and compared their level with control groups by using the quantitative RT-PCR method. The ACE gene expression was significantly increase in TAA rats as compare to control rats specifies that TAA induced changes in ACE gene of kidney, elevated renal ACE has been correlated with increase hypertensive end organ renal damage. The quantity of ACE gene were diminish in our rats who received β-Carotene after TAA is administered, for this reason they seemed to be defended against increased ACE levels in kidney bought by TAA. In pre- and post-treatment groups, we studied the role of β-Carotene against thioacetamide in the kidney of Wistar rats. Experimental confirmation from our study illustrates that β-Carotene can certainly work as a successful radical-trapping antioxidant our results proved that TAA injury increased lipid peroxidation and diminish antioxidant GSH, SOD and CAT in renal tissue. Since β-Carotene administration recover renal lipid peroxidation and antioxidants, it give the impression that β-Carotene protects renal tissue against thioacetamide-induced oxidative damage.

Determining the Effects of Geraniol on Liver Regeneration Via the Nuclear Factor kB Pathway After Partial Hepatectomy.

PubMed

Ceyhan, Emre; Canbek, Mediha

2017-05-01

Context • Nuclear factor kB (NF-κB) is a dimeric transcription factor that is involved in the regulation of regenerative and apoptosic genes and plays a key role in liver regeneration after a partial hepatectomy (PH). Complementary medicine is used to treat various diseases and can be obtained from a large number of plants that are found in nature. One such plant is geraniol, and no studies have yet occurred assessing its in vivo effects on liver regeneration. Objective • The current study intended to assess the effects of geraniol on liver regeneration after a 70% PH in rats. Design • The research team studied geraniol in a rat model in vivo. Setting • The study took place in the medical and surgical experimental research center at Eskisehir Osmangazi University (Eskisehir, Turkey). Animals • The animals were Wistar albino male rats. Intervention • The rats were divided into 8 groups with 6 rats in each group. Two groups were the sham control groups. The other 6 groups received an injection of a single dose of saline, the negative control; silymarin, the negative control; or geraniol, the intervention. The injections were given intraperitoneally immediately after PH. A laparotomy was performed on the rats all of those groups at either 24 h or 48 h after the PH. Outcome Measures • Using the reverse transcription (RT)- polymerase chain reaction (PCR) method (RT-PCR) and Western blot analysis, the NF-κB, tumor necrosis factor α, and interleukin 6 gene expression and protein levels were measured. Moreover, the levels of the heat shock proteins (HSPs) HSP27 and HSP60 were examined by Western blot. Results • The data showed that geraniol had a significant role (P < .05) in increasing the process of liver regeneration when given intraperitoneally, and it protected the liver as assessed by histology and the HSP levels. In rats receiving 100 mg/kg geraniol intraperitoneally, the agent induced hepatic regeneration 24 h and 48 h after PH (70%).

Thymidine kinase 1 as a molecular target for boron neutron capture therapy of brain tumors

PubMed Central

Barth, Rolf F.; Yang, Weilian; Wu, Gong; Swindall, Michele; Byun, Youngjoo; Narayanasamy, Sureshbabu; Tjarks, Werner; Tordoff, Kevin; Moeschberger, Melvin L.; Eriksson, Staffan; Binns, Peter J.; Riley, Kent J.

2008-01-01

The purpose of the present study was to evaluate the effectiveness of a 3-carboranyl thymidine analogue (3CTA), 3-[5-{2-(2,3-dihydroxyprop-1-yl)-o-carboran-1-yl}pentan-1-yl] thymidine, designated N5–2OH, for boron neutron capture therapy (BNCT) of brain tumors using the RG2 rat glioma model. Target validation was established using the thymidine kinase (TK) 1(+) wild-type, murine L929 cell line and its TK1(−) mutant counterpart, which were implanted s.c. (s.c.) into nude mice. Two intratumoral (i.t.) injections of 10B-enriched N5–2OH were administered to tumor-bearing mice at 2-hour intervals, after which BNCT was carried out at the Massachusetts Institute of Technology (MIT) Research Reactor. Thirty days after BNCT, mice bearing TK1(+) L929 tumors had a 15× reduction in tumor volume compared with TK1(−) controls. Based on these favorable results, BNCT studies were then initiated in rats bearing intracerebral (i.c.) RG2 gliomas, after i.c. administration of N5–2OH by Alzet osmotic pumps, either alone or in combination with i.v. (i.v.) boronophenylalanine (BPA), a drug that has been used clinically. The mean survival times (MSTs) of RG2 glioma bearing rats were 45.6 ± 7.2 days, 35.0 ± 3.3days, and 52.9 ± 8.9 days, respectively, for animals that received N5–2OH, BPA, or both. The differences between the survival plots of rats that received N5–2OH and BPA alone were highly significant (P = 0.0003). These data provide proof-of-principle that a 3CTA can function as a boron delivery agent for NCT. Further studies are planned to design and synthesize 3CTAs with enhanced chemical and biological properties, and increased therapeutic efficacy. PMID:18981415

Protective role of Hibiscus sabdariffa calyx extract against streptozotocin induced sperm damage in diabetic rats

PubMed Central

Idris, Muhd Hanis Md; Budin, Siti Balkis; Osman, Mohamad; Mohamed, Jamaludin

2012-01-01

Diabetes mellitus contributes to male sexual dysfunction and infertility by modulating oxidative damage. To date, a number of studies have demonstrated antioxidant properties of Hibiscus sabdariffa Linn. This study was designed to investigate the effects of H. sabdariffa UKMR-2 variety on sperm functioning of streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were allotted into four groups, namely control group (C), H. sabdariffa extract (HSE) group, diabetes group (D) and diabetes plus HSE group (D+HSE). HSE (100 mg/ kg/body weight) was administered orally for 28 consecutive days. After 28-days of supplementation, the rats were sacrificed to obtain epididymal sperm. Administration of HSE significantly lowered the level of fasting blood glucose and increased plasma insulin level in D+HSE group as compared to D group (p<0.05). Sperm quality in the D+HSE group was improved with significantly higher sperm concentrations (p<0.05) and sperm motility (p<0.001) as well as lower percentage of sperm abnormality (p<0.05) as compared to the diabetic group. Plasma follicle-stimulating hormone (FSH) level was significantly elevated (p<0.05) in D+HSE group than in D group while no significant alteration in plasma testosterone and luteinizing hormone (LH) level were seen between groups. In conclusion, this study suggested that H. sabdariffa UKMR-2 variety has a potential protective role against diabetes-induced sperm damage. PMID:27847454

Protective role of Hibiscus sabdariffa calyx extract against streptozotocin induced sperm damage in diabetic rats.

PubMed

Idris, Muhd Hanis Md; Budin, Siti Balkis; Osman, Mohamad; Mohamed, Jamaludin

2012-01-01

Diabetes mellitus contributes to male sexual dysfunction and infertility by modulating oxidative damage. To date, a number of studies have demonstrated antioxidant properties of Hibiscus sabdariffa Linn. This study was designed to investigate the effects of H. sabdariffa UKMR-2 variety on sperm functioning of streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were allotted into four groups, namely control group (C), H. sabdariffa extract (HSE) group, diabetes group (D) and diabetes plus HSE group (D+HSE). HSE (100 mg/ kg/body weight) was administered orally for 28 consecutive days. After 28-days of supplementation, the rats were sacrificed to obtain epididymal sperm. Administration of HSE significantly lowered the level of fasting blood glucose and increased plasma insulin level in D+HSE group as compared to D group (p<0.05). Sperm quality in the D+HSE group was improved with significantly higher sperm concentrations (p<0.05) and sperm motility (p<0.001) as well as lower percentage of sperm abnormality (p<0.05) as compared to the diabetic group. Plasma follicle-stimulating hormone (FSH) level was significantly elevated (p<0.05) in D+HSE group than in D group while no significant alteration in plasma testosterone and luteinizing hormone (LH) level were seen between groups. In conclusion, this study suggested that H. sabdariffa UKMR-2 variety has a potential protective role against diabetes-induced sperm damage.

Mast cells in the sheep, hedgehog and rat forebrain

PubMed Central

MICHALOUDI, HELEN C.; PAPADOPOULOS, GEORGIOS C.

1999-01-01

The study was designed to reveal the distribution of various mast cell types in the forebrain of the adult sheep, hedgehog and rat. Based on their histochemical and immunocytochemical characteristics, mast cells were categorised as (1) connective tissue-type mast cells, staining metachromatically purple with the toluidine blue method, or pale red with the Alcian blue/safranin method, (2) mucosal-type or immature mast cells staining blue with the Alcian blue/safranin method and (3) serotonin immunopositive mast cells. All 3 types of brain mast cells in all species studied were located in both white and grey matter, often associated with intraparenchymal blood vessels. Their distribution pattern exhibited interspecies differences, while their number varied considerably not only between species but also between individuals of each species. A distributional left-right asymmetry, with more cells present on the left side, was observed in all species studied but it was most prominent in the sheep brain. In the sheep, mast cells were abundantly distributed in forebrain areas, while in the hedgehog and the rat forebrain, mast cells were less widely distributed and were relatively or substantially fewer in number respectively. A limited number of brain mast cells, in all 3 species, but primarily in the rat, were found to react both immunocytochemically to 5-HT antibody and histochemically with Alcian blue/safranin staining. PMID:10634696

77 FR 3 - Airworthiness Directives; Dassault Aviation Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-03

... (RAT) transformer rectifier units (TRUs). This AD was prompted by a report of incorrect design of the... an unsafe condition for the specified products. The MCAI states: The manufacturer of the Transformer..., certificated in any category; equipped with any ram air turbine (RAT) transformer rectifier unit (TRU) having...

TRANSGENERATIONAL (IN UTERO/LACTATIONAL) EXPOSURE PROTOCOL TO INVESTIGATE THE EFFECTS OF ENDOCRINE DISRUPTING COMPOUNDS (EDCS) IN RATS

EPA Science Inventory

This protocol is designed to evaluate the effects of Endocrine Disrupting Compounds (EDCs) through fetal (transplacental) and/or neonatal (via the dam's milk) exposure during the critical periods of reproductive organogenesis in the rat. Continued direct exposure to the F1 pups...

Acute intraperitoneal administration of taurine decreases the glycemia and reduces food intake in type 1 diabetic rats.

PubMed

Gomez, Rosane; Caletti, Greice; Arbo, Bruno Dutra; Hoefel, Ana Lúcia; Schneider, Ricardo; Hansen, Alana Witt; Pulcinelli, Rianne Remus; Freese, Luana; Bandiera, Solange; Kucharski, Luiz Carlos; Barros, Helena Maria Tanhauser

2018-07-01

Taurine, an amino acid with antioxidant and osmoregulatory properties, has been studied for its possible antidiabetic properties in type 1 and type 2 diabetic animals. In type 2 diabetic mice, taurine decreases blood glucose through increased insulin secretion and insulin receptor sensitization. However, insulin is absent in type 1 diabetic individuals. The aim of this study was to evaluate the effects of taurine on parameters related to the energy balance that could explain the metabolic action of this amino acid in type 1 diabetic rats. Control and streptozotocin-induced diabetic rats received saline or taurine (100 mg/kg/day), intraperitoneally, for 30 days. Parameters such as palatable food intake, gastrointestinal transit rate, serum glucose, insulin, leptin, and glucagon levels were measured 60 min after the last taurine administration. Liver, kidneys, heart, and retroperitoneal fat were dissected and weighted. Glycogen levels were measured in the liver and soleus muscle. Our results showed that acute taurine administration decreased glycemia. It also decreased food intake in diabetic rats, without affecting other metabolic parameters. Altogether, our results suggest that in type 1 diabetic rats, taurine decreases blood glucose by a non-insulin-dependent mechanism. Due to the safety profile of taurine, and its effect on glycemia, this amino acid may help to design new drugs to add benefit to insulin therapy in type 1 diabetic individuals. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Blood biochemistry and hematological changes in rats after administration of a mixture of three anesthetic agents

PubMed Central

OCHIAI, Yuichiro; BABA, Atushi; HIRAMATSU, Mio; TOYOTA, Naoto; WATANABE, Toshihiko; YAMASHITA, Kazuto; YOKOTA, Hiroshi; IWANO, Hidetomo

2017-01-01

Currently, given the concerns regarding animal welfare, it is required that anesthesia or analgesia be used during surgery in experimental animals. Therefore, it is important to understand how anesthesia affects the health conditions of experimental animals. In this study, rat blood biochemistry and hematological changes were examined following administration of a mixture of three anesthetic agents—medetomidine, midazolam and butorphanol (MMB). One of three MMB dose combinations was subcutaneously administered to rats. After 1 hr, rats were treated with atipamezole, to reverse the anesthetic effects. Blood biochemistry and hematological parameters were assessed at 1, 4 and 24 hr post-MMB treatment. We also recorded body weight and food intake at 0, 2, 4, 6 and 24 hr post-MMB administration. Following MMB administration, transient increases were observed in glucose (GLUC) levels, hematocrit (HCT) values and hemoglobin (HGB) levels, whereas transient decreases were observed in total protein (TP) content and white blood cell (WBC) counts. Most of these parameters returned to control values 24 hr following MMB administration. Additionally, body weight and food intake decreased in MMB-treated rats. In conclusion, intermediate and high doses of MMB changed some blood biochemistry and hematological parameters, body weight and food intake. In contrast, low-dose MMB did not cause these effects. Therefore, depending on the experimental design, MMB may influence the results of studies that use laboratory animals. Consequently, anesthetic agents used in laboratory animals should be chosen based on detailed knowledge of their pharmacological effects. PMID:29249748

Changes in nerve conduction and Pi/PCr ratio during denervation-reinnervation of the gastrocsoleus muscles of rats

NASA Technical Reports Server (NTRS)

Lai, K. S.; Jaweed, M. M.; Seestead, R.; Herbison, G. J.; Ditunno, J. F. Jr; McCully, K.; Chance, B.

1992-01-01

The purpose of this investigation was to study the changes in nerve conduction and phosphate metabolites of the gastrocsoleus muscles of rats during denervation-reinnervation. Sixteen male Sprague-Dawley rats underwent unilateral crush-denervation of the left sciatic nerves at the sciatic notch. Six rats were used for measurement of motor conduction latency and action potential amplitude of the gastrocsoleus muscle by stimulating the sciatic nerve at one, two and eight weeks after nerve crush. The other ten rats were designated for evaluation of the ratio of inorganic phosphorous (Pi) to phosphocreatine (PCr) by a 31P-phosphoenergetic spectrometer at two weeks and eight weeks after nerve crush. None of the sciatic nerves showed conduction to the gastrocsoleus at one or two weeks after nerve crush. At eight weeks postcrush, the motor conduction latency returned to within normal limits, whereas the action potential amplitude was only 55% of the normal. For the eight-week period of study, the Pi/PCr ratio of the normal control muscles ranged between 0.09 +/- 0.02 and 0.11 +/- 0.02 (mean +/- SD). The denervated muscles showed an increase of Pi/PCr ratio by 54% at two weeks postcrush, compared to the respective contralateral control sides. The ratios returned to the normal value by eight weeks postcrush. In summary, these data suggested that the metabolic recovery of the crush-denervated muscle followed the same pattern as the parameters of nerve conduction.

Voluntary exercise enhances activity rhythms and ameliorates anxiety- and depression-like behaviors in the sand rat model of circadian rhythm-related mood changes.

PubMed

Tal-Krivisky, Katy; Kronfeld-Schor, Noga; Einat, Haim

2015-11-01

Physical exercise is a non-pharmacological treatment for affective disorders. The mechanisms of its effects are unknown although some suggest a relationship to synchronization of circadian rhythms. One way to explore mechanisms is to utilize animal models. We previously demonstrated that the diurnal fat sand rat is an advantageous model for studying the interactions between photoperiods and mood. The current study was designed to evaluate the effects of voluntary exercise on activity rhythms and anxiety and depression-like behaviors in sand rats as a step towards better understanding of the underlying mechanisms. Male sand rats were housed in short photoperiod (SP; 5h light/19 h dark) or neutral light (NP; 12h light/12h dark) regimens for 3 weeks and divided into subgroups with or without running wheels. Activity was monitored for 3 additional weeks and then animals were tested in the elevated plus-maze, the forced swim test and the social interaction test. Activity rhythms were enhanced by the running wheels. As hypothesized, voluntary exercise had significant effects on SP animals' anxiety- and depression-like behaviors but not on NP animals. Results are discussed in the context of interactions between physical exercise, circadian rhythms and mood. We suggest that the sand rat model can be used to explore the underlying mechanism of the effects of physical exercise for mood disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Dietary nucleotide supplementation raises erythrocyte 2, 3-diphosphoglycerate concentration in neonatal rats.

PubMed

Scopesi, F; Verkeste, C M; Paola, D; Gazzolo, D; Pronzato, M A; Bruschettini, P L; Marinari, U M

1999-03-01

The present study was designed to test if dietary intake of nucleotides increases erythrocyte 2,3-diphosphoglycerate (2,3-DPG) in neonatal rats. To this end, rat pups were fed a nucleotide-supplemented formula (S, n = 14) from d 9 until d 16 after birth. The results were compared with those obtained from a group of breast-fed pups (C, n = 14) and a group of pups artificially fed with nucleotide-free formula (NS, n = 14). Neonatal weight, 2,3-DPG concentration, hematocrit (Hct) and hemoglobin concentration (Hb) were determined before the experiment (d 9) and after 7 d of treatment (d 16). In all groups, 2,3-DPG concentration was greater at d 16 than d 9, and the increase was greater in the S group than in the NS group. Alterations in neonatal weight, Hct and Hb concentration did not differ among the groups. On d 16 the 2, 3-DPG/Hb ratio, reflecting the affinity of hemoglobin for oxygen, was significantly higher in the C and S groups than in the NS group. We conclude that in neonatal rats, dietary nucleotides increase erythrocyte 2,3-DPG concentration. Studies need to be conducted in humans to assess the effect of this increase on both neonatal peripheral hemodynamics and metabolism in this species.

Anti-fibrosis effects of Huisheng oral solution in CCl4-induced hepatic fibrosis in rat.

PubMed

Li, Wenting; Wu, Yuanbo; Zhu, Chuanlong; Wang, Zheng; Gao, Rentao; Wu, Quan

2014-01-01

Some gradient of Huisheng oral solution (HOS) has been reported to have anti-fibrosis activity. This study was designed to investigate whether HOS could inhibit liver fibrosis and to elucidate its molecular mechanism of action. Hepatic fibrosis model in rat was induced by subcutaneous injection of CCl4. Rats in the treatment group were administrated with HOS intragastrically. Hematoxylin and eosin (H and E) staining and Masson's trichrome staining were used to examine the changes in liver pathology. Levels of ALT, AST, LDH, hyaluronic acid (HA) and laminin (LN) in serum and hydroxyproline (Hyp) in liver were detected by biochemical examination and radioimmunoassay, respectively. The expression and distribution of Smad3, TGF-β1, α-SMA and TIMP-1 were observed and the active TGF-β1 was tested. Our data demonstrated that HOS alleviated CCl4-induced collagen deposition in liver tissue, improved liver condition and liver function in rats. HOS also significantly reduced the expression and distribution of Smad3, TGF-β1, α-SMA and TIMP-1 as well as decreased active TGF-β1. This study revealed that HOS attenuates the development of liver fibrosis through suppressing the TGF-β1 pathway. It provides us a new approach to treatment of liver fibrosis.

Combination cell therapy with mesenchymal stem cells and neural stem cells for brain stroke in rats.

PubMed

Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Razi, Zahra; Delavari, Somayeh; Shakibajahromi, Benafsheh; Sarvestani, Fatemeh Sabet; Kazemi, Sepehr; Semsar, Maryam

2015-05-01

Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats.

Immunomodulatory potential of Anacyclus pyrethrum (L.) and Mucuna pruriens (L.) In male albino rats.

PubMed

Yousaf, F; Shahid, M; Riaz, M; Atta, A; Fatima, H

2017-01-01

The present study was designed to investigate the immunomodulatory potential of Anacyclus pyrethrum roots and Mucuna pruriens seeds in male albino rats. The roots of A. pyrethrum and seeds of M. pruriens were extracted with methanolic solvent (70:30) and administered at dose concentrations of 50, 100 and 200 mg/Kg body weight to healthy male rats. The immune system of rats was suppressed by injecting carbon tetrachloride to animals in the toxic control group and test group animals. Cell-mediated immune response of animals was examined by performing neutrophil adhesion test and the humoral immune response was evaluated by determining serum immunoglobulin levels of the animals under study. The administration of methanolic extracts of A. pyrethrum roots and M. pruriens seeds significantly (p less than 0.05) increased the neutrophil adhesion to the nylon fiber. Increase in % neutrophil adhesion was observed in animals treated with 200 mg of each plant extract. Significant (p less than 0.05) improvement in immunoglobulin levels was recorded in the extract treated group animals, showing that the root extract of A. pyrethrum and seed extract of M. pruriens have immunomodulatory potential. We therefore conclude that the tested extracts can be used as immunomodulatory agents to stimulate the immune system.

Studies on cerebral protection of digoxin against hypoxic-ischemic brain damage in neonatal rats.

PubMed

Peng, Kaiwei; Tan, Danfeng; He, Miao; Guo, Dandan; Huang, Juan; Wang, Xia; Liu, Chentao; Zheng, Xiangrong

2016-08-17

Hypoxic-ischemic brain damage (HIBD) is a major cause of neonatal acute deaths and chronic nervous system damage. Our present study was designed to investigate the possible neuroprotective effect of digoxin-induced pharmacological preconditioning after hypoxia-ischemia and underlying mechanisms. Neonatal rats were assigned randomly to control, HIBD, or HIBD+digoxin groups. Pharmacological preconditioning was induced by administration of digoxin 72 h before inducing HIBD by carotid occlusion+hypoxia. Behavioral assays, and neuropathological and apoptotic assessments were performed to examine the effects; the expression of Na/K ATPase was also assessed. Rats in the HIBD group showed deficiencies on the T-maze, radial water maze, and postural reflex tests, whereas the HIBD+digoxin group showed significant improvements on all behavioral tests. The rats treated with digoxin showed recovery of pathological conditions, increased number of neural cells and proliferative cells, and decreased number of apoptotic cells. Meanwhile, an increased expression level of Na/K ATPase was observed after digoxin preconditioning treatment. The preconditioning treatment of digoxin contributed toward an improved functional recovery and exerted a marked neuroprotective effect including promotion of cell proliferation and reduction of apoptosis after HIBD, and the neuroprotective action was likely associated with increased expression of Na/K ATPase.

Absorption Kinetics of the Main Conjugated Linoleic Acid Isomers in Commercial-Rich Oil after Oral Administration in Rats.

PubMed

Rodríguez-Alcalá, Luís M; Ares, Irma; Fontecha, Javier; Martínez-Larrañaga, María-Rosa; Anadón, Arturo; Martínez, María-Aránzazu

2017-09-06

This study aimed to assess the oral absorption and plasma kinetics of two main isomers contained in commercial conjugated linoleic acid (CLA)-rich oil (Tonalin TG-80), rumenic acid (RA), and C18:2 trans-10, cis-12. The isomer plasma disposition after the single oral dose of 3000 mg of Tonalin TG-80/kg, containing 1200 mg/kg of each isomer, was studied in rats. The isomer plasma concentrations were determined by gas chromatography with flame ionization detection. The plasma kinetics showed rapid oral absorption of RA and C18:2 trans-10, cis-12 (t 1/2a 0.34 ± 0.09 and 0.53 ± 0.01 h) and slow elimination (t 1/2β 25.68 ± 3.29 and 18.12 ± 1.71 h); the maximal isomer plasma concentrations (C max ) of 8.48 ± 0.98 and 7.67 ± 0.80 μg mL -1 , respectively, were estimated at 2.08 ± 0.14 and 2.26 ± 0.11 h. Our results from a preclinical kinetic study in rats help to design future studies in humans for evaluating the CLA isomer dose-response.

[Urine metabonomic study on long-term use of total ginsenosides in rats].

PubMed

Xie, Xie; Chen, Shao-Qiu; Lv, Ying-Fang; Wang, Xiao-Yan; Jia, Wei

2014-12-01

Due to its effect of systems regulation and promotion on body, Ginseng is always referred to be long-term used as a dietary supplement. But it was still unclear about its target of the tonic effects and also the side-effects long-term use may bring. Urine metabolomic method is suitable for long-term studies of pharmaco-dynamics, pharmacology and toxicology of traditional Chinese medicine because of its characteristics of non-invasive and monitoring the whole-body metabolism. This study was designed to detect the dynamic variation of rat urine metabolome along with a long-term administration of total ginsenosides using GC-TOF based metabolomic technology. Our result showed that either short-term or chronic administration of ginsenosides did not impact the rat urine metabolome significantly (as the PCA subgroup was not successful). By comparison, the short-term (1-3 w) dose of ginsenosides had the biggest metabolic influence including TCA cycle, catecholamines and neurotransmitter amino acids. Medium-term (6-10 w) dose had a gradually lower effect and long-term (27 w) dose almost had no effect. Our study indicates that both short and long-term administration of ginsenosides showed almost no obvious side-effect on the experimental animals.

Oral treatment with complement factor C5a receptor (CD88) antagonists inhibits experimental periodontitis in rats.

PubMed

Breivik, T; Gundersen, Y; Gjermo, P; Taylor, S M; Woodruff, T M; Opstad, P K

2011-12-01

The complement activation product 5a (C5a) is a potent mediator of the innate immune response to infection, and may thus also importantly determine the development of periodontitis. The present study was designed to explore the effect of several novel, potent and orally active C5a receptor (CD88) antagonists (C5aRAs) on the development of ligature-induced periodontitis in an animal model. Three different cyclic peptide C5aRAs, termed PMX205, PMX218 and PMX273, were investigated. Four groups of Wistar rats (n = 10 in each group) were used. Starting 3 d before induction of experimental periodontitis, rats either received one of the C5aRas (1-2 mg/kg) in the drinking water or received drinking water only. Periodontitis was assessed when the ligatures had been in place for 14 d. Compared with control rats, PMX205- and PMX218-treated rats had significantly reduced periodontal bone loss. The findings suggest that complement activation, and particularly C5a generation, may play a significant role in the development and progression of periodontitis. Blockade of the major C5a receptor, CD88, with specific inhibitors such as PMX205, may offer novel treatment options for periodontitis. © 2011 John Wiley & Sons A/S.

Protective effects of agmatine on doxorubicin-induced chronic cardiotoxicity in rat.

PubMed

Yarmohmmadi, Fatemeh; Rahimi, Nastaran; Faghir-Ghanesefat, Hedyeh; Javadian, Nina; Abdollahi, Alireza; Pasalar, Parvin; Jazayeri, Farahnaz; Ejtemaeemehr, Shahram; Dehpour, Ahmad Reza

2017-02-05

The detrimental cardio-toxic effect of doxorubicin, an effective chemotherapeutic agent, limited its clinical use. It has been claimed that doxorubicin cardio-toxicity occurs through calcium ions (Ca 2+ ) overload and reactive oxygen species production. Agmatine, an endogenous imidazoline receptor agonist, induce uptake of cytosolic Ca 2+ and cause an increase in activity of calcium pumps, including Ca 2+ -ATPase. Also it shows self-scavenging effect against reactive oxygen species production. Therefore, present study was designed to investigate the effects of agmatine against chronic cardio-toxicity of doxorubicin in rats. Male wistar rats were intraperitoneally injected with doxorubicin and agmatine four times a week for a month. Agmatine significantly alleviate the adverse effect of doxorubicin on left ventricular papillary muscle stimulation threshold and contractibility. Chronic co-administration of agmatine with doxorubicin blocked electrocardiographic changes induced by doxorubicin. In addition, agmatine improved body weight and decreased the mortality rate of animals by doxorubicin. Moreover, reversing the doxorubicin induced myocardial lesions was observed in animals treated by agmatine. A significant rise in the total antioxidant capacity of rat plasma was achieved in agmatine-treated animals in comparison to doxorubicin. To conclude, agmatine may improve therapeutic outcomes of doxorubicin since it exerts protective effects against doxorubicin-induced chronic cardiotoxicity in rats. Copyright © 2016 Elsevier B.V. All rights reserved.

Anti-inflammatory and antipyretic properties of Corchorus olitorius aqueous root extract in Wistar rats.

PubMed

Owoyele, Bamidele V; Oyewole, Aboyeji L; Alimi, Modupe L; Sanni, Shukurat A; Oyeleke, Sabitiu A

2015-07-01

This study was designed to provide information about the antipyretic and anti-inflammatory effects of Corchorus olitorius root. Thirty male Wistar rats were divided into six groups of five animals each; the control and reference groups were administered normal saline (10 mL/kg) and indomethacin (5 mg/kg), respectively, whereas the remaining four groups were administered aqueous extract of C. olitorius at doses of 25, 50, 100, or 200 mg/kg, respectively. Pyrexia was induced by injecting 10 mL/kg of 20% (w/v) brewer's yeast suspension into the dorsum of rats, whereas inflammation was induced through an injection of 0.1% carrageenan into the right hind paw of each rat and through a subcutaneous implantation of a 30-g sterilized cotton pellet into the groin of each rat. The results showed that C. olitorius root extract (p<0.05) decreased the elevated temperature after brewer's yeast injection compared with the 17 h (pre-drug) temperature. In the inflammatory tests, the paw sizes and granuloma weights in the test groups were significantly (p<0.05) decreased compared with the control group. Corchorus olitorius root is another good source of phytomedicine that can be used effectively to treat inflammation and pyrexia that accompany some diseases.

Rapamycin Enhances Repressed Autophagy and Attenuates Aggressive Progression in a Rat Model of IgA Nephropathy.

PubMed

Liu, Di; Liu, Yexin; Chen, Guochun; He, Liyu; Tang, Chengyuan; Wang, Chang; Yang, Danyi; Li, Huiqiong; Dong, Zheng; Liu, Hong

2017-01-01

IgA nephropathy (IgAN) has been considered to be the most frequent form of primary glomerulonephritis that occurs worldwide with a variety of factors involved in its occurrence and development. The impact of autophagy in IgAN, however, remains partially unclear. This study was designed to investigate the effects of rapamycin in an IgAN model. After establishing an IgAN rat model, SD rats were divided into 4 groups: control, control + rapamycin, IgAN, IgAN + rapamycin. Proteinuria and the pathological changes and the level of autophagy of kidney were texted. Identify the expression of phosphorylation and total mammalian target of rapamycin (mTOR) and s6k1 as well as cyclin D1 in the kidney of rats through Western blot and immunohistochemistry. With rapamycin treatment, we observed a significant reduction in the progression of proteinuria as well as alleviation of pathological lesions in IgAN rats. Besides, autophagy was inhibited, while the mTOR/S6k1 pathway was activated and expression of cyclin D1 was increased in IgAN. Rapamycin treatment increased autophagy and decreased the expression of cyclin D1. These results may suggest that mTOR-mediated autophagy inhibition may result in mesangial cell proliferation in IgAN. © 2017 S. Karger AG, Basel.

Replay of Episodic Memories in the Rat.

PubMed

Panoz-Brown, Danielle; Iyer, Vishakh; Carey, Lawrence M; Sluka, Christina M; Rajic, Gabriela; Kestenman, Jesse; Gentry, Meredith; Brotheridge, Sydney; Somekh, Isaac; Corbin, Hannah E; Tucker, Kjersten G; Almeida, Bianca; Hex, Severine B; Garcia, Krysten D; Hohmann, Andrea G; Crystal, Jonathon D

2018-05-21

Vivid episodic memories in people have been characterized as the replay of multiple unique events in sequential order [1-3]. The hippocampus plays a critical role in episodic memories in both people and rodents [2, 4-6]. Although rats remember multiple unique episodes [7, 8], it is currently unknown if animals "replay" episodic memories. Therefore, we developed an animal model of episodic memory replay. Here, we show that rats can remember a trial-unique stream of multiple episodes and the order in which these events occurred by engaging hippocampal-dependent episodic memory replay. We document that rats rely on episodic memory replay to remember the order of events rather than relying on non-episodic memories. Replay of episodic memories survives a long retention-interval challenge and interference from the memory of other events, which documents that replay is part of long-term episodic memory. The chemogenetic activating drug clozapine N-oxide (CNO), but not vehicle, reversibly impairs episodic memory replay in rats previously injected bilaterally in the hippocampus with a recombinant viral vector containing an inhibitory designer receptor exclusively activated by a designer drug (DREADD; AAV8-hSyn-hM4Di-mCherry). By contrast, two non-episodic memory assessments are unaffected by CNO, showing selectivity of this hippocampal-dependent impairment. Our approach provides an animal model of episodic memory replay, a process by which the rat searches its representations in episodic memory in sequential order to find information. Our findings using rats suggest that the ability to replay a stream of episodic memories is quite old in the evolutionary timescale. Copyright © 2018 Elsevier Ltd. All rights reserved.

Familiarity-Based Stimulus Generalization of Conditioned Suppression

PubMed Central

2017-01-01

We report that stimulus novelty/familiarity is able to modulate stimulus generalization and discuss the theoretical implications of novelty/familiarity coding. Rats in Skinner boxes received clicker → shock pairings before generalization testing to a tone. Before clicker training, different groups of rats received preexposure treatments designed to systematically modulate the clicker and the tone’s novelty and familiarity. Rats whose preexposure matched novelty/familiarity (i.e., either both or neither clicker and tone were preexposed) showed enhanced suppression to the tone relative to rats whose preexposure mixed novelty/familiarity (i.e., only clicker or tone was preexposed). This was not the result of sensory preconditioning to clicker and tone. PMID:28383938

Oral treatment with Euterpe oleracea Mart. (açaí) extract improves cardiac dysfunction and exercise intolerance in rats subjected to myocardial infarction

PubMed Central

2014-01-01

Background This study was designed to evaluate the cardioprotective effects of Euterpe oleracea Mart., popularly known as “açaí”, on rats subjected to myocardial infarction (MI). Methods Hydroalcoholic extracts of açaí were obtained from a decoction of the seeds. Two male Wistar rat groups were delineated: 1) the sham-operated group (control, n = 6), with no surgical amendment, and 2) the MI group (n = 12), in which the anterior descendent coronary artery was occluded during surgery. MI group was divided into two subgroups, in which rats were either treated with hydroalcoholic extract of Euterpe oleracea seeds (100 mg/kg/day p.o.) or received no treatment. Treatment began on the day of surgery, and lasted 4 weeks. Subsequently, rats were subject to an exercise test protocol, hemodynamic evaluation, and histological analysis of the left ventricle. Groups were compared using one-way analysis of variance (ANOVA), followed by Dunnett’s test. Results The total running distance of sham rats was 1339.0 ± 276.6 m, MI rats was 177.6 ± 15.8 m (P < 0.05), and MI-açaí rats was 969.9 ± 362.2 m. Systolic arterial pressure was significantly decreased in MI rats (86.88 ± 4.62 mmHg) compared to sham rats (115.30 ± 7.24 mmHg; P < 0.05). Açaí treatment prevented a reduction in systolic arterial pressure (130.00 ± 8.16 mmHg) compared to MI rats (P < 0.05). Left ventricular (LV) end-diastolic pressure was significantly augmented in MI rats (17.62 ± 1.21 mmHg) compared to sham rats (4.15 ± 1.60 mmHg; P < 0.05), but was 3.69 ± 2.69 mmHg in açaí-treated rats (P < 0.05 vs. MI). The LV relaxation rate (-dp/dt) was reduced in MI rats compared to the sham group, whereas açaí treatment prevented this reduction. Açaí treatment prevented cardiac hypertrophy and LV fibrosis in MI rats. Conclusions Euterpe oleracea treatment of MI rats prevented the development of exercise intolerance, cardiac hypertrophy, fibrosis, and dysfunction. PMID:25000822

Prevention of anemia alleviates heart hypertrophy in copper deficient rats

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

Lure, M.D.; Fields, M.; Lewis, C.G.

1991-03-11

The present investigation was designed to examine the role of anemia in the cardiomegaly and myocardial pathology of copper deficiency. Weanling rats were fed a copper deficient diet containing either starch (ST) or fructose (FRU) for five weeks. Six rats consuming the FRU diet were intraperitoneally injected once a week with 1.0 ml/100g bw of packed red blood cells (RBC) obtained from copper deficient rats fed ST. FRU rats injected with RBC did not develop anemia. Additionally, none of the injected rats exhibited heart hypertrophy or gross pathology and all survived. In contrast, non-injected FRU rats were anemic, exhibited severemore » signs of copper deficiency which include heart hypertrophy with gross pathology, and 44% died. Maintaining the hematocrit with RBC injections resulted in normal heart histology and prevented the mortality associated with the fructose x copper interaction. The finding suggest that the anemia associated with copper deficiency contributes to heart pathology.« less

Effect of Korean Red Ginseng treatment on the gene expression profile of diabetic rat retina

PubMed Central

Yang, Hana; Son, Gun Woo; Park, Hye Rim; Lee, Seung Eun; Park, Yong Seek

2015-01-01

Background Korean Red Ginseng (KRG) is a herbal medicine used in Asian countries and is very popular for its beneficial biological properties. Diabetes mellitus (DM) and its complications are rapidly becoming a global public health concern. The literature on transcriptional changes induced by KRG in rat models of diabetic retinopathy is limited. Considering these facts, we designed this study to determine whether retinopathy-associated genes are altered in retinas of rats with DM and whether the induced changes are reversed by KRG. Methods Male Sprague–Dawley rats were intravenously injected with streptozotocin (50 mg/kg body weight) to induce DM, following which, KRG powder (200 mg/kg body weight) was orally administered to the KRG-treated DM rat group for 10 wks. The rats were then sacrificed, and their retinas were harvested for total RNA extraction. Microarray gene expression profiling was performed on the extracted RNA samples. Results From among > 31,000 genes investigated, the expression of 268 genes was observed to be upregulated and that of 58 genes was downregulated, with twofold altered expression levels in the DM group compared with those in the control group. Moreover, 39 genes were upregulated more than twofold and 84 genes were downregulated in the KRG-treated group compared to the DM group. The expression of the genes was significantly reversed by KRG treatment; some of these genes were analyzed further to verify the results of the microarray experiments. Conclusion Taken together, our data suggest that reversed changes in the gene expression may mediate alleviating activities of KRG in rats with diabetic retinopathy. PMID:26843816

Interdependency between mechanical parameters and afferent nerve discharge in remodeled diabetic Goto-Kakizaki rat intestine

PubMed Central

Zhao, Jingbo; Yang, Jian; Liao, Donghua; Gregersen, Hans

2017-01-01

Background Gastrointestinal disorders are very common in diabetic patients, but the pathogenesis is still not well understood. Peripheral afferent nerves may be involved due to the complex regulation of gastrointestinal function by the enteric nervous system. Objective We aimed to characterize the stimulus–response function of afferent fibers innervating the jejunum in the Goto-Kakizaki (GK) type 2 diabetic rat model. A key question is whether changes in afferent firing arise from remodeled tissue or from adaptive afferent processes. Design Seven 32-week-old male GK rats and seven age-matched normal Wistar rats were studied. Firing from mesenteric afferent nerves was recorded in excised jejunal segments of seven GK rats and seven normal Wistar rats during ramp test, stress relaxation test, and creep test. The circumferential stress–strain, spike rate increase ratio (SRIR), and single unit firing rates were calculated for evaluation of interdependency of the mechanical stimulations and the afferent nerve discharge. Results Elevated sensitivity to mechanical stimuli was found for diabetic nerve bundles and single unit activity (P<0.05). The stress relaxed less in the diabetic intestinal segment (P<0.05). Linear association between SRIR and the thickness of circumferential muscle layer was found at high stress levels as well as for SRIR and the glucose level. Conclusion Altered viscoelastic properties and elevated mechanosensitivity were found in the GK rat intestine. The altered nerve signaling is related to muscle layer remodeling and glucose levels and may contribute to gastrointestinal symptoms experienced by diabetic patients. PMID:29238211