Camel Milk Beneficial Effects on Treating Gentamicin Induced Alterations in Rats

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Abdulrahman K. Al-Asmari

2014-01-01

Full Text Available The potential effect of camel milk (CM against gentamicin (GM induced biochemical changes in the rat serum was evaluated. Four groups of six albino rats were used for control, CM fed, injected with GM(i.p., and then fed and injected with GM. The results showed that the administration of GM significantly altered the levels of aspartate aminotransferase (AST, alanine aminotransferase (ALT, alkaline phosphatase (ALP, and lactate dehydrogenase (LDH activity in rat serum. CM restored these parameters to almost their normal range in group IV. Additionally, the present study showed that injection of rats with gentamicin caused an increase in malondialdehyde (MDA and myeloperoxidase (MPO activity while the antioxidant enzymes like superoxide dismutase (SOD and glutathione s-transferase (GST activity decreased significantly (P≤0.05. Administration of CM significantly (P≤0.05 inhibited the formation of MDA and activity of MPO and upregulated the antioxidant enzymes (SOD and GST activity. The overall findings of this study demonstrated that pretreatment with CM gave protection against GM induced hepatic damage possibly by inhibiting oxidative stress and inflammation, and hence camel milk can be identified as a new therapeutic agent.

Neurodegeneration caused by expression of human truncated tau leads to progressive neurobehavioural impairment in transgenic rats.

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Hrnkova, Miroslava; Zilka, Norbert; Minichova, Zuzana; Koson, Peter; Novak, Michal

2007-01-26

Human truncated tau protein is an active constituent of the neurofibrillary degeneration in sporadic Alzheimer's disease. We have shown that modified tau protein, when expressed as a transgene in rats, induced AD characteristic tau cascade consisting of tau hyperphosphorylation, formation of argyrophilic tangles and sarcosyl-insoluble tau complexes. These pathological changes led to the functional impairment characterized by a variety of neurobehavioural symptoms. In the present study we have focused on the behavioural alterations induced by transgenic expression of human truncated tau. Transgenic rats underwent a battery of behavioural tests involving cognitive- and sensorimotor-dependent tasks accompanied with neurological assessment at the age of 4.5, 6 and 9 months. Behavioural examination of these rats showed altered spatial navigation in Morris water maze resulting in less time spent in target quadrant (popen field was not influenced by transgene expression. However beam walking test revealed that transgenic rats developed progressive sensorimotor disturbances related to the age of tested animals. The disturbances were most pronounced at the age of 9 months (p<0.01). Neurological alterations indicating impaired reflex responses were other added features of behavioural phenotype of this novel transgenic rat. These results allow us to suggest that neurodegeneration, caused by the non-mutated human truncated tau derived from sporadic human AD, result in the neuronal dysfunction consequently leading to the progressive neurobehavioural impairment.

PANCREATIC HYPERTROPHY IN RATS CAUSED BY CHICKPEA (Cicer arietinum L. PROTEIN INTAKE

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O. L. TAVANO

2008-10-01

Full Text Available

The objectives of this work were demonstrate the occurrence of pancreatic hypertrophy in rats, caused by chickpea protein intake, and the possible relation to the presence of trypsin inhibitors in the protein samples. The principal protein fractions of chickpea were isolated, the effect of heating was also tested (121°C/15 min. The heated chickpea diets did not cause significant pancreatic hypertrophy in rats, in relation to the casein control group. Only unheated chickpea flour and albumin diets caused pancreatic weight increases correlating to the presence of trypsin inhibitors in these samples. Apart from the trypsin inhibitor activity the other chickpea protein components appear not to exert any alteration in pancreatic weight.

Dietary taurine alters ascorbic acid metabolism in rats fed diets containing polychlorinated biphenyls.

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Mochizuki, H; Oda, H; Yokogoshi, H

2000-04-01

The effect of dietary taurine on ascorbic acid metabolism and hepatic drug-metabolizing enzymes was investigated in rats fed diets containing polychlorinated biphenyls (PCB) to determine whether taurine has an adaptive and protective function in xenobiotic-treated animals. Young male Wistar rats (60 g) were fed diets containing 0 or 0.2 g/kg diet PCB with or without 30 g/kg diet of taurine for 14 d. The rats fed the PCB-containing diets had greater liver weight, higher ascorbic acid concentrations in the liver and spleen and greater hepatic cytochrome P-450 contents than control rats that were not treated with PCB (P ascorbic acid excretion was enhanced, and serum cholesterol concentration (especially HDL-cholesterol) was significantly elevated compared with those in control rats. Dietary taurine significantly potentiated the increases in the urinary excretion of ascorbic acid and the rise in the levels of cytochrome P-450 which were caused by PCB treatment. On the other hand, the supplementation of taurine to control diet did not alter these variables. Taurine may enhance the hepatic drug-metabolizing systems, leading to the stimulation of the ascorbic acid metabolism in rats fed diets containing PCB.

The ultrastructural alterations in rat corneas with experimentally-induced diabetes mellitus

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Take, G.; Karabay, G.; Erdogan, D.; Duyar, I.

2006-01-01

To examine the ultrastructural changes of rat corneas in streptozotocin (STZ) induced diabetes mellitus and the and the follow-up insulin treatment. Sprague-Dawley type rats were used for experimental procedures during the period from January to April 2003 at Baskent University, Ankara, Turkey. Rats were studied in four groups: group 1: controls, group 2 sham controls (single dose IV sodium citrate); group 3 STZ-induced diabetes mellitus (Single dose 45mg/kg STZ intravenously), group 4: diabetes mellitus + insulin treatment (8U/day). We observed degenerative changes in the epithelial layer, stromal keratocytes and endothelial cells in diabetic group. In contrast, the corneal layers have revealed positive alterations in the insulin-treated group. The statistical analysis, showed significant narrowing in the epithelial layer in the diabetic group (p0.02), whereas thickening was observed in the epithelial basement membrane and Descemet's membrane (p=0.002). It was determined that that diabetes mellitus causes degenerative changes in cornea, which are positively influenced by short-term insulin treatment. (author)

Acoustic alterations of ultrasonic vocalization in rat pups induced by perinatal hypothyroidism.

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Wada, Hiromi

2017-03-01

Perinatal hypothyroidism causes serious damage to auditory functions that are essential for vocalization development. In rat pups, perinatal hypothyroidism potentially affects the development of ultrasonic vocalization (USV) as a result of hearing deficits. This study examined the effect of perinatal hypothyroidism on the development of USVs in rat pups. Twelve pregnant rats were divided into three groups and treated with the anti-thyroid drug methimazole (MMI) via drinking water, from gestational day 15 to postnatal day (PND) 21. The MMI concentration (w/v) was 0% (control group), 0.01% (low-dose group), or 0.015% (high-dose group). After birth, the pups were individually separated from the dam and littermates on PNDs 5, 10, 15, and 20, and their USVs were recorded for 5min. On PNDs 5 and 10, compared with the control group, the low- and high-dose groups exhibited reductions of both frequency-modulated and downward USVs. On PND 15, however, the low- and high-dose groups displayed increases in number, duration, and amplitude of USVs compared with those in the control group. Lower body weights were observed for the low- and high-dose groups than for the control group. Total thyroxine concentrations in plasma were dose-dependently reduced. The onset of auditory functions appeared on PNDs 11-14. Thus, the rat pups were unable to hear externally produced USVs before PND 11. USVs emitted on PNDs 5 and 10 might have been spontaneous and independent of the pups' own or littermate-emitted USVs. The developmental retardation of vocalization-related organs or muscles might underlie the acoustic alterations of USVs on PNDs 5 and 10. The greater number, duration, and amplitude of USVs on PND 15, after which the hearing onset occurred, suggested that the elevation of auditory thresholds occurred as a result of hearing deficits in the low- and high-dose groups. Perinatal hypothyroidism appears to have caused acoustic alterations in the USV development. Copyright © 2016 Elsevier

Arsenic moiety in gallium arsenide is responsible for neuronal apoptosis and behavioral alterations in rats

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Flora, Swaran J.S.; Bhatt, Kapil; Mehta, Ashish

2009-01-01

Gallium arsenide (GaAs), an intermetallic semiconductor finds widespread applications in high frequency microwave and millimeter wave, and ultra fast supercomputers. Extensive use of GaAs has led to increased exposure to humans working in semiconductor industry. GaAs has the ability to dissociate into its constitutive moieties at physiological pH and might be responsible for the oxidative stress. The present study was aimed at evaluating, the principle moiety (Ga or As) in GaAs to cause neurological dysfunction based on its ability to cause apoptosis, in vivo and in vitro and if this neuronal dysfunction translated to neurobehavioral changes in chronically exposed rats. Result indicated that arsenic moiety in GaAs was mainly responsible for causing oxidative stress via increased reactive oxygen species (ROS) and nitric oxide (NO) generation, both in vitro and in vivo. Increased ROS further caused apoptosis via mitochondrial driven pathway. Effects of oxidative stress were also confirmed based on alterations in antioxidant enzymes, GPx, GST and SOD in rat brain. We noted that ROS induced oxidative stress caused changes in the brain neurotransmitter levels, Acetylcholinesterase and nitric oxide synthase, leading to loss of memory and learning in rats. The study demonstrates for the first time that the slow release of arsenic moiety from GaAs is mainly responsible for oxidative stress induced apoptosis in neuronal cells causing behavioral changes.

Pregnancy swimming causes short- and long-term neuroprotection against hypoxia-ischemia in very immature rats.

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Sanches, Eduardo Farias; Durán-Carabali, Luz Elena; Tosta, Andrea; Nicola, Fabrício; Schmitz, Felipe; Rodrigues, André; Siebert, Cassiana; Wyse, Angela; Netto, Carlos

2017-09-01

BackgroundHypoxia-ischemia (HI) is a major cause of neurological damage in preterm newborn. Swimming during pregnancy alters the offspring's brain development. We tested the effects of swimming during pregnancy in the very immature rat brain.MethodsFemale Wistar rats (n=12) were assigned to the sedentary (SE, n=6) or the swimming (SW, n=6) group. From gestational day 0 (GD0) to GD21 the rats in the SW group were made to swim for 20 min/day. HI on postnatal day (PND) 3 rats caused sensorimotor and cognitive impairments. Animals were distributed into SE sham (SESH), sedentary HIP3 (SEHI), swimming sham (SWSH), and swimming HIP3 (SWHI) groups. At PND4 and PND5, Na + /K + -ATPase activity and brain-derived neurotrophic factor (BDNF) levels were assessed. During lactation and adulthood, neurological reflexes, sensorimotor, anxiety-related, and cognitive evaluations were made, followed by histological assessment at PND60.ResultsAt early stages, swimming caused an increase in hippocampal BDNF levels and in the maintenance of Na + /K + -ATPase function in the SWHI group. The SWHI group showed smaller lesions and the preservation of white matter tracts. SEHI animals showed a delay in reflex maturation, which was reverted in the SWHI group. HIP3 induced spatial memory deficits and hypomyelination in SEHI rats, which was reverted in the SWHI group.ConclusionSwimming during pregnancy neuroprotected the brains against HI in very immature neonatal rats.

Exercise alters resting state functional connectivity of motor circuits in Parkinsonian rats

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Wang, Zhuo; Guo, Yumei; Myers, Kalisa G.; Heintz, Ryan; Peng, Yu-Hao; Maarek, Jean-Michel I.; Holschneider, Daniel P.

2014-01-01

Few studies have examined changes in functional connectivity after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise on the resting-state functional connectivity (rsFC) of motor circuits of rats subjected to bilateral 6-hydroxydopamine lesion of the dorsal striatum. Our results showed substantial similarity between lesion-induced changes in rsFC in the rats and alterations in rsFC reported in Parkinson’s disease subjects, including disconnection of the dorsolateral striatum. Exercise in lesioned rats resulted in: (a) normalization of many of the lesion-induced alterations in rsFC, including reintegration of the dorsolateral striatum into the motor network; (b) emergence of the ventrolateral striatum as a new broadly connected network hub; (c) increased rsFC among the motor cortex, motor thalamus, basal ganglia, and cerebellum. Our results showed for the first time that long-term exercise training partially reversed lesion-induced alterations in rsFC of the motor circuits, and in addition enhanced functional connectivity in specific motor pathways in the Parkinsonian rats, which could underlie recovery in motor functions observed in these rats. PMID:25219465

Cartap and carbofuran induced alterations in serum lipid profile of Wistar rats.

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Rai, Devendra K; Rai, Prashant Kumar; Gupta, Aradhna; Watal, Geeta; Sharma, Bechan

2009-04-01

Wistar rats of 6-8 weeks in age weighing between 120-150 g were exposed to the fixed doses of each of the carbamate pesticides such as cartap (50% LD(50)) and carbofuran (50% LD(50)) as well as a combination of these two with 25% LD(50) of each for one week. The effect of treatments was studied in terms of serum lipid parameters such as high-density lipoprotein, total cholesterol, triglyceride, low-density lipoprotein and very low-density lipoprotein. Treatment with individual doses of carbofuran (50% LD(50)) and cartap (50 % LD(50)) caused significant alterations in the levels of serum lipid parameters. The pesticides treatment resulted in marked decrease in the level of serum high-density lipoprotein where as that of other lipids got significantly elevated. Further, the rats exhibited relatively higher impact of pesticides when treated with the compounds in combination (25 % LD(50) of each). The results indicated that these compounds when used together may exert enhanced effect on the levels of serum lipids in rat.

Acute fluoride poisoning alters myocardial cytoskeletal and AMPK signaling proteins in rats.

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Panneerselvam, Lakshmikanthan; Raghunath, Azhwar; Perumal, Ekambaram

2017-02-15

Our previous findings revealed that increased oxidative stress, apoptosis and necrosis were implicated in acute fluoride (F - ) induced cardiac dysfunction apart from hypocalcemia and hyperkalemia. Cardiac intermediate filaments (desmin and vimentin) and cytoskeleton linker molecule vinculin plays an imperative role in maintaining the architecture of cardiac cytoskeleton. In addition, AMPK is a stress activated kinase that regulates the energy homeostasis during stressed state. The present study was aimed to examine the role of cytoskeletal proteins and AMPK signaling molecules in acute F - induced cardiotoxicity in rats. In order to study this, male Wistar rats were treated with single oral doses of 45 and 90mg/kgF - for 24h. Acute F - intoxicated rats showed declined cytoskeletal protein expression of desmin, vimentin and vinculin in a dose dependent manner compared to control. A significant increase in phosphorylation of AMPKα (Thr172), AMPKß1 (Ser108) and Acetyl-coA carboxylase (ACC) (Ser79) in the myocardium and associated ATP deprivation were found in acute F - intoxicated rats. Further, ultra-structural studies confirmed myofibril lysis with interruption of Z lines, dilated sarcoplasmic reticulum and damaged mitochondrion were observed in both the groups of F - intoxicated rats. Taken together, these findings reveal that acute F - exposure causes sudden heart failure by altering the expression of cytoskeletal proteins and AMPK signaling molecules. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A Vegetable, Launaea taraxacifolia, Mitigated Mercuric Chloride Alteration of the Microanatomy of Rat Brain.

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Owoeye, Olatunde; Arinola, Ganiyu O

2017-11-02

Mercuric chloride is an environmental pollutant that affects the nervous systems of mammals. Oxidative damage is one of the mechanisms of its toxicity, and antioxidants should mitigate this effect. A vegetable with antioxidant activity is Launaea taraxacifolia, whose ethanolic extract (EELT) was investigated in this experiment to determine its effect against mercuric chloride (MC) intoxication in rat brain. Thirty male Wistar rats were randomly assigned into five groups (n = 6) as follows: control; propylene glycol; EELT (400 mg/kg bwt) for 19 days; MC (HgCl 2 ) (4 mg/bwt) for 5 days from day 15 of the experiment; EELT+ MC, EELT (400 mg/kg bwt) for 14 days + MC (4 mg/bwt) for 5 days from day 15 of the experiment. All treatments were administered orally by gastric gavage. Behavioral tests were conducted on the 20th day, and rats were euthanized the same day. Blood and brain tissue were examined with regard to microanatomical parameters. Data were analyzed using analysis of variance with statistical significance set at p cerebral cortex, dentate gyrus, cornu ammonis 3, and cerebellum of rats. Treatment with EELT prior to MC administration significantly reduced the effect of MC on the hematological, behavioral, and ameliorated histological alterations of the brain. These findings may be attributed partially to the antioxidant property of EELT, which demonstrated protective effects against MC-induced behavioral parameters and alteration of microanatomy of rats' cerebral cortex, hippocampus, and cerebellum. In conclusion, EELT may be a valuable agent for further investigation in the prevention of acute neuropathy caused by inorganic mercury intoxication.

Onion and garlic extracts as potential antidotes for cadmium-induced biochemical alterations in prostate glands of rats.

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Ola-Mudathir, F K; Suru, S M

2015-11-01

Cadmium (Cd) has been implicated in increased prostate gland malignancy risk in both wildlife and humans. This study examines the chemoprotective roles of onion and garlic extracts on Cd-induced biochemical alterations in the prostate glands of rats. Adult male Wistar rats were randomly divided into nine groups: control group received double distilled water; Cd group received Cd alone (1.5 mg/100 g bwt per day); extract-treated groups were pre-treated with varied doses of onion and/or garlic extract (0.5 ml and 1.0 ml/100 g bwt per day) for 1 week and then co-treated with Cd (1.5 mg/100 g bwt per day) for additional 3 weeks. Oxidant/antioxidant status and acid phosphatase (ACPtotal and ACPprostatic ) activity were examined in prostate glands. Cd intoxication caused a marked (P garlic extract significantly minimised these alterations. The onion extract offered a dose-dependent protection. Our findings suggest a chemoprotective capability for onion and garlic extracts against Cd-induced biochemical alteration in the prostate glands. © 2014 Blackwell Verlag GmbH.

Quercetin does not alter the oral bioavailability of Atorvastatin in rats.

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Koritala, Rekha; Challa, Siva Reddy; Ragam, Satheesh Kumar; Geddam, Lal Babu; Venkatesh Reddy Challa, Venkatesh Reddy; Devi, Renuka; Sattenapalli, Srinu; Babu, Narendra

2015-09-01

The study was undertaken to evaluate the effect of Quercetin on the pharmacokinetics of Atorvastatin Calcium. In-vivo Pharmacokinetic studies were performed on rats in a single dose study and multiple dose study. Rats were treated with Quercetin (10 mg/kg) and Atorvastatin Calcium (20 mg/kg) orally and blood samples were collected at (0) pretreatment and 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 24 hours post treatment. Plasma concentrations of Atorvastatin were estimated by HPLC method. Quercetin treatment did not significantly alter the pharmacokinetic parameters of atorvastatin like AUC(0-24), AUC(0-α) , T(max), C(max) and T(½) in both single dose and multiple dose studies of Atorvastatin Calcium. Quercetin does not alter the oral bioavailability of Atorvastatin Calcium in rats.

Comparison of gene expression profiles altered by comfrey and riddelliine in rat liver.

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Guo, Lei; Mei, Nan; Dial, Stacey; Fuscoe, James; Chen, Tao

2007-11-01

Comfrey (Symphytum officinale) is a perennial plant and has been consumed by humans as a vegetable, a tea and an herbal medicine for more than 2000 years. It, however, is hepatotoxic and carcinogenic in experimental animals and hepatotoxic in humans. Pyrrolizidine alkaloids (PAs) exist in many plants and many of them cause liver toxicity and/or cancer in humans and experimental animals. In our previous study, we found that the mutagenicity of comfrey was associated with the PAs contained in the plant. Therefore, we suggest that carcinogenicity of comfrey result from those PAs. To confirm our hypothesis, we compared the expression of genes and processes of biological functions that were altered by comfrey (mixture of the plant with PAs) and riddelliine (a prototype of carcinogenic PA) in rat liver for carcinogenesis in this study. Groups of 6 Big Blue Fisher 344 rats were treated with riddelliine at 1 mg/kg body weight by gavage five times a week for 12 weeks or fed a diet containing 8% comfrey root for 12 weeks. Animals were sacrificed one day after the last treatment and the livers were isolated for gene expression analysis. The gene expressions were investigated using Applied Biosystems Rat Whole Genome Survey Microarrays and the biological functions were analyzed with Ingenuity Analysis Pathway software. Although there were large differences between the significant genes and between the biological processes that were altered by comfrey and riddelliine, there were a number of common genes and function processes that were related to carcinogenesis. There was a strong correlation between the two treatments for fold-change alterations in expression of drug metabolizing and cancer-related genes. Our results suggest that the carcinogenesis-related gene expression patterns resulting from the treatments of comfrey and riddelliine are very similar, and PAs contained in comfrey are the main active components responsible for carcinogenicity of the plant.

Stress-induced changes in circadian rhythms of body temperature and activity in rats are not caused by pacemaker changes

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Meerlo, P; vandenHoofdakker, RH; Koolhaas, JM; Daan, S

1997-01-01

Previous work has shown that social stress in rats (i.e., defeat by an aggressive male conspecific) causes a variety of behavioral and physiological changes including alterations in the daily rhythms of body temperature and activity. To study the role of the circadian pacemaker in these

A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

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Xu, D. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Wu, Y.; Liu, F.; Liu, Y.S.; Shen, L.; Lei, Y.Y.; Liu, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Qin, J. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Zhang, C. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Chen, L.B. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, J. [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, H., E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

2012-11-01

Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury

A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

International Nuclear Information System (INIS)

Xu, D.; Wu, Y.; Liu, F.; Liu, Y.S.; Shen, L.; Lei, Y.Y.; Liu, J.; Ping, J.; Qin, J.; Zhang, C.; Chen, L.B.; Magdalou, J.; Wang, H.

2012-01-01

Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury

Effect of alterations in glomerular charge on deposition of cationic and anionic antibodies to fixed glomerular antigens in the rat.

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Adler, S; Baker, P; Pritzl, P; Couser, W G

1985-07-01

Reduction of the negative charge of the glomerular capillary wall alters its charge- and size-selective properties. To investigate the effect of alteration in glomerular charge properties on antibody localization, we prepared cationic and anionic fractions of antibodies to subepithelial and glomerular basement membrane (GBM) antigens, and compared their deposition in normal rats and rats treated with protamine sulfate or aminonucleoside of puromycin to reduce capillary wall charge. IgG antibodies were eluted from kidneys of rats with active Heymann's nephritis (AICN), passive Heymann's nephritis (PHN), or anti-GBM nephritis (NTN), separated into cationic and anionic fractions, and radiolabeled with iodine 125 or iodine 131. Relative antibody content of each fraction was determined by incubation with an excess of glomerular antigen. Varying amounts of cationic and anionic IgG eluted from kidneys of rats with AICN or PHN were injected into 24 normal or protamine sulfate-treated rats. Glomerular binding of all antibodies was highly correlated with IgG delivery to the kidney. The ratio of cationic to anionic antibody deposited in the glomeruli of normal rats after 4 hours was 1.08 +/- 0.07 for AICN eluate and 0.37 +/- 0.04 for PHN eluate. The ratios were not significantly different in animals pretreated with protamine sulfate (1.15 +/- 0.06 and 0.44 +/- 0.06, respectively; P greater than 0.05). Varying amounts of cationic and anionic IgG eluted from kidneys of rats with NTN were injected into 10 normal rats and four rats treated with aminonucleoside of puromycin. Glomerular binding of antibody was again highly correlated with IgG delivery to the kidney. The ratio of cationic to anionic antibody deposited in the glomeruli of normal rats after 1 hour was 1.03 +/- 0.06, and was not significantly altered in rats treated with aminonucleoside of puromycin (1.05 +/- 0.03, P greater than 0.5). Proteinuria in PHN rats was also unaffected by treatment with protamine sulfate for

Altered hypothalamic protein expression in a rat model of Huntington's disease.

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Wei-na Cong

Full Text Available Huntington's disease (HD is a neurodegenerative disorder, which is characterized by progressive motor impairment and cognitive alterations. Changes in energy metabolism, neuroendocrine function, body weight, euglycemia, appetite function, and circadian rhythm can also occur. It is likely that the locus of these alterations is the hypothalamus. We used the HD transgenic (tg rat model bearing 51 CAG repeats, which exhibits similar HD symptomology as HD patients to investigate hypothalamic function. We conducted detailed hypothalamic proteome analyses and also measured circulating levels of various metabolic hormones and lipids in pre-symptomatic and symptomatic animals. Our results demonstrate that there are significant alterations in HD rat hypothalamic protein expression such as glial fibrillary acidic protein (GFAP, heat shock protein-70, the oxidative damage protein glutathione peroxidase (Gpx4, glycogen synthase1 (Gys1 and the lipid synthesis enzyme acylglycerol-3-phosphate O-acyltransferase 1 (Agpat1. In addition, there are significant alterations in various circulating metabolic hormones and lipids in pre-symptomatic animals including, insulin, leptin, triglycerides and HDL, before any motor or cognitive alterations are apparent. These early metabolic and lipid alterations are likely prodromal signs of hypothalamic dysfunction. Gaining a greater understanding of the hypothalamic and metabolic alterations that occur in HD, could lead to the development of novel therapeutics for early interventional treatment of HD.

Effect of L-ascorbic acid on nickel-induced alterations in serum lipid profiles and liver histopathology in rats.

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Das, Kusal K; Gupta, Amrita Das; Dhundasi, Salim A; Patil, Ashok M; Das, Swastika N; Ambekar, Jeevan G

2006-01-01

Nickel exposure greatly depletes intracellular ascorbate and alters ascorbate-cholesterol metabolism. We studied the effect of the simultaneous oral treatment with L-ascorbic acid (50 mg/100 g body weight (BW) and nickel sulfate (2.0 mg/100 g BW, i.p) on nickelinduced changes in serum lipid profiles and liver histopathology. Nickel-treated rats showed a significant increase in serum low-density lipoprotein-cholesterol, total cholesterol, triglycerides, and a significant decrease in serum high-density lipoprotein-cholesterol. In the liver, nickel sulfate caused a loss of normal architecture, fatty changes, extensive vacuolization in hepatocytes, eccentric nuclei, and Kupffer cell hypertrophy. Simultaneous administration of L-ascorbic acid with nickel sulfate improved both the lipid profile and liver impairments when compared with rats receiving nickel sulfate only. The results indicate that L-ascorbic acid is beneficial in preventing nickel-induced lipid alterations and hepatocellular damage.

Opium can differently alter blood glucose, sodium and potassium in male and female rats.

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Karam, Gholamreza Asadi; Rashidinejad, Hamid Reza; Aghaee, Mohammad Mehdi; Ahmadi, Jafar; Rahmani, Mohammad Reza; Mahmoodi, Mehdi; Azin, Hosein; Mirzaee, Mohammad Reza; Khaksari, Mohammad

2008-04-01

To determine the effects of opium on serum glucose, potassium and sodium in male and female Wistar rat, opium solution (60 mg/kg) injected intraperitoneally and the same volume of distilled water was used as control (7 rats in each group). Blood samples were collected at 0, 30, 60, 120, 240 and 360 minutes after injection from orbit cavity and the values of serum glucose, sodium (Na(+)) and potassium (K(+)) were measured. The data were then analyzed by the repeated measure ANOVA based on sex and case-control group. P opium solution injection, in female rats compared to a control group. However, the male rats had this rise at 30, 60 and 120 minutes after opium solution injection compared to control group. While serum glucose in male rats was significantly higher than females at 30, 60 and 120 minutes, this value was higher in the female rats at 360 minutes. Therefore, serum glucose alterations following opium injection was significantly different in groups and in the sexes at different times. Sodium (Na(+)) rose at 60, 240 and 360 minutes significantly in all rats compared to control group. However, sodium alteration following opium injection was significantly different only between treated and control groups but sex-independent at all times. Potassium (K(+)) increased significantly at 60, 120, 240 and 360 minutes in male rats, compared to a control group. In female rats K(+) significantly raised at 30, 120, 240 and 360 minutes. Therefore, the alteration of K(+) in male and female rats was found time dependent and sex independent. According to our results, opium increased serum glucose in male and female rats differently, and it interferes with metabolic pathways differently on a gender dependent basis. Opium raised serum Na(+) and K(+), thus it interfere with water regulation and blood pressure via different mechanism.

Prenatal cocaine exposure alters alpha2 receptor expression in adolescent rats

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Silvers Janelle M

2006-04-01

Full Text Available Abstract Background Prenatal cocaine exposure produces attentional deficits which to persist through early childhood. Given the role of norepinephrine (NE in attentional processes, we examined the forebrain NE systems from prenatal cocaine exposed rats. Cocaine was administered during pregnancy via the clinically relevant intravenous route of administration. Specifically, we measured α2-adrenergic receptor (α2-AR density in adolescent (35-days-old rats, using [3H]RX821002 (5 nM. Results Sex-specific alterations of α2-AR were found in the hippocampus and amygdala of the cocaine-exposed animals, as well as an upregulation of α2-AR in parietal cortex. Conclusion These data suggest that prenatal cocaine exposure results in a persistent alteration in forebrain NE systems as indicated by alterations in receptor density. These neurochemical changes may underlie behavioral abnormalities observed in offspring attentional processes following prenatal exposure to cocaine.

Effect of Resveratrol on Hematological and Biochemical Alterations in Rats Exposed to Fluoride

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Nurgül Atmaca

2014-01-01

Full Text Available We investigated the protective effects of resveratrol on hematological and biochemical changes induced by fluoride in rats. A total of 28 rats were divided into 4 groups: control, resveratrol, fluoride, and fluoride/resveratrol (n=7 each, for a total of 21 days of treatment. Blood samples were taken and hematological and biochemical parameters were measured. Compared to the control group, the fluoride-treated group showed significant differences in several hematological parameters, including decreases in WBC, RBC, and PLT counts and neutrophil ratio. The group that received resveratrol alone showed a decrease in WBC count compared to the control group. Furthermore, in comparison to the control group, the fluoride group showed significantly increased ALT enzyme activity and decreased inorganic phosphorus level. The hematological and biochemical parameters in the fluoride + resveratrol treated group were similar to control group. In the fluoride + resveratrol group, resveratrol restored the changes observed following fluoride treatment, including decreased counts of WBC, RBC, and PLT, decreased neutrophil ratio and inorganic phosphorus levels, and elevated ALT enzyme activity. The present study showed that fluoride caused adverse effects in rats and that resveratrol reduced hematological and biochemical alterations produced by fluoride exposure.

Altered gene-expression profile in rat plasma and promoted body ...

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Altered gene-expression profile in rat plasma and promoted body and brain development ... The study was aimed to explore how the prenatal EE impacts affect the ... positively promote the body and nervous system development of offspring, ...

Altered glucose kinetics in diabetic rats during Gram-negative infection

International Nuclear Information System (INIS)

Lang, C.H.; Dobrescu, C.; Bagby, G.J.; Spitzer, J.J.

1987-01-01

The present study examined the purported exacerbating effect of sepsis on glucose metabolism in diabetes. Diabetes was induced in rats by an intravenous injection of 70 or 45 mg/kg streptozotocin. The higher dose produced severe diabetes, whereas the lower dose of streptozotocin produced a miler, latent diabetes. After a chronic diabetic state had developed for 4 wk, rats had catheters implanted and sepsis induced by intraperitoneal injections of live Escherichia coli. After 24 h of sepsis the blood glucose concentration was unchanged in nondiabetics and latent diabetics, but glucose decreased from 15 to 8 mM in the septic severe diabetic group. This decrease in blood glucose was not accompanied by alterations in the plasma insulin concentration. Glucose turnover, assessed by the constant intravenous infusion of [6- 3 H]- and [U- 14 C]glucose, was elevated in the severe diabetic group, compared with either latent diabetics or nondiabetics. Sepsis increased the rate of glucose disappearance in nondiabetic rats but had no effect in either group of diabetic animals. Sepsis also failed to alter the insulinogenic index, used to estimate the insulin secretory capacity, in diabetic rats. Thus the present study suggests that the imposition of nonlethal Gram-negative sepsis on severe diabetic animals does not further impair glucose homeostasis and that the milder latent diabetes was not converted to a more severe diabetic state by the septic challenge

Rat brain CYP2D enzymatic metabolism alters acute and chronic haloperidol side-effects by different mechanisms.

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Miksys, Sharon; Wadji, Fariba Baghai; Tolledo, Edgor Cole; Remington, Gary; Nobrega, Jose N; Tyndale, Rachel F

2017-08-01

Risk for side-effects after acute (e.g. parkinsonism) or chronic (e.g. tardive dyskinesia) treatment with antipsychotics, including haloperidol, varies substantially among people. CYP2D can metabolize many antipsychotics and variable brain CYP2D metabolism can influence local drug and metabolite levels sufficiently to alter behavioral responses. Here we investigated a role for brain CYP2D in acutely and chronically administered haloperidol levels and side-effects in a rat model. Rat brain, but not liver, CYP2D activity was irreversibly inhibited with intracerebral propranolol and/or induced by seven days of subcutaneous nicotine pre-treatment. The role of variable brain CYP2D was investigated in rat models of acute (catalepsy) and chronic (vacuous chewing movements, VCMs) haloperidol side-effects. Selective inhibition and induction of brain, but not liver, CYP2D decreased and increased catalepsy after acute haloperidol, respectively. Catalepsy correlated with brain, but not hepatic, CYP2D enzyme activity. Inhibition of brain CYP2D increased VCMs after chronic haloperidol; VCMs correlated with brain, but not hepatic, CYP2D activity, haloperidol levels and lipid peroxidation. Baseline measures, hepatic CYP2D activity and plasma haloperidol levels were unchanged by brain CYP2D manipulations. Variable rat brain CYP2D alters side-effects from acute and chronic haloperidol in opposite directions; catalepsy appears to be enhanced by a brain CYP2D-derived metabolite while the parent haloperidol likely causes VCMs. These data provide novel mechanistic evidence for brain CYP2D altering side-effects of haloperidol and other antipsychotics metabolized by CYP2D, suggesting that variation in human brain CYP2D may be a risk factor for antipsychotic side-effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Ligation of the left renal vein in epm1-wistar rats: functional and morphologic alterations in the kidneys, testes and suprarenal glands

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José Carlos Costa Baptista-Silva

Full Text Available OBJECTIVE: The ligation of the left renal vein (LLVR in man is a contraversial procedure in view of the risks of lesion to the renal parenchyma. With the objective of studying the morphologic and functional alterations caused by these lesions, we conducted experimental research with rats. MATERIAL AND METHODS: 64 male adult EPM1-WISTAR rats were used, divided into 8 groups - 4 for LLRV and four for control. Each LLRV group and corresponding control group were sacrificed progressively on the 7th, 15th, 30th and 60th day after the initial surgery. RESULTS: We found morphofunctional alterations only in animals that underwent LLRV in the four periods of sacrifice.The proteinuria creatinine in serum, testosterone in serum and serum corticosterone in serum showed practically no alteration in relation to the normal values for rats. Statistically significant severe histological lesions were found in the kidneys and testes of the LLRV groups. Lesions in the suprarenal glands were also present in these groups, but no sufficient to demonstrate statistical significance CONCLUSION: Based on these results we can conclude that the ligation of the left renal vein is a procedure of high risk in these animals.

[The effect of N-stearoylethanolamine on liver phospholipid composition of rats with insulin resistance caused by alimentary obesity].

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Onopchenko, O V; Kosiakova, H V; Horid'ko, T M; Klimashevskyĭ, V M; Hula, N M

2014-01-01

We used alimentary obesity-induced insulin resistance (IR) model in rats to investigate the influence of N-stearoylethanolamine on the content of phospholipids and their fatty acid composition. Our results show that prolonged high-fat diet triggers considerable aberrations in the composition of main phospholipids in the liver and can be one of the causes of IR in rats. In particular, the increase of phosphatidylcholine, phosphatidylethanolamine and significant decrease of other phospholipids: lysophosphatidylcholine, lysophosphatidylethanolamine, sphingomyelin, phosphatidylinositol, phosphatidylserine and diphosphaglicerol were observed. The levels of monounsaturated (erucic, nervonic, oleic) and polyunsaturated (eicosatrienoic, docosatrienoic, arachidonic) fatty acids were increased; meanwhile the content of diunsaturated acids was decreased. The NSE administration (50 mg/kg of body weight) caused restoration of the phospholipids content in the liver of rats with diet-induced IR that highly correlated with the decrease in plasma insulin level and the improvement of insulin sensitivity. Moreover, the effect of NSE was accompanied by the normalization of fatty acids composition of phospholipids that could be related to modulating influence of NSE on the activity of the main fatty acid desaturases. It is known that the imbalance in phospholipid composition of the rat liver causes substantial metabolic alterations that are associated with the development of IR. Accordingly, the compensations of the imbalance by NSE can help to restore insulin sensitivity, inhibit the development of obesity, IR and type 2 diabetes.

Neurotransmitter alteration in a testosterone propionate-induced polycystic ovarian syndrome rat model.

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Chaudhari, Nirja K; Nampoothiri, Laxmipriya P

2017-02-01

Polycystic ovarian syndrome (PCOS), one of the leading causes of infertility seen in women, is characterized by anovulation and hyperandrogenism, resulting in ovarian dysfunction. In addition, associations of several metabolic complications like insulin resistance, obesity, dyslipidemia and psychological co-morbidities are well known in PCOS. One of the major factors influencing mood and the emotional state of mind is neurotransmitters. Also, these neurotransmitters are very crucial for GnRH release. Hence, the current study investigates the status of neurotransmitters in PCOS. A PCOS rat model was developed using testosterone. Twenty-one-day-old rats were subcutaneously injected with 10 mg/kg body weight of testosterone propionate (TP) for 35 days. The animals were validated for PCOS characteristics by monitoring estrus cyclicity, serum testosterone and estradiol levels and by histological examination of ovarian sections. Neurotransmitter estimation was carried out using fluorometric and spectrophotometric methods. TP-treated animals demonstrated increased serum testosterone levels with unaltered estradiol content, disturbed estrus cyclicity and many peripheral cysts in the ovary compared to control rats mimicking human PCOS. Norepinephrine (NE), dopamine, serotonin, γ-amino butyric acid (GABA) and epinephrine levels were significantly low in TP-induced PCOS rats compared to control ones, whereas the activity of acetylcholinesterase in the PCOS brain was markedly elevated. Neurotransmitter alteration could be one of the reasons for disturbed gonadotropin-releasing hormone (GnRH) release, consequently directing the ovarian dysfunction in PCOS. Also, decrease in neurotransmitters, mainly NE, serotonin and dopamine (DA) attributes to mood disorders like depression and anxiety in PCOS.

Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

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Woodman, Andrew G; Mah, Richard; Keddie, Danae; Noble, Ronan M N; Panahi, Sareh; Gragasin, Ferrante S; Lemieux, Hélène; Bourque, Stephane L

2018-06-01

Prenatal iron deficiency alters fetal developmental trajectories, which results in persistent changes in organ function. Here, we studied the effects of prenatal iron deficiency on fetal kidney and liver mitochondrial function. Pregnant Sprague-Dawley rats were fed partially or fully iron-restricted diets to induce a state of moderate or severe iron deficiency alongside iron-replete control rats. We assessed mitochondrial function via high-resolution respirometry and reactive oxygen species generation via fluorescence microscopy on gestational d 21. Hemoglobin levels were reduced in dams in the moderate (-31%) and severe groups (-54%) compared with controls, which was accompanied by 55% reductions in fetal hemoglobin levels in both moderate and severe groups versus controls. Male iron-deficient kidneys exhibited globally reduced mitochondrial content and respiration, as well as increased cytosolic superoxide and decreased NO. Female iron-deficient kidneys exhibited complex II down-regulation and increased mitochondrial oxidative stress. Male iron-deficient livers exhibited reduced complex IV respiration and increased cytosolic superoxide, whereas female liver tissues exhibited no alteration in oxidant levels or mitochondrial function. These findings indicate that prenatal iron deficiency causes changes in mitochondrial content and function as well as oxidant status in a sex- and organ-dependent manner, which may be an important mechanism that underlies the programming of cardiovascular disease.-Woodman, A. G., Mah, R., Keddie, D., Noble, R. M. N., Panahi, S., Gragasin, F. S., Lemieux, H., Bourque, S. L. Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

Mainstream cigarette smoke exposure alters cytochrome P4502G1 expression in F344 rat olfactory mucosa

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Hotchkiss, J.A.; Nikula, K.J.; Lewis, J.L.; Finch, G.L.; Belinsky, S.A.; Dahl, A.R.

1994-01-01

Inhalation of mainstream cigarette smoke (MCS) by rats results in multifocal rhinitis, mucous hypersecretion, nasal epithelial hyperplasia and metaplasia, and focal olfactory mucosal atrophy. In humans, cigarette smoking causes long-term, dose-related alterations in olfactory function in both current and former smokers. An olfactory-specific cytochrome P450 has been identified in rabbits and rats. The presence of olfactory-specific P450s, as well as relatively high levels of other biotransformation enzymes, such as NADPH-cytochrome P450 reductase and UDP-glucuronosyl transferase, in the olfactory neuroepithelium suggest that these enzyme systems may play a role in olfaction. This hypothesis is strengthened by the observation that, in rats, the temporal gene activation of P4502G1 coincides with the postnatal increase in the sensitivity of olfactory response to odorants. The purpose of this investigation was to examine the effect of MCS exposure on P4502G1 protein expression

Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

International Nuclear Information System (INIS)

Liu, Yansong; Xu, Dan; Feng, Jianghua; Kou, Hao; Liang, Gai; Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin; Magdalou, Jacques; Wang, Hui

2012-01-01

The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by 1 H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine ingestion

Developmental vitamin D deficiency alters multiple neurotransmitter systems in the neonatal rat brain.

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Kesby, James P; Turner, Karly M; Alexander, Suzanne; Eyles, Darryl W; McGrath, John J; Burne, Thomas H J

2017-11-01

Epidemiological evidence suggests that developmental vitamin D (DVD) deficiency is a risk factor for neuropsychiatric disorders, such as schizophrenia. DVD deficiency in rats is associated with altered brain structure and adult behaviours indicating alterations in dopamine and glutamate signalling. Developmental alterations in dopamine neurotransmission have also been observed in DVD-deficient rats but a comprehensive assessment of brain neurochemistry has not been undertaken. Thus, the current study determined the regional concentrations of dopamine, noradrenaline, serotonin, glutamine, glutamate and γ-aminobutyric acid (GABA), and associated metabolites, in DVD-deficient neonates. Sprague-Dawley rats were fed a vitamin D deficient diet or control diet six weeks prior to mating until birth and housed under UVB-free lighting conditions. Neurotransmitter concentration was assessed by high-performance liquid chromatography on post-mortem neonatal brain tissue. Ubiquitous reductions in the levels of glutamine (12-24%) were observed in DVD-deficient neonates compared with control neonates. Similarly, in multiple brain regions DVD-deficient neonates had increased levels of noradrenaline and serine compared with control neonates. In contrast, increased levels of dopamine and decreased levels of serotonin in DVD-deficient neonates were limited to striatal subregions compared with controls. Our results confirm that DVD deficiency leads to changes in multiple neurotransmitter systems in the neonate brain. Importantly, this regionally-based assessment in DVD-deficient neonates identified both widespread neurotransmitter changes (glutamine/noradrenaline) and regionally selective neurotransmitter changes (dopamine/serotonin). Thus, vitamin D may have both general and local actions depending on the neurotransmitter system being investigated. Taken together, these data suggest that DVD deficiency alters neurotransmitter systems relevant to schizophrenia in the developing rat

Intrauterine Growth Restriction Alters the Postnatal Development of the Rat Cerebellum.

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McDougall, Annie R A; Wiradjaja, Vanny; Azhan, Aminath; Li, Anqi; Hale, Nadia; Wlodek, Mary E; Hooper, Stuart B; Wallace, Megan J; Tolcos, Mary

2017-01-01

Intrauterine growth restriction (IUGR) is a major cause of antenatal brain injury. We aimed to characterize cerebellar deficits following IUGR and to investigate the potential underlying cellular and molecular mechanisms. At embryonic day 18, pregnant rats underwent either sham surgery (controls; n = 23) or bilateral uterine vessel ligation to restrict blood flow to fetuses (IUGR; n = 20). Offspring were collected at postnatal day 2 (P2), P7, and P35. Body weights were reduced at P2, P7, and P35 in IUGR offspring (p < 0.05) compared with controls. At P7, the width of the external granule layer (EGL) was 30% greater in IUGR than control rats (p < 0.05); there was no difference in the width of the proliferative zone or in the density of Ki67-positive cells in the EGL. Bergmann glia were disorganized at P7 and P35 in IUGR pups, and by P35, there was a 10% decrease in Bergmann glial fiber density (p < 0.05) compared with controls. At P7, trophoblast antigen-2 (Trop2) mRNA and protein levels in the cerebellum were decreased by 88 and 40%, respectively, and astrotactin 1 mRNA levels were increased by 20% in the IUGR rats (p < 0.05) compared with controls; there was no difference in ASTN1 protein. The expressions of other factors known to regulate cerebellar development (astrotactin 2, brain-derived neurotrophic factor, erb-b2 receptor tyrosine kinase 4, neuregulin 1, sonic hedgehog and somatostatin) were not different between IUGR and control rats at P7 or P35. These data suggest that damage to the migratory scaffold (Bergmann glial fibers) and alterations in the genes that influence migration (Trop2 and Astn1) may underlie the deficits in postnatal cerebellar development following IUGR. © 2017 S. Karger AG, Basel.

Chronic ethanol intake leads to structural and molecular alterations in the rat endometrium.

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Martinez, Marcelo; Milton, Flora A; Pinheiro, Patricia Fernanda F; Almeida-Francia, Camila C D; Cagnon-Quitete, Valeria H A; Tirapelli, Luiz F; Padovani, Carlos Roberto; Chuffa, Luiz Gustavo A; Martinez, Francisco Eduardo

2016-05-01

We described the effects of low- and high-dose ethanol intake on the structure and apoptosis signaling of the uterine endometrium of UChA and UChB rats (animals with voluntary ethanol consumption). Thirty adult female rats, 90 days old, were divided into three groups (n = 10/group): UChA rats fed with 10% (v/v) ethanol ad libitum (free choice for water or ethanol) drinking Chronic ethanol intake leads to structural and molecular alterations in the uterine endometrium of UCh rats, regardless of low- or high-dose consumption, promoting reproductive disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

The effect of N-stearoylethanolamine on liver phospholipid composition of rats with insulin resistance caused by alimentary obesity

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O. V. Onopchenko

2014-02-01

Full Text Available We used alimentary obesity-induced insulin resistance (IR model in rats to investigate the influence of N-stearoylethanolamine on the content of phospholipids and their fatty acid composition. Our results show that prolonged high-fat diet triggers considerable aberrations in the composition of main phospholipids in the liver and can be one of the causes of IR in rats. In particular, the increase of phosphatidylcholine, phosphatidylethanolamine and significant decrease of other phospholipids: lysophosphatidylcholine, lysophosphatidylethanolamine, sphingomyelin, phosphatidylinositol, phosphatidylserine and diphosphaglicerol were observed. The levels of monounsaturated (erucic, nervonic, oleic and polyunsaturated (eicosatrienoic, docosatrienoic, arachidonic fatty acids were increased; meanwhile the content of diunsaturated acids was decreased. The NSE administration (50 mg/kg of body weight caused restoration of the phospholipids content in the liver of rats with diet-induced IR that highly correlated with the decrease in plasma insulin level and the improvement of insulin sensitivity. Moreover, the effect of NSE was accompanied by the normalization of fatty acids composition of phospholipids that could be related to modulating influen­ce of NSE on the activity of the main fatty acid desaturases. It is known that the imbalance in phospholipid composition of the rat liver causes substantial metabolic alterations that are associated with the development of IR. Accordingly, the compensations of the imbalance by NSE can help to restore insulin sensitivity, inhibit the development of obesity, IR and type 2 diabetes.

HIV-1 transgene expression in rats causes oxidant stress and alveolar epithelial barrier dysfunction

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Jacob Barbara A

2009-02-01

Full Text Available Abstract Background HIV-infected individuals are at increased risk for acute and chronic airway disease even though there is no evidence that the virus can infect the lung epithelium. Although HIV-related proteins including gp120 and Tat can directly cause oxidant stress and cellular dysfunction, their effects in the lung are unknown. The goal of this study was to determine the effects of HIV-1 transgene expression in rats on alveolar epithelial barrier function. Alveolar epithelial barrier function was assessed by determining lung liquid clearance in vivo and alveolar epithelial monolayer permeability in vitro. Oxidant stress in the alveolar space was determined by measuring the glutathione redox couple by high performance liquid chromatography, and the expression and membrane localization of key tight junction proteins were assessed. Finally, the direct effects of the HIV-related proteins gp120 and Tat on alveolar epithelial barrier formation and tight junction protein expression were determined. Results HIV-1 transgene expression caused oxidant stress within the alveolar space and impaired epithelial barrier function even though there was no evidence of overt inflammation within the airways. The expression and membrane localization of the tight junction proteins zonula occludens-1 and occludin were decreased in alveolar epithelial cells from HIV-1 transgenic rats. Further, treating alveolar epithelial monolayers from wild type rats in vitro with recombinant gp120 or Tat for 24 hours reproduced many of the effects on zonula occludens-1 and occludin expression and membrane localization. Conclusion Taken together, these data indicate that HIV-related proteins cause oxidant stress and alter the expression of critical tight junction proteins in the alveolar epithelium, resulting in barrier dysfunction.

Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

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Luo, Hanwen [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Deng, Zixin; Liu, Lian; Shen, Lang; Kou, Hao; He, Zheng [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, Jie; Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Ma, Lu [Department of Epidemiology and Health Statistics, Public Health School of Wuhan University, Wuhan 430071 (China); Chen, Liaobin, E-mail: lbchen@whu.edu.cn [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

2014-02-01

Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine

Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

International Nuclear Information System (INIS)

Luo, Hanwen; Deng, Zixin; Liu, Lian; Shen, Lang; Kou, Hao; He, Zheng; Ping, Jie; Xu, Dan; Ma, Lu; Chen, Liaobin; Wang, Hui

2014-01-01

Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine

Repeated dose oral toxicity of inorganic mercury in wistar rats: biochemical and morphological alterations

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M. D. Jegoda

2013-06-01

Full Text Available Aim: The study was conducted to find out the possible toxic effect of mercuric chloride (HgCl2 at the histological, biochemical, and haematological levels in the wistar rats for 28 days. Materials and Methods: The biochemical and hematological alteration were estimated in four groups of rat (each group contain ten animals, which were treated with 0 (control, 2, 4, and 8 mg/kg body weight of HgCl2 through oral gavage. At the end of study all rats were sacrificed and subjected for histopathology. Result: A significantly (P < 0.05 higher level of serum alanine amino transferase (ALT, gamma Glutamyle Transferase, and creatinine were recorded in treatment groups, while the level of alkaline phosphtase (ALP was significantly decreased as compared to the control group. The toxic effect on hematoclogical parameter was characterized by significant decrease in hemoglobin, packed cell volume, total erythrocytes count, and total leukocyte count. Gross morphological changes include congestion, severe haemorrhage, necrosis, degenerative changes in kidneys, depletion of lymphocyte in spleen, decrease in concentration of mature spermatocyte, and edema in testis. It was notable that kidney was the most affected organ. Conclusion: Mercuric chloride (HgCl caused dose-dependent toxic effects on blood parameters and kidney. [Vet World 2013; 6(8.000: 563-567

Altered brain serotonergic neurotransmission following caffeine withdrawal produces behavioral deficits in rats.

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Khaliq, Saima; Haider, Saida; Naqvi, Faizan; Perveen, Tahira; Saleem, Sadia; Haleem, Darakhshan Jabeen

2012-01-01

Caffeine administration has been shown to enhance performance and memory in rodents and humans while its withdrawal on the other hand produces neurobehavioral deficits which are thought to be mediated by alterations in monoamines neurotransmission. A role of decreased brain 5-HT (5-hydroxytryptamine, serotonin) levels has been implicated in impaired cognitive performance and depression. Memory functions of rats were assessed by Water Maze (WM) and immobility time by Forced Swim Test (FST). The results of this study showed that repeated caffeine administration for 6 days at 30 mg/kg dose significantly increases brain 5-HT (pcaffeine. Withdrawal of caffeine however produced memory deficits and significantly increases the immobility time of rats in FST. The results of this study are linked with caffeine induced alterations in serotonergic neurotransmission and its role in memory and depression.

Histological alterations in the liver of rats induced by different gold nanoparticle sizes, doses and exposure duration

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Abdelhalim Mohamed

2012-01-01

Full Text Available Abstract Background Nanoparticles (NPs can potentially cause adverse effects on organ, tissue, cellular, subcellular and protein levels due to their unusual physicochemical properties. Advances in nanotechnology have identified promising candidates for many biological and biomedical applications. Since the properties of NPs differ from that of their bulk materials, they are being increasingly exploited for medical uses and other industrial applications. The aim of the present study was to investigate the particle-size effect of gold nanoparticles (GNPs on the hepatic tissue in an attempt to cover and understand the toxicity and the potential threat of their therapeutic and diagnostic use. Methods To investigate particle-size effect of GNPs on the hepatic tissue, a total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 ul of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days. Results In comparison with respective control rats, exposure to GNPs doses has produced alterations in the hepatocytes, portal triads and the sinusoids. The alterations in the hepatocytes were mainly summarized as hydropic degeneration, cloudy swelling, fatty degeneration, portal and lobular infiltrate by chronic inflammatory cells and congestive dilated central veins. Conclusions The induced histological alterations might be an indication of injured hepatocytes due to GNPs toxicity that became unable to deal with the accumulated residues resulting from metabolic and structural disturbances caused by these NPs. These alterations were size-dependent with smaller ones induced the most effects and related with time exposure of GNPs. The appearance of hepatocytes cytoplasmic degeneration and nuclear destruction may suggest that GNPs interact with proteins and enzymes of the hepatic tissue interfering with the antioxidant defense mechanism and leading to reactive oxygen species (ROS generation which in turn may induce stress in the hepatocytes to

Previous climatic alterations are caused by the sun

International Nuclear Information System (INIS)

Groenaas, Sigbjoern

2003-01-01

The article surveys the scientific results of previous research into the contribution of the sun to climatic alterations. The author concludes that there is evidence of eight cold periods after the last ice age and that the alterations largely were due to climate effects from the sun. However, these effects are only causing a fraction of the registered global warming. It is assumed that the human activities are contributing to the rest of the greenhouse effect

Mechanisms of Imidacloprid-Induced Alteration of Hypothalamic-Pituitary-Adrenal (HPA Axis after Subchronic Exposure in Male Rats

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Alya Annabi

2015-11-01

Full Text Available Imidacloprid (IMI is known to target the nicotinic acetylcholine receptors (nAChRs in insects, and potentially in mammals. However, IMI toxicity on mammalian tissues has not been adequately evaluated. The aim of the present study was to examine whether IMI induced functional impairment in hypthalamic-pituitary-adrenal (HPA axis tissues. An oral exposure of 40 mg IMI/kg for 28 days in male rats caused a significant increase in malondialdehyde (MDA level. The antioxidant catalase, superoxide dismutase, and glutathione S-transferase showed various alterations following administration, but a significantly depleted thiol (SH groups was only recorded in hypothalamic tissues. The increase in the relative weight of adrenal glands and the increased adrenal cholesterol and plasma adrenocorticotropic hormone (ACTH levels are indicative of general adaptation syndrome. The hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased, highlighting the alteration of cholinergic transmission. In conclusion, the findings obtained show that chronic exposure to IMI may alter biochemical processes of HPA axis.

Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

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Liu, Yansong [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China); Feng, Jianghua, E-mail: jianghua.feng@xmu.edu.cn [Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071 (China); Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, 361005 (China); Kou, Hao; Liang, Gai [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin [Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China)

2012-07-15

The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by {sup 1}H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine

Brain Metabolism Alterations Induced by Pregnancy Swimming Decreases Neurological Impairments Following Neonatal Hypoxia-Ischemia in Very Immature Rats

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Eduardo F. Sanches

2018-06-01

Full Text Available Introduction: Prematurity, through brain injury and altered development is a major cause of neurological impairments and can result in motor, cognitive and behavioral deficits later in life. Presently, there are no well-established effective therapies for preterm brain injury and the search for new strategies is needed. Intra-uterine environment plays a decisive role in brain maturation and interventions using the gestational window have been shown to influence long-term health in the offspring. In this study, we investigated whether pregnancy swimming can prevent the neurochemical metabolic alterations and damage that result from postnatal hypoxic-ischemic brain injury (HI in very immature rats.Methods: Female pregnant Wistar rats were divided into swimming (SW or sedentary (SE groups. Following a period of adaptation before mating, swimming was performed during the entire gestation. At postnatal day (PND3, rat pups from SW and SE dams had right common carotid artery occluded, followed by systemic hypoxia. At PND4 (24 h after HI, the early neurochemical profile was measured by 1H-magnetic resonance spectroscopy. Astrogliosis, apoptosis and neurotrophins protein expression were assessed in the cortex and hippocampus. From PND45, behavioral testing was performed. Diffusion tensor imaging and neurite orientation dispersion and density imaging were used to evaluate brain microstructure and the levels of proteins were quantified.Results: Pregnancy swimming was able to prevent early metabolic changes induced by HI preserving the energetic balance, decreasing apoptotic cell death and astrogliosis as well as maintaining the levels of neurotrophins. At adult age, swimming preserved brain microstructure and improved the performance in the behavioral tests.Conclusion: Our study points out that swimming during gestation in rats could prevent prematurity related brain damage in progeny with high translational potential and possibly interesting cost

Propolis Protection from Toxicity Caused by Aluminium Chloride in Male Rats

International Nuclear Information System (INIS)

Mangood, S.A.; Kamal, A.M.; Haggag, A.M.

2012-01-01

Propolis is a resinous natural hive product derived from plant exudate collected by honey bees and has been extensively used in folk medicine. The present study was undertaken to determine the effectiveness of propolis in alleviating the toxicity of aluminium chloride (AlCl 3 )on some hematological and biochemical parameters of male albino rats. Twenty four male albino rats were arranged into 4 equal groups; control group, aluminium group (34 mg AlCl 3 /kg/day), propolis group (100μg propolis/rat)and aluminium plus propolis group. Rats were orally administered their respective doses daily for 30 days. AlCl 3 caused significant decrease in hemoglobin (Hb), red blood cell count (RBC), hematocrit (Ht), total and differential leucocyte count (TLC) when compared to control. On the other hand, aluminium administration caused a significant increase in urea, uric acid, creatinin, bilirubin, the content of phosphorous, alanine aminotransferase (ALT) and asparate aminotransferase (AST) and significant decrease in total protein, albumin, globulin and calcium when compared to control. The administration of propolis alleviated the toxic effect of AlCl 3 in experimental rats. It could be concluded thal propolis my afford protection from toxicity caused by aluminium chloride in male albino rats

Chronic unpredictable stress alters gene expression in rat single dentate granule cells

NARCIS (Netherlands)

Qin, Y.J.; Karst, H.; Joëls, M.

2004-01-01

The rat adrenal hormone corticosterone binds to low and high affinity receptors, discretely localized in brain, including the dentate gyrus. Differential activation of the two receptor types under physiological conditions alters gene expression and functional characteristics of hippocampal neurones.

Long-Time Choledochal Clamping in Wistar Rats Causes Biliary Obstruction Progressing to Hepatic Fibrosis.

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Jorge, G D L; Tártaro, R R; Escanhoela, C A F; Boin, I D F S F

2016-09-01

Biliary complications are important causes of morbidity and mortality in patients undergoing hepatic surgery. The aim of the study was to evaluate late liver alterations after a long period of choledochal clamping in Wistar rats. Ten male Wistar rats, weighing 304 grams, anesthetized with sodium thiopental (25 mg/kg) and xylazine (10 mg/kg) intravenously, were distributed into 2 groups: the choledochal clamping group (CCG) and the operation sham group (OSG), with 5 animals each submitted to an abdominal incision. In the CCG, the choledochal was isolated, dissected, and clamped with a microvascular clamp for 40 minutes. After this occlusion time, the clamp was removed and the incision was closed. In the OSG the animals, under normal conditions, were submitted only to anesthesia and laparotomy for choledochal manipulation. In all animals, after the 31st day, a hepatic biopsy was carried out for histology and blood biochemical tests: total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase. The animals were euthanized under anesthesia. This research was approved by the Ethics Committee on Animal Use (CEUA, Unicamp, No. 2511-1). In the CCG, 100% of the animals showed bile duct dilatation, ductular proliferation, and portal inflammatory infiltrate; 60% showed regenerative nodule formation; and 80% had porta-porta septa and foci of necrosis, all of which were not found in the OSG. All CCG group biochemical tests had significant increases (P Wistar rats caused hepatic dysfunction and biochemical and histological injuries with degrees of distortion to the hepatic architecture. Copyright © 2016 Elsevier Inc. All rights reserved.

Diethylnitrosamine initiation does not alter clofibric acid-induced hepatocarcinogenesis in the rat.

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Michel, Cecile; Desdouets, Chantal; Slaoui, Mohamed; Isaacs, Kevin Robert; Roberts, Ruth Angela; Boitier, Eric

2007-09-01

Clofibric acid (CLO) is a nongenotoxic hepatocarcinogen in rodents that causes altered hepatocellular foci and/or neoplasms. Initiation by DNA-damaging agents such as diethylnitrosamine (DEN) accelerates focus and tumor appearance and could therefore significantly contribute to shortening of the regulatory 2-year rodent carcinogenicity bioassays. However, it is crucial to evaluate the histological and molecular impact of initiation with DEN on hepatocarcinogenesis promoted by CLO. Male F344 rats were given a single nonnecrogenic injection of DEN (0 or 30 mg/kg) followed by Control diet or CLO (5000 ppm) in diet for up to 20 months. Histopathology and gene expression profiling were performed in liver tumors and surrounding nontumoral liver tissues. The molecular signature of DEN was characterized and its histopathological and immunohistopathological effects on focus and tumor types were also determined. Although foci and tumors appeared earlier in the DEN+CLO-treated group compared to the group treated with CLO alone, DEN had little impact on gene expression in nontumoral tissues since the gene expression profiles were highly similar between Control and DEN-treated rats, and DEN+CLO- and CLO-treated rats. Finally, tumors obtained from DEN+CLO and CLO-treated groups displayed highly correlated gene expression profiles (r>0.83, independently of the time-point). The pathways involved in tumor development revealed by Gene Ontology functional analysis are similar when driven either by spontaneous initiation or by a chemically induced initiation step. Our work described here may contribute to the design optimization of shorter preclinical tests for the evaluation of the nongenotoxic hepatocarcinogenic potential of drugs under development.

Chronic scream sound exposure alters memory and monoamine levels in female rat brain.

Science.gov (United States)

Hu, Lili; Zhao, Xiaoge; Yang, Juan; Wang, Lumin; Yang, Yang; Song, Tusheng; Huang, Chen

2014-10-01

Chronic scream sound alters the cognitive performance of male rats and their brain monoamine levels, these stress-induced alterations are sexually dimorphic. To determine the effects of sound stress on female rats, we examined their serum corticosterone levels and their adrenal, splenic, and thymic weights, their cognitive performance and the levels of monoamine neurotransmitters and their metabolites in the brain. Adult female Sprague-Dawley rats, with and without exposure to scream sound (4h/day for 21 day) were tested for spatial learning and memory using a Morris water maze. Stress decreased serum corticosterone levels, as well as splenic and adrenal weight. It also impaired spatial memory but did not affect the learning ability. Monoamines and metabolites were measured in the prefrontal cortex (PFC), striatum, hypothalamus, and hippocampus. The dopamine (DA) levels in the PFC decreased but the homovanillic acid/DA ratio increased. The decreased DA and the increased 5-hydroxyindoleacetic acid (5-HIAA) levels were observed in the striatum. Only the 5-HIAA level increased in the hypothalamus. In the hippocampus, stress did not affect the levels of monoamines and metabolites. The results suggest that scream sound stress influences most physiologic parameters, memory, and the levels of monoamine neurotransmitter and their metabolites in female rats. Copyright © 2014. Published by Elsevier Inc.

Infrequent alterations of the P53 gene in rat skin cancers induced by ionising-radiation

International Nuclear Information System (INIS)

Jin, Y.; Burns, F.J.; Garte, S.J.; Hosselet, S.; New York Univ., NY

1996-01-01

Radiation carcinogenesis almost certainly involves multiple genetic alterations. Identification of such genetic alterations would provide information to help understand better the molecular mechanism or radiation carcinogenesis. The energy released by ionizing radiation has the potential to produce DNA strand breaks, major gene deletions or rearrangements, and other base damages. Alterations of the p53 gene, a common tumour suppressor gene altered in human cancers, were examined in radiation-induced rat skin cancers. Genomic DNA from a total of 33rat skin cancers induced by ionizing radiation was examined by Southern blot hybridization for abnormal restriction fragment patterns in the p53 gene. A abnormal p53 restriction pattern was found in one of 16 cancers induced by electron radiation and in one of nine cancers induced by neon ions. The genomic DNA from representative cancers, including the two with an abnormal restriction pattern was further examined by polymerase chain reaction amplification and direct sequencing in exons 5-8 of the p53 gene. The results showed that one restriction fragment length polymorphism (RFLP)-positive cancer induced by electron radiation had a partial gene deletion which was defined approximately between exons 2-8, while none of the other cancers showed sequence changes. Our results indicate that the alterations in the critical binding region of the p53 gene are infrequent in rat skin cancers induced by either electron or neon ion radiation. (Author)

A hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion.

Science.gov (United States)

Xu, D; Wu, Y; Liu, F; Liu, Y S; Shen, L; Lei, Y Y; Liu, J; Ping, J; Qin, J; Zhang, C; Chen, L B; Magdalou, J; Wang, H

2012-11-01

Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic-pituitary-adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

Moderate perinatal thyroid hormone insufficiency alters visual system function in adult rats.

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Boyes, William K; Degn, Laura; George, Barbara Jane; Gilbert, Mary E

2018-04-21

Thyroid hormone (TH) is critical for many aspects of neurodevelopment and can be disrupted by a variety of environmental contaminants. Sensory systems, including audition and vision are vulnerable to TH insufficiencies, but little data are available on visual system development at less than severe levels of TH deprivation. The goal of the current experiments was to explore dose-response relations between graded levels of TH insufficiency during development and the visual function of adult offspring. Pregnant Long Evans rats received 0 or 3 ppm (Experiment 1), or 0, 1, 2, or 3 ppm (Experiment 2) of propylthiouracil (PTU), an inhibitor of thyroid hormone synthesis, in drinking water from gestation day (GD) 6 to postnatal day (PN) 21. Treatment with PTU caused dose-related reductions of serum T4, with recovery on termination of exposure, and euthyroidism by the time of visual function testing. Tests of retinal (electroretinograms; ERGs) and visual cortex (visual evoked potentials; VEPs) function were assessed in adult offspring. Dark-adapted ERG a-waves, reflecting rod photoreceptors, were increased in amplitude by PTU. Light-adapted green flicker ERGs, reflecting M-cone photoreceptors, were reduced by PTU exposure. UV-flicker ERGs, reflecting S-cones, were not altered. Pattern-elicited VEPs were significantly reduced by 2 and 3 ppm PTU across a range of stimulus contrast values. The slope of VEP amplitude-log contrast functions was reduced by PTU, suggesting impaired visual contrast gain. Visual contrast gain primarily reflects function of visual cortex, and is responsible for adjusting sensitivity of perceptual mechanisms in response to changing visual scenes. The results indicate that moderate levels of pre-and post-natal TH insufficiency led to alterations in visual function of adult rats, including both retinal and visual cortex sites of dysfunction. Copyright © 2018. Published by Elsevier B.V.

Mitochondrial Morphofunctional Alterations in Smooth Muscle Cells of Aorta in Rats

Science.gov (United States)

Tarán, Mariana; Llorens, Candelaria; Balceda, Ariel; Scribano, María de La Paz; Pons, Patricia; Moya, Mónica

2014-01-01

In an experimental model of atherogenesis induced by hyperfibrinogenemia (HF), the pharmacological response of vitamin E was studied in order to assess its antioxidant effect on the mitochondrial morphofunctional alterations in aortic smooth muscle cells. Three groups of male rats were used: (Ctr) control, (AI) atherogenesis induced for 120 days, and (AIE) atherogenesis induced for 120 days and treated with vitamin E. HF was induced by adrenalin injection (0.1 mg/day/rat) for 120 days. AIE group was treated with the administration of 3.42 mg/day/rat of vitamin E for 105 days after the first induction. Mitochondria morphology was analyzed by electronic microscopy (EM) and mitochondrial complexes (MC) by spectrophotometry. In group AI the total and mean number of mitochondria reduced significantly, the intermembranous matrix increased, and swelling was observed with respect to Ctr and AIE (P < 0.01). These damages were related to a significant decrease in the activity of citrate synthase and complexes I, II, III, and IV in group AI in comparison to Ctr (P < 0.001). Similar behavior was presented by group AI compared to AIE (P < 0.001). These results show that vitamin E produces a significative regression of inflammatory and oxidative stress process and it resolved the morphofunctional mitochondrial alterations in this experimental model of atherogenic disease. PMID:24653842

Pentoxifylline Ameliorates Glomerular Basement Membrane Ultrastructural Changes Caused by Gentamicin Administration in Rats

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Nenad Stojiljković

2009-08-01

Full Text Available Gentamicin is commonly used for the treatment of severe gram negative bacterial infections but inevi-tably cause renal failure during prolonged use. The aim of our study was to emphasize protective effects of pentoxifylline on glomerular basement membrane (GBM alterations induced by gentamicin in rats. Experiments were done on 40 male Wistar rats divided in three experimental groups. GM-group was treated daily with gentamicin in dose of 100 mg/kg during 8 days. PTX-group was treated daily with pentoxifylline in dose of 45 mg/kg and the same dose of gentamicin as in GM-group during 8 days. The control group received 1 ml/day saline intraperitoneally. Morphometric parameter measured during the analysis was glomerular basement membrane thickness. In GM-group of animals glomeruli were en-larged and GMB was diffusely and unequally thickened with neutrophil cells infiltration. In proximal tu-bules epithelial cells, vacuolization of cytoplasm with coagulation-type necrosis were observed. In PTX-group of animals glomeruli were somewhat enlarged and GBM was thickened only in some segments. Coagulation-type necrosis was not found. Blood urea and serum creatinine concentration in GM-group were significantly elevated in comparison with PTX-group while potassium level was decreased. Our results suggest that PTX has protective effects on GBM and proximal tubules in GM-treated rats.

Maternal mobile phone exposure alters intrinsic electrophysiological properties of CA1 pyramidal neurons in rat offspring.

Science.gov (United States)

Razavinasab, Moazamehosadat; Moazzami, Kasra; Shabani, Mohammad

2016-06-01

Some studies have shown that exposure to electromagnetic field (EMF) may result in structural damage to neurons. In this study, we have elucidated the alteration in the hippocampal function of offspring Wistar rats (n = 8 rats in each group) that were chronically exposed to mobile phones during their gestational period by applying behavioral, histological, and electrophysiological tests. Rats in the EMF group were exposed to 900 MHz pulsed-EMF irradiation for 6 h/day. Whole cell recordings in hippocampal pyramidal cells in the mobile phone groups did show a decrease in neuronal excitability. Mobile phone exposure was mostly associated with a decrease in the number of action potentials fired in spontaneous activity and in response to current injection in both male and female groups. There was an increase in the amplitude of the afterhyperpolarization (AHP) in mobile phone rats compared with the control. The results of the passive avoidance and Morris water maze assessment of learning and memory performance showed that phone exposure significantly altered learning acquisition and memory retention in male and female rats compared with the control rats. Light microscopy study of brain sections of the control and mobile phone-exposed rats showed normal morphology.Our results suggest that exposure to mobile phones adversely affects the cognitive performance of both female and male offspring rats using behavioral and electrophysiological techniques. © The Author(s) 2014.

Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

Energy Technology Data Exchange (ETDEWEB)

Bitencourt, C.S. [Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Duarte, C.G.; Azzolini, A.E.C.S.; Assis-Pandochi, A.I. [Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

2012-03-02

Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production.

Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

International Nuclear Information System (INIS)

Bitencourt, C.S.; Duarte, C.G.; Azzolini, A.E.C.S.; Assis-Pandochi, A.I.

2012-01-01

Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production

Social exclusion intensifies anxiety-like behavior in adolescent rats.

Science.gov (United States)

Lee, Hyunchan; Noh, Jihyun

2015-05-01

Social connection reduces the physiological reactivity to stressors, while social exclusion causes emotional distress. Stressful experiences in rats result in the facilitation of aversive memory and induction of anxiety. To determine the effect of social interaction, such as social connection, social exclusion and equality or inequality, on emotional change in adolescent distressed rats, the emotional alteration induced by restraint stress in individual rats following exposure to various social interaction circumstances was examined. Rats were assigned to one of the following groups: all freely moving rats, all rats restrained, rats restrained in the presence of freely moving rats and freely moving rats with a restrained rat. No significant difference in fear-memory and sucrose consumption between all groups was found. Change in body weight significantly increased in freely moving rats with a restrained rat, suggesting that those rats seems to share the stressful experience of the restrained rat. Interestingly, examination of the anxiety-like behavior revealed only rats restrained in the presence of freely moving rats to have a significant increase, suggesting that emotional distress intensifies in positions of social exclusion. These results demonstrate that unequally excluded social interaction circumstances could cause the amplification of distressed status and anxiety-related emotional alteration. Copyright © 2015 Elsevier B.V. All rights reserved.

Arrest in ciliated cell expansion on the bronchial lining of adult rats caused by chronic exposure to industrial noise

International Nuclear Information System (INIS)

Oliveira, Maria Joao R.; Pereira, Antonio S.; Ferreira, Paula G.; Guimara-tilde es, Laura; Freitas, Diamantino; Carvalho, Antonio P.O.; Grande, Nuno R.; Aguas, Artur P.

2005-01-01

Workers chronically exposed to high-intensity/low-frequency noise at textile plants show increased frequency of respiratory infections. This phenomenon prompted the herein investigation on the cytology of the bronchial epithelium of Wistar rats submitted to textile noise. Workplace noise from a cotton-mill room of a textile factory was recorded and reproduced in a sound-insulated animal room. The Wistar rats were submitted to a weekly schedule of noise treatment that was similar to that of the textile workers (8h/day, 5 days/week). Scanning electron microscopy (SEM) was used to compare the fine morphology of the inner surface of the bronchi in noise-exposed and control rats. SEM quantitative cytology revealed that exposure to noise for 5-7 months caused inhibition in the natural expansion of the area occupied by ciliated cells on the bronchial epithelium as adult rats grow older. This difference between noise-exposed and age-matched control rats was statistically significant (P0.05) and documents that the cytology of the rat bronchial epithelium is mildly altered by noise exposure. The decrease in the area of bronchial cilia may impair the mucociliar clearance of the respiratory airways and, thus, increase vulnerability to respiratory infection

Repeated Sleep Restriction in Adolescent Rats Altered Sleep Patterns and Impaired Spatial Learning/Memory Ability

Science.gov (United States)

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

Ursodeoxycholic acid alleviates cholestasis-induced histophysiological alterations in the male reproductive system of bile duct-ligated rats.

Science.gov (United States)

Saad, Ramadan A; Mahmoud, Yomna I

2014-12-01

Ursodeoxycholic acid is the most widely used drug for treating cholestatic liver diseases. However, its effect on the male reproductive system alterations associated with cholestasis has never been studied. Thus, this study aimed to investigate the effect of ursodeoxycholic acid on cholestasis-induced alterations in the male reproductive system. Cholestasis was induced by bile duct ligation. Bile duct-ligated rats had higher cholestasis biomarkers and lower levels of testosterone, LH and FSH than did the Sham rats. They also had lower reproductive organs weights, and lower sperm motility, density and normal morphology than those of Sham rats. Histologically, these animals suffered from testicular tubular atrophy, interstitial edema, thickening of basement membranes, vacuolation, and depletion of germ cells. After ursodeoxycholic acid administration, cholestasis-induced structural and functional alterations were significantly ameliorated. In conclusion, ursodeoxycholic acid can ameliorate the reproductive complications of chronic cholestasis in male patients, which represents an additional benefit to this drug. Copyright © 2014 Elsevier Inc. All rights reserved.

Alterations in the molecular species of rat liver lecithin by corn-oil feeding to essential fatty acid-deficient rats as a function of time

NARCIS (Netherlands)

Golde, L.M.G. van; Pieterson, W.A.; Deenen, L.L.M. van

1968-01-01

The present paper describes, as a function of time, the qualitative and quantitative alterations in the molecular species pattern of rat liver lecithin which are observed when corn oil is fed to essential fatty acid-deficient rats. One of the most important changes observed was a very rapid

Oxaliplatin Alters Expression of T1R2 Receptor and Sensitivity to Sweet Taste in Rats.

Science.gov (United States)

Ohishi, Akihiro; Nishida, Kentaro; Yamanaka, Yuri; Miyata, Ai; Ikukawa, Akiko; Yabu, Miharu; Miyamoto, Karin; Bansho, Saho; Nagasawa, Kazuki

2016-01-01

As one of the adverse effects of oxaliplatin, a key agent in colon cancer chemotherapy, a taste disorder is a severe issue in a clinical situation because it decreases the quality of life of patients. However, there is little information on the mechanism underlying the oxaliplatin-induced taste disorder. Here, we examined the molecular and behavioral characteristics of the oxaliplatin-induced taste disorder in rats. Oxaliplatin (4-16 mg/kg) was administered to Sprague-Dawley (SD) rats intraperitoneally for 2 d. Expression levels of mRNA and protein of taste receptors in circumvallate papillae (CP) were measured by real-time quantitative polymerase chain reaction (PCR) and immunohistochemistry, respectively. Taste sensitivity was assessed by their behavioral change using a brief-access test. Morphological change of the taste buds in CP was evaluated by hematoxyline-eosin (HE) staining, and the number of taste cells in taste buds was counted by immunohistochemical analysis. Among taste receptors, the expression levels of mRNA and protein of T1R2, a sweet taste receptor subunit, were increased transiently in CP of oxaliplatin-administered rats on day 7. In a brief-access test, the lick ratio was decreased in oxaliplatin-administered rats on day 7 and the alteration was recovered to the control level on day 14. There was no detectable alteration in the morphology of taste buds, number of taste cells or plasma zinc level in oxaliplatin-administered rats. These results suggest that decreased sensitivity to sweet taste in oxaliplatin-administered rats is due, at least in part, to increased expression of T1R2, while these alterations are reversible.

Sex-related differences in cadmium-induced alteration of drug action in the rat

Energy Technology Data Exchange (ETDEWEB)

Schnell, R.C.; Pence, D.H.; Prosser, T.D.; Miya, T.S.

1976-01-01

Three days after pretreatment of rats of both sexes with cadmium (2 mg/kg, i.p.), the duration of hypnosis induced by hexobarbital (75 mg/kg, i.p.) was potentiated in males but not females. Likewise, similar treatment with cadmium leads to significant inhibition of the metabolism of hexobarbital by hepatic microsomal enzymes obtained from male but not female animals. These data suggest that there is a sex-related difference in the ability of cadmium to alter drug action in rats.

Early life ethanol exposure causes long-lasting disturbances in rat mesenchymal stem cells via epigenetic modifications

International Nuclear Information System (INIS)

Leu, Yu-Wei; Chu, Pei-Yi; Chen, Chien-Min; Yeh, Kun-Tu; Liu, Yu Ming; Lee, Yen-Hui; Kuo, Shan-Tsu; Hsiao, Shu-Huei

2014-01-01

Highlights: • Ethanol exposure alters proliferation and differentiation of MSCs. • Ethanol exposure suppresses osteogenesis and adipogenesis of MSCs. • H3K27me3-associated genes/pathways are affected in ethanol-exposed MSCs. • Expression of lineage-specific genes is dysregulated in ethanol-exposed MSCs. - Abstract: Fetal alcohol syndrome (FAS) is a birth defect due to maternal alcohol consumption during pregnancy. Because mesenchymal stem cells (MSCs) are the main somatic stem cells in adults and may contribute to tissue homeostasis and repair in adulthood, we investigated whether early life ethanol exposure affects MSCs and contributes to the propensity for disease onset in later life. Using a rodent model of FAS, we found that ethanol exposure (5.25 g/kg/day) from postnatal days 4 to 9 in rat pups (mimic of human third trimester) caused long-term anomalies in bone marrow-derived MSCs. MSCs isolated from ethanol-exposed animals were prone to neural induction but resistant to osteogenic and adipogenic inductions compared to their age-matched controls. The altered differentiation may contribute to the severe trabecular bone loss seen in ethanol-exposed animals at 3 months of age as well as overt growth retardation. Expression of alkaline phosphatase, osteocalcin, aP2, and PPARγ were substantially inhibited, but BDNF was up-regulated in MSCs isolated from ethanol-exposed 3 month-old animals. Several signaling pathways were distorted in ethanol-exposed MSCs via altered trimethylation at histone 3 lysine 27. These results demonstrate that early life ethanol exposure can have long-term impacts in rat MSCs by both genetic and epigenetic mechanisms

Early life ethanol exposure causes long-lasting disturbances in rat mesenchymal stem cells via epigenetic modifications

Energy Technology Data Exchange (ETDEWEB)

Leu, Yu-Wei [Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 621, Taiwan (China); Chu, Pei-Yi [Department of Pathology, Show Chwan Memorial Hospital, Changhua 500, Taiwan (China); Chen, Chien-Min [Division of Neurosurgery, Changhua Christian Hospital, Changhua 500, Taiwan (China); Yeh, Kun-Tu [Department of Pathology, Changhua Christian Hospital, Changhua 500, Taiwan (China); Liu, Yu Ming; Lee, Yen-Hui; Kuo, Shan-Tsu [Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 621, Taiwan (China); Hsiao, Shu-Huei, E-mail: bioshh@ccu.edu.tw [Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 621, Taiwan (China)

2014-10-24

Highlights: • Ethanol exposure alters proliferation and differentiation of MSCs. • Ethanol exposure suppresses osteogenesis and adipogenesis of MSCs. • H3K27me3-associated genes/pathways are affected in ethanol-exposed MSCs. • Expression of lineage-specific genes is dysregulated in ethanol-exposed MSCs. - Abstract: Fetal alcohol syndrome (FAS) is a birth defect due to maternal alcohol consumption during pregnancy. Because mesenchymal stem cells (MSCs) are the main somatic stem cells in adults and may contribute to tissue homeostasis and repair in adulthood, we investigated whether early life ethanol exposure affects MSCs and contributes to the propensity for disease onset in later life. Using a rodent model of FAS, we found that ethanol exposure (5.25 g/kg/day) from postnatal days 4 to 9 in rat pups (mimic of human third trimester) caused long-term anomalies in bone marrow-derived MSCs. MSCs isolated from ethanol-exposed animals were prone to neural induction but resistant to osteogenic and adipogenic inductions compared to their age-matched controls. The altered differentiation may contribute to the severe trabecular bone loss seen in ethanol-exposed animals at 3 months of age as well as overt growth retardation. Expression of alkaline phosphatase, osteocalcin, aP2, and PPARγ were substantially inhibited, but BDNF was up-regulated in MSCs isolated from ethanol-exposed 3 month-old animals. Several signaling pathways were distorted in ethanol-exposed MSCs via altered trimethylation at histone 3 lysine 27. These results demonstrate that early life ethanol exposure can have long-term impacts in rat MSCs by both genetic and epigenetic mechanisms.

Social and physical environment alter cocaine conditioned place preference and dopaminergic markers in adolescent male rats.

Science.gov (United States)

Zakharova, E; Miller, J; Unterwald, E; Wade, D; Izenwasser, S

2009-10-20

This study was done to determine whether social and environmental factors alter cocaine reward and proteins implicated in mediating drug reward in rats during early adolescence. On postnatal day (PND) 23, rats were housed under conditions where both social (number of rats per cage) and environmental (availability of toys) factors were manipulated. Socially isolated rats were housed alone impoverished with no toys (II) or enriched with toys (IE). Social rats were housed two rats/cage with no toys (SI2) or with toys (SE2), or three/cage with (SE3) or without (SI3) toys. On PND 43, cocaine conditioned place preference (CPP) sessions began with the post-test done on PND 47. Cocaine CPP was established in response to 5 or 10 mg/kg cocaine in II rats, and CPP was decreased with the addition of cage mates or toys. No CPP was seen to any dose in SI3 or SE3 rats. Enriched housing (SE3) increased dopamine transporter (DAT) protein in the nucleus accumbens compared to II. There also were differential effects of cocaine on tyrosine hydroxylase and DAT depending on housing, with both increased by cocaine in II but not SE3 rats. DARPP-32 was unchanged by housing or cocaine, while phospho-Thr(34)-DARPP-32 was increased by cocaine treatment across conditions. Thus, both social and environmental enrichment decrease cocaine CPP during adolescence and different housing alters proteins that regulate dopaminergic neurotransmission in a manner that may account for the observed differences in cocaine-induced reward.

Metabonomic Analysis Reveals Efficient Ameliorating Effects of Acupoint Stimulations on the Menopause-caused Alterations in Mammalian Metabolism

Science.gov (United States)

Zhang, Limin; Wang, Yulan; Xu, Yunxiang; Lei, Hehua; Zhao, Ying; Li, Huihui; Lin, Xiaosheng; Chen, Guizhen; Tang, Huiru

2014-01-01

Acupoint stimulations are effective in ameliorating symptoms of menopause which is an unavoidable ageing consequence for women. To understand the mechanistic aspects of such treatments, we systematically analyzed the effects of acupoint laser-irradiation and catgut-embedding on the ovariectomy-induced rat metabolic changes using NMR and GC-FID/MS methods. Results showed that ovariectomization (OVX) caused comprehensive metabolic changes in lipid peroxidation, glycolysis, TCA cycle, choline and amino acid metabolisms. Both acupoint laser-irradiation and catgut-embedding ameliorated the OVX-caused metabonomic changes more effectively than hormone replacement therapy (HRT) with nilestriol. Such effects of acupoint stimulations were highlighted in alleviating lipid peroxidation, restoring glucose homeostasis and partial reversion of the OVX-altered amino acid metabolism. These findings provided new insights into the menopause effects on mammalian biochemistry and beneficial effects of acupoint stimulations in comparison with HRT, demonstrating metabonomics as a powerful approach for potential applications in disease prognosis and developments of effective therapies.

Downregulation of transient receptor potential M6 channels as a cause of hypermagnesiuric hypomagnesemia in obese type 2 diabetic rats.

Science.gov (United States)

Takayanagi, Kaori; Shimizu, Taisuke; Tayama, Yosuke; Ikari, Akira; Anzai, Naohiko; Iwashita, Takatsugu; Asakura, Juko; Hayashi, Keitaro; Mitarai, Tetsuya; Hasegawa, Hajime

2015-06-15

We assessed the expression profile of Mg(2+)-transporting molecules in obese diabetic rats as a cause of hypermagnesiuric hypomagnesemia, which is involved in the development of insulin resistance, hypertension, and coronary diseases. Kidneys were obtained from male Otsuka Long-Evans Tokushima fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) obese diabetic rats at the ages of 16, 24, and 34 wk. Expression profiles were studied by real-time PCR and immunohistochemistry together with measurements of urine Mg(2+) excretion. Urine Mg(2+) excretion was increased in 24-wk-old OLETF rats and hypomagnesemia was apparent in 34-wk-old OLETF rats but not in LETO rats (urine Mg(2+) excretion: 0.16 ± 0.01 μg·min(-1)·g body wt(-1) in 24-wk-old LETO rats and 0.28 ± 0.01 μg·min(-1)·g body wt(-1) in 24-wk-old OLETF rats). Gene expression of transient receptor potential (TRP)M6 was downregulated (85.5 ± 5.6% in 34-wk-old LETO rats and 63.0 ± 3.5% in 34-wk-old OLETF rats) concomitant with Na(+)-Cl(-) cotransporter downregulation, whereas the expression of claudin-16 in tight junctions of the thick ascending limb of Henle was not different. The results of the semiquantitative analysis of immunohistochemistry were consistent with these findings (TRPM6: 0.49 ± 0.04% in 16-wk-old LETO rats, 0.10 ± 0.01% in 16-wk-old OLETF rats, 0.52 ± 0.03% in 24-wk-old LETO rats, 0.10 ± 0.01% in 24-wk-old OLETF rats, 0.48 ± 0.02% in 34-wk-old LETO rats, and 0.12 ± 0.02% in 34-wk-old OLETF rats). Gene expression of fibrosis-related proinflammatory cytokines as well as histological changes showed that the hypermagnesiuria-related molecular changes and tubulointerstitial nephropathy developed independently. TRPM6, located principally in distal convoluted tubules, appears to be a susceptible molecule that causes hypermagnesiuric hypomagnesemia as a tubulointerstitial nephropathy-independent altered tubular function in diabetic nephropathy. Copyright © 2015 the American Physiological

Alterations of polyunsaturated fatty acid metabolism in ovarian tissues of polycystic ovary syndrome rats.

Science.gov (United States)

Huang, Rong; Xue, Xinli; Li, Shengxian; Wang, Yuying; Sun, Yun; Liu, Wei; Yin, Huiyong; Tao, Tao

2018-03-30

The metabolism of polyunsaturated fatty acids (PUFAs) remains poorly characterized in ovarian tissues of patients with polycystic ovary syndrome (PCOS). This study aimed to explore alterations in the levels of PUFAs and their metabolites in serum and ovarian tissues in a PCOS rat model treated with a high-fat diet and andronate. Levels of PUFAs and their metabolites were measured using gas/liquid chromatography-mass spectrometry after the establishment of a PCOS rat model. Only 3 kinds of PUFAs [linoleic acid, arachidonic acid (AA) and docosahexaenoic acid] were detected in both the circulation and ovarian tissues of the rats, and their concentrations were lower in ovarian tissues than in serum. Moreover, significant differences in the ovarian levels of AA were observed between control, high-fat diet-fed and PCOS rats. The levels of prostaglandins, AA metabolites via the cyclooxygenase (COX) pathway, in ovarian tissues of the PCOS group were significantly increased compared to those in the controls. Further studies on the mechanism underlying this phenomenon showed a correlation between decreased expression of phosphorylated cytosolic phospholipase A2 (p-cPLA2) and increased mRNA and protein expression of COX2, potentially leading to a deeper understanding of altered AA and prostaglandin levels in ovarian tissues of PCOS rats. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Time-Dependent Structural Alteration of Rituximab Analyzed by LC/TOF-MS after a Systemic Administration to Rats.

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Yuki Otani

Full Text Available Therapeutic monoclonal antibodies (mAbs have heterogeneities in their structures. Multiple studies have reported that the variety of post-translational modifications could affect the pharmacokinetic profiles or pharmacological potencies of therapeutic mAbs. Taking into the account that the structural modification of mAbs would affect the efficacy, it is worth investigating the structural alteration of therapeutic mAbs in the blood and the relationship between their structures and pharmacological effects. Herein, we have developed the method to isolate rituximab from plasma in which endogenous IgGs interfere the detection of rituximab, and successfully developed the analytical method with a liquid chromatograph time-of-flight mass spectrometer to detect the structure of rituximab in plasma with errors less than 30 parts per millions. Eight types of carbohydrate chains in rituximab were detected by this method. Interestingly, time-dependent changes in carbohydrate chains such as AAF (G2F and GnGn (G0 were observed in rats, although the amino acids were stable. Additionally, these structural changes were observed via incubation in plasma as in the rat experiment, suggesting that a certain type of enzyme in plasma caused the alterations of the carbohydrate chains. The present analytical methods could clarify the actual pharmacokinetics of therapeutic mAbs, and help to evaluate the interindividual variations in pharmacokinetics and efficacy.

BDNF expression in the hippocampus of maternally separated rats: does Bifidobacterium breve 6330 alter BDNF levels?

Science.gov (United States)

O'Sullivan, E; Barrett, E; Grenham, S; Fitzgerald, P; Stanton, C; Ross, R P; Quigley, E M M; Cryan, J F; Dinan, T G

2011-09-01

Brain-derived neurotrophic factor (BDNF) is of interest because of its putative role in stress and psychiatric disorders. Maternal separation is used as an animal model of early-life stress and of irritable bowel syndrome (IBS). Animals exposed to the paradigm show altered gut function together with heightened levels of arousal and corticosterone. Some probiotic organisms have been shown to be of benefit in IBS and influence the brain-gut axis. Our objective was to investigate the effects of maternal separation on BDNF under basal conditions and in response to the probiotic Bifidobacterium breve 6330. The study implemented the maternal separation model which we have previously described. Polymerase chain reaction and in situ hybridisation were performed to measure the effect of maternal separation on both BDNF total variants and BDNF splice variant (exon) IV in the hippocampus. Maternally separated and non-separated rats were treated with B. breve 6330, to investigate the effect of this probiotic on BDNF total variant and BDNF exon IV expression. Maternal separation increased BDNF total variants (Pbreve 6330 increased BDNF total variants (Pbreve 6330 did not alter BDNF levels in the maternally separated rats. Maternal separation caused a marked increase in BDNF in the hippocampus. While B. breve 6330 influenced BDNF in normal animals, it had no significant effect on BDNF in those which were maternally separated. We have demonstrated that an orally administered probiotic can influence hippocampal BDNF.

Alterations of p75 neurotrophin receptor and Myelin transcription factor 1 in the hippocampus of perinatal phencyclidine treated rats.

Science.gov (United States)

Andrews, Jessica L; Newell, Kelly A; Matosin, Natalie; Huang, Xu-Feng; Fernandez-Enright, Francesca

2015-12-03

Postnatal administration of phencyclidine (PCP) in rodents causes major disturbances to neurological processes resulting in severe modifications to normal behavioral traits into adulthood. It is routinely used to model psychiatric disorders such as schizophrenia, producing many of the dysfunctional processes in the brain that are present in this devastating disorder, including elevated levels of apoptosis during neurodevelopment and disruptions to myelin and plasticity processes. Lingo-1 (or Leucine-rich repeat and immunoglobulin domain-containing protein) is responsible for negatively regulating neurite outgrowth and the myelination of axons. Recent findings using a postmortem human brain cohort showed that Lingo-1 signaling partners in the Nogo receptor (NgR)/p75/TNF receptor orphan Y (TROY) signaling complex, and downstream signaling partners With No Lysine (K) (WNK1) and Myelin transcription factor 1 (Myt1), play a significant part in schizophrenia pathophysiology. Here we have examined the implication of Lingo-1 and its signaling partners in a neurodevelopmental model of schizophrenia using PCP to determine if these pathways are altered in the hippocampus throughout different stages of neurodevelopment. Male Sprague-Dawley rats were injected subcutaneously with PCP (10mg/kg) or saline solution on postnatal days (PN) 7, 9, and 11. Rats (n=6/group) were sacrificed at PN12, 5weeks, or 14weeks. Relative expression levels of Lingo-1 signaling proteins were examined in the hippocampus of the treated rats. p75 and Myt1 were decreased (0.001≤p≤0.011) in the PCP treated rats at PN12. There were no significant changes in any of the tested proteins at 5weeks (p>0.05). At 14weeks, p75, TROY, and Myt1 were increased in the PCP treated rats (0.014≤p≤0.022). This is the first report of an alteration in Lingo-1 signaling proteins in the rat hippocampus, both directly after PCP treatment in early development and in adulthood. Based on our results, we propose that

Gene alterations in radiation-induced F344 rat lung tumors

International Nuclear Information System (INIS)

Kelly, G.; Hahn, F.F.

1994-01-01

The p53 tumor suppressor gene is frequently altered in all major histopathologic types of human lung tumors. Reported p53 mutations include base substitutions, allelic loss, rearrangements, and deletions. Point mutations resulting in base substitutions are clustered within a highly conserved region of the gene encoding exons 508, and mutations in this region substantially extend the half-life of the p53 protein. In addition to its prominent importance in lung carcinogenesis, the p53 gene plays a critical role in the cellular response to genetic damage caused by radiation. Specifically, the protein product of p53 induces a pause or block at the G 1 to S boundary of the cell cycle following radiation-caused DNA damage. This G 1 block may allow the cell time to repair the damaged DNA prior to replication. Cells lacking a functional p53 protein fail to pause for repair and consequently accumulate mutations in the genome at an accelerated rate. p53 has also been implicated as a controlling factor in apoptosis or in programmed cell death induced by DNA-damaging agents, such as ionizing radiation. The p53 gene is mutated in approximately 50% of squamous cell carcinomas from uranium miners who inhaled high doses of radon daughters. The purpose of the present study was to determine if a similar percentage of squamous cell carcinomas with p53 mutations developed in the lungs of rats exposed to aerosols of 239 PuO 2

Hypothyroidism during neonatal and perinatal period induced by thyroidectomy of the mother causes depressive-like behavior in prepubertal rats

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Marisol Pineda-Reynoso

2010-04-01

Full Text Available Marisol Pineda-Reynoso, Edgar Cano-Europa, Vanessa Blas-Valdivia, Adelaida Hernandez-Garcia, Margarita Franco-Colin, Rocio Ortiz-ButronDepartamento de Fisiología ‘Mauricio Russek Berman,’ Escuela Nacional de Ciencias Biológicas, IPN, Carpio y Plan de Ayala, MéxicoAbstract: The objective of this study was to see if neonatal and perinatal hypothyroidism caused anxiety and depressive-like behaviors. Twenty female Wistar rats were randomly divided into two groups: 1 thyroidectomy caused hypothyroidism, in which the thyroid gland had been removed and the parathyroid reimplanted; and 2 false thyroidectomy. The thyroidectomy was made on rats anesthetized with ketamine-xylazine. The rats were mated and one day after giving birth, eight pups were assigned to each group randomly and they were distributed into two groups: a hypothyroid group containing male pups of a hypothyroid mother with a hypothyroid wet nurse; and a euthyroid group of male pups of a euthyroid mother with a euthyroid wet nurse. We analyzed the behavioral test at a prepubertal age. The neonatal and perinatal hypothyroidism caused by the mother’s thyroidectomy caused a decrease in body weight and length. We found that the neonatal and perinatal hypothyroidism enhanced the total exploratory activity without affecting social contact and the time spent in the open and closed arms in an elevated plus-maze. The hypothyroidism caused immobility without altering the lower climbing duration in the swimming test. This study shows a novel model to cause neonatal and perinatal hypothyroidism without using pharmacological drugs. We demonstrated that hypothyroid animals had a reduction in body weight and length, a retardation of neurodevelopment, and they had depressive-like behavior.Keywords: perinatal hypothyroidism, thyroidectomy, thyroid hormone, behavior, metabolism

Electroconvulsive Stimulation, but not Chronic Restraint Stress, Causes Structural Alterations in Adult Rat Hippocampus

DEFF Research Database (Denmark)

Olesen, Mikkel V.; Wörtwein, Gitta; Pakkenberg, Bente

2015-01-01

The neurobiological mechanisms underlying depression are not fully understood. Only a few previous studies have used validated stereological methods to test how stress and animal paradigms of depression affect adult hippocampal neurogenesis and whether antidepressant therapy can counteract possible...... changes in an animal model. Thus, in this study we applied methods that are state of the art in regard to stereological cell counting methods. Using a validated rat model of depression in combination with a clinically relevant schedule of electroconvulsive stimulation, we estimated the total number...... of newly formed neurons in the hippocampal subgranular zone. Also estimated were the total number of neurons and the volume of the granule cell layer in adult rats subjected to chronic restraint stress and electroconvulsive stimulation either alone or in combination. We found that chronic restraint stress...

Adrenalectomy mediated alterations in adrenergic activation of adenylate cyclase in rat liver

International Nuclear Information System (INIS)

El-Refai, M.; Chan, T.

1986-01-01

Adrenalectomy caused a large increase in the number of β-adrenergic binding sites on liver plasma membranes as measured by 125 I-iodocyanopindolol (22 and 102 fmol/mg protein for control and adrenalectomized (ADX) rats). Concomitantly an increase in the number of binding sites for 3 H-yohimbine was also observed (104 and 175 fmol/mg protein for control and adx membranes). Epinephrine-stimulated increase in cyclic AMP accumulation in isolated hepatocytes were greater in cells from ADX rats. This increase in β-adrenergic mediated action was much less than what may be expected as a result of the increase in the β-adrenergic binding in ADX membranes. In addition phenoxybenzamine (10 μM) further augmented this action of epinephrine in both control and ADX cells. To test the hypothesis that the increase in the number of the inhibitory α 2 -adrenergic receptors in adrenalectomy is responsible for the muted β-adrenergic response, the authors injected rats with pertussis toxin (PT). This treatment may cause the in vivo ribosylation of the inhibitory binding protein (Ni). Adenylate cyclase (AC) activity in liver plasma membranes prepared from treated and untreated animals was measured. In contrast with control rats, treatment of ADX rats with PT resulted in a significant increase in the basal activity of AC (5.5 and 7.7 pmol/mg protein/min for untreated and treated rats respectively). Isoproterenol (10 μM), caused AC activity to increase to 6.5 and 8.4 pmol/mg protein/min for membranes obtained from ADX untreated and ADX treated rats respectively. The α-adrenergic antagonists had no significant effect on the β-adrenergic-mediated activation of AC in liver plasma membranes from PT treated control and ADX rats. The authors conclude that the β-adrenergic activation of AC is attenuated by Ni protein both directly and as a result of activation of α-adrenergic receptors

Alterations in primary motor cortex neurotransmission and gene expression in hemi-parkinsonian rats with drug-induced dyskinesia.

Science.gov (United States)

Lindenbach, D; Conti, M M; Ostock, C Y; Dupre, K B; Bishop, C

2015-12-03

Treatment of Parkinson's disease (PD) with dopamine replacement relieves symptoms of poverty of movement, but often causes drug-induced dyskinesias. Accumulating clinical and pre-clinical evidence suggests that the primary motor cortex (M1) is involved in the pathophysiology of PD and that modulating cortical activity may be a therapeutic target in PD and dyskinesia. However, surprisingly little is known about how M1 neurotransmitter tone or gene expression is altered in PD, dyskinesia or associated animal models. The present study utilized the rat unilateral 6-hydroxydopamine (6-OHDA) model of PD/dyskinesia to characterize structural and functional changes taking place in M1 monoamine innervation and gene expression. 6-OHDA caused dopamine pathology in M1, although the lesion was less severe than in the striatum. Rats with 6-OHDA lesions showed a PD motor impairment and developed dyskinesia when given L-DOPA or the D1 receptor agonist, SKF81297. M1 expression of two immediate-early genes (c-Fos and ARC) was strongly enhanced by either L-DOPA or SKF81297. At the same time, expression of genes specifically involved in glutamate and GABA signaling were either modestly affected or unchanged by lesion and/or treatment. We conclude that M1 neurotransmission and signal transduction in the rat 6-OHDA model of PD/dyskinesia mirror features of human PD, supporting the utility of the model to study M1 dysfunction in PD and the elucidation of novel pathophysiological mechanisms and therapeutic targets. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Exposure to radio-frequency electromagnetic waves alters acetylcholinesterase gene expression, exploratory and motor coordination-linked behaviour in male rats.

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Obajuluwa, Adejoke Olukayode; Akinyemi, Ayodele Jacob; Afolabi, Olakunle Bamikole; Adekoya, Khalid; Sanya, Joseph Olurotimi; Ishola, Azeez Olakunle

2017-01-01

Humans in modern society are exposed to an ever-increasing number of electromagnetic fields (EMFs) and some studies have demonstrated that these waves can alter brain function but the mechanism still remains unclear. Hence, this study sought to investigate the effect of 2.5 Ghz band radio-frequency electromagnetic waves (RF-EMF) exposure on cerebral cortex acetylcholinesterase (AChE) activity and their mRNA expression level as well as locomotor function and anxiety-linked behaviour in male rats. Animals were divided into four groups namely; group 1 was control (without exposure), group 2-4 were exposed to 2.5 Ghz radiofrequency waves from an installed WI-FI device for a period of 4, 6 and 8 weeks respectively. The results revealed that WiFi exposure caused a significant increase in anxiety level and affect locomotor function. Furthermore, there was a significant decrease in AChE activity with a concomitant increase in AChE mRNA expression level in WiFi exposed rats when compared with control. In conclusions, these data showed that long term exposure to WiFi may lead to adverse effects such as neurodegenerative diseases as observed by a significant alteration on AChE gene expression and some neurobehavioral parameters associated with brain damage.

GSM 900 MHz Microwave RadiationInduced Alterations of Insulin Level and Histopathological Changes of Liver and Pancreas in Rat

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Mortazavi S. M. J.

2016-12-01

Full Text Available Background: The rapidly increasing use of mobile phones has led to public concerns about possible health effects of these popular communication devices. This study is an attempt to investigate the effects of radiofrequency (RF radiation produced by GSM mobile phones on the insulin release in rats. Methods: Forty two female adult Sprague Dawley rats were randomly divided into 4 groups. Group1 were exposed to RF radiation 6 hours per day for 7 days. Group 2 received sham exposure (6 hours per day for 7 days. Groups 3 and 4 received RF radiation 3 hours per day for 7 days and sham exposure (3 hours per day, respectively. The specific absorption rate (SAR of RF was 2.0W/kg. Results: Our results showed that RF radiations emitted from mobile phone could not alter insulin release in rats. However, mild to severe inflammatory changes in the portal spaces of the liver of rats as well as damage in the cells of islet of Langerhans were observed. These changes were linked with the duration of the exposures. Conclusion: RF exposure can induce inflammatory changes in the liver as well causing damage in the cells of islet of Langerhans.

Beneficial Effects of Coenzyme Q10 in Reduction of Testicular Tissue Alteration Following Induction of Diabetes in Adult Rats

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Kianifard Davoud

2015-03-01

Full Text Available Background and Aims: Various types of infertility are associated with uncontrolled hyperglycemia and diabetes. Development of oxidative stress is one the most important factors in the alteration of spermatogenesis in diabetic conditions. Consequently, the reduction of oxidative stress with antioxidant compounds can be effective in the reduction of tissue alterations. The aim of this study was to evaluate the efficacy of coenzyme Q10 in improvement of spermatogenesis in adult diabetic rats. Material and Methods: 32 adult rats were divided into four groups of control and treatment. Coenzyme Q10 (10 mg/kg body weight - b.w. was administrated to one control and one diabetic (intraperitoneal injection of 45 mg/kg b.w. of Streptozotocin groups. Blood concentrations of FSH, LH and Testosterone were measured. Histology of testicular tissue and sperm analysis were considered for evaluation of spermatogenesis. Results: Administration of Coenzyme Q10 led to increase of pituitary gonadotropins levels in diabetic rats. Testosterone levels were not changed significantly. Testicular morphology, spermatogenic indices and sperm analysis were improved in treated diabetic rats. Conclusions: The results of this study suggest that the use of Coenzyme Q10 has positive effects in reduction of spermatogenic alterations following induction of experimental diabetes in rats.

Cannabis sativa (Marijuana) alters blood chemistry and the cytoarchitecture of some organs in Sprague Dawley rat models.

Science.gov (United States)

Abey, Nosarieme Omoregie

2018-06-01

There is evidence that Cannabis whose active ingredient is tetrahydrocannabinol (THC) is the most commonly abused neuroactive substance, among young adults. This work investigated the effects of Cannabis sativa on the cytoarchitecture of some key organs and the blood chemistry of rat models. Twenty-one (21) male Sprague Dawley rats were fed different percentage of cannabis chow (0%, 5% and 10%) for a period of seven (7) weeks. Rats were subjected to intermittent cognitive function test and sacrificed after the seventh week, collecting the blood, brain and other important tissues for analysis which include; brain total protein and nitric oxide concentration, blood chemistry and histopathology. Results revealed a dose-dependent decline in the cognitive function, statistically significant decrease in the brain total protein and nitric oxide. Histopathology revealed significant hypertrophy in the heart, hypercellularity in neuronal cells, prominent sinusoids cytoarchitecture of the hepatocytes and vascular congestion in the seminiferous tubules of testes. There was a statistically significant difference in the plasma ALP, ALT, AST level between controls and the cannabis test groups. Cannabis use caused cellular damage through mediation of imbalance and altered cytoarchitecture which may affects the overall health of dependent user. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chronic intermittent hyperoxia alters the development of the hypoxic ventilatory response in neonatal rats.

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Logan, Sarah; Tobin, Kristina E; Fallon, Sarah C; Deng, Kevin S; McDonough, Amy B; Bavis, Ryan W

2016-01-01

Chronic exposure to sustained hyperoxia alters the development of the respiratory control system, but the respiratory effects of chronic intermittent hyperoxia have rarely been investigated. We exposed newborn rats to short, repeated bouts of 30% O2 or 60% O2 (5 bouts h(-1)) for 4-15 days and then assessed their hypoxic ventilatory response (HVR; 10 min at 12% O2) by plethysmography. The HVR tended to be enhanced by intermittent hyperoxia at P4 (early phase of the HVR), but it was significantly reduced at P14-15 (primarily late phase of the HVR) compared to age-matched controls; the HVR recovered when individuals were returned to room air and re-studied as adults. To investigate the role of carotid body function in this plasticity, single-unit carotid chemoafferent activity was recorded in vitro. Intermittent hyperoxia tended to decrease spontaneous action potential frequency under normoxic conditions but, contrary to expectations, hypoxic responses were only reduced at P4 (not at P14) and only in rats exposed to higher O2 levels (i.e., intermittent 60% O2). Rats exposed to intermittent hyperoxia had smaller carotid bodies, and this morphological change may contribute to the blunted HVR. In contrast to rats exposed to intermittent hyperoxia beginning at birth, two weeks of intermittent 60% O2 had no effect on the HVR or carotid body size of rats exposed beginning at P28; therefore, intermittent hyperoxia-induced respiratory plasticity appears to be unique to development. Although both intermittent and sustained hyperoxia alter carotid body development and the HVR of rats, the specific effects and time course of this plasticity differs. Copyright © 2015 Elsevier B.V. All rights reserved.

Differential Rearing Alters Forced Swim Test Behavior, Fluoxetine Efficacy, and Post-Test Weight Gain in Male Rats

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Arndt, David L.; Peterson, Christy J.; Cain, Mary E.

2015-01-01

Environmental factors play a key role in the etiology of depression. The rodent forced swim test (FST) is commonly used as a preclinical model of depression, with increases in escape-directed behavior reflecting antidepressant effects, and increases in immobility reflecting behavioral despair. Environmental enrichment leads to serotonergic alterations in rats, but it is unknown whether these alterations may influence the efficacy of common antidepressants. Male Sprague-Dawley rats were reared in enriched (EC), standard (SC), or isolated (IC) conditions. Following the rearing period, fluoxetine (10 or 20 mg/kg, i.p.) was administered 23.5 hrs, 5 hrs, and 1 hr before locomotor and FST measures. Following locomotor testing and FST exposure, rats were weighed to assess fluoxetine-, FST-, and environmental condition-induced moderations in weight gain. Results revealed an antidepressant effect of environmental enrichment and a depressant effect of isolation. Regardless of significant fluoxetine effects on locomotor activity, fluoxetine generally decreased swimming and increased immobility in all three environmental conditions, with IC-fluoxetine (10 mg/kg) rats and EC-fluoxetine (20 mg/kg) rats swimming less than vehicle counterparts. Subchronic 20 mg/kg fluoxetine also induced significant weight loss, and differential rearing appeared to moderate weight gain following FST stress. These results suggest that differential rearing has the ability to alter FST behaviors, fluoxetine efficacy, and post-stressor well-being. Moreover, 20 mg/kg fluoxetine, administered subchronically, may lead to atypical effects of those commonly observed in the FST, highlighting the importance and impact of both environmental condition and dosing regimen in common animal models of depression. PMID:26154768

Differential Rearing Alters Forced Swim Test Behavior, Fluoxetine Efficacy, and Post-Test Weight Gain in Male Rats.

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David L Arndt

Full Text Available Environmental factors play a key role in the etiology of depression. The rodent forced swim test (FST is commonly used as a preclinical model of depression, with increases in escape-directed behavior reflecting antidepressant effects, and increases in immobility reflecting behavioral despair. Environmental enrichment leads to serotonergic alterations in rats, but it is unknown whether these alterations may influence the efficacy of common antidepressants. Male Sprague-Dawley rats were reared in enriched (EC, standard (SC, or isolated (IC conditions. Following the rearing period, fluoxetine (10 or 20 mg/kg, i.p. was administered 23.5 hrs, 5 hrs, and 1 hr before locomotor and FST measures. Following locomotor testing and FST exposure, rats were weighed to assess fluoxetine-, FST-, and environmental condition-induced moderations in weight gain. Results revealed an antidepressant effect of environmental enrichment and a depressant effect of isolation. Regardless of significant fluoxetine effects on locomotor activity, fluoxetine generally decreased swimming and increased immobility in all three environmental conditions, with IC-fluoxetine (10 mg/kg rats and EC-fluoxetine (20 mg/kg rats swimming less than vehicle counterparts. Subchronic 20 mg/kg fluoxetine also induced significant weight loss, and differential rearing appeared to moderate weight gain following FST stress. These results suggest that differential rearing has the ability to alter FST behaviors, fluoxetine efficacy, and post-stressor well-being. Moreover, 20 mg/kg fluoxetine, administered subchronically, may lead to atypical effects of those commonly observed in the FST, highlighting the importance and impact of both environmental condition and dosing regimen in common animal models of depression.

Differential Rearing Alters Forced Swim Test Behavior, Fluoxetine Efficacy, and Post-Test Weight Gain in Male Rats.

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Arndt, David L; Peterson, Christy J; Cain, Mary E

2015-01-01

Environmental factors play a key role in the etiology of depression. The rodent forced swim test (FST) is commonly used as a preclinical model of depression, with increases in escape-directed behavior reflecting antidepressant effects, and increases in immobility reflecting behavioral despair. Environmental enrichment leads to serotonergic alterations in rats, but it is unknown whether these alterations may influence the efficacy of common antidepressants. Male Sprague-Dawley rats were reared in enriched (EC), standard (SC), or isolated (IC) conditions. Following the rearing period, fluoxetine (10 or 20 mg/kg, i.p.) was administered 23.5 hrs, 5 hrs, and 1 hr before locomotor and FST measures. Following locomotor testing and FST exposure, rats were weighed to assess fluoxetine-, FST-, and environmental condition-induced moderations in weight gain. Results revealed an antidepressant effect of environmental enrichment and a depressant effect of isolation. Regardless of significant fluoxetine effects on locomotor activity, fluoxetine generally decreased swimming and increased immobility in all three environmental conditions, with IC-fluoxetine (10 mg/kg) rats and EC-fluoxetine (20 mg/kg) rats swimming less than vehicle counterparts. Subchronic 20 mg/kg fluoxetine also induced significant weight loss, and differential rearing appeared to moderate weight gain following FST stress. These results suggest that differential rearing has the ability to alter FST behaviors, fluoxetine efficacy, and post-stressor well-being. Moreover, 20 mg/kg fluoxetine, administered subchronically, may lead to atypical effects of those commonly observed in the FST, highlighting the importance and impact of both environmental condition and dosing regimen in common animal models of depression.

Visual deprivation alters dendritic bundle architecture in layer 4 of rat visual cortex.

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Gabbott, P L; Stewart, M G

2012-04-05

The effect of visual deprivation followed by light exposure on the tangential organisation of dendritic bundles passing through layer 4 of the rat visual cortex was studied quantitatively in the light microscope. Four groups of animals were investigated: (I) rats reared in an environment illuminated normally--group 52 dL; (II) rats reared in the dark until 21 days postnatum (DPN) and subsequently light exposed for 31 days-group 21/31; (III) rats dark reared until 52 DPN and then subsequently light exposed for 3 days--group 3 dL; and (IV) rats totally dark reared until 52 DPN--group 52 DPN. Each group contained five animals. Semithin 0.5-1-μm thick resin-embedded sections were collected from tangential sampling levels through the middle of layer 4 in area 17 and stained with Toluidine Blue. These sections were used to quantitatively analyse the composition and distribution of dendritic clusters in the tangential plane. The key result of this study indicates a significant reduction in the mean number of medium- and small-sized dendritic profiles (diameter less than 2 μm) contributing to clusters in layer 4 of groups 3 dL and 52 dD compared with group 21/31. No differences were detected in the mean number of large-sized dendritic profiles composing a bundle in these experimental groups. Moreover, the mean number of clusters and their tangential distribution in layer 4 did not vary significantly between all four groups. Finally, the clustering parameters were not significantly different between groups 21/31 and the normally reared group 52 dL. This study demonstrates, for the first time, that extended periods of dark rearing followed by light exposure can alter the morphological composition of dendritic bundles in thalamorecipient layer 4 of rat visual cortex. Because these changes occur in the primary region of thalamocortical input, they may underlie specific alterations in the processing of visual information both cortically and subcortically during periods of

Neuroprotective role of curcumin on the hippocampus against the structural and serological alterations of streptozotocin-induced diabetes in Sprague Dawely rats.

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Faheem, Nermeen Mohammed; El Askary, Ahmad

2017-06-01

Diabetes mellitus causes impaired memory and cognitive functions. The hippocampus plays a key role in memory and learning. Curcumin attenuates diabetic nephropathy in vivo . Curcumin has shown a neurogenic effect and cognition-enhancing potential in aged rats. The aim of this study is to evaluate the possible protective role of curcumin on the histological and serological changes of the hippocampus in diabetic rats. Forty albino rats were divided into four groups, ten rats each. Group 1 control rats, group 2 rats received curcumin orally (200 mg/kg/day for six weeks), group 3 rats were injected intraperitoneally with streptozotocin (STZ) (100 mg/kg, single dose), group 4 received a single injection of STZ and received curcumin orally for six weeks. Paraffin sections of hippocampus were prepared and stained with hematoxylin and eosin stain, and immnunohistochemical staining for GFAP and caspase-3. Morphometrical and statistical analyses were performed. Glycemic status and parameters of oxidative stress was measured. Examination of hippocampus of diabetic rats showed disorganization of small pyramidal cells in CA1, many cellular losses in the pyramidal cells of CA3, many degenerated granule cells in the dentate gyrus. GFAP positive astrocyte and caspase-3 positive neuron counts were significantly increased. There were significant serum glucose elevation and significant lowered levels of oxidative stress parameters as compared to control rats. Curcumin administration improved the structural and serological alterations of the hippocampus with significant reduction in serum glucose level. Curcumin ameliorates the deterious effect of diabetes on the hippocampus through its antioxidant, antiapoptotic and anti-inflammatory efficacies.

Effect of altered thyroid states on the distribution of intraperitoneally injected cadmium-109 in rats

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Mann, S.J.

1975-01-01

Metals bind to proteins in the blood and are transported in this bound state. The synthesis of proteins is altered in disease states. There may be an increase, a decrease, or a change in the protein fraction makeup, depending on the type and severity of the disease. Total protein synthesis is increased in hyperthyroidism; decreased in hypothyroidism. These changes alter the uptake and distribution of minerals and metals. This study was designed to determine the effect of altered thyroid states on the distribution of cadmium, a toxic environmental pollutant, in rats. The main experiment consisted of injecting rats with Cd-109 after 15 days of drug pretreatment for induction of hypothyroidism and hyperthyroidism. Cadmium levels in the samples were expressed as percentage of activity per organ (P) and percentage of activity per gram of tissue (A). The results showed that drug treatment affected organ weights. Hypothyroid livers weighed significantly less than hyperthyroid and euthyroid livers. Kidney and spleen weights of all three treatment groups were significantly different from each other. Those of hypothyroid rats weighed the least; those of hyperthyroid rats weighed the most. Expressed as P values, livers of the three treatment groups were not different, but hyperthyroid kidneys and spleens had significantly higher levels of cadmium. The A values of hypothyroid livers, kidneys, and spleens were higher than those of the other two treatment groups. Bone, muscle, testes, and blood samples showed extensive variability, and for this reason statistical analyses were not run. There were trends, but it was evident that the overall treatment effects on cadmium levels in these tissues were negligible

Fenitrothion induced oxidative stress and morphological alterations of sperm and testes in male sprague-dawley rats

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Taib, Izatus Shima; Budin, Siti Balkis; Ghazali, Ahmad Rohi; Jayusman, Putri Ayu; Louis, Santhana Raj; Mohamed, Jamaludin

2013-01-01

OBJECTIVE: Fenitrothion residue is found primarily in soil, water and food products and can lead to a variety of toxic effects on the immune, hepatobiliary and hematological systems. However, the effects of fenitrothion on the male reproductive system remain unclear. This study aimed to evaluate the effects of fenitrothion on the sperm and testes of male Sprague-Dawley rats. METHODS: A 20 mg/kg dose of fenitrothion was administered orally by gavages for 28 consecutive days. Blood sample was obtained by cardiac puncture and dissection of the testes and cauda epididymis was performed to obtain sperm. The effects of fenitrothion on the body and organ weight, biochemical and oxidative stress, sperm characteristics, histology and ultrastructural changes in the testes were evaluated. RESULTS: Fenitrothion significantly decreased the body weight gain and weight of the epididymis compared with the control group. Fenitrothion also decreased plasma cholinesterase activity compared with the control group. Fenitrothion altered the sperm characteristics, such as sperm concentration, sperm viability and normal sperm morphology, compared with the control group. Oxidative stress markers, such as malondialdehyde, protein carbonyl, total glutathione and glutathione S-transferase, were significantly increased and superoxide dismutase activity was significantly decreased in the fenitrothion-treated group compared with the control group. The histopathological and ultrastructural examination of the testes of the fenitrothion-treated group revealed alterations corresponding with the biochemical changes compared with the control group. CONCLUSION: A 20 mg/kg dose of fenitrothion caused deleterious effects on the sperm and testes of Sprague-Dawley rats. PMID:23420164

Fenitrothion induced oxidative stress and morphological alterations of sperm and testes in male sprague-dawley rats

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Izatus Shima Taib

2013-01-01

Full Text Available OBJECTIVE: Fenitrothion residue is found primarily in soil, water and food products and can lead to a variety of toxic effects on the immune, hepatobiliary and hematological systems. However, the effects of fenitrothion on the male reproductive system remain unclear. This study aimed to evaluate the effects of fenitrothion on the sperm and testes of male Sprague-Dawley rats. METHODS: A 20 mg/kg dose of fenitrothion was administered orally by gavages for 28 consecutive days. Blood sample was obtained by cardiac puncture and dissection of the testes and cauda epididymis was performed to obtain sperm. The effects of fenitrothion on the body and organ weight, biochemical and oxidative stress, sperm characteristics, histology and ultrastructural changes in the testes were evaluated. RESULTS: Fenitrothion significantly decreased the body weight gain and weight of the epididymis compared with the control group. Fenitrothion also decreased plasma cholinesterase activity compared with the control group. Fenitrothion altered the sperm characteristics, such as sperm concentration, sperm viability and normal sperm morphology, compared with the control group. Oxidative stress markers, such as malondialdehyde, protein carbonyl, total glutathione and glutathione S-transferase, were significantly increased and superoxide dismutase activity was significantly decreased in the fenitrothion-treated group compared with the control group. The histopathological and ultrastructural examination of the testes of the fenitrothion-treated group revealed alterations corresponding with the biochemical changes compared with the control group. CONCLUSION: A 20 mg/kg dose of fenitrothion caused deleterious effects on the sperm and testes of Sprague-Dawley rats.

Protective effect of Psidium guajava leaf extract on altered carbohydrate metabolism in streptozotocin-induced diabetic rats.

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Khan, Haseena Banu Hedayathullah; Shanmugavalli, R; Rajendran, Deepa; Bai, Mookambikai Ramya; Sorimuthu, Subramanian

2013-12-01

Psidium guajava is an important plant of high medicinal value and has been used in traditional systems of medicine against various ailments. The antidiabetic effect of the ethanolic extract of Psidium guajava leaves and also its protective effect on altered glucose metabolism was evaluated in streptozotocin (stz)-induced diabetic rat model. Diabetes was induced in rats by means of intraperitoneal injection of 50-mg/kg body weight (b.wt.) of stz. Diabetes-induced rats were randomly divided into two groups. One group of rats was treated with Psidium guajava leaf extract at a dosage of 300-mg/kg b.wt. and the other group of rats was treated with the standard drug glyclazide at a dosage of 5-mg/kg b.wt. for 30 days. The blood glucose levels, plasma insulin, Hb, HbA1c were measured. The effect on the drug on altered glucose metabolizing enzymes were also studied. Treatment with Psidium guajava extract showed a significant reduction in blood glucose and HbA1c levels and a significant increase in plasma insulin levels. The drug also significantly restored the activities of carbohydrate metabolizing enzymes. This suggests that the potential antidiabetic effect of the ethanolic extract of the Psidium guajava leaves may be due to the presence of flavonoids and other phenolic components present in the drug.

In utero exposure to chloroquine alters sexual development in the male fetal rat

International Nuclear Information System (INIS)

Clewell, Rebecca A.; Pluta, Linda; Thomas, Russell S.; Andersen, Melvin E.

2009-01-01

Chloroquine (CQ), a drug that has been used extensively for the prevention and treatment of malaria, is currently considered safe for use during pregnancy. However, CQ has been shown to disrupt steroid homeostasis in adult rats and similar compounds, such as quinacrine, inhibit steroid production in the Leydig cell in vitro. To explore the effect of in utero CQ exposure on fetal male sexual development, pregnant Sprague-Dawley rats were given a daily dose of either water or chloroquine diphosphate from GD 16-18 by oral gavage. Chloroquine was administered as 200 mg/kg CQ base on GD 16, followed by two maintenance doses of 100 mg/kg CQ base on GD 16 and 18. Three days of CQ treatment resulted in reduced maternal and fetal weight on GD 19 and increased necrosis and steatosis in the maternal liver. Fetal livers also displayed mild lipid accumulation. Maternal serum progesterone was increased after CQ administration. Fetal testes testosterone, however, was significantly decreased. Examination of the fetal testes revealed significant alterations in vascularization and seminiferous tubule development after short-term CQ treatment. Anogenital distance was not altered. Microarray and RT-PCR showed down-regulation of several genes associated with cholesterol transport and steroid synthesis in the fetal testes. This study indicates that CQ inhibits testosterone synthesis and normal testis development in the rat fetus at human relevant doses.

Chronic consumption of fructose rich soft drinks alters tissue lipids of rats

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Botezelli Jose D

2010-06-01

Full Text Available Abstract Background Fructose-based diets are apparently related to the occurrence of several metabolic dysfunctions, but the effects of the consumption of high amounts of fructose on body tissues have not been well described. The aim of this study was to analyze the general characteristics and the lipid content of different tissues of rats after chronic ingestion of a fructose rich soft drink. Methods Forty-five Wistar rats were used. The rats were divided into three groups (n = 15 and allowed to consume water (C, light Coca Cola ® (L or regular Coca Cola® (R as the sole source of liquids for eight weeks. Results The R group presented significantly higher daily liquid intake and significantly lower food intake than the C and L groups. Moreover, relative to the C and L groups, the R group showed higher triglyceride concentrations in the serum and liver. However, the L group animals presented lower values of serum triglycerides and cholesterol than controls. Conclusions Based on the results, it can be concluded that daily ingestion of a large amount of fructose- rich soft drink resulted in unfavorable alterations to the lipid profile of the rats.

Alterations in blood pressure, antioxidant status and caspase 8 expression in cobalt chloride-induced cardio-renal dysfunction are reversed by Ocimum gratissimum and gallic acid in Wistar rats.

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Akinrinde, A S; Oyagbemi, A A; Omobowale, T O; Asenuga, E R; Ajibade, T O

2016-07-01

The protective abilities of the chloroform extract of Ocimum gratissimum (COG) and gallic acid against cobalt chloride (CoCl2) - induced cardiac and renal toxicity were evaluated. Rats were exposed to CoCl2 (350ppm) for 7 days, either alone, or in combination with COG (100 and 200mg/kg) or gallic acid (120mg/kg). CoCl2 given alone, caused significant increases (pgallic acid treatment significantly reduced (pgallic acid by modulation of CoCl2-induced alterations in blood pressure, antioxidant status and pro-apoptotic caspase 8 in Wistar rats. Copyright © 2016 Elsevier GmbH. All rights reserved.

Mesolimbic dopamine function is not altered during continuous chronic treatment of rats with typical or atypical neuroleptic drugs

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Rupniak, N M.J.; Hall, M D; Kelly, E; Fleminger, S; Kilpatrick, G; Jenner, P; Marsden, C D

1985-01-01

Rats were treated continuously for up to 20 months with either haloperidol (1.4-1.6 mg/kg/day), sulpiride (102-109 mg/kg/day) or clozapine (24-27 mg/kg/day). Bsub(max) for specific mesolimbic binding of TH-spiperone, TH-N, n-propylnorapomorphine or TH-piflutixol did not differ in tissue taken from animals treated for up to 12 months with haloperidol, sulpiride or clozapine by comparison to age-matched control rats. Mesolimbic dopamine (50 M)-stimulated adenylate cyclase activity was not altered in any drug treatment group. Spontaneous locomotor activity was transiently decreased during treatment with haloperidol for 1 or 3 months, but not by chronic sulpiride or clozapine treatment. Locomotor activity was not consistently increased in any drug treatment group. After 20 months of continuous drug treatment, focal bilateral application of dopamine (12.5 or 25 g) into the nucleus accumbens caused equivalent increases in locomotor activity in control rats and in animals receiving haloperidol, sulpiride of clozapine. These findings suggest that dopamine receptor blockade is not maintained in the mesolimbic area following chronic treatment with haloperidol, sulpiride or clozapine, and indicate that, under these conditions, clozapine and sulpiride may not act selectively on mesolimbic dopamine receptors. (Author).

Mesolimbic dopamine function is not altered during continuous chronic treatment of rats with typical or atypical neuroleptic drugs

International Nuclear Information System (INIS)

Rupniak, N.M.J.; Hall, M.D.; Kelly, E.; Fleminger, S.; Kilpatrick, G.; Jenner, P.; Marsden, C.D.

1985-01-01

Rats were treated continuously for up to 20 months with either haloperidol (1.4-1.6 mg/kg/day), sulpiride (102-109 mg/kg/day) or clozapine (24-27 mg/kg/day). Bsub(max) for specific mesolimbic binding of 3 H-spiperone, 3 H-N, n-propylnorapomorphine or 3 H-piflutixol did not differ in tissue taken from animals treated for up to 12 months with haloperidol, sulpiride or clozapine by comparison to age-matched control rats. Mesolimbic dopamine (50 μM)-stimulated adenylate cyclase activity was not altered in any drug treatment group. Spontaneous locomotor activity was transiently decreased during treatment with haloperidol for 1 or 3 months, but not by chronic sulpiride or clozapine treatment. Locomotor activity was not consistently increased in any drug treatment group. After 20 months of continuous drug treatment, focal bilateral application of dopamine (12.5 or 25 μg) into the nucleus accumbens caused equivalent increases in locomotor activity in control rats and in animals receiving haloperidol, sulpiride of clozapine. These findings suggest that dopamine receptor blockade is not maintained in the mesolimbic area following chronic treatment with haloperidol, sulpiride or clozapine, and indicate that, under these conditions, clozapine and sulpiride may not act selectively on mesolimbic dopamine receptors. (Author)

Alteration of renal excretion pathways in gentamicin-induced renal injury in rats.

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Ma, Yan-Rong; Luo, Xuan; Wu, Yan-Fang; Zhang, Tiffany; Zhang, Fan; Zhang, Guo-Qiang; Wu, Xin-An

2018-02-20

The kidney plays a major part in the elimination of many drugs and their metabolites, and drug-induced kidney injury commonly alters either glomerular filtration or tubular transport, or both. However, the renal excretion pathway of drugs has not been fully elucidated at different stages of renal injury. This study aimed to evaluate the alteration of renal excretion pathways in gentamicin (GEN)-induced renal injury in rats. Results showed that serum cystatin C, creatinine and urea nitrogen levels were greatly increased by the exposure of GEN (100 mg kg -1 ), and creatinine concentration was increased by 39.7% by GEN (50 mg kg -1 ). GEN dose-dependently upregulated the protein expression of rOCT1, downregulated rOCT2 and rOAT1, but not affected rOAT2. Efflux transporters, rMRP2, rMRP4 and rBCRP expressions were significantly increased by GEN(100), and the rMATE1 level was markedly increased by GEN(50) but decreased by GEN(100). GEN(50) did not alter the urinary excretion of inulin, but increased metformin and furosemide excretion. However, GEN(100) resulted in a significant decrease of the urinary excretion of inulin, metformin and p-aminohippurate. In addition, urinary metformin excretions in vivo were significantly decreased by GEN(100), but slightly increased by GEN(50). These results suggested that GEN(50) resulted in the induction of rOCTs-rMATE1 and rOAT3-rMRPs pathway, but not changed the glomerular filtration rate, and GEN(100)-induced acute kidney injury caused the downregulated function of glomerular filtration -rOCTs-rMATE1 and -rOAT1-rMRPs pathway. Copyright © 2018 John Wiley & Sons, Ltd.

Rat hippocampal alterations could underlie behavioral abnormalities induced by exposure to moderate noise levels.

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Uran, S L; Aon-Bertolino, M L; Caceres, L G; Capani, F; Guelman, L R

2012-08-30

Noise exposure is known to affect auditory structures in living organisms. However, it should not be ignored that many of the effects of noise are extra-auditory. Previous findings of our laboratory demonstrated that noise was able to induce behavioral alterations that are mainly related to the cerebellum (CE) and the hippocampus (HC). Therefore, the aim of this work was to reveal new data about the vulnerability of developing rat HC to moderate noise levels through the assessment of potential histological changes and hippocampal-related behavioral alterations. Male Wistar rats were exposed to noise (95-97 dB SPL, 2h daily) either for 1 day (acute noise exposure, ANE) or between postnatal days 15 and 30 (sub-acute noise exposure, SANE). Hippocampal histological evaluation as well as short (ST) and long term (LT) habituation and recognition memory assessments were performed. Results showed a mild disruption in the different hippocampal regions after ANE and SANE schemes, along with significant behavioral abnormalities. These data suggest that exposure of developing rats to noise levels of moderate intensity is able to trigger changes in the HC, an extra-auditory structure of the Central Nervous System (CNS), that could underlie the observed behavioral effects. Copyright © 2012 Elsevier B.V. All rights reserved.

A novel mutation causing nephronophthisis in the Lewis polycystic kidney rat localises to a conserved RCC1 domain in Nek8

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McCooke John K

2012-08-01

Full Text Available Abstract Background Nephronophthisis (NPHP as a cause of cystic kidney disease is the most common genetic cause of progressive renal failure in children and young adults. NPHP is characterized by abnormal and/or loss of function of proteins associated with primary cilia. Previously, we characterized an autosomal recessive phenotype of cystic kidney disease in the Lewis Polycystic Kidney (LPK rat. Results In this study, quantitative trait locus analysis was used to define a ~1.6Mbp region on rat chromosome 10q25 harbouring the lpk mutation. Targeted genome capture and next-generation sequencing of this region identified a non-synonymous mutation R650C in the NIMA (never in mitosis gene a- related kinase 8 ( Nek8 gene. This is a novel Nek8 mutation that occurs within the regulator of chromosome condensation 1 (RCC1-like region of the protein. Specifically, the R650C substitution is located within a G[QRC]LG repeat motif of the predicted seven bladed beta-propeller structure of the RCC1 domain. The rat Nek8 gene is located in a region syntenic to portions of human chromosome 17 and mouse 11. Scanning electron microscopy confirmed abnormally long cilia on LPK kidney epithelial cells, and fluorescence immunohistochemistry for Nek8 protein revealed altered cilia localisation. Conclusions When assessed relative to other Nek8 NPHP mutations, our results indicate the whole propeller structure of the RCC1 domain is important, as the different mutations cause comparable phenotypes. This study establishes the LPK rat as a novel model system for NPHP and further consolidates the link between cystic kidney disease and cilia proteins.

[Study on sperm damage caused by trichloroethylene in male rats].

Science.gov (United States)

Wu, De-sheng; Yang, Lin-qing; Huang, Sui; Liu, Jian-jun; Xu, Xin-yun; Huang, Hai-yan; Gong, Chun-mei; Hu, Gong-hua; Liu, Qing-cheng; Yang, Xi-fei; Hong, Wen-xu; Zhou, Li; Huang, Xin-feng; Yuan, Jian-hui; Zhuang, Zhi-xiong

2013-11-01

To study in vitro sperm damage caused by trichloroethylene in male rats. Sperms of Sprague-Dawley (SD) rats were collected 4 hours after being contaminated by trichloroethylene of 0, 2, 4, 6, 8, and 10 mmol/L in vitro. Giemsa staining was performed to observe the morphological changes of sperms, and flow cytometer was used to detect the changes in mitochondrial membrane potential. The sperm motilities in 6, 8, and 10 mmol/L trichloroethylene groups decreased significantly compared with that in control group (P trichloroethylene groups were significantly higher than that in control group (Ptrichloroethylene groups and control group (Ptrichloroethylene can reduce sperm motility and increase the aberration rate and apoptosis rate of sperms in male SD rats.

Gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters retinoid homeostasis in maternal and perinatal tissues of the Holtzman rat

International Nuclear Information System (INIS)

Kransler, Kevin M.; Tonucci, David A.; McGarrigle, Barbara P.; Napoli, Joseph L.; Olson, James R.

2007-01-01

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), one of the most widely studied environmental contaminants, causes a variety of adverse health effects including teratogenesis and altered development which may be related to disruptions in retinoid homeostasis. The purpose of this study was to determine the effect that gestational administration of TCDD has on retinoid homeostasis in both pregnant Holtzman rats and developing fetuses and neonates. A single oral dose of TCDD (0, 1.5, 3, or 6 μg/kg) was administered to pregnant rats on gestation day 10, with fetuses analyzed on gestation days 17 and 20, and neonates analyzed on post natal day 7. Exposure to TCDD generally produced decreases in the concentrations of retinyl esters, such as retinyl palmitate, and retinol in maternal and perinatal liver and lung, while increasing levels in the maternal kidney. Additionally, perinatal hepatic retinol binding protein 1-dependent retinyl ester hydrolysis was also decrease by TCDD. Sensitivity of the developing perinates to TCDD appeared to have an age-related component demonstrated by an increased rate of mortality and significant alterations to body weight and length on post natal day 7 relative to that observed at gestation day 20. A unique observation made in this study was a significant decrease in lung weight observed in the perinates exposed to TCDD. Taken together, these data demonstrate that TCDD significantly alters retinoid homeostasis in tissues of the developing fetus and neonate, suggesting that their unique sensitivity to TCDD may at least be in part the result of altered retinoid homeostasis

Developmental hyperoxia alters CNS mechanisms underlying hypoxic ventilatory depression in neonatal rats.

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Hill, Corey B; Grandgeorge, Samuel H; Bavis, Ryan W

2013-12-01

Newborn mammals exhibit a biphasic hypoxic ventilatory response (HVR), but the relative contributions of carotid body-initiated CNS mechanisms versus central hypoxia on ventilatory depression during the late phase of the HVR are not well understood. Neonatal rats (P4-5 or P13-15) were treated with a nonselective P2 purinergic receptor antagonist (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, or PPADS; 125mgkg(-1), i.p.) to pharmacologically denervate the peripheral chemoreceptors. At P4-5, rats reared in normoxia showed a progressive decline in ventilation during a 10-min exposure to 12% O2 (21-28% decrease from baseline). No hypoxic ventilatory depression was observed in the older group of neonatal rats (i.e., P13-15), suggesting that the contribution of central hypoxia to hypoxic ventilatory depression diminishes with age. In contrast, rats reared in moderate hyperoxia (60% O2) from birth exhibited no hypoxic ventilatory depression at either age studied. Systemic PPADS had no effect on the ventilatory response to 7% CO2, suggesting that the drug did not cross the blood-brain barrier. These findings indicate that (1) CNS hypoxia depresses ventilation in young, neonatal rats independent of carotid body activation and (2) hyperoxia alters the development of CNS pathways that modulate the late phase of the hypoxic ventilatory response. Copyright © 2013 Elsevier B.V. All rights reserved.

Inorganic mercury exposure in drinking water alters essential metal homeostasis in pregnant rats without altering rat pup behavior.

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Oliveira, Cláudia S; Oliveira, Vitor A; Costa, Lidiane M; Pedroso, Taíse F; Fonseca, Mariana M; Bernardi, Jamile S; Fiuza, Tiago L; Pereira, Maria E

2016-10-01

The aim of this work was to investigate the effects of HgCl 2 exposure in the doses of 0, 10 and 50μg Hg 2+ /mL in drinking water during pregnancy on tissue essential metal homeostasis, as well as the effects of HgCl 2 exposure in utero and breast milk on behavioral tasks. Pregnant rats exposed to both inorganic mercury doses presented high renal Hg content and an increase in renal Cu and hepatic Zn levels. Mercury exposure increased fecal Hg and essential metal contents. Pups exposed to inorganic Hg presented no alterations in essential metal homeostasis or in behavioral task markers of motor function. In conclusion, this work showed that the physiologic pregnancy and lactation states protected the offspring from adverse effects of low doses of Hg 2+ . This protection is likely to be related to the endogenous scavenger molecule, metallothionein, which may form an inert complex with Hg 2+ . Copyright © 2016 Elsevier Inc. All rights reserved.

Red wine polyphenols prevent metabolic and cardiovascular alterations associated with obesity in Zucker fatty rats (Fa/Fa.

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Abdelali Agouni

Full Text Available BACKGROUND: Obesity is associated with increased risks for development of cardiovascular diseases. Epidemiological studies report an inverse association between dietary flavonoid consumption and mortality from cardiovascular diseases. We studied the potential beneficial effects of dietary supplementation of red wine polyphenol extract, Provinols, on obesity-associated alterations with respect to metabolic disturbances and cardiovascular functions in Zucker fatty (ZF rats. METHODOLOGY/PRINCIPAL FINDINGS: ZF rats or their lean littermates received normal diet or supplemented with Provinols for 8 weeks. Provinols improved glucose metabolism by reducing plasma glucose and fructosamine in ZF rats. Moreover, it reduced circulating triglycerides and total cholesterol as well as LDL-cholesterol in ZF rats. Echocardiography measurements demonstrated that Provinols improved cardiac performance as evidenced by an increase in left ventricular fractional shortening and cardiac output associated with decreased peripheral arterial resistances in ZF rats. Regarding vascular function, Provinols corrected endothelial dysfunction in aortas from ZF rats by improving endothelium-dependent relaxation in response to acetylcholine (Ach. Provinols enhanced NO bioavailability resulting from increased nitric oxide (NO production through enhanced endothelial NO-synthase (eNOS activity and reduced superoxide anion release via decreased expression of NADPH oxidase membrane sub-unit, Nox-1. In small mesenteric arteries, although Provinols did not affect the endothelium-dependent response to Ach; it enhanced the endothelial-derived hyperpolarizing factor component of the response. CONCLUSIONS/SIGNIFICANCE: Use of red wine polyphenols may be a potential mechanism for prevention of cardiovascular and metabolic alterations associated with obesity.

Role of fetal nutrient restriction and postnatal catch-up growth on structural and mechanical alterations of rat aorta.

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Gutiérrez-Arzapalo, Perla Y; Rodríguez-Rodríguez, Pilar; Ramiro-Cortijo, David; López de Pablo, Ángel L; López-Giménez, María Rosario; Condezo-Hoyos, Luis; Greenwald, Stephen E; González, Maria Del Carmen; Arribas, Silvia M

2017-12-26

Intrauterine growth restriction (IUGR), induced by maternal undernutrition, leads to impaired aortic development. This is followed by hypertrophic remodelling associated with accelerated growth during lactation. Fetal nutrient restriction is associated with increased aortic compliance at birth and at weaning, but not in adult animals. This mechanical alteration may be related to a decreased perinatal collagen deposition. Aortic elastin scaffolds purified from young male and female IUGR animals also exhibit increased compliance, only maintained in adult IUGR females. These mechanical alterations may be related to differences in elastin deposition and remodelling. Fetal undernutrition induces similar aortic structural and mechanical alterations in young male and female rats. Our data argue against an early mechanical cause for the sex differences in hypertension development induced by maternal undernutrition. However, the larger compliance of elastin in adult IUGR females may contribute to the maintenance of a normal blood pressure level. Fetal undernutrition programmes hypertension development, males being more susceptible. Deficient fetal elastogenesis and vascular growth is a possible mechanism. We investigated the role of aortic mechanical alterations in a rat model of hypertension programming, evaluating changes at birth, weaning and adulthood. Dams were fed ad libitum (Control) or 50% of control intake during the second half of gestation (maternal undernutrition, MUN). Offspring aged 3 days, 21 days and 6 months were studied. Blood pressure was evaluated in vivo. In the thoracic aorta we assessed gross structure, mechanical properties (intact and purified elastin), collagen and elastin content and internal elastic lamina (IEL) organization. Only adult MUN males developed hypertension (systolic blood pressure: MUN males  = 176.6 ± 5.6 mmHg; Control males  = 136.1 ± 4.9 mmHg). At birth MUN rats were lighter, with smaller aortic cross-sectional area

Altered Expression of Endoplasmic Reticulum Stress Associated Genes in Hippocampus of Learned Helpless Rats: Relevance to Depression Pathophysiology

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Matthew A. Timberlake

2016-01-01

Full Text Available The unfolded protein response (UPR is an evolutionarily conserved defensive mechanism that is used by cells to correct misfolded proteins that accumulate in the endoplasmic reticulum. These proteins are misfolded as a result of physical stress on a cell and initiate a host of downstream effects that govern processes ranging from inflammation to apoptosis. To examine whether UPR system plays a role in depression, we examined the expression of genes that are part of the three different pathways for UPR activation, namely GRP78, GRP94, ATF6, XBP-1, ATF4 and CHOP using an animal model system that distinguishes vulnerability (learned helpless, LH from resistance (non-learned helpless, NLH to develop depression. Rats were exposed to inescapable shock on day 1 and day 7 and were tested for escape latency on day 14. Rats not given shock but tested for escape latency were used as tested control (TC. Plasma corticosterone levels were measured. Expression levels of various UPR associated genes were determined in hippocampus using qPCR. We found that the corticosterone level was higher in LH rats compared with TC and NLH rats. Expression of GRP78, GRP94, ATF6 and XBP-1 were significantly upregulated in LH rats compared with TC or NLH rats, whereas NLH rats did not show such changes. Expression levels of ATF4 and CHOP showed trends towards upregulation but were not significantly altered in LH or NLH group. Our data show strong evidence of altered UPR system in depressed rats, which could be associated with development of depressive behavior.

Model applied to wistar rats for analysis of atrial alteration radioinduced: role of the TGFBeta1 cytokine on the lesions development

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Silva, Viviane Fernandes da; Andrade, Cherley Borba V. de; Nascimento, Ana Lucia Rosa do; Silva, Claudia Marcello da; Ribeiro, Andreia Fortes; Mandarim-de-Lacerda, Carlos Alberto; Carvalho, Jorge Jose de; Almeida, Carlos Eduardo de

2009-01-01

This paper develops a radiobiological model on Wistar rats for evaluation of atrium radioinduced alterations. Male Wistar rats were anaesthetised, immobilized and irradiated with 500, 1000 and 1500 cGy irradiated doses in the cardiac volume, pre-define through tomography. The animals were sacrificed after 15 days irradiation. The atriums were collected, fixed in formaldehyde and soaked into paraffin. A part of samples were dyed with hematoxyline-eosin (HE) and another submitted to immunohistochemistry for visualization of the cytokine TGFbeta1 expression. The observation of samples with HE indicated lesions om blood vessels and discrete inflamed infiltrated on some samples. The immunohistochemistry shown an intense expression of the TGFbeta1 cytokine, mainly on the only intine of the blood vessels. The data indicate that the atria develop alterations compatible to inflammatory answer as reaction to the damage caused by the tissue irradiation, and this answer is responsible by the production of TGFbeta1 cytokine, considered a cytokine pro-fibrotic on various models of cardiac disease. The lesions at atrium level can reflect on the correct functioning of the system generator of cardiac impulse, and can induce arrythmias and to prejudice the production of natriuretic peptides, molecules involved on the cardiac homeostasis

Diphenyl ditelluride impairs short-term memory and alters neurochemical parameters in young rats.

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Stangherlin, Eluza Curte; Rocha, João Batista Teixeira; Nogueira, Cristina Wayne

2009-01-01

The aim of this study was to investigate if maternal exposure to 0.03 mg/kg of diphenyl ditelluride (PhTe)2 during the first 14 days of lactational period in Wistar rats alters recognition memory and neurochemical parameters in young rats. Object recognition memory task, evaluation of synaptosomal [3H]glutamate uptake and release as well as cerebral Na+/K+ATPase activity were evaluated in 4 week-old rats. There were no significant specific overt signs of maternal intoxication. The body weight gain of rats was similar among groups. (PhTe)2-exposed group showed a significantly lower time exploring the novel object when compared to the performance of the control group in short-term memory (STM) test. In addition, (PhTe)2 significantly inhibited synaptosomal [3H]glutamate uptake and cerebral Na+/K+ATPase activity in animals. The synaptosomal [3H]glutamate release was similar between (PhTe)2 and control groups. In conclusion, the present study establishes that young rats presented cognitive impairment after exposure to (PhTe)2 via maternal milk, demonstrated by the performance of animals in object recognition memory task. The possible mechanism involved in (PhTe)2 action in memory of recognition might involve inhibition of cerebral Na+/K+ATPase activity and synaptosomal [3H]glutamate uptake.

The Protective Effect of Proponyl-L-Carnitine Against Ultrastructural Alterations in Cardiac Muscle of Irradiated and / or diabetic Rats

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Abu Nour, S.M.; Abdel-Azeem, M.G.; El-Nashar, D.E.M.

2011-01-01

Heart dysfunction in chronic diabetes has been observed to be associated with depressed myofibrillar adenosine triphosphatase activities. Oxidative stress a factor implicated in the heart injury may contribute towards some of these alterations. The present study was designed to evaluate the efficacy of L-carnitine on gamma radiation and diabetes induced oxidative damage in the heart by investigating alterations in the ultrastructural level. Streptozotocin was intraperitoneally injected (i.p) to rats at a dose of 28 mg/Kg b.wt / day for 2 weeks pre-irradiation. In irradiated groups, animals were exposed to 6.5 Gy whole body gamma radiation. L-carnitine was intraperitoneally injected (i.p) to rats at a dose of 250 mg/Kg b.wt/day for 2 weeks pre-irradiation. Animals were sacrificed on the 7th day after irradiation. The results demonstrated that the whole body exposure of rats to ionizing radiation induce oxidative stress which showed alterations on the ultrastructural level included dis organization with mayofibrillolysis relatively intact z-band (Z), fibrosis, swollen mitochondria, apoptotic nuclei and thickened walls of capillaries. In diabetic rats cardio muscle focal loss of myofilaments, also swelling of mitochondria and rupture of sacroplasmic reticulum, apoptotic nuclei with dilation of capillaries were evident. Administration of L-carnitine pre-irradiation has improved the ultrastructural alterations of the heart tissue. It is proposed that the oxidative stress is associated with a deficit in the status of the antioxidant defense system which may play a critical role in subcellular remodeling, calcium-handling abnormalities and subsequent diabetic cardiomyopathy

Alterations of the tunica vasculosa lentis in the rat model of retinopathy of prematurity.

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Favazza, Tara L; Tanimoto, Naoyuki; Munro, Robert J; Beck, Susanne C; Garcia Garrido, Marina; Seide, Christina; Sothilingam, Vithiyanjali; Hansen, Ronald M; Fulton, Anne B; Seeliger, Mathias W; Akula, James D

2013-08-01

To study the relationship between retinal and tunica vasculosa lentis (TVL) disease in retinopathy of prematurity (ROP). Although the clinical hallmark of ROP is abnormal retinal blood vessels, the vessels of the anterior segment, including the TVL, are also altered. ROP was induced in Long-Evans pigmented and Sprague Dawley albino rats; room-air-reared (RAR) rats served as controls. Then, fluorescein angiographic images of the TVL and retinal vessels were serially obtained with a scanning laser ophthalmoscope near the height of retinal vascular disease, ~20 days of age, and again at 30 and 64 days of age. Additionally, electroretinograms (ERGs) were obtained prior to the first imaging session. The TVL images were analyzed for percent coverage of the posterior lens. The tortuosity of the retinal arterioles was determined using Retinal Image multiScale Analysis (Gelman et al. in Invest Ophthalmol Vis Sci 46:4734-4738, 2005). In the youngest ROP rats, the TVL was dense, while in RAR rats, it was relatively sparse. By 30 days, the TVL in RAR rats had almost fully regressed, while in ROP rats, it was still pronounced. By the final test age, the TVL had completely regressed in both ROP and RAR rats. In parallel, the tortuous retinal arterioles in ROP rats resolved with increasing age. ERG components indicating postreceptoral dysfunction, the b-wave, and oscillatory potentials were attenuated in ROP rats. These findings underscore the retinal vascular abnormalities and, for the first time, show abnormal anterior segment vasculature in the rat model of ROP. There is delayed regression of the TVL in the rat model of ROP. This demonstrates that ROP is a disease of the whole eye.

Forward conditioning with wheel running causes place aversion in rats.

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Masaki, Takahisa; Nakajima, Sadahiko

2008-09-01

Backward pairings of a distinctive chamber as a conditioned stimulus and wheel running as an unconditioned stimulus (i.e., running-then-chamber) can produce a conditioned place preference in rats. The present study explored whether a forward conditioning procedure with these stimuli (i.e., chamber-then-running) would yield place preference or aversion. Confinement of a rat in one of two distinctive chambers was followed by a 20- or 60-min running opportunity, but confinement in the other was not. After four repetitions of this treatment (i.e., differential conditioning), a choice preference test was given in which the rat had free access to both chambers. This choice test showed that the rats given 60-min running opportunities spent less time in the running-paired chamber than in the unpaired chamber. Namely, a 60-min running opportunity after confinement in a distinctive chamber caused conditioned aversion to that chamber after four paired trials. This result was discussed with regard to the opponent-process theory of motivation.

Repeated exposure of adult rats to transient oxidative stress induces various long-lasting alterations in cognitive and behavioral functions.

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Yoshio Iguchi

Full Text Available Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX to adult rats to transiently reduce glutathione levels. Repeated administration of CHX did not affect the acquisition or motivation of an appetitive instrumental behavior (lever pressing rewarded by a food outcome under a progressive ratio schedule. In addition, response discrimination and reversal learning were not affected. However, acute CHX administration blunted the sensitivity of the instrumental performance to outcome devaluation, and this effect was prolonged in rats with a history of repeated CHX exposure, representing pro-depression-like phenotypes. On the other hand, repeated CHX administration reduced immobility in forced swimming tests and blunted acute cocaine-induced behaviors, implicating antidepressant-like effects. Multivariate analyses segregated a characteristic group of behavioral variables influenced by repeated CHX administration. Taken together, these findings suggest that repeated administration of CHX to adult rats did not cause a specific mental disorder, but it induced long-term alterations in behavioral and cognitive functions, possibly related to specific neural correlates.

Theophylline, a methylxanthine drug induces osteopenia and alters calciotropic hormones, and prophylactic vitamin D treatment protects against these changes in rats

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Pal, Subhashis; Khan, Kainat; China, Shyamsundar Pal; Mittal, Monika; Porwal, Konica; Shrivastava, Richa; Taneja, Isha; Hossain, Zakir; Mandalapu, Dhanaraju; Gayen, Jiaur R.; Wahajuddin, Muhammad; Sharma, Vishnu Lal; Trivedi, Arun K.; Sanyal, Sabyasachi; Bhadauria, Smrati; Godbole, Madan M.; Gupta, Sushil K.; Chattopadhyay, Naibedya

2016-01-01

The drug, theophylline is frequently used as an additive to medications for people suffering from chronic obstructive pulmonary diseases (COPD). We studied the effect of theophylline in bone cells, skeleton and parameters related to systemic calcium homeostasis. Theophylline induced osteoblast apoptosis by increasing reactive oxygen species production that was caused by increased cAMP production. Bone marrow levels of theophylline were higher than its serum levels, indicating skeletal accumulation of this drug. When adult Sprague-Dawley rats were treated with theophylline, bone regeneration at fracture site was diminished compared with control. Theophylline treatment resulted in a time-dependent (at 4- and 8 weeks) bone loss. At 8 weeks, a significant loss of bone mass and deterioration of microarchitecture occurred and the severity was comparable to methylprednisone. Theophylline caused formation of hypomineralized osteoid and increased osteoclast number and surface. Serum bone resorption and formation marker were respectively higher and lower in the theophylline group compared with control. Bone strength was reduced by theophylline treatment. After 8 weeks, serum 25-D3 and liver 25-hydroxylases were decreased in theophylline group than control. Further, theophylline treatment reduced serum 1, 25-(OH) 2 vitamin D 3 (1,25-D3), and increased parathyroid hormone and fibroblast growth factor-23. Theophylline treated rats had normal serum calcium and phosphate but displayed calciuria and phosphaturia. Co-administration of 25-D3 with theophylline completely abrogated theophylline-induced osteopenia and alterations in calcium homeostasis. In addition, 1,25-D3 protected osteoblasts from theophylline-induced apoptosis and the attendant oxidative stress. We conclude that theophylline has detrimental effects in bone and prophylactic vitamin D supplementation to subjects taking theophylline could be osteoprotective. - Highlights: • Theophylline induced osteoblast apoptosis

Theophylline, a methylxanthine drug induces osteopenia and alters calciotropic hormones, and prophylactic vitamin D treatment protects against these changes in rats

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Pal, Subhashis; Khan, Kainat; China, Shyamsundar Pal; Mittal, Monika; Porwal, Konica [Division of Endocrinology and Center for Research in Anabolic Skeletal Target in Health and Illness (ASTHI), Central Drug Research Institute - CDRI, Council of Scientific and Industrial Research (CSIR), Lucknow 226021 (India); Shrivastava, Richa [Division of Toxicology, CDRI-CSIR, Lucknow 226021 (India); Taneja, Isha; Hossain, Zakir [Pharmacokinetics and Metabolism Division, CDRI-CSIR, Lucknow 226021 (India); Mandalapu, Dhanaraju [Division of Medicinal and Process Chemistry, CDRI-CSIR, Lucknow 226021 (India); Gayen, Jiaur R.; Wahajuddin, Muhammad [Pharmacokinetics and Metabolism Division, CDRI-CSIR, Lucknow 226021 (India); Sharma, Vishnu Lal [Division of Medicinal and Process Chemistry, CDRI-CSIR, Lucknow 226021 (India); Trivedi, Arun K.; Sanyal, Sabyasachi [Division of Biochemistry, CDRI-CSIR, Lucknow 226021 (India); Bhadauria, Smrati [Division of Toxicology, CDRI-CSIR, Lucknow 226021 (India); Godbole, Madan M.; Gupta, Sushil K. [Department of Medical Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014 (India); Chattopadhyay, Naibedya, E-mail: n_chattopadhyay@cdri.res.in [Division of Endocrinology and Center for Research in Anabolic Skeletal Target in Health and Illness (ASTHI), Central Drug Research Institute (CDRI), Council of Scientific and Industrial Research - CSIR, Lucknow 226021 (India)

2016-03-15

The drug, theophylline is frequently used as an additive to medications for people suffering from chronic obstructive pulmonary diseases (COPD). We studied the effect of theophylline in bone cells, skeleton and parameters related to systemic calcium homeostasis. Theophylline induced osteoblast apoptosis by increasing reactive oxygen species production that was caused by increased cAMP production. Bone marrow levels of theophylline were higher than its serum levels, indicating skeletal accumulation of this drug. When adult Sprague-Dawley rats were treated with theophylline, bone regeneration at fracture site was diminished compared with control. Theophylline treatment resulted in a time-dependent (at 4- and 8 weeks) bone loss. At 8 weeks, a significant loss of bone mass and deterioration of microarchitecture occurred and the severity was comparable to methylprednisone. Theophylline caused formation of hypomineralized osteoid and increased osteoclast number and surface. Serum bone resorption and formation marker were respectively higher and lower in the theophylline group compared with control. Bone strength was reduced by theophylline treatment. After 8 weeks, serum 25-D3 and liver 25-hydroxylases were decreased in theophylline group than control. Further, theophylline treatment reduced serum 1, 25-(OH){sub 2} vitamin D{sub 3} (1,25-D3), and increased parathyroid hormone and fibroblast growth factor-23. Theophylline treated rats had normal serum calcium and phosphate but displayed calciuria and phosphaturia. Co-administration of 25-D3 with theophylline completely abrogated theophylline-induced osteopenia and alterations in calcium homeostasis. In addition, 1,25-D3 protected osteoblasts from theophylline-induced apoptosis and the attendant oxidative stress. We conclude that theophylline has detrimental effects in bone and prophylactic vitamin D supplementation to subjects taking theophylline could be osteoprotective. - Highlights: • Theophylline induced osteoblast

Differential population responses of native and alien rodents to an invasive predator, habitat alteration and plant masting.

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Fukasawa, Keita; Miyashita, Tadashi; Hashimoto, Takuma; Tatara, Masaya; Abe, Shintaro

2013-12-22

Invasive species and anthropogenic habitat alteration are major drivers of biodiversity loss. When multiple invasive species occupy different trophic levels, removing an invasive predator might cause unexpected outcomes owing to complex interactions among native and non-native prey. Moreover, external factors such as habitat alteration and resource availability can affect such dynamics. We hypothesized that native and non-native prey respond differently to an invasive predator, habitat alteration and bottom-up effects. To test the hypothesis, we used Bayesian state-space modelling to analyse 8-year data on the spatio-temporal patterns of two endemic rat species and the non-native black rat in response to the continual removal of the invasive small Indian mongoose on Amami Island, Japan. Despite low reproductive potentials, the endemic rats recovered better after mongoose removal than did the black rat. The endemic species appeared to be vulnerable to predation by mongooses, whose eradication increased the abundances of the endemic rats, but not of the black rat. Habitat alteration increased the black rat's carrying capacity, but decreased those of the endemic species. We propose that spatio-temporal monitoring data from eradication programmes will clarify the underlying ecological impacts of land-use change and invasive species, and will be useful for future habitat management.

Hormone therapy alters the composition of the vaginal microflora in ovariectomized rats.

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Bezirtzoglou, E; Voidarou, Ch; Papadaki, A; Tsiotsias, A; Kotsovolou, O; Konstandi, M

2008-05-01

The aim of the present study was to evaluate the alterations that may take place in the bacterial genital tract flora in the absence of ovarian hormones. The role of hormone replacement therapy was also assessed. For this purpose, various bacteria were identified from the vaginal flora of ovariectomized and sham operated female rats, following the Bergey's manual criteria. The data of this study showed that substantial differences exist in the vaginal bacterial microflora between ovariectomized and normal cyclic rats. Ovariectomy was associated with a lower total bacterial load that may be due mainly to the absence of Lactobacillus. Anaerobic bacteria were also absent. Streptococcus and Enterococcus were also not favored in an environment lacking the ovarian hormones. In contrast, C. perfringens, Bacteroides, S. epidermidis, and S. aureus were detected in high numbers in ovariectomized rats. In terms of the impact of hormone replacement therapy on vaginal flora, only estradiol (EE2) restored Lactobacillus levels in ovariectomized rats, whereas all hormonal schemes used brought Streptococcus, Clostridium lec (-), and C. perfringens, the spore and vegetative forms, close to those detected in normal cyclic female rats. In conclusion, ovarian hormones appeared to be regulatory factors that favor the presence of a broad variety of bacteria, which are members of the normal genital tract flora. On the other hand, ovariectomy modifies the vaginal microbial profile, and hormone replacement therapy based mainly on schemes containing EE2 could alleviate this disturbance.

Impact of streptozotocin on altering normal glucose homeostasis during insulin testing in diabetic rats compared to normoglycemic rats

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Qinna NA

2015-05-01

altered when different initial blood glucose levels of STZ diabetic rats were selected for testing. Such findings emphasize the importance of selecting predefined and unified glucose levels when using STZ as a diabetogenic agent in experimental protocols evaluating new antidiabetic agents and insulin delivery systems. Keywords: protein delivery, animal model, diabetes mellitus, experimental, antidiabetic agents, streptozotocin 

Paternal stress prior to conception alters DNA methylation and behaviour of developing rat offspring.

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Mychasiuk, R; Harker, A; Ilnytskyy, S; Gibb, R

2013-06-25

Although there has been an abundance of research focused on offspring outcomes associated with maternal experiences, there has been limited examination of the relationship between paternal experiences and offspring brain development. As spermatogenesis is a continuous process, experiences that have the ability to alter epigenetic regulation in fathers may actually change developmental trajectories of offspring. The purpose of this study was to examine the effects of paternal stress prior to conception on behaviour and the epigenome of both male and female developing rat offspring. Male Long-Evans rats were stressed for 27 consecutive days and then mated with control female rats. Early behaviour was tested in offspring using the negative geotaxis task and the open field. At P21 offspring were sacrificed and global DNA methylation levels in the hippocampus and frontal cortex were analysed. Paternal stress prior to conception altered behaviour of all offspring on the negative geotaxis task, delaying acquisition of the task. In addition, male offspring demonstrated a reduction in stress reactivity in the open field paradigm spending more time than expected in the centre of the open field. Paternal stress also altered DNA methylation patterns in offspring at P21, global methylation was reduced in the frontal cortex of female offspring, but increased in the hippocampus of both male and female offspring. The results from this study clearly demonstrate that paternal stress during spermatogenesis can influence offspring behaviour and DNA methylation patterns, and these affects occur in a sex-dependent manner. Development takes place in the centre of a complex interaction between maternal, paternal, and environmental influences, which combine to produce the various phenotypes and individual differences that we perceive. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Gene expression profile and genomic alterations in colonic tumours induced by 1,2-dimethylhydrazine (DMH) in rats

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Femia, Angelo Pietro; Luceri, Cristina; Toti, Simona; Giannini, Augusto; Dolara, Piero; Caderni, Giovanna

2010-01-01

Azoxymethane (AOM) or 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in rats shares many phenotypical similarities with human sporadic colon cancer and is a reliable model for identifying chemopreventive agents. Genetic mutations relevant to human colon cancer have been described in this model, but comprehensive gene expression and genomic analysis have not been reported so far. Therefore, we applied genome-wide technologies to study variations in gene expression and genomic alterations in DMH-induced colon cancer in F344 rats. For gene expression analysis, 9 tumours (TUM) and their paired normal mucosa (NM) were hybridized on 4 × 44K Whole rat arrays (Agilent) and selected genes were validated by semi-quantitative RT-PCR. Functional analysis on microarray data was performed by GenMAPP/MappFinder analysis. Array-comparative genomic hybridization (a-CGH) was performed on 10 paired TUM-NM samples hybridized on Rat genome arrays 2 × 105K (Agilent) and the results were analyzed by CGH Analytics (Agilent). Microarray gene expression analysis showed that Defcr4, Igfbp5, Mmp7, Nos2, S100A8 and S100A9 were among the most up-regulated genes in tumours (Fold Change (FC) compared with NM: 183, 48, 39, 38, 36 and 32, respectively), while Slc26a3, Mptx, Retlna and Muc2 were strongly down-regulated (FC: -500; -376, -167, -79, respectively). Functional analysis showed that pathways controlling cell cycle, protein synthesis, matrix metalloproteinases, TNFα/NFkB, and inflammatory responses were up-regulated in tumours, while Krebs cycle, the electron transport chain, and fatty acid beta oxidation were down-regulated. a-CGH analysis showed that four TUM out of ten had one or two chromosomal aberrations. Importantly, one sample showed a deletion on chromosome 18 including Apc. The results showed complex gene expression alterations in adenocarcinomas encompassing many altered pathways. While a-CGH analysis showed a low degree of genomic imbalance, it is interesting to

Social defeat stress causes depression-like behavior with metabolite changes in the prefrontal cortex of rats.

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Yi-Yun Liu

Full Text Available Major depressive disorder is a serious mental disorder with high morbidity and mortality. The role of social stress in the development of depression remains unclear. Here, we used the social defeat stress paradigm to induce depression-like behavior in rats, then evaluated the behavior of the rats and measured metabolic changes in the prefrontal cortex using gas chromatography-mass spectrometry. Within the first week after the social defeat procedure, the sucrose preference test (SPT, open field test (OFT, elevated plus maze (EPM and forced swim test (FST were conducted to examine the depressive-like and anxiety-like behaviors. For our metabolite analysis, multivariate statistics were applied to observe the distribution of all samples and to differentiate the socially defeated group from the control group. Ingenuity pathway analysis was used to find the potential relationships among the differential metabolites. In the OFT and EPM, there were no significant differences between the two experimental groups. In the SPT and FST, socially defeated rats showed less sucrose intake and longer immobility time compared with control rats. Metabolic profiling identified 25 significant variables with good predictability. Ingenuity pathways analysis revealed that "Hereditary Disorder, Neurological Disease, Lipid Metabolism" was the most significantly altered network. Stress-induced alterations of low molecular weight metabolites were observed in the prefrontal cortex of rats. Particularly, lipid metabolism, amino acid metabolism, and energy metabolism were significantly perturbed. The results of this study suggest that repeated social defeat can lead to metabolic changes and depression-like behavior in rats.

Social defeat stress causes depression-like behavior with metabolite changes in the prefrontal cortex of rats.

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Liu, Yi-Yun; Zhou, Xin-Yu; Yang, Li-Ning; Wang, Hai-Yang; Zhang, Yu-Qing; Pu, Jun-Cai; Liu, Lan-Xiang; Gui, Si-Wen; Zeng, Li; Chen, Jian-Jun; Zhou, Chan-Juan; Xie, Peng

2017-01-01

Major depressive disorder is a serious mental disorder with high morbidity and mortality. The role of social stress in the development of depression remains unclear. Here, we used the social defeat stress paradigm to induce depression-like behavior in rats, then evaluated the behavior of the rats and measured metabolic changes in the prefrontal cortex using gas chromatography-mass spectrometry. Within the first week after the social defeat procedure, the sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM) and forced swim test (FST) were conducted to examine the depressive-like and anxiety-like behaviors. For our metabolite analysis, multivariate statistics were applied to observe the distribution of all samples and to differentiate the socially defeated group from the control group. Ingenuity pathway analysis was used to find the potential relationships among the differential metabolites. In the OFT and EPM, there were no significant differences between the two experimental groups. In the SPT and FST, socially defeated rats showed less sucrose intake and longer immobility time compared with control rats. Metabolic profiling identified 25 significant variables with good predictability. Ingenuity pathways analysis revealed that "Hereditary Disorder, Neurological Disease, Lipid Metabolism" was the most significantly altered network. Stress-induced alterations of low molecular weight metabolites were observed in the prefrontal cortex of rats. Particularly, lipid metabolism, amino acid metabolism, and energy metabolism were significantly perturbed. The results of this study suggest that repeated social defeat can lead to metabolic changes and depression-like behavior in rats.

Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration.

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McFadden, Lisa M; Hoonakker, Amanda J; Vieira-Brock, Paula L; Stout, Kristen A; Sawada, Nicole M; Ellis, Jonathan D; Allen, Scott C; Walters, Elliot T; Nielsen, Shannon M; Gibb, James W; Alburges, Mario E; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

2011-08-01

Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent [i.e., postnatal day (PND) 40] rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a "challenge" high-dose METH regimen when administered at PND90. Mechanisms underlying this "resistance" were thus investigated. Results revealed that biweekly METH treatment throughout development attenuated both the acute and persistent deficits in VMAT2 function, as well as the acute hyperthermia, caused by a challenge METH treatment. Pharmacokinetic alterations did not appear to contribute to the protection afforded by the biweekly treatment. Maintenance of METH-induced hyperthermia abolished the protection against both the acute and persistent VMAT2-associated deficits suggesting that alterations in thermoregulation were caused by exposure of rats to METH during development. These findings suggest METH during development prevents METH-induced hyperthermia and the consequent METH-related neurotoxicity. Copyright © 2011 Wiley-Liss, Inc.

Altered expression of glycosaminoglycans in metastatic 13762NF rat mammary adenocarcinoma cells

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Steck, P.A.; Cheong, P.H.; Nakajima, M.; Yung, W.K.A.; Moser, R.P.; Nicolson, G.L.

1987-01-01

A difference in the expression and metabolism of [ 35 S]sulfated glycosaminoglycans between rat mammary tumor cells derived from a primary tumor and those from its metastatic lesions has been observed. Cells from the primary tumor possessed about equal quantities of chondroitin sulfate and heparan sulfate on their cell surfaces but released fourfold more chondroitin sulfate than heparan sulfate into their medium. In contrast, cells from distal metastatic lesions expressed approximately 5 times more heparan sulfate than chondroitin sulfate in both medium and cell surface fractions. This was observed to be the result of differential synthesis of the glycosaminoglycans and not of major structural alterations of the individual glycosaminoglycans. The degree of sulfation and size of heparan sulfate were similar for all cells examined. However, chondroitin sulfate, observed to be only chondroitin 4-sulfate, from the metastases-derived cells had a smaller average molecular weight on gel filtration chromatography and showed a decreased quantity of sulfated disaccharides upon degradation with chondroitin ABC lyase compared to the primary tumor derived cells. Major qualitative or quantitative alterations were not observed for hyaluronic acid among the various 13762NF cells. The metabolism of newly synthesized sulfated glycosaminoglycans was also different between cells from primary tumor and metastases. A pulse-chase kinetics study demonstrated that both heparan sulfate and chondroitin sulfate were degraded by the metastases-derived cells, whereas the primary tumor derived cells degraded only heparan sulfate and degraded it at a slower rate. These results suggested that altered glycosaminoglycan expression and metabolism may be associated with the metastatic process in 13762NF rat mammary tumor cells

Acid reflux directly causes sleep disturbances in rat with chronic esophagitis.

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Kenichi Nakahara

Full Text Available BACKGROUND & AIMS: Gastroesophageal reflux disease (GERD is strongly associated with sleep disturbances. Proton pump inhibitor (PPI therapy improves subjective but not objective sleep parameters in patients with GERD. This study aimed to investigate the association between GERD and sleep, and the effect of PPI on sleep by using a rat model of chronic acid reflux esophagitis. METHODS: Acid reflux esophagitis was induced by ligating the transitional region between the forestomach and the glandular portion and then wrapping the duodenum near the pylorus. Rats underwent surgery for implantation of electrodes for electroencephalogram and electromyogram recordings, and they were transferred to a soundproof recording chamber. Polygraphic recordings were scored by using 10-s epochs for wake, rapid eye movement sleep, and non-rapid eye movement (NREM sleep. To examine the role of acid reflux, rats were subcutaneously administered a PPI, omeprazole, at a dose of 20 mg/kg once daily. RESULTS: Rats with reflux esophagitis presented with several erosions, ulcers, and mucosal thickening with basal hyperplasia and marked inflammatory infiltration. The reflux esophagitis group showed a 34.0% increase in wake (232.2±11.4 min and 173.3±7.4 min in the reflux esophagitis and control groups, respectively; p<0.01 accompanied by a reduction in NREM sleep during light period, an increase in sleep fragmentation, and more frequent stage transitions. The use of omeprazole significantly improved sleep disturbances caused by reflux esophagitis, and this effect was not observed when the PPI was withdrawn. CONCLUSIONS: Acid reflux directly causes sleep disturbances in rats with chronic esophagitis.

Haemato-biochemical alterations induced by lead acetate toxicity in wistar rats

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S. G. Suradkar

Full Text Available An experiment was conducted to study the haemato-biochemical alterations induced by lead acetate toxicity in 48 Wistar rats of either sex, divided uniformly into four different groups. The rats of group I received only deionised water as control while, group II, III and IV were given lead acetate @ 1 PPM, 100 PPM and 1000 PPM, in drinking deionised water respectively for 28 days. In group III and IV dose dependant significant (P<0.05 reductions in TEC, Hb, PCV and TLC were observed. No significant change was observed in neutrophil, eosinophil, basophil and monocyte count in any treatment groups, whereas the lymphocyte count decreased significantly (P<0.05 in group III and IV. A dose dependant significant (P<0.05 increase in AST, ALP, AKP, GGT, BUN and creatinine was experiential while TP and albumin levels were decreased in group III and IV. [Vet World 2009; 2(11.000: 429-431

Alteration in Memory and Electroencephalogram Waves with Sub-acute Noise Stress in Albino Rats and Safeguarded by Scoparia dulcis.

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Loganathan, Sundareswaran; Rathinasamy, Sheeladevi

2016-01-01

Noise stress has different effects on memory and novelty and the link between them with an electroencephalogram (EEG) has not yet been reported. To find the effect of sub-acute noise stress on the memory and novelty along with EEG and neurotransmitter changes. Eight-arm maze (EAM) and Y-maze to analyze the memory and novelty by novel object test. Four groups of rats were used: Control, control treated with Scoparia dulcis extract, noise exposed, and noise exposed which received Scoparia extract. The results showed no marked difference observed between control and control treated with Scoparia extract on EAM, Y-maze, novel object test, and EEG in both prefrontal and occipital region, however, noise stress exposed rats showed significant increase in the reference memory and working memory error in EAM and latency delay, triad errors in Y-maze, and prefrontal and occipital EEG frequency rate with the corresponding increase in plasma corticosterone and epinephrine, and significant reduction in the novelty test, and significant reduction in the novelty test, amplitude of prefrontal, occipital EEG, and acetylcholine. These noise stress induced changes in EAM, Y-maze, novel object test, and neurotransmitters were significantly prevented when treated with Scoparia extract and these changes may be due to the normalizing action of Scoparia extract on the brain, which altered due to noise stress. Noise stress exposure causes EEG, behavior, and neurotransmitter alteration in the frontoparietal and occipital regions mainly involved in planning and recognition memoryOnly the noise stress exposed animals showed the significant alteration in the EEG, behavior, and neurotransmittersHowever, these noise stress induced changes in EEG behavior and neurotransmitters were significantly prevented when treated with Scoparia extractThese changes may be due to the normalizing action of Scoparia dulcis (adoptogen) on the brain which altered by noise stress. Abbreviations used: EEG

Role of endoplasmic reticulum stress-induced apoptosis in rat thyroid toxicity caused by excess fluoride and/or iodide.

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Liu, Hongliang; Hou, Changchun; Zeng, Qiang; Zhao, Liang; Cui, Yushan; Yu, Linyu; Wang, Lingzhi; Zhao, Yang; Nie, Junyan; Zhang, Bin; Wang, Aiguo

2016-09-01

Excess fluoride and iodide coexist in drinking water in many regions, but few studies have investigated the single or interactive effects on thyroid in vivo. In our study, Wistar rats were exposed to excess fluoride and/or iodide through drinking water for 2 or 8 months. The structure and function of the thyroid, cells apoptosis and the expression of inositol-requiring enzyme 1 (IRE1) pathway-related factors were analyzed. Results demonstrated that excess fluoride and/or iodide could change thyroid follicular morphology and alter thyroid hormone levels in rats. After 8 months treatment, both single and co-exposure of the two microelements could raise the thyroid cells apoptosis. However, the expressions of IRE1-related factors were only increased in fluoride-alone and the combined groups. In conclusion, thyroid structure and thyroid function were both affected by excess fluoride and/or iodide. IRE1-induced apoptosis were involved in this cytotoxic process caused by fluoride or the combination of two microelements. Copyright © 2016 Elsevier B.V. All rights reserved.

Chronic cigarette smoke exposure adversely alters 14C-arachidonic acid metabolism in rat lungs, aortas and platelets

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Lubawy, W.C.; Valentovic, M.A.; Atkinson, J.E.; Gairola, G.C.

1983-01-01

Male rats were exposed to freshly generated cigarette smoke once daily, 5 times a week for 10 weeks. Inhalation of smoke was verified by elevated carboxyhemoglobin in blood sampled immediately after smoke exposure and by increased lung aryl hydrocarbon hydroxylase activity 24 hours after the last smoke exposure. Aortic rings isolated from smoke-exposed rats synthesized less prostacyclin (PGI2) from 14 C-arachidonic acid than rings from sham rats. Platelets from smoke-exposed rats synthesized more thromboxane (TXA2) from 14 C-arachidonic acid than platelets from room controls but not those from sham rats. Lung microsomes from smoke-exposed rats synthesized more TXA2 and had a lower PGI2/TXA2 ratio than lung microsomes from room controls and shams. It is concluded that chronic cigarette smoke exposure alters arachidonic acid metabolism in aortas, platelets and lungs in a manner resulting in decreased PGI2 and increased TXA2, thereby creating a condition favoring platelet aggregation and a variety of cardiovascular diseases

Alterations to prepulse inhibition magnitude and latency in adult rats following neonatal treatment with domoic acid and social isolation rearing.

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Marriott, Amber L; Tasker, R Andrew; Ryan, Catherine L; Doucette, Tracy A

2016-02-01

Deficits in perceptual, informational, and attentional processing are consistently identified as a core feature in schizophrenia and related neuropsychiatric disorders. Neonatal injections of low doses of the AMPA/kainate agonist domoic acid (DOM) have previously been shown to alter various aspects of perceptual and attentional processing in adult rats. The current study investigated the effects of combined neonatal DOM treatment with isolation rearing on prepulse inhibition behaviour and relevant neurochemical measures, to assess the usefulness of these paradigms in modeling neurodevelopmental disorders. Daily subcutaneous injections of DOM (20 μg/kg) or saline were administered to male and female rat pups from postnatal days (PND) 8-14. After weaning, rats were either housed alone or in groups of 4. Both the magnitude and latency of prepulse inhibition were determined in adulthood (approximately 4.5 months of age) and post-mortem brain tissue was assayed using Western blot. Social isolation alone significantly lowered PPI magnitude in male (but not female) rats while DOM treatment appeared to make animals refractory to this effect. Combining social isolation and DOM treatment caused an additive decrease in PPI startle latency. No statistically significant differences were found in the expression of D1, D2, TH, GAD65 or GAD67 protein in either the prefrontal cortex or hippocampus, although some tendencies toward differences were noted. We conclude that both neonatal low-dose DOM and social isolation affect prepulse inhibition in rats but that each paradigm exerts these effects through different neuronal signalling systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Altered explorative strategies and reactive coping style in the FSL rat model of depression

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Salvatore eMagara

2015-04-01

Full Text Available Modeling depression in animals is based on the observation of behaviors interpreted as analogue to human symptoms. Typical tests used in experimental depression research are designed to evoke an either-or outcome. It is known that explorative and coping strategies are relevant for depression, however these aspects are generally not considered in animal behavioral testing. Here we investigate the Flinders Sensitive Line (FSL, a rat model of depression, compared to the Sprague-Dawley (SD rat in three independent tests where the animals are allowed to express a more extensive behavioral repertoire. The multivariate concentric square field™ (MCSF and the novel cage tests evoke exploratory behaviors in a novel environment and the home cage change test evokes social behaviors in the re-establishment of a social hierarchy. In the MCSF test, FSL rats exhibited less exploratory drive and more risk-assessment behavior compared to SD rats. When re-exposed to the arena, FSL, but not SD rats, increased their exploratory behavior compared to the first trial and displayed risk-assessment behavior to the same extent as SD rats. Thus, the behavior of FSL rats was more similar to that of SDs when the rats were familiar with the arena. In the novel cage test FSL rats exhibited a reactive coping style, consistent with the reduced exploration observed in the MCSF. Reactive coping is associated with less aggressive behavior. Accordingly, FSL rats displayed less aggressive behavior in the home cage change test. Taken together, our data show that FSL rats express altered explorative behavior and reactive coping style. Reduced interest is a core symptom of depression, and individuals with a reactive coping style are more vulnerable to the disease. Our results support the use of FSL rats as an animal model of depression and increase our understanding of the FSL rat beyond the behavioral dimensions targeted by the traditional depression-related tests.

Intermittent hypoxia alters dose dependent caffeine effects on renal prostanoids and receptors in neonatal rats.

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Beharry, Kay D; Cai, Charles L; Soontarapornchai, Kultida; Ahmad, Taimur; Valencia, Gloria B; Aranda, Jacob V

2018-01-01

Caffeine, one of the most commonly prescribed drugs in preterm neonates, is given in standard or suprapharmacologic doses. Although known as a diuretic, its effects in the neonatal kidneys are not well studied. We tested the hypothesis that neonatal intermittent hypoxia (IH) and high caffeine doses (HCD) alter renal regulators of vasomotor tone and water balance. Newborn rats were randomized to room air, hyperoxia, or IH and treated with standard or high caffeine doses; or placebo saline. Renal prostanoids; histopathology; and cyclooxygenase (COX), prostanoid receptor, and aquaporin (AQP) immunoreactivity were determined. HCD in IH caused severe pathological changes in the glomeruli and proximal tubules, consistent with acute kidney injury. This was associated with reductions in anthropometric growth, PGI 2, and IP, DP, and AQP-4 immunoreactivity, well as a robust increase in COX-2, suggesting that the use of HCD should be avoided in preterm infants who experience frequent IH episodes. Published by Elsevier Inc.

Alterations in monoamines level in discrete brain regions and other peripheral tissues in young and adult male rats during experimental hyperthyroidism.

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Hassan, Wafaa A; Rahman, Taghride Abdel; Aly, Mona S; Shahat, Asmaa S

2013-08-01

The present study was conducted to investigate the effect of experimentally-induced hyperthyroidism on dopamine (DA), norepinephrine (NE) and serotonin (5-HT) levels in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats (60 rats of each age). Hyperthyroidism was induced by daily s.c. injection of L-thyroxine (L-T4, 500 μg/kg body wt.) for 21 consecutive days. Induction of hyperthyroidism caused a significant elevation in DA and 5-HT levels in most of the tissues studied of both young and adult animals after 7, 14, and 21 days. NE content significantly decreased after 21 days in most of the brain regions examined and after 14 and 21 days in blood plasma of young rats following hyperthyroidism. In adult rats, NE content decreased after 14 and 21 days in cardiac muscle and after 21 days only in adrenal gland. It may be suggested that the changes in monoamines level induced by hyperthyroidism may be due to disturbance in the synthesis, turnover and release of these amines through the neurons impairment or may attributed to an alteration pattern of their synthesis and/or degradative enzymes or changes in the sensitivity of their receptors. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

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

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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.

Alterations of metallothionein isomers in Hg{sup 0}-exposed rat brain

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Yasutake, A. [Biochemistry Section, National Institute for Minamata Disease, Minamata, Kumamoto 867-0008 (Japan); Nagano, M. [Morikawa Kenkodo Co., Ltd., 2170 Taguchi, Kosa, Kamimashiki, Kumamoto 861-4616 (Japan); Hirayama, K. [Kumamoto University College of Medical Science, Kuhonji, Kumamoto 862-0976 (Japan)

2003-01-01

Previously we found that exposure to mercury vapor effectively induced brain metallothionein (MT) in rats. Here, using FPLC-gel chromatography, we examined time-dependent alterations in the MT isomers, MT-I/II and MT-III, following 3 weeks of exposure. Rats were exposed to mercury vapor at 8.3 mg/m{sup 3} for 15 h in total over 5 consecutive days. Total MT levels in rat cerebrum and cerebellum increased by 65% and 155%, respectively, 24 h after the final exposure. The increased levels in both tissues remained unchanged for at least 2 weeks after termination of exposure. Interestingly, most MT in control rat cerebrum and cerebellum was accounted for by MT-III, with MT-I/II being less than 10%. Through mercury vapor exposure, MT-I/II was quickly induced to a significant extent in both tissues, reaching a level comparable to that of MT-III. The induction rate of MT-I/II in the cerebellum was somewhat higher than in the cerebrum. Chromatograms showed that the MT-I/II thus induced began to decline at an early stage in both tissues. In the cerebrum, the amount of MT-I/II on day 22 was about 30% of the maximum level on day 1. On the other hand, the induction of MT-III was not that dramatic, but it did become evident, at least in the latter stage, when MT-I/II had begun to decrease. Thus, though the induction rate of MT-III was not as high as MT-I/II, it was sustained throughout the experimental period. (orig.)

Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour.

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Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

2016-01-26

Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects.We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model.Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males.

Asthma pregnancy alters postnatal development of chromaffin cells in the rat adrenal medulla.

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Xiu-Ming Wu

Full Text Available Adrenal neuroendocrine plays an important role in asthma. The activity of the sympathoadrenal system could be altered by early life events. The effects of maternal asthma during pregnancy on the adrenal medulla of offspring remain unknown.This study aims to explore the influence of maternal asthma during pregnancy on the development and function of adrenal medulla in offspring from postnatal day 3 (P3 to postnatal day 60 (P60. Asthmatic pregnant rats (AP, nerve growth factor (NGF-treated pregnant rats (NP and NGF antibody-treated pregnant rats (ANP were sensitized and challenged with ovalbumin (OVA; NP and ANP were treated with NGF and NGF antibody respectively. Offspring rats from the maternal group were divided into four groups: offspring from control pregnant rats (OCP, offspring from AP (OAP, offspring from NP (ONP, and offspring from ANP (OANP. The expressions of phenylethanolamine N-methyltransferase (PNMT protein in adrenal medulla were analyzed. The concentrations of epinephrine (EPI, corticosterone and NGF in serum were measured. Adrenal medulla chromaffin cells (AMCC were prone to differentiate into sympathetic nerve cells in OAP and ONP. Both EPI and PNMT were decreased in OAP from P3 to P14, and then reached normal level gradually from P30 to P60, which were lower from birth to adulthood in ONP. Corticosterone concentration increased significantly in OAP and ONP.Asthma pregnancy may promote AMCC to differentiate into sympathetic neurons in offspring rats and inhibit the synthesis of EPI, resulting in dysfunction of bronchial relaxation.

Altered astrocyte glutamate transporter regulation of hypothalamic neurosecretory neurons in heart failure rats.

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Potapenko, Evgeniy S; Biancardi, Vinicia C; Zhou, Yiqiang; Stern, Javier E

2012-08-01

Neurohumoral activation, which includes augmented plasma levels of the neurohormone vasopressin (VP), is a common finding in heart failure (HF) that contributes to morbidity and mortality in this disease. While an increased activation of magnocellular neurosecretory cells (MNCs) and enhanced glutamate function in HF is well documented, the precise underlying mechanisms remain to be elucidated. Here, we combined electrophysiology and protein measurements to determine whether altered glial glutamate transporter function and/or expression occurs in the hypothalamic supraoptic nucleus (SON) during HF. Patch-clamp recordings obtained from MNCs in brain slices show that pharmacological blockade of astrocyte glutamate transporter 1 (GLT1) function [500 μM dihydrokainate (DHK)], resulted in a persistent N-methyl-D-aspartate receptor (NMDAR)-mediated inward current (tonic I(NMDA)) in sham rats, an effect that was significantly smaller in MNCs from HF rats. In addition, we found a diminished GLT1 protein content in plasma membrane (but not cytosolic) fractions of SON punches in HF rats. Conversely, astrocyte GLAST expression was significantly higher in the SON of HF rats, while nonselective blockade of glutamate transport activity (100 μM TBOA) evoked an enhanced tonic I(NMDA) activation in HF rats. Steady-state activation of NMDARs by extracellular glutamate levels was diminished during HF. Taken together, these results support a shift in the relative expression and function of two major glial glutamate transporters (from GLT1 to GLAST predominance) during HF. This shift may act as a compensatory mechanism to preserve an adequate basal glutamate uptake level in the face of an enhanced glutamatergic afferent activity in HF rats.

Neonatal exposure to bisphenol A alters the hypothalamic-pituitary-thyroid axis in female rats.

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Fernandez, Marina O; Bourguignon, Nadia S; Arocena, Paula; Rosa, Matías; Libertun, Carlos; Lux-Lantos, Victoria

2018-03-15

Bisphenol A (BPA) is a component of polycarbonate plastics, epoxy resins and polystyrene found in many common products. Several reports revealed potent in vivo and in vitro effects. In this study we analyzed the effects of the exposure to BPA in the hypothalamic-pituitary-thyroid axis in female rats, both in vivo and in vitro. Female Sprague-Dawley rats were injected sc from postnatal day 1 (PND1) to PND10 with BPA: 500 μg 50 μl -1 oil (B500), or 50 μg 50 μl -1 (B50), or 5 μg 50 μl -1 (B5). Controls were injected with 50 μl vehicle during the same period. Neonatal exposure to BPA did not modify TSH levels in PND13 females, but it increased them in adults in estrus. Serum T4 was lower in B5 and B500 with regards to Control, whereas no difference was seen in T3. No significant differences were observed in TRH, TSHβ and TRH receptor expression between groups. TSH release from PPC obtained from adults in estrus was also higher in B50 with regard to Control. In vitro 24 h pre-treatment with BPA or E 2 increased basal TSH as well as prolactin release. On the other hand, both BPA and E 2 lowered the response to TRH. The results presented here show that the neonatal exposure to BPA alters the hypothalamic pituitary-thyroid axis in adult rats in estrus, possibly with effects on the pituitary and thyroid. They also show that BPA alters TSH release from rat PPC through direct actions on the pituitary. Copyright © 2018 Elsevier B.V. All rights reserved.

Pre-existing differences and diet-induced alterations in striatal dopamine systems of obesity-prone rats.

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Vollbrecht, Peter J; Mabrouk, Omar S; Nelson, Andrew D; Kennedy, Robert T; Ferrario, Carrie R

2016-03-01

Interactions between pre-existing differences in mesolimbic function and neuroadaptations induced by consumption of fatty, sugary foods are thought to contribute to human obesity. This study examined basal and cocaine-induced changes in striatal neurotransmitter levels without diet manipulation and D2 /D3 dopamine receptor-mediated transmission prior to and after consumption of "junk-foods" in obesity-prone and obesity-resistant rats. Microdialysis and liquid chromatography-mass spectrometry were used to determine basal and cocaine-induced changes in neurotransmitter levels in real time with cocaine-induced locomotor activity. Sensitivity to the D2 /D3 dopamine receptor agonist quinpirole was examined before and after restricted junk-food exposure. Selectively bred obesity-prone and obesity-resistant rats were used. Cocaine-induced locomotion was greater in obesity-prone rats versus obesity-resistant rats prior to diet manipulation. Basal and cocaine-induced increases in dopamine and serotonin levels did not differ. Obesity-prone rats were more sensitive to the D2 receptor-mediated effects of quinpirole, and junk-food produced modest alterations in quinpirole sensitivity in obesity-resistant rats. These data show that mesolimbic systems differ prior to diet manipulation in susceptible versus resistant rats, and that consumption of fatty, sugary foods produce different neuroadaptations in these populations. These differences may contribute to enhanced food craving and an inability to limit food intake in susceptible individuals. © 2016 The Obesity Society.

Myocardial Perfusion and Function Are Distinctly Altered by Sevoflurane Anesthesia in Diet-Induced Prediabetic Rats.

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van den Brom, Charissa E; Boly, Chantal A; Bulte, Carolien S E; van den Akker, Rob F P; Kwekkeboom, Rick F J; Loer, Stephan A; Boer, Christa; Bouwman, R Arthur

2016-01-01

Preservation of myocardial perfusion during surgery is particularly important in patients with increased risk for perioperative complications, such as diabetes. Volatile anesthetics, like sevoflurane, have cardiodepressive effects and may aggravate cardiovascular complications. We investigated the effect of sevoflurane on myocardial perfusion and function in prediabetic rats. Rats were fed a western diet (WD; n = 18) or control diet (CD; n = 18) for 8 weeks and underwent (contrast) echocardiography to determine perfusion and function during baseline and sevoflurane exposure. Myocardial perfusion was estimated based on the product of microvascular filling velocity and blood volume. WD-feeding resulted in a prediabetic phenotype characterized by obesity, hyperinsulinemia, hyperlipidemia, glucose intolerance, and hyperglycemia. At baseline, WD-feeding impaired myocardial perfusion and systolic function compared to CD-feeding. Exposure of healthy rats to sevoflurane increased the microvascular filling velocity without altering myocardial perfusion but impaired systolic function. In prediabetic rats, sevoflurane did also not affect myocardial perfusion; however, it further impaired systolic function. Diet-induced prediabetes is associated with impaired myocardial perfusion and function in rats. While sevoflurane further impaired systolic function, it did not affect myocardial perfusion in prediabetic rats. Our findings suggest that sevoflurane anesthesia leads to uncoupling of myocardial perfusion and function, irrespective of the metabolic state.

Leucine-rich diet alters the 1H-NMR based metabolomic profile without changing the Walker-256 tumour mass in rats.

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Viana, Laís Rosa; Canevarolo, Rafael; Luiz, Anna Caroline Perina; Soares, Raquel Frias; Lubaczeuski, Camila; Zeri, Ana Carolina de Mattos; Gomes-Marcondes, Maria Cristina Cintra

2016-10-03

Cachexia is one of the most important causes of cancer-related death. Supplementation with branched-chain amino acids, particularly leucine, has been used to minimise loss of muscle tissue, although few studies have examined the effect of this type of nutritional supplementation on the metabolism of the tumour-bearing host. Therefore, the present study evaluated whether a leucine-rich diet affects metabolomic derangements in serum and tumour tissues in tumour-bearing Walker-256 rats (providing an experimental model of cachexia). After 21 days feeding Wistar female rats a leucine-rich diet, distributed in L-leucine and LW-leucine Walker-256 tumour-bearing groups, we examined the metabolomic profile of serum and tumour tissue samples and compared them with samples from tumour-bearing rats fed a normal protein diet (C - control; W - tumour-bearing groups). We utilised 1 H-NMR as a means to study the serum and tumour metabolomic profile, tumour proliferation and tumour protein synthesis pathway. Among the 58 serum metabolites examined, we found that 12 were altered in the tumour-bearing group, reflecting an increase in activity of some metabolic pathways related to energy production, which diverted many nutrients toward tumour growth. Despite displaying increased tumour cell activity (i.e., higher Ki-67 and mTOR expression), there were no differences in tumour mass associated with changes in 23 metabolites (resulting from valine, leucine and isoleucine synthesis and degradation, and from the synthesis and degradation of ketone bodies) in the leucine-tumour group. This result suggests that the majority of nutrients were used for host maintenance. A leucine rich-diet, largely used to prevent skeletal muscle loss, did not affect Walker 256 tumour growth and led to metabolomic alterations that may partially explain the positive effects of leucine for the whole tumour-bearing host.

Combinational chelation therapy abrogates lead-induced neurodegeneration in rats

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Pachauri, Vidhu; Saxena, Geetu; Mehta, Ashish; Mishra, Deepshikha; Flora, Swaran J.S.

2009-01-01

Lead, a ubiquitous and potent neurotoxicant causes oxidative stress which leads to numerous neurobehavioral and physiological alterations. The ability of lead to bind sulfhydryl groups or compete with calcium could be one of the reasons for its debilitating effects. In the present study, we addressed: i) if chelation therapy could circumvent the altered oxidative stress and prevent neuronal apoptosis in chronic lead-intoxicated rats, ii) whether chelation therapy could reverse biochemical and behavioral changes, and iii) if mono or combinational therapy with captopril (an antioxidant) and thiol chelating agents (DMSA/MiADMSA) is more effective than individual thiol chelator in lead-exposed rats. Results indicated that lead caused a significant increase in reactive oxygen species, nitric oxide, and intracellular free calcium levels along with altered behavioral abnormalities in locomotor activity, exploratory behavior, learning, and memory that were supported by changes in neurotransmitter levels. A fall in membrane potential, release of cytochrome c, and DNA damage indicated mitochondrial-dependent apoptosis. Most of these alterations showed significant recovery following combined therapy with captopril with MiADMSA and to a smaller extend with captopril + DMSA over monotherapy with these chelators. It could be concluded from our present results that co-administration of a potent antioxidant (like captopril) might be a better treatment protocol than monotherapy to counter lead-induced oxidative stress. The major highlight of the work is an interesting experimental evidence of the efficacy of combinational therapy using an antioxidant with a thiol chelator in reversing neurological dystrophy caused due to chronic lead exposure in rats.

Clerodendron glandulosum Coleb., Verbenaceae, ameliorates high fat diet-induced alteration in lipid and cholesterol metabolism in rats

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RN Jadeja

Full Text Available The present study was undertaken to evaluate the efficacy of freeze dried extract of Clerodendron glandulosum Coleb., Verbenaceae, leaves (FECG on alteration in lipid and cholesterol metabolism in high fat diet fed hyperlipidemic rats. Plasma and hepatic lipid profiles, lipid and cholesterol metabolizing enzymes in target tissues and fecal total lipids and bile acid contents were evaluated in FECG treated normolipidemic and hyperlipidemic rats. These results were compared with synthetic hypolipidemic drug Lovastatin (LVS. Results indicate that FECG was able to positively regulate induced experimental hyperlipidemia by significant alteration in plasma and tissue lipid profiles. These results can be attributed to reduced absorption, effective elimination and augmented catabolism of lipids and cholesterol possibly due to high content of saponin and phytosterols in C. glandulosum. Use of C. glandulosum extract as a potential therapeutic agent against hypercholesterolemia and hypertriglyceridemia is indicated.

The N-Methyl-d-Aspartate Receptor Antagonist MK-801 Prevents Thallium-Induced Behavioral and Biochemical Alterations in the Rat Brain.

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Osorio-Rico, Laura; Villeda-Hernández, Juana; Santamaría, Abel; Königsberg, Mina; Galván-Arzate, Sonia

2015-01-01

Thallium (Tl(+)) is a toxic heavy metal capable of increasing oxidative damage and disrupting antioxidant defense systems. Thallium invades the brain cells through potassium channels, increasing neuronal excitability, although until now the possible role of glutamatergic transmission in this event has not been investigated. Here, we explored the possible involvement of a glutamatergic component in the Tl(+)-induced toxicity through the N-methyl-d-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) in rats. The effects of MK-801 (1 mg/kg, intraperitoneally [ip]) on early (24 hours) motor alterations, lipid peroxidation, reduced glutathione (GSH) levels, and GSH peroxidase activity induced by Tl(+) acetate (32 mg/kg, ip) were evaluated in adult rats. MK-801 attenuated the Tl(+)-induced hyperactivity and lipid peroxidation in the rat striatum, hippocampus and midbrain, and produced mild effects on other end points. Our findings suggest that glutamatergic transmission via NMDA receptors might be involved in the Tl(+)-induced altered regional brain redox activity and motor performance in rats. © The Author(s) 2015.

Minocycline restores cognitive-relative altered proteins in young bile duct-ligated rat prefrontal cortex.

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Li, Shih-Wen; Chen, Yu-Chieh; Sheen, Jiunn-Ming; Hsu, Mei-Hsin; Tain, You-Lin; Chang, Kow-Aung; Huang, Li-Tung

2017-07-01

Bile duct ligation (BDL) model is used to study hepatic encephalopathy accompanied by cognitive impairment. We employed the proteomic analysis approach to evaluate cognition-related proteins in the prefrontal cortex of young BDL rats and analyzed the effect of minocycline on these proteins and spatial memory. BDL was induced in young rats at postnatal day 17. Minocycline as a slow-release pellet was implanted into the peritoneum. Morris water maze test and two-dimensional liquid chromatography-tandem mass spectrometry were used to evaluate spatial memory and prefrontal cortex protein expression, respectively. We used 2D/LC-MS/MS to analyze for affected proteins in the prefrontal cortex of young BDL rats. Results were verified with Western blotting, immunohistochemistry, and quantitative real-time PCR. The effect of minocycline in BDL rats was assessed. BDL induced spatial deficits, while minocycline rescued it. Collapsin response mediator protein 2 (CRMP2) and manganese-dependent superoxide dismutase (MnSOD) were upregulated and nucleoside diphosphate kinase B (NME2) was downregulated in young BDL rats. BDL rats exhibited decreased levels of brain-derived neurotrophic factor (BDNF) mRNA as compared with those by the control. However, minocycline treatment restored CRMP2 and NME2 protein expression, BDNF mRNA level, and MnSOD activity to control levels. We demonstrated that BDL altered the expression of CRMP2, NME2, MnSOD, and BDNF in the prefrontal cortex of young BDL rats. However, minocycline treatment restored the expression of the affected mediators that are implicated in cognition. Copyright © 2017 Elsevier Inc. All rights reserved.

Carbonated soft drinks alter hepatic cytochrome P450 isoform expression in Wistar rats.

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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.

Neonatal systemic inflammation in rats alters retinal vessel development and simulates pathologic features of retinopathy of prematurity.

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Hong, Hye Kyoung; Lee, Hyun Ju; Ko, Jung Hwa; Park, Ji Hyun; Park, Ji Yeon; Choi, Chang Won; Yoon, Chang-Hwan; Ahn, Seong Joon; Park, Kyu Hyung; Woo, Se Joon; Oh, Joo Youn

2014-05-15

Alteration of retinal angiogenesis during development leads to retinopathy of prematurity (ROP) in preterm infants, which is a leading cause of visual impairment in children. A number of clinical studies have reported higher rates of ROP in infants who had perinatal infections or inflammation, suggesting that exposure of the developing retina to inflammation may disturb retinal vessel development. Thus, we investigated the effects of systemic inflammation on retinal vessel development and retinal inflammation in neonatal rats. To induce systemic inflammation, we intraperitoneally injected 100 μl lipopolysaccharide (LPS, 0.25 mg/ml) or the same volume of normal saline in rat pups on postnatal days 1, 3, and 5. The retinas were extracted on postnatal days 7 and 14, and subjected to assays for retinal vessels, inflammatory cells and molecules, and apoptosis. We found that intraperitoneal injection of LPS impaired retinal vessel development by decreasing vessel extension, reducing capillary density, and inducing localized overgrowth of abnormal retinal vessels and dilated peripheral vascular ridge, all of which are characteristic findings of ROP. Also, a large number of CD11c+ inflammatory cells and astrocytes were localized in the lesion of abnormal vessels. Further analysis revealed that the number of major histocompatibility complex (MHC) class IIloCD68loCD11bloCD11chi cells in the retina was higher in LPS-treated rats compared to controls. Similarly, the levels of TNF-α, IL-1β, and IL-12a were increased in LPS-treated retina. Also, apoptosis was increased in the inner retinal layer where retinal vessels are located. Our data demonstrate that systemic LPS-induced inflammation elicits retinal inflammation and impairs retinal angiogenesis in neonatal rats, implicating perinatal inflammation in the pathogenesis of ROP.

Peripheral tumors alter neuroinflammatory responses to lipopolysaccharide in female rats.

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Pyter, Leah M; El Mouatassim Bih, Sarah; Sattar, Husain; Prendergast, Brian J

2014-03-13

Cancer is associated with an increased prevalence of depression. Peripheral tumors induce inflammatory cytokine production in the brain and depressive-like behaviors. Mounting evidence indicates that cytokines are part of a pathway by which peripheral inflammation causes depression. Neuroinflammatory responses to immune challenges can be exacerbated (primed) by prior immunological activation associated with aging, early-life infection, and drug exposure. This experiment tested the hypothesis that peripheral tumors likewise induce neuroinflammatory sensitization or priming. Female rats with chemically-induced mammary carcinomas were injected with either saline or lipopolysaccharide (LPS, 250μg/kg; i.p.), and expression of mRNAs involved in the pathway linking inflammation and depression (interleukin-1beta [Il-1β], CD11b, IκBα, indolamine 2,3-deoxygenase [Ido]) was quantified by qPCR in the hippocampus, hypothalamus, and frontal cortex, 4 or 24h post-treatment. In the absence of LPS, hippocampal Il-1β and CD11b mRNA expression were elevated in tumor-bearing rats, whereas Ido expression was reduced. Moreover, in saline-treated rats basal hypothalamic Il-1β and CD11b expression were positively correlated with tumor weight; heavier tumors, in turn, were characterized by more inflammatory, necrotic, and granulation tissue. Tumors exacerbated CNS proinflammatory gene expression in response to LPS: CD11b was greater in hippocampus and frontal cortex of tumor-bearing relative to tumor-free rats, IκBα was greater in hippocampus, and Ido was greater in hypothalamus. Greater neuroinflammatory responses in tumor-bearing rats were accompanied by attenuated body weight gain post-LPS. The data indicate that neuroinflammatory pathways are potentiated, or primed, in tumor-bearing rats, which may exacerbate future negative behavioral consequences. Copyright © 2014 Elsevier B.V. All rights reserved.

Glucose metabolic alterations in hippocampus of diabetes mellitus rats and the regulation of aerobic exercise.

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Li, Jingjing; Liu, Beibei; Cai, Ming; Lin, Xiaojing; Lou, Shujie

2017-11-04

Diabetes could negatively affect the structures and functions of the brain, especially could cause the hippocampal dysfunction, however, the potential metabolic mechanism is unclear. The aim of this study was to investigate the changes of glucose metabolism in hippocampus of diabetes mellitus rats and the regulation of aerobic exercise, and to analyze the possible mechanisms. A rat model of type 2 diabetes mellitus was established by high-fat diet feeding in combination with STZ intraperitoneal injection, then 4 weeks of aerobic exercise was conducted. The glucose metabolites and key enzymes involved in glucose metabolism in hippocampus were respectively detected by GC/MS based metabolomics and western blot. Metabolomics results showed that compared with control rats, the level of citric acid was significantly decreased, while the levels of lactic acid, ribose 5-phosphate, xylulose 5-phosphate and glucitol were significantly increased in the diabetic rat. Compared with diabetic rats, the level of citric acid was significantly increased, while the lactic acid, ribose 5-phosphate and xylulose 5-phosphate were significantly decreased in the diabetic exercise rats. Western blot results showed that lower level of citrate synthase and oxoglutarate dehydrogenase, higher level of aldose reductase and glucose 6-phosphatedehydrogenase were found in the diabetic rats when compared to control rats. After 4 weeks of aerobic exercise, citrate synthase was upregulated and glucose 6-phosphatedehydrogenase was downregulated in the diabetic rats. These results suggest that diabetes could cause abnormal glucose metabolism, and aerobic exercise plays an important role in regulating diabetes-induced disorder of glucose metabolism in the hippocampus. Copyright © 2017 Elsevier B.V. All rights reserved.

Kidney gene expression analysis in a rat model of intrauterine growth restriction reveals massive alterations of coagulation genes.

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Buffat, Christophe; Boubred, Farid; Mondon, Françoise; Chelbi, Sonia T; Feuerstein, Jean-Marc; Lelièvre-Pégorier, Martine; Vaiman, Daniel; Simeoni, Umberto

2007-11-01

In this study, low birth weight was induced in rats by feeding the dams with a low-protein diet during pregnancy. Kidneys from the fetuses at the end of gestation were collected and showed a reduction in overall and relative weight, in parallel with other tissues (heart and liver). This reduction was associated with a reduction in nephrons number. To better understand the molecular basis of this observation, a transcriptome analysis contrasting kidneys from control and protein-deprived rats was performed, using a platform based upon long isothermic oligonucleotides, strengthening the robustness of the results. We could identify over 1800 transcripts modified more than twice (772 induced and 1040 repressed). Genes of either category were automatically classified according to functional criteria, making it possible to bring to light a large cluster of genes involved in coagulation and complement cascades. The promoters of the most induced and most repressed genes were contrasted for their composition in putative transcription factor binding sites, suggesting an overrepresentation of the AP1R binding site, together with the transcription induction of factors actually binding to this site in the set of induced genes. The induction of coagulation cascades in the kidney of low-birth-weight rats provides a putative rationale for explaining thrombo-endothelial disorders also observed in intrauterine growth-restricted human newborns. These alterations in the kidneys have been reported as a probable cause for cardiovascular diseases in the adult.

Long-term hippocampal glutamate synapse and astrocyte dysfunctions underlying the altered phenotype induced by adolescent THC treatment in male rats.

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Zamberletti, Erica; Gabaglio, Marina; Grilli, Massimo; Prini, Pamela; Catanese, Alberto; Pittaluga, Anna; Marchi, Mario; Rubino, Tiziana; Parolaro, Daniela

2016-09-01

Cannabis use has been frequently associated with sex-dependent effects on brain and behavior. We previously demonstrated that adult female rats exposed to delta-9-tetrahydrocannabinol (THC) during adolescence develop long-term alterations in cognitive performances and emotional reactivity, whereas preliminary evidence suggests the presence of a different phenotype in male rats. To thoroughly depict the behavioral phenotype induced by adolescent THC exposure in male rats, we treated adolescent animals with increasing doses of THC twice a day (PND 35-45) and, at adulthood, we performed a battery of behavioral tests to measure affective- and psychotic-like symptoms as well as cognition. Poorer memory performance and psychotic-like behaviors were present after adolescent THC treatment in male rats, without alterations in the emotional component. At cellular level, the expression of the NMDA receptor subunit, GluN2B, as well as the levels of the AMPA subunits, GluA1 and GluA2, were significantly increased in hippocampal post-synaptic fractions from THC-exposed rats compared to controls. Furthermore, increases in the levels of the pre-synaptic marker, synaptophysin, and the post-synaptic marker, PSD95, were also present. Interestingly, KCl-induced [(3)H]D-ASP release from hippocampal synaptosomes, but not gliosomes, was significantly enhanced in THC-treated rats compared to controls. Moreover, in the same brain region, adolescent THC treatment also resulted in a persistent neuroinflammatory state, characterized by increased expression of the astrocyte marker, GFAP, increased levels of the pro-inflammatory markers, TNF-α, iNOS and COX-2, as well as a concomitant reduction of the anti-inflammatory cytokine, IL-10. Notably, none of these alterations was observed in the prefrontal cortex (PFC). Together with our previous findings in females, these data suggest that the sex-dependent detrimental effects induced by adolescent THC exposure on adult behavior may rely on its

Hydrolysed inulin alleviates the azoxymethane-induced preneoplastic aberrant crypt foci by altering selected intestinal microbiota in Sprague-Dawley rats.

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Pattananandecha, Thanawat; Sirilun, Sasithorn; Duangjitcharoen, Yodsawee; Sivamaruthi, Bhagavathi Sundaram; Suwannalert, Prasit; Peerajan, Sartjin; Chaiyasut, Chaiyavat

2016-09-01

Context Inulin, a non-digestible carbohydrate isolated from Helianthus tuberosus L. (Asteraceae), has been shown to alter the gut beneficial bacteria including Lactobacillus spp. and Bifidobacteria. Inulin also influences the activities of intestinal microbiota that could prevent the colon cancer development. Objective This study determines the effect of hydrolysed inulin with different degrees of polymerisation on alteration of intestinal microbiota and their activities on azoxymethane (AOM)-induced preneoplastic aberrant crypt foci (ACF) in rats. Materials and methods Seventy-two male Sprague-Dawley rats were randomly divided into six groups (three control and three AOM-treated groups) and the animal were fed with either a normal diet or diet containing 10% of long-chain inulin (InuL) or short-chain inulin (InuS), respectively, for 17 weeks. Colon cancer was induced in rats by injecting AOM subcutaneously at the 8th and 9th week of the study period. At the end of the experiment, cecal contents of rats were examined for selected microbiota, organic acids, putrefactive compounds and microbial enzymes. ACF formation was microscopically examined. Results The inulin diets significantly increased the weight and decreased the pH of the caecal content. The rats fed with InuL-supplemented diet showed approximately 2.9- and 6.8-fold increases in the biomass of Lactobacillus spp. and Bifidobacteria, respectively. Naive and AOM-treated rats fed with inulin-supplemented diet showed ∼1.3- and ∼2.2-fold decreases in the biomass of Escherichia coli and Salmonella enterica serovar Typhi, respectively. Inulins significantly decreased the colonic concentration of phenol, p-cresol and indole. Reduction in the activity of microbial enzymes such as β-glucuronidase, azoreductase and nitroreductase were observed in inulin-treated animals. Reduction in the ACF formation has been observed in inulin-treated groups. Discussion and conclusion The present study demonstrates that dietary

Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle.

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Lee, Yang; Fluckey, James D; Chakraborty, Sanjukta; Muthuchamy, Mariappan

2017-07-01

Insulin resistance is a well-known risk factor for obesity, metabolic syndrome (MetSyn) and associated cardiovascular diseases, but its mechanisms are undefined in the lymphatics. Mesenteric lymphatic vessels from MetSyn or LPS-injected rats exhibited impaired intrinsic contractile activity and associated inflammatory changes. Hence, we hypothesized that insulin resistance in lymphatic muscle cells (LMCs) affects cell bioenergetics and signaling pathways that consequently alter contractility. LMCs were treated with different concentrations of insulin or glucose or both at various time points to determine insulin resistance. Onset of insulin resistance significantly impaired glucose uptake, mitochondrial function, oxygen consumption rates, glycolysis, lactic acid, and ATP production in LMCs. Hyperglycemia and hyperinsulinemia also impaired the PI3K/Akt while enhancing the ERK/p38MAPK/JNK pathways in LMCs. Increased NF-κB nuclear translocation and macrophage chemoattractant protein-1 and VCAM-1 levels in insulin-resistant LMCs indicated activation of inflammatory mechanisms. In addition, increased phosphorylation of myosin light chain-20, a key regulator of lymphatic muscle contraction, was observed in insulin-resistant LMCs. Therefore, our data elucidate the mechanisms of insulin resistance in LMCs and provide the first evidence that hyperglycemia and hyperinsulinemia promote insulin resistance and impair lymphatic contractile status by reducing glucose uptake, altering cellular metabolic pathways, and activating inflammatory signaling cascades.-Lee, Y., Fluckey, J. D., Chakraborty, S., Muthuchamy, M. Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle. © FASEB.

Phenobarbital Induces Alterations in the Proteome of Hepatocytes and Mesenchymal Cells of Rat Livers

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Klepeisz, Philip; Sagmeister, Sandra; Haudek-Prinz, Verena; Pichlbauer, Melanie; Grasl-Kraupp, Bettina; Gerner, Christopher

2013-01-01

Preceding studies on the mode of action of non-genotoxic hepatocarcinogens (NGCs) have concentrated on alterations induced in hepatocytes (HCs). A potential role of non-parenchymal liver cells (NPCs) in NGC-driven hepatocarcinogenesis has been largely neglected so far. The aim of this study is to characterize NGC-induced alterations in the proteome profiles of HCs as well as NPCs. We chose the prototypic NGC phenobarbital (PB) which was applied to male rats for a period of 14 days. The livers of PB-treated rats were perfused by collagenase and the cell suspensions obtained were subjected to density gradient centrifugation to separate HCs from NPCs. In addition, HCs and NPC isolated from untreated animals were treated with PB in vitro. Proteome profiling was done by CHIP-HPLC and ion trap mass spectrometry. Proteome analyses of the in vivo experiments showed many of the PB effects previously described in HCs by other methods, e.g. induction of phase I and phase II drug metabolising enzymes. In NPCs proteins related to inflammation and immune regulation such as PAI-1 and S100-A10, ADP-ribosyl cyclase 1 and to cell migration such as kinesin-1 heavy chain, myosin regulatory light chain RLC-A and dihydropyrimidinase-related protein 1 were found to be induced, indicating major PB effects on these cells. Remarkably, in vitro treatment of HCs and NPCs with PB hardly reproduced the proteome alterations observed in vivo, indicating differences of NGC induced responses of cells at culture conditions compared to the intact organism. To conclude, the present study clearly demonstrated that PB induces proteome alterations not only in HCs but also in NPCs. Thus, any profound molecular understanding on the mode of action of NGCs has to consider effects on cells of the hepatic mesenchyme. PMID:24204595

Phenobarbital induces alterations in the proteome of hepatocytes and mesenchymal cells of rat livers.

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Philip Klepeisz

Full Text Available Preceding studies on the mode of action of non-genotoxic hepatocarcinogens (NGCs have concentrated on alterations induced in hepatocytes (HCs. A potential role of non-parenchymal liver cells (NPCs in NGC-driven hepatocarcinogenesis has been largely neglected so far. The aim of this study is to characterize NGC-induced alterations in the proteome profiles of HCs as well as NPCs. We chose the prototypic NGC phenobarbital (PB which was applied to male rats for a period of 14 days. The livers of PB-treated rats were perfused by collagenase and the cell suspensions obtained were subjected to density gradient centrifugation to separate HCs from NPCs. In addition, HCs and NPC isolated from untreated animals were treated with PB in vitro. Proteome profiling was done by CHIP-HPLC and ion trap mass spectrometry. Proteome analyses of the in vivo experiments showed many of the PB effects previously described in HCs by other methods, e.g. induction of phase I and phase II drug metabolising enzymes. In NPCs proteins related to inflammation and immune regulation such as PAI-1 and S100-A10, ADP-ribosyl cyclase 1 and to cell migration such as kinesin-1 heavy chain, myosin regulatory light chain RLC-A and dihydropyrimidinase-related protein 1 were found to be induced, indicating major PB effects on these cells. Remarkably, in vitro treatment of HCs and NPCs with PB hardly reproduced the proteome alterations observed in vivo, indicating differences of NGC induced responses of cells at culture conditions compared to the intact organism. To conclude, the present study clearly demonstrated that PB induces proteome alterations not only in HCs but also in NPCs. Thus, any profound molecular understanding on the mode of action of NGCs has to consider effects on cells of the hepatic mesenchyme.

Di-(2 ethylhexyl phthalate and flutamide alter gene expression in the testis of immature male rats

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Yu Frank H

2009-09-01

Full Text Available Abstract We previously demonstrated that the androgenic and anti-androgenic effects of endocrine disruptors (EDs alter reproductive function and exert distinct effects on developing male reproductive organs. To further investigate these effects, we used an immature rat model to examine the effects of di-(2 ethylhexyl phthalate (DEHP and flutamide (Flu on the male reproductive system. Immature male SD rats were treated daily with DEHP and Flu on postnatal days (PNDs 21 to 35, in a dose-dependent manner. As results, the weights of the testes, prostate, and seminal vesicle and anogenital distances (AGD decreased significantly in response to high doses of DEHP or Flu. Testosterone (T levels significantly decreased in all DEHP- treated groups, whereas luteinizing hormone (LH plasma levels were not altered by any of the two treatments at PND 36. However, treatment with DEHP or Flu induced histopathological changes in the testes, wherein degeneration and disorders of Leydig cells, germ cells and dilatation of tubular lumen were observed in a dose-dependent manner. Conversely, hyperplasia and denseness of Leydig, Sertoli and germ cells were observed in rats given with high doses of Flu. The results by cDNA microarray analysis indicated that 1,272 genes were up-regulated by more than two-fold, and 1,969 genes were down-regulated in response to DEHP, Flu or both EDs. These genes were selected based on their markedly increased or decreased expression levels. These genes have been also classified on the basis of gene ontology (e.g., steroid hormone biosynthetic process, regulation of transcription, signal transduction, metabolic process, biosynthetic process.... Significant decreases in gene expression were observed in steroidogenic genes (i.e., Star, Cyp11a1 and Hsd3b. In addition, the expression of a common set of target genes, including CaBP1, Vav2, Plcd1, Lhx1 and Isoc1, was altered following exposure to EDs, suggesting that they may be marker genes to

Enalapril alters the formation of the collagen matrix in spontaneously hypertensive rats

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Alfredo de Souza Bomfim

2003-07-01

Full Text Available OBJECTIVE: To assess the effect of the inhibition of the angiotensin-converting enzyme on the collagen matrix (CM of the heart of newborn spontaneously hypertensive rats (SHR during embryonic development. METHODS: The study comprised the 2 following groups of SHR (n=5 each: treated group - rats conceived from SHR females treated with enalapril maleate (15 mg. kg-1.day-1 during gestation; and nontreated group - offspring of nontreated females. The newborns were euthanized within the first 24 hours after birth and their hearts were removed and processed for histological study. Three fields per animal were considered for computer-assisted digital analysis and determination of the volume densities (Vv of the nuclei and CM. The images were segmented with the aid of Image Pro Plus® 4.5.029 software (Media Cybernetics. RESULTS: No difference was observed between the treated and nontreated groups in regard to body mass, cardiac mass, and the relation between cardiac and body mass. A significant reduction in the Vv[matrix] and a concomitant increase in the Vv[nuclei] were observed in the treated group as compared with those in the nontreated group. CONCLUSION: The treatment with enalapril of hypertensive rats during pregnancy alters the collagen content and structure of the myocardium of newborns.

Radioimmunoassay for thyroid hormones determination on rats progeny with hypothyroidism and hyperthyroidism

International Nuclear Information System (INIS)

Silveira, Maria F.G.; Danda, Karina P.N.; Luna, Taciana F.; Souza, Grace M.; Catanho, Maria T.J.A.; Bernardo-Filho, Mario; Moura, Egberto G.

2002-01-01

The onset of fetal thyroid function occurs about 17-18 days after conception in the rat. The maternal hypothyroidism or hyperthyroidism which occur during gestation provokes alteration, the hormonal modification in the newborn rats was analyzed. The hypothyroidism was induced in normal dams, which were being treated for 7 days with methimazole (in the of 0,03 % in drinking water) before mating. The hyperthyroidism was induced in normal dams, which were being treated for 2 days with T 4 (2μg per 100 g body wt/day) before mating. It was seen that the rat which was born from hypothyroid or hyperthyroid dams suffered alteration on its T 4 levels concerning the days 10,20,30 and 60 after birth. The administration of methimazole or thyroxine affects the fetal thyroid gland function, causing alteration of both T 4 levels, even after the birth, indicating that the maternal hypothyroidism or hyperthyroidism influence on the post-natal life of the rat. (author)

Leptin Intake at Physiological Doses Throughout Lactation in Male Wistar Rats Normalizes the Decreased Density of Tyrosine Hydroxylase-Immunoreactive Fibers in the Stomach Caused by Mild Gestational Calorie Restriction

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Nara Szostaczuk

2018-03-01

Full Text Available Introduction: Gestational under nutrition in rats has been shown to decrease expression of sympathetic innervation markers in peripheral tissues of offspring, including the stomach. This has been linked to lower gastric secretion and decreased circulating levels of ghrelin. Considering the critical role of leptin intake during lactation in preventing obesity and reversing adverse developmental programming effects, we aimed to find out whether leptin supplementation may reverse the above mentioned alterations caused by mild gestational calorie restriction.Methods: Three groups of male rats were studied at a juvenile age (25 days old and during adulthood (3 and 6 months old: the offspring of ad libitum fed dams (controls, the offspring of dams that were diet restricted (20% from days 1 to 12 of gestation (CR, and CR rats supplemented with a daily oral dose of leptin (equivalent to 5 times the average amount they could receive each day from maternal milk throughout lactation (CR-Leptin. The density of TyrOH-immunoreactive (TyrOH+ fibers and the levels of Tyrosine hydroxylase (TyrOH—used as potential markers of functional sympathetic innervation—were measured in stomach. Plasma leptin and ghrelin levels were also determined.Results: Twenty five-day-old CR rats, but not CR-Leptin rats, displayed lower density of TyrOH+ fibers (−46% and TyrOH levels (−47% in stomach compared to controls. Alterations in CR animals were mitigated at 6 months of age, and differences were not significant. Adult CR-Leptin animals showed higher plasma ghrelin levels than CR animals, particularly at 3 months (+16%, and a lower leptin/ghrelin ratio (−28 and −37% at 3 and 6 months, respectively.Conclusion: Leptin intake during lactation is able to reverse the alterations in the density of TyrOH+ fibers in the stomach and normalize the increased leptin/ghrelin ratio linked to a mild gestational calorie restriction in rats, supporting the relevance of leptin as an

Environmental prenatal stress eliminates brain and maternal behavioral sex differences and alters hormone levels in female rats.

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Del Cerro, M C R; Ortega, E; Gómez, F; Segovia, S; Pérez-Laso, C

2015-07-01

Environmental prenatal stress (EPS) has effects on fetuses that are long-lasting, altering their hormone levels, brain morphology and behavior when they reach maturity. In previous research, we demonstrated that EPS affects the expression of induced maternal behavior (MB), the neuroendocrine system, and morphology of the sexually dimorphic accessory olfactory bulb (AOB) involved in reproductive behavior patterns. The bed nucleus of the accessory olfactory tract (BAOT) is another vomeronasal (VN) structure that plays an inhibitory role in rats in the expression of induced maternal behavior in female and male virgins. In the present study, we have ascertained whether the behavioral, neuroendocrine, and neuromorphological alterations of the AOB found after EPS also appear in the BAOT. After applying EPS to pregnant rats during the late gestational period, in their female offspring at maturity we tested induced maternal behavior, BAOT morphology and plasma levels of testosterone (T), estradiol (E2), progesterone (P), adrenocorticotropic hormone (ACTH) and corticosterone (Cpd B). EPS: a) affected the induction of MB, showed a male-like pattern of care for pups, b) elevated plasma levels of Cpd B and reduced E2 in comparison with the controls, and c) significantly increased the number of BAOT neurons compared to the control females and comparable to the control male group. These findings provide further evidence that stress applied to pregnant rats produces long-lasting behavioral, endocrine and neuroanatomical alterations in the female offspring that are evident when they become mature. Copyright © 2015 Elsevier Inc. All rights reserved.

Sympathetic regulation and anterior cingulate cortex volume are altered in a rat model of chronic back pain.

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Touj, Sara; Houle, Sébastien; Ramla, Djamel; Jeffrey-Gauthier, Renaud; Hotta, Harumi; Bronchti, Gilles; Martinoli, Maria-Grazia; Piché, Mathieu

2017-06-03

Chronic pain is associated with autonomic disturbance. However, specific effects of chronic back pain on sympathetic regulation remain unknown. Chronic pain is also associated with structural changes in the anterior cingulate cortex (ACC), which may be linked to sympathetic dysregulation. The aim of this study was to determine whether sympathetic regulation and ACC surface and volume are affected in a rat model of chronic back pain, in which complete Freund Adjuvant (CFA) is injected in back muscles. Sympathetic regulation was assessed with renal blood flow (RBF) changes induced by electrical stimulation of a hind paw, while ACC structure was examined by measuring cortical surface and volume. RBF changes and ACC volume were compared between control rats and rats injected with CFA in back muscles segmental (T10) to renal sympathetic innervation or not (T2). In rats with CFA, chronic inflammation was observed in the affected muscles in addition to increased nuclear factor-kappa B (NF-kB) protein expression in corresponding spinal cord segments (p=0.01) as well as decreased ACC volume (pchronic pain at T2 (p'schronic back pain alters sympathetic functions through non-segmental mechanisms, possibly by altering descending regulatory pathways from ACC. Yet, segmental somato-sympathetic reflexes may compete with non-segmental processes depending on the back region affected by pain and according to the segmental organization of the sympathetic nervous system. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

[Crabtree effect caused by ketoses in isolated rat hepatocytes].

Science.gov (United States)

Martínez, P; Carrascosa, J M; Núñez de Castro, I

1982-01-01

Oxygen uptake and glycolytic activity were studied in hepatocytes isolated from fed rats. The addition of fructose or tagatose resulted in a 38% and 31% inhibition of cellular respiration respectively. The addition of 10 mM D-glyceraldehyde caused a slight Crabtree effect. Glucose, L-sorbose, or glycerol failed to modify oxygen consumption. Only incubation in the presence of fructose showed a high aerobic glycolysis measured by lactate production.

Altered aortic and cremaster muscle prostaglandin synthesis in diabetic rats

International Nuclear Information System (INIS)

Myers, T.O.; Messina, E.J.; Rodrigues, A.M.; Gerritsen, M.E.

1985-01-01

Alterations in the synthesis and release of prostaglandins have been reported in humans and animal models of diabetes mellitus. In the present study synthesis and release of prostaglandins by thoracic aorta and cremaster muscle of rats with streptozotocin-induced diabetes of 8 wk duration was compared with age-matched controls. Prostaglandin synthesis was assessed by the measurement of immunoreactive prostaglandin E2 (PGE2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) release and by quantifying metabolism of exogenous [1- 14 C]arachidonic acid by thoracic aortic rings and minced cremaster muscle. These studies indicate that diminished prostacyclin (PGI2) and/or PGE2 production is not a general feature of all diabetic vascular tissues, suggesting that large and small blood vessels may not be similarly affected by diabetes in regard to the metabolism of exogenous arachidonic acid and the synthesis and release of prostaglandins. Furthermore, the vascular changes often observed in conjunction with diabetes, i.e., alterations in vascular reactivity and microangiopathy in small blood vessels and atherosclerosis of large blood vessels may be related in some way to the segmental differences observed in prostaglandin synthesis

Ex-vivo diffusion MRI reveals microstructural alterations in stress-sensitive brain regions: A chronic mild stress recovery study

DEFF Research Database (Denmark)

Khan, Ahmad Raza; Hansen, Brian; Wiborg, Ove

Depression is a leading cause of disability worldwide and causes significant microstructural alterations in stress-sensitive brain regions. However, the potential recovery of these microstructural alterations has not previously been investigated, which we, therefore, set out to do using diffusion...... MRI (d-MRI) in the chronic mild stress (CMS) rat model of depression. This study reveals significant microstructural alterations after 8 weeks of recovery, in the opposite direction to change induced by stress in the acute phase of the experiment. Such findings may be useful in the prognosis...... of depression or for monitoring treatment response....

Radioprotection of whole-body γ-irradiation-induced alteration in some haematological parameters by cysteine, vitamin E and their combination in rats

International Nuclear Information System (INIS)

Shaheen, A.A.; Hassan, S.M.

1991-01-01

Radioprotective effect of cysteine, vitamin E and their combination on γ-irradiation-induced alteration in some haematological parameters in male rats has been studied 24 and 48 hrs after whole-body γ-irradiation at a dose level of 7.5 Gy. The results of this study reveal that γ-irradiation caused a significant decrease in red blood cells (RBCs) count with insignificant change in hemoglobin level, 24 and 48 hrs postirradiation, γ-irradiated rats showed as well a progressive decrease in their blood ATP, and serum-SH levels with a significant increase in blood glutathione (GSH) level. Administration of cysteine or vitamin E preceeding γ-radiation exposure gave a significant radioprotection to the above haematological parameters. However, combination of both agents afforded a better protection, so that most of the measured parameters were restored to the pre-irradiated values. Finally, the data demonstrate that the radioprotection provided by combined adminsistration of vitamin E and cysteine is feasible and perhaps, even more efficient against radiation injury to RBCs. This will appreciate the usage of such combination in protecting the patient during radiotherapy. (orig.) [de

Vitamin K2 improves femoral bone strength without altering bone mineral density in gastrectomized rats.

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Iwamoto, Jun; Sato, Yoshihiro; Matsumoto, Hideo

2014-01-01

Gastrectomy (GX) induces osteopenia in rats. The present study examined the skeletal effects of vitamin K2 in GX rats. Thirty male Sprague-Dawley rats (12 wk old) were randomized by the stratified weight method into the following three groups of 10 animals each: sham operation (control) group; GX group; and GX+oral vitamin K2 (menatetrenone, 30 mg/kg, 5 d/wk) group. Treatment was initiated at 1 wk after surgery. After 6 wk of treatment, the bone mineral content (BMC), bone mineral density (BMD), and mechanical strength of the femoral diaphysis and distal metaphysis were determined by peripheral quantitative computed tomography and mechanical strength tests, respectively. GX induced decreases in the BMC, BMD, and ultimate force of the femoral diaphysis and distal metaphysis. Vitamin K2 did not significantly influence the BMC or BMD of the femoral diaphysis or distal metaphysis in GX rats, but attenuated the decrease in the ultimate force and increased the stiffness of the femoral diaphysis. The present study showed that administration of vitamin K2 to GX rats improved the bone strength of the femoral diaphysis without altering the BMC or BMD, suggesting effects of vitamin K2 on the cortical bone quality.

Extremely Low Frequency (ELF) Vertical Electric Field Exposure of Rats: Irradiation Facility

Science.gov (United States)

1977-05-01

altered inside an animal cage even with wet or dry litter and full food and water containers. Rats weighing approximately 300 g in adjacent cages caused...with guard circuit Field inside empty cage Field inside complete cage ( litter (wet or dry) + food + water) Field variations caused by 300 g rat...blanket 250 Iron 60 Broiler 130 Hair dryer 40 Vaporizer 40 Refrigerator 60 Color TV 30 Stereo 90 Coffee pot 30 Vacuum cleaner 16 Clock radio

Vitamin A deficiency alters the pulmonary parenchymal elastic modulus and elastic fiber concentration in rats

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Holmes Amey J

2005-07-01

Full Text Available Abstract Background Bronchial hyperreactivity is influenced by properties of the conducting airways and the surrounding pulmonary parenchyma, which is tethered to the conducting airways. Vitamin A deficiency (VAD is associated with an increase in airway hyperreactivity in rats and a decrease in the volume density of alveoli and alveolar ducts. To better define the effects of VAD on the mechanical properties of the pulmonary parenchyma, we have studied the elastic modulus, elastic fibers and elastin gene-expression in rats with VAD, which were supplemented with retinoic acid (RA or remained unsupplemented. Methods Parenchymal mechanics were assessed before and after the administration of carbamylcholine (CCh by determining the bulk and shear moduli of lungs that that had been removed from rats which were vitamin A deficient or received a control diet. Elastin mRNA and insoluble elastin were quantified and elastic fibers were enumerated using morphometric methods. Additional morphometric studies were performed to assess airway contraction and alveolar distortion. Results VAD produced an approximately 2-fold augmentation in the CCh-mediated increase of the bulk modulus and a significant dampening of the increase in shear modulus after CCh, compared to vitamin A sufficient (VAS rats. RA-supplementation for up to 21 days did not reverse the effects of VAD on the elastic modulus. VAD was also associated with a decrease in the concentration of parenchymal elastic fibers, which was restored and was accompanied by an increase in tropoelastin mRNA after 12 days of RA-treatment. Lung elastin, which was resistant to 0.1 N NaOH at 98°, decreased in VAD and was not restored after 21 days of RA-treatment. Conclusion Alterations in parenchymal mechanics and structure contribute to bronchial hyperreactivity in VAD but they are not reversed by RA-treatment, in contrast to the VAD-related alterations in the airways.

MicroRNA changes in rat mesentery and serum associated with drug-induced vascular injury

International Nuclear Information System (INIS)

Thomas, Roberta A.; Scicchitano, Marshall S.; Mirabile, Rosanna C.; Chau, Nancy T.; Frazier, Kendall S.; Thomas, Heath C.

2012-01-01

Regulatory miRNAs play a role in vascular biology and are involved in biochemical and molecular pathways dysregulated during vascular injury. Collection and integration of functional miRNA data into these pathways can provide insight into pathogenesis at the site of injury; the same technologies applied to biofluids may provide diagnostic or surrogate biomarkers. miRNA was analyzed from mesentery and serum from rats given vasculotoxic compounds for 4 days. Fenoldopam, dopamine and midodrine each alter hemodynamics and are associated with histologic evidence of vascular injury, while yohimbine is vasoactive but does not cause histologic evidence of vascular injury in rat. There were 38 and 35 miRNAs altered in a statistically significant manner with a fold change of 2 or greater in mesenteries of fenoldopam- and dopamine-dosed rats, respectively, with 9 of these miRNAs shared. 10 miRNAs were altered in rats given midodrine; 6 were shared with either fenoldopam or dopamine. In situ hybridization demonstrated strong expression and co-localization of miR-134 in affected but not in adjacent unaffected vessels. Mesenteric miRNA expression may provide clarity or avenues of research into mechanisms involved in vascular injury once the functional role of specific miRNAs becomes better characterized. 102 miRNAs were altered in serum from rats with drug-induced vascular injury. 10 miRNAs were commonly altered in serum from dopamine and either fenoldopam or midodrine dosed rats; 18 of these 102 were also altered in mesenteries from rats with drug-induced vascular injury, suggesting their possible utility as peripheral biomarkers. -- Highlights: ► Mesentery and serum were examined from rats given vasoactive compounds for 4 days. ► 72 miRNAs were altered in mesenteries from rats with vascular injury. ► miR-134 was localized to affected but not adjacent unaffected vessels. ► 102 miRNAs were changed in serum from rats with vascular injury. ► 18 miRNAs changed in both

Exposure to a northern contaminant mixture (NCM alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats.

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Ryan J Mailloux

Full Text Available Non-alcoholic fatty liver disease (NAFLD, defined by the American Liver Society as the buildup of extra fat in liver cells that is not caused by alcohol, is the most common liver disease in North America. Obesity and type 2 diabetes are viewed as the major causes of NAFLD. Environmental contaminants have also been implicated in the development of NAFLD. Northern populations are exposed to a myriad of persistent organic pollutants including polychlorinated biphenyls, organochlorine pesticides, flame retardants, and toxic metals, while also affected by higher rates of obesity and alcohol abuse compared to the rest of Canada. In this study, we examined the impact of a mixture of 22 contaminants detected in Inuit blood on the development and progression of NAFLD in obese JCR rats with or without co-exposure to 10% ethanol. Hepatosteatosis was found in obese rat liver, which was worsened by exposure to 10% ethanol. NCM treatment increased the number of macrovesicular lipid droplets, total lipid contents, portion of mono- and polyunsaturated fatty acids in the liver. This was complemented by an increase in hepatic total cholesterol and cholesterol ester levels which was associated with changes in the expression of genes and proteins involved in lipid metabolism and transport. In addition, NCM treatment increased cytochrome P450 2E1 protein expression and decreased ubiquinone pool, and mitochondrial ATP synthase subunit ATP5A and Complex IV activity. Despite the changes in mitochondrial physiology, hepatic ATP levels were maintained high in NCM-treated versus control rats. This was due to a decrease in ATP utilization and an increase in creatine kinase activity. Collectively, our results suggest that NCM treatment decreases hepatic cholesterol export, possibly also increases cholesterol uptake from circulation, and promotes lipid accumulation and alters ATP homeostasis which exacerbates the existing hepatic steatosis in genetically obese JCR rats with

Aerobic interval exercise improves parameters of nonalcoholic fatty liver disease (NAFLD) and other alterations of metabolic syndrome in obese Zucker rats.

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Kapravelou, Garyfallia; Martínez, Rosario; Andrade, Ana M; Nebot, Elena; Camiletti-Moirón, Daniel; Aparicio, Virginia A; Lopez-Jurado, Maria; Aranda, Pilar; Arrebola, Francisco; Fernandez-Segura, Eduardo; Bermano, Giovanna; Goua, Marie; Galisteo, Milagros; Porres, Jesus M

2015-12-01

Metabolic syndrome (MS) is a group of metabolic alterations that increase the susceptibility to cardiovascular disease and type 2 diabetes. Nonalcoholic fatty liver disease has been described as the liver manifestation of MS. We aimed to test the beneficial effects of an aerobic interval training (AIT) protocol on different biochemical, microscopic, and functional liver alterations related to the MS in the experimental model of obese Zucker rat. Two groups of lean and obese animals (6 weeks old) followed a protocol of AIT (4 min at 65%-80% of maximal oxygen uptake, followed by 3 min at 50%-65% of maximal oxygen uptake for 45-60 min, 5 days/week, 8 weeks of experimental period), whereas 2 control groups remained sedentary. Obese rats had higher food intake and body weight (P metabolism and increased the liver protein expression of PPARγ, as well as the gene expression of glutathione peroxidase 4 (P < 0.001). The training protocol also showed significant effects on the activity of hepatic antioxidant enzymes, although this action was greatly influenced by rat phenotype. The present data suggest that AIT protocol is a feasible strategy to improve some of the plasma and liver alterations featured by the MS.

The Alterations in the Expression and Function of P-Glycoprotein in Vitamin A-Deficient Rats as well as the Effect of Drug Disposition in Vivo

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Yubang Wang

2015-12-01

Full Text Available This study was aimed to investigate whether vitamin A deficiency could alter P-GP expression and function in tissues of rats and whether such effects affected the drug distribution in vivo of vitamin A-deficient rats. We induced vitamin A-deficient rats by giving them a vitamin A-free diet for 12 weeks. Then, Abcb1/P-GP expression was evaluated by qRT-PCR and Western blot. qRT-PCR analysis revealed that Abcb1a mRNA levels were increased in hippocampus and liver. In kidney, it only showed an upward trend. Abcb1b mRNA levels were increased in hippocampus, but decreased in cerebral cortex, liver and kidney. Western blot results were in good accordance with the alterations of Abcb1b mRNA levels. P-GP function was investigated through tissue distribution and body fluid excretion of rhodamine 123 (Rho123, and the results proclaimed that P-GP activities were also in good accordance with P-GP expression in cerebral cortex, liver and kidney. The change of drug distribution was also investigated through the tissue distribution of vincristine, and the results showed a significantly upward trend in all indicated tissues of vitamin A-deficient rats. In conclusion, vitamin A deficiency may alter Abcb1/P-GP expression and function in rat tissues, and the alterations may increase drug activity/toxicity through the increase of tissue accumulation.

Consequences of age on ischemic wound healing in rats: altered antioxidant activity and delayed wound closure.

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Moor, Andrea N; Tummel, Evan; Prather, Jamie L; Jung, Michelle; Lopez, Jonathan J; Connors, Sarah; Gould, Lisa J

2014-04-01

Advertisements targeted at the elderly population suggest that antioxidant therapy will reduce free radicals and promote wound healing, yet few scientific studies substantiate these claims. To better understand the potential utility of supplemental antioxidant therapy for wound healing, we tested the hypothesis that age and tissue ischemia alter the balance of endogenous antioxidant enzymes. Using a bipedicled skin flap model, ischemic and non-ischemic wounds were created on young and aged rats. Wound closure and the balance of the critical antioxidants superoxide dismutase and glutathione in the wound bed were determined. Ischemia delayed wound closure significantly more in aged rats. Lower superoxide dismutase 2 and glutathione in non-ischemic wounds of aged rats indicate a basal deficit due to age alone. Ischemic wounds from aged rats had lower superoxide dismutase 2 protein and activity initially, coupled with decreased ratios of reduced/oxidized glutathione and lower glutathione peroxidase activity. De novo glutathione synthesis, to restore redox balance in aged ischemic wounds, was initiated as evidenced by increased glutamate cysteine ligase. Results demonstrate deficiencies in two antioxidant pathways in aged rats that become exaggerated in ischemic tissue, culminating in profoundly impaired wound healing and prolonged inflammation.

Altitude training induced alterations in erythrocyte rheological properties: a controlled comparison study in rats.

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Bor-Kucukatay, Melek; Colak, Ridvan; Erken, Gülten; Kilic-Toprak, Emine; Kucukatay, Vural

2014-01-01

Altitude training is frequently used by athletes to improve sea-level performance. However, the objective benefits of altitude training are controversial. This study aimed to investigate the possible alterations in hemorheological parameters in response to altitude training. Sprague Dawley rats, were divided into 6 groups: live low-train low (LLTL), live high-train high (LHTH), live high-train low (LHTL) and their controls live high and low (LHALC), live high (LHC), live low (LLC). LHC and LHTH groups were exposed to hypoxia (15% O2, altitudes of 3000 m), 4 weeks. LHALC and LHTL were exposed to 12 hours hypoxia/normoxia per day, 4 weeks. Hypoxia was maintained by a hypoxic tent. The training protocol corresponded to 60-70% of maximal exercise capacity. Rats of training groups ran on treadmill for 20-30 min/day, 4 days/week, 4 weeks. Erythrocyte deformability of LHC group was increased compared to LHALC and LLC. Deformability of LHTH group was higher than LHALC and LLTL groups. No statistically significant alteration in erythrocyte aggregation parameters was observed. There were no significant relationships between RBC deformability and exercise performance. The results of this study show that, living (LHC) and training at altitude (LHTH) seems more advantageous in hemorheological point of view.

Fluoride Alteration of [3H]Glucose Uptake in Wistar Rat Brain and Peripheral Tissues.

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Rogalska, Anna; Kuter, Katarzyna; Żelazko, Aleksandra; Głogowska-Gruszka, Anna; Świętochowska, Elżbieta; Nowak, Przemysław

2017-04-01

The present study was designed to investigate the role of postnatal fluoride intake on [3H]glucose uptake and transport in rat brain and peripheral tissues. Sodium fluoride (NaF) in a concentration of 10 or 50 ppm was added to the drinking water of adult Wistar rats. The control group received distilled water. After 4 weeks, respective plasma fluoride levels were 0.0541 ± 0.0135 μg/ml (control), 0.0596 ± 0.0202 μg/ml (10 ppm), and 0.0823 ± 0.0199 μg/ml (50 ppm). Although plasma glucose levels were not altered in any group, the plasma insulin level in the fluoride (50 ppm) group was elevated (0.72 ± 0.13 μg/ml) versus the control group (0.48 ± 0.24 μg/ml) and fluoride (10 ppm) group. In rats receiving fluoride for 4 weeks at 10 ppm in drinking water, [3H]glucose uptake was unaltered in all tested parts of the brain. However, in rats receiving fluoride at 50 ppm, [3H]glucose uptake in cerebral cortex, hippocampus, and thalamus with hypothalamus was elevated, versus the saline group. Fluoride intake had a negligible effect on [3H]glucose uptake by peripheral tissues (liver, pancreas, stomach, small intestine, atrium, aorta, kidney, visceral tissue, lung, skin, oral mucosa, tongue, salivary gland, incisor, molars, and jawbone). In neither fluoride group was glucose transporter proteins 1 (GLUT 1) or 3 (GLUT 3) altered in frontal cortex and striatum versus control. On the assumption that increased glucose uptake (by neural tissue) reasonably reflects neuronal activity, it appears that fluoride damage to the brain results in a compensatory increase in glucose uptake and utilization without changes in GLUT 1 and GLUT 3 expression.

Effect of ionizing radiation on rat parotid gland

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Boraks, George; Tampelini, Flavio Silva; Pereira, Kleber Fernando; Chopard, Renato Paulo [University of Sao Paulo (USP), SP (Brazil). Inst. of Biomedical Sciences. Dept. of Anatomy]. E-mail: rchopard@usp.br

2008-01-15

A common side effect of radiotherapy used in the treatment of oral cancer is the occurrence of structural and physiological alterations of the salivary glands due to exposure to ionizing radiation, as demonstrated by conditions such as decreased salivary flow. The present study evaluated ultrastructural alterations in the parotid glands of rats receiving a fractionated dose (1,500-cGy) of radiation emitted by a Cesium-137 source and rats that were not subjected to ionizing radiation. After sacrifice, the parotid glands were removed and examined by transmission electron microscopy. Damage such as cytoplasmic vacuolisation, dilatation of the endoplasmic reticulum and destruction of mitochondria, as well as damage to the cellular membrane of acinar cells, were observed. These findings lead to the conclusion that ionizing radiation promotes alterations in the glandular parenchyma, and that these alterations are directly related to the dose level of absorbed radiation. Certain phenomena that appear in the cytoplasm and nuclear material indicate that ionizing radiation causes acinar cell death (apoptosis). (author)

Alterations in cardiomyocyte function after pulmonary treatment with stainless steel welding fume in rats.

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Popstojanov, Risto; Antonini, James M; Salmen, Rebecca; Ye, Morgan; Zheng, Wen; Castranova, Vincent; Fekedulegn, Desta B; Kan, Hong

2014-01-01

Welding fume is composed of a complex of different metal particulates. Pulmonary exposure to different welding fumes may exert a negative impact on cardiac function, although the underlying mechanisms remain unclear. To explore the effect of welding fumes on cardiac function, Sprague-Dawley rats were exposed by intratracheal instillation to 2 mg/rat of manual metal arc hard surfacing welding fume (MMA-HS) once per week for 7 wk. Control rats received saline. Cardiomyocytes were isolated enzymatically at d 1 and 7 postexposure. Intracellular calcium ([Ca(2+)]i) transients (fluorescence ratio) were measured on the stage of an inverted phase-contrast microscope using a myocyte calcium imaging/cell length system. Phosphorylation levels of cardiac troponin I (cTnI) were determined by Western blot. The levels of nonspecific inflammatory marker C-reactive protein (CRP) and proinflammatory cytokine interleukin-6 (IL-6) in serum were measured by enzyme-linked immunosorbent assay (ELISA). Contraction of isolated cardiomyocytes was significantly reduced at d 1 and d 7 postexposure. Intracellular calcium levels were decreased in response to extracellular calcium stimulation at d 7 postexposure. Changes of intracellular calcium levels after isoprenaline hydrochloride (ISO) stimulation were not markedly different between groups at either time point. Phosphorylation levels of cTnI in the left ventricle were significantly lower at d 1 postexposure. The serum levels of CRP were not markedly different between groups at either time point. Serum levels of IL-6 were not detectable in both groups. Cardiomyocyte alterations observed after welding fume treatment were mainly due to alterations in intracellular calcium handling and phosphorylation levels of cTnI.

Ascorbic acid ameliorates behavioural deficits and neuropathological alterations in rat model of Alzheimer's disease.

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Olajide, Olayemi Joseph; Yawson, Emmanuel Olusola; Gbadamosi, Ismail Temitayo; Arogundade, Tolulope Timothy; Lambe, Ezra; Obasi, Kosisochukwu; Lawal, Ismail Tayo; Ibrahim, Abdulmumin; Ogunrinola, Kehinde Yomi

2017-03-01

Exploring the links between neural pathobiology and behavioural deficits in Alzheimer's disease (AD), and investigating substances with known therapeutic advantages over subcellular mechanisms underlying these dysfunctions could advance the development of potent therapeutic molecules for AD treatment. Here we investigated the efficacy of ascorbic acid (AA) in reversing aluminium chloride (AlCl 3 )-induced behavioural deficits and neurotoxic cascades within prefrontal cortex (PFC) and hippocampus of rats. A group of rats administered oral AlCl 3 (100mg/kg) daily for 15days showed degenerative changes characterised by significant weight loss, reduced exploratory/working memory, frontal-dependent motor deficits, cognitive decline, memory dysfunction and anxiety during behavioural assessments compared to control. Subsequent analysis showed that oxidative impairment-indicated by depleted superoxide dismutase and lipid peroxidation (related to glutathione-S-transferase activity), cholinergic deficits seen by increased neural acetylcholinesterase (AChE) expression and elevated lactate dehydrogenase underlie behavioural alterations. Furthermore, evidences of proteolysis were seen by reduced Nissl profiles in neuronal axons and dendrites which correspond to apoptotic changes observed in H&E staining of PFC and hippocampal sections. Interestingly, AA (100mg/kg daily for 15days) significantly attenuated behavioural deficits in rats through inhibition of molecular and cellular stressor proteins activated by AlCl 3. Our results showed that the primary mechanisms underlying AA therapeutic advantages relates closely with its abilities to scavenge free radicals, prevent membrane lipid peroxidation, modulate neuronal bioenergetics, act as AChE inhibitor and through its anti-proteolytic properties. These findings suggest that supplementing endogenous AA capacity through its pharmacological intake may inhibit progression of AD-related neurodegenerative processes and behavioural

Changes in radiosensitivity of male sex hormones in rats maintained on kelthane contaminated feed

International Nuclear Information System (INIS)

Abughadeer, A.R.M.

1995-01-01

Alteration of sex hormones levels in male rats after whole body gamma irradiation (6.5 Gy) has been studied. The hormonal response of irradiated rats fed on experimental feed contaminated with organo chlorine insecticide 'kelthane' (200 mg/kg body weight) for different time intervals (3,6 and 12 weeks), has been also investigated. Investigations included measurements of testes/body weight ratio; Testosterone; Follicle Stimulating Hormone (FSH); luteinizing hormone (LH) and prolactin levels in serum and testes homogenate of treated rats. The data indicate that whole body gamma irradiation causes significant alteration in all tested parameters except for the testosterone level. Normal rats fed on 'kelthane' contaminated feed, showed significant alteration in all tested parameters, which increased with the prolongation of 'kelthane' exposure period. Double treatment of 'kelthane' and irradiation resulted in more pronounced alterations. It can be concluded that the male sex hormones in rats fed on 'kelthane', were more sensitive to whole body gamma irradiation. Moreover, male sex hormones have shown reliable reliable dose/effect relationship for either radiation or pesticide internal contamination. This suggests their possible use as markers in early diagnosis of radiation exposure and pesticides toxication syndromes. 3 tabs

Altered carbohydrate, lipid, and xenobiotic metabolism by liver from rats flown on Cosmos 1887

Science.gov (United States)

Merrill, A. H. Jr; Hoel, M.; Wang, E.; Mullins, R. E.; Hargrove, J. L.; Jones, D. P.; Popova, I. A.; Merrill AH, J. r. (Principal Investigator)

1990-01-01

To determine the possible biochemical effects of prolonged weightlessness on liver function, samples of liver from rats that had flown aboard Cosmos 1887 were analyzed for protein, glycogen, and lipids as well as the activities of a number of key enzymes involved in metabolism of these compounds and xenobiotics. Among the parameters measured, the major differences were elevations in the glycogen content and hydroxymethylglutaryl-CoA (HMG-CoA) reductase activities for the rats flown on Cosmos 1887 and decreases in the amount of microsomal cytochrome P-450 and the activities of aniline hydroxylase and ethylmorphine N-demethylase, cytochrome P-450-dependent enzymes. These results support the earlier finding of differences in these parameters and suggest that altered hepatic function could be important during spaceflight and/or the postflight recovery period.

Multidimensional study of orofacial chronic neuropathic pain: An experimental study in rats.

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Claudia Daniela Montes-Angeles

2017-10-01

Full Text Available Orofacial neuropathic chronic pain (NCP is frequently attributed to lesions caused by orofacial surgeries and dental treatments. There are many experimental models available to study orofacial NCP, however, many are extremely painful for the animal due to the amplitude of the innervated region. A previously proposed mental nerve constriction model, mNC, was used in this project. Forty Wistar rats were randomly divided into two groups: one group included rats with mNC (n=20, and another rats with sham lesions (n=20. Through the use of the fixed ratio program and the progressive program, a decrease of motivation for a sweet substance, caused by the lesion, was evaluated. The possibility of alterations in cognitive learning and adaptation abilities was also assessed using the go/no-go behavioral task. The mNC group showed low induced and spontaneously evoked pain responses, as well as a decrease in the motivation for sucrose, a sign of anhedonia. This decrease does not depend on taste processing. Finally, although no alterations in the learning-memory process were observed, the mNC group did show alterations when adapting to a new rule.

Dietary supplementation of tiger nut alters biochemical parameters relevant to erectile function in l-NAME treated rats.

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Olabiyi, Ayodeji A; Carvalho, Fabiano B; Bottari, Nathieli B; Lopes, Thauan F; da Costa, Pauline; Stefanelo, Naiara; Morsch, Vera M; Akindahunsi, Afolabi A; Oboh, Ganiyu; Schetinger, Maria Rosa

2018-07-01

Tiger nut tubers have been reportedly used for the treatment of erectile dysfunction (ED) in folk medicine without scientific basis. Hence, this study evaluated the effect of tiger nut on erectile dysfunction by assessing biochemical parameters relevant to ED in male rats by nitric oxide synthase (NOS) inhibitor, Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME) treatment. Rats were divided into five groups (n = 10) each: Control group; l-NAME plus basal diet; l-NAME plus Sildenafil citrate; diet supplemented processed tiger nut (20%) plus l-NAME;diet supplemented raw tiger nut (20%) plus l-NAME. l-NAME pre-treatment (40 mg/kg/day) lasted for 14 days. Arginase, acetycholinesterase (AChE) and adenosine deaminase (ADA) activities as well as nitric oxide levels (NO) in serum, brain and penile tissue were measured. l-NAME increased the activity of arginase, AChE and ADA and reduced NO levels. However, dietary supplementation with tiger nut caused a reduction on the activities of the above enzymes and up regulated nitric oxide levels when compared to the control group. The effect of tiger nut supplemented diet may be said to prevent alterations of the activities of the enzymes relevant in erectile function. Quercetin was revealed to be the most active component of tiger nut tuber by HPLC finger printing. Copyright © 2018. Published by Elsevier Ltd.

Sub-acute deltamethrin and fluoride toxicity induced hepatic oxidative stress and biochemical alterations in rats.

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Dubey, Nitin; Khan, Adil Mehraj; Raina, Rajinder

2013-09-01

The current study investigated the effects of deltamethrin, fluoride (F(-)) and their combination on the hepatic oxidative stress and consequent alterations in blood biochemical markers of hepatic damage in rats. Significant hepatic oxidative stress and hepatic damage were observed in the toxicant exposed groups. These changes were higher in the deltamethrin-F(-) co-exposure treatment group, depicting a positive interaction between the two chemicals.

Effect of Euterpe oleracea Mart. (Açaí) Oil on Dyslipidemia Caused by Cocos nucifera L. Saturated Fat in Wistar Rats.

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Faria E Souza, Belmira S; Carvalho, Helison O; Taglialegna, Talisson; Barros, Albenise Santana A; da Cunha, Edilson Leal; Ferreira, Irlon Maciel; Keita, Hady; Navarrete, Andres; Carvalho, José Carlos Tavares

2017-09-01

Dyslipidemia is caused by disturbances in lipid metabolism that lead to chronic elevations of serum lipids, especially low-density lipoprotein (LDL)-cholesterol and triglycerides, increasing the risk of metabolic syndrome, obesity, diabetes, atherogenic processes, and cardiovascular diseases. The oil from the fruits of Euterpe oleracea (OFEO) is rich in unsaturated fatty acids with potential for treating alterations in lipid metabolism. In this study, we aimed to investigate the effect of OFEO on hyperlipidemia induced by Cocos nucifera L. saturated fat (GSC) in Wistar rats. Chromatographic profile showed that unsaturated fatty acids account for 66.08% in OFEO, predominately oleic acid (54.30%), and saturated fatty acids (palmitic acid 31.6%) account for 33.92%. GSC-induced dyslipidemia resulted in an increase in total cholesterol, LDL-cholesterol, triglycerides, glucose, and liver and abdominal fat, as well as atherogenic processes in the thoracic aorta. OFEO treatment did not reduce hypertriglyceridemia, but did reduce total cholesterol and LDL-cholesterol, thus contributing to the antiatherogenic action of OFEO. OFEO treatment inhibited the formation of atheromatous plaques in the vascular endothelium of the treated rats, as well as those who were treated with simvastatin. The results obtained suggest that OFEO has an antiatherogenic effect in a rat model of dyslipidemia.

The Alteration of Emotion Regulation Precedes the Deficits in Interval Timing in the BACHD Rat Model for Huntington Disease

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Daniel Garces

2018-05-01

Full Text Available Huntington disease (HD is an autosomal dominantly inherited, progressive neurodegenerative disorder which is accompanied by executive dysfunctions and emotional alteration. The aim of the present study was to assess the impact of emotion/stress on on-going highly demanding cognitive tasks, i.e., temporal processing, as a function of age in BACHD rats (a “full length” model of HD. Middle-aged (4–6 months and old (10–12 months rats were first trained on a 2 vs. 8-s temporal discrimination task, and then exposed to a series of bisection tests under normal and stressful (10 mild unpredictable foot-shocks conditions. The animals were then trained on a peak interval task, in which reinforced fixed-interval (FI 30-s trials were randomly intermixed with non-reinforced probe trials. After training, the effect of stress upon time perception was again assessed. Sensitivity to foot-shocks was also assessed independently. The results show effects of both age and genotype, with largely greater effects in old BACHD animals. The older BACHD animals had impaired learning in both tasks, but reached equivalent levels of performance as WT animals at the end of training in the temporal discrimination task, while remaining impaired in the peak interval task. Whereas sensitivity to foot-shock did not differ between BACHD and WT rats, delivery of foot-shocks during the test sessions had a disruptive impact on temporal behavior in WT animals, an effect which increased with age. In contrast, BACHD rats, independent of age, did not show any significant disruption under stress. In conclusion, BACHD rats showed a disruption in temporal learning in late symptomatic animals. Age-related modification in stress-induced impairment of temporal control of behavior was also observed, an effect which was greatly reduced in BACHD animals, thus confirming previous results suggesting reduced emotional reactivity in HD animals. The results suggest a staggered onset in cognitive

Adrenergic mechanism responsible for pathological alteration in gastric mucosal blood flow in rats with ulcer bleeding

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Semyachkina-Glushkovskaya, O. V.; Pavlov, A. N.; Semyachkin-Glushkovskiy, I. A.; Gekalyuk, A. S.; Ulanova, M. V.; Lychagov, V. V.; Tuchin, V. V.

2014-09-01

The adrenergic system plays an important role in regulation of central and peripheral circulation in normal state and during hemorrhage. Because the impaired gastric mucosal blood flow (GMBF) is the major cause of gastroduodenal lesions, including ulcer bleeding (UB), we studied the adrenergic mechanism responsible for regulation of GMBF in rats with a model of stress-induced UB (SUB) using the laser Doppler flowmetry (LDF). First, we examined the effect of adrenaline on GMBF in rats under normal state and during UB. In all healthy animals the submucosal adrenaline injection caused a decrease in local GMBF. During UB the submucosal injection of adrenaline was accompanied by less pronounced GMBF suppression in 30,3% rats with SUB vs. healthy ones. In 69,7% rats with SUB we observed the increase in local GMBF after submucosal injection of adrenaline. Second, we studied the sensitivity of gastric β2-adrenoreceptors and the activity of two factors which are involved in β2-adrenomediated vasorelaxation-KATP -channels and NO. The effects of submucosal injection of isoproterenol, ICI118551 and glybenclamide on GMBF as well as NO levels in gastric tissue were significantly elevated in rats with SUB vs. healthy rats. Thus, our results indicate that high activation of gastric β2-adrenoreceptors associated with the increased vascular KATP -channels activity and elevated NO production is the important adrenergic mechanism implicated in the pathogenesis of UB.

Alterations in brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in the brain regions of a learned helplessness rat model and the antidepressant effects of a TrkB agonist and antagonist.

Science.gov (United States)

Shirayama, Yukihiko; Yang, Chun; Zhang, Ji-chun; Ren, Qian; Yao, Wei; Hashimoto, Kenji

2015-12-01

Role of brain-derived neurotrophic factor (BDNF)-TrkB signaling in a learned helplessness (LH) model of depression was investigated. LH rats showed a reduction of BDNF in the medial prefrontal cortex (mPFC), CA3, and dentate gyrus (DG) of the hippocampus, whereas LH rats showed an increase in BDNF in the nucleus accumbens (NAc). Furthermore, levels of proBDNF, a BDNF precursor, were higher in the mPFC, but lower in the NAc, of LH rats. A single bilateral infusion of a TrkB agonist 7,8-DHF, but not a TrkB antagonist ANA-12, into the infralimbic (IL) of mPFC, DG, and CA3, but not the prelimbic (PrL) of mPFC, exerted antidepressant effects in LH rats. In contrast, a single bilateral infusion of ANA-12, but not 7,8-DHF, into the core and shell of NAc exerted antidepressant-like effects in LH rats, with more potent effects observed for the NAc core than for NAc shell. Interestingly, a single administration of 7,8-DHF (10mg/kg, i.p.) significantly improved a decreased phosphorylation of TrkB in the mPFC, CA3, and DG of LH rats. Additionally, ANA-12 (0.5mg/kg, i.p.) significantly improved an increased phosphorylation of TrkB in the NAc of LH rats. In conclusion, these results suggest that LH causes depression-like behavior by altering BDNF in the brain regions, and that proBDNF-BDNF processing and transport may be altered in the mPFC-NAc circuit of LH rats. Therefore, TrkB agonists might exert antidepressant effects by stimulating TrkB in the IL, CA3, and DG, while TrkB antagonists might exert antidepressant effects by blocking TrkB in the NAc. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Radish juice and corn oil as adjuvants that decrease the destructive alterations in hypoglycemia rats subjected to gamma irradiation

International Nuclear Information System (INIS)

Hanafy, N.

2007-01-01

This study was performed to investigate the decrease in different biochemical and histopathological alterations that may occur following the oral administration of aqueous extract of radish at the dose level (50 mg/100 g body weight) and the addition of 10% corn oil to the diet of hypoglycemia rats and /or exposed to 6 Gy of gamma radiation. The experiment included normal male albino rats and hypoglycemia ones.The hypoglycemia rats divided into tow groups; the first group was treated with radish juice or radish juice with diet containing corn oil and the other group was hypoglycemia rats exposed to 6 Gy of gamma radiation then treated also with radish juice or radish juice with diet containing 10% corn oil. Biochemical analysis included levels of blood sugar, total lipids, cholesterol, total protein and albumin, in addition to the activity of AST and ALT were evaluated. The level of TBARs and the histopathological changes in liver and kidney were also investigated. Treatment of irradiated hypoglycemia rats with radish juice either alone or combined with a diet containing 10% corn oil reverse the serum fasting glucose level nearly to the control level. Amelioration in lipid profile was recorded after the treatment of the hypoglycemia rats or those hypoglycemia irradiated then treated with radish juice and fed on a diet containing 10% corn oil. Also, significant amelioration was occurred in liver transaminases, total proteins, albumin and creatinine levels as compared to those of hypoglycemia group. TBARs levels showed remarkable decrease in liver and kidney tissues in comparison with control and hypoglycemia rats and/or gamma irradiated levels when it is treated with radish juice and diet containing corn oil. Also, the histopathological changes of the same tissues revealed the same trend. From the different observations , it is possible to conclude that treatment of rats with radish juice in addition to feeding on diet containing 10% corn oil could reduce the

Effects of X irradiation on the cytoskeleton of rat alveolar macrophages in vitro

International Nuclear Information System (INIS)

Ladyman, S.J.; Townsend, K.M.S.; Edwards, C.

1984-01-01

The three-dimensional visualization of Triton X-100 resistant cytoskeletons has been used to demonstrate that an absorbed dose of 120 Gy from X rays causes a distinctive and reproducible alteration of the cytoskeleton of intact rat alveolar macrophages in vitro. The alteration has also been shown to be rapidly and completely ''repaired'' and to be apparently similar to alterations caused by colchicine but dissimilar to those caused by cytochalasin B. From these observations and those of other workers who have studied the irradiation of extracted microtubular proteins in vitro, the authors think it likely that microtubules rather than microfilaments are the radiosensitive component of the macrophage cytoskeleton

Dietary Broccoli Alters Rat Cecal Microbiota to Improve Glucoraphanin Hydrolysis to Bioactive Isothiocyanates

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Xiaoji Liu

2017-03-01

Full Text Available Broccoli consumption brings many health benefits, including reducing the risk of cancer and inflammatory diseases. The objectives of this study were to identify global alterations in the cecal microbiota composition using 16S rRNA sequencing analysis and glucoraphanin (GRP hydrolysis to isothiocyanates ex vivo by the cecal microbiota, following different broccoli diets. Rats were randomized to consume AIN93G (control or different broccoli diets; AIN93G plus cooked broccoli, a GRP-rich powder, raw broccoli, or myrosinase-treated cooked broccoli. Feeding raw or cooked broccoli for four days or longer both changed the cecal microbiota composition and caused a greater production of isothiocyanates ex vivo. A more than two-fold increase in NAD(PH: quinone oxidoreductase 1 activity of the host colon mucosa after feeding cooked broccoli for seven days confirmed the positive health benefits. Further studies revealed that dietary GRP was specifically responsible for the increased microbial GRP hydrolysis ex vivo, whereas changes in the cecal microbial communities were attributed to other broccoli components. Interestingly, a three-day withdrawal from a raw broccoli diet reversed the increased microbial GRP hydrolysis ex vivo. Findings suggest that enhanced conversion of GRP to bioactive isothiocyanates by the cecal microbiota requires four or more days of broccoli consumption and is reversible.

Dietary Broccoli Alters Rat Cecal Microbiota to Improve Glucoraphanin Hydrolysis to Bioactive Isothiocyanates.

Science.gov (United States)

Liu, Xiaoji; Wang, Yanling; Hoeflinger, Jennifer L; Neme, Bárbara P; Jeffery, Elizabeth H; Miller, Michael J

2017-03-10

Broccoli consumption brings many health benefits, including reducing the risk of cancer and inflammatory diseases. The objectives of this study were to identify global alterations in the cecal microbiota composition using 16S rRNA sequencing analysis and glucoraphanin (GRP) hydrolysis to isothiocyanates ex vivo by the cecal microbiota, following different broccoli diets. Rats were randomized to consume AIN93G (control) or different broccoli diets; AIN93G plus cooked broccoli, a GRP-rich powder, raw broccoli, or myrosinase-treated cooked broccoli. Feeding raw or cooked broccoli for four days or longer both changed the cecal microbiota composition and caused a greater production of isothiocyanates ex vivo. A more than two-fold increase in NAD(P)H: quinone oxidoreductase 1 activity of the host colon mucosa after feeding cooked broccoli for seven days confirmed the positive health benefits. Further studies revealed that dietary GRP was specifically responsible for the increased microbial GRP hydrolysis ex vivo, whereas changes in the cecal microbial communities were attributed to other broccoli components. Interestingly, a three-day withdrawal from a raw broccoli diet reversed the increased microbial GRP hydrolysis ex vivo. Findings suggest that enhanced conversion of GRP to bioactive isothiocyanates by the cecal microbiota requires four or more days of broccoli consumption and is reversible.

Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire

DEFF Research Database (Denmark)

Ostrov, David A; Grant, Barry J; Pompeu, Yuri A

2012-01-01

cells, thus causing the equivalent of an alloreactive T-cell response. Indeed, we identified specific self-peptides that are presented only in the presence of abacavir and that were recognized by T cells of hypersensitive patients. The assays that we have established can be applied to test additional...... unclear. Here we show that abacavir can bind within the F pocket of the peptide-binding groove of HLA-B*57:01, thereby altering its specificity. This provides an explanation for HLA-linked idiosyncratic adverse drug reactions, namely that drugs can alter the repertoire of self-peptides presented to T...

Acid reflux directly causes sleep disturbances in rat with chronic esophagitis.

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Nakahara, Kenichi; Fujiwara, Yasuhiro; Tsukahara, Takuya; Yamagami, Hirokazu; Tanigawa, Tetsuya; Shiba, Masatsugu; Tominaga, Kazunari; Watanabe, Toshio; Urade, Yoshihiro; Arakawa, Tetsuo

2014-01-01

Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Proton pump inhibitor (PPI) therapy improves subjective but not objective sleep parameters in patients with GERD. This study aimed to investigate the association between GERD and sleep, and the effect of PPI on sleep by using a rat model of chronic acid reflux esophagitis. Acid reflux esophagitis was induced by ligating the transitional region between the forestomach and the glandular portion and then wrapping the duodenum near the pylorus. Rats underwent surgery for implantation of electrodes for electroencephalogram and electromyogram recordings, and they were transferred to a soundproof recording chamber. Polygraphic recordings were scored by using 10-s epochs for wake, rapid eye movement sleep, and non-rapid eye movement (NREM) sleep. To examine the role of acid reflux, rats were subcutaneously administered a PPI, omeprazole, at a dose of 20 mg/kg once daily. Rats with reflux esophagitis presented with several erosions, ulcers, and mucosal thickening with basal hyperplasia and marked inflammatory infiltration. The reflux esophagitis group showed a 34.0% increase in wake (232.2±11.4 min and 173.3±7.4 min in the reflux esophagitis and control groups, respectively; preflux esophagitis, and this effect was not observed when the PPI was withdrawn. Acid reflux directly causes sleep disturbances in rats with chronic esophagitis.

The Colonic Microbiome and Epithelial Transcriptome Are Altered in Rats Fed a High-Protein Diet Compared with a Normal-Protein Diet.

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Mu, Chunlong; Yang, Yuxiang; Luo, Zhen; Guan, Leluo; Zhu, Weiyun

2016-03-01

A high-protein diet (HPD) can produce hazardous compounds and reduce butyrate-producing bacteria in feces, which may be detrimental to gut health. However, information on whether HPD affects intestinal function is limited. The aim of this study was to determine the impact of an HPD on the microbiota, microbial metabolites, and epithelial transcriptome in the colons of rats. Adult male Wistar rats were fed either a normal-protein diet (20% protein, 56% carbohydrate) or an HPD (45% protein, 30% carbohydrate) for 6 wk (n = 10 rats per group, individually fed). After 6 wk, the colonic microbiome, microbial metabolites, and epithelial transcriptome were determined. Compared with the normal-protein diet, the HPD adversely altered the colonic microbiota by increasing (P 0.7, P < 0.05) with genes and metabolites generally regarded as being involved in disease pathogenesis, suggesting these bacteria may mediate the detrimental effects of HPDs on colonic health. Our findings suggest that the HPD altered the colonic microbial community, shifted the metabolic profile, and affected the host response in the colons of rats toward an increased risk of colonic disease. © 2016 American Society for Nutrition.

Skin changes in streptozotocin-induced diabetic rats.

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Andrade, Thiago Antônio Moretti; Masson-Meyers, Daniela Santos; Caetano, Guilherme Ferreira; Terra, Vânia Aparecida; Ovidio, Paula Payão; Jordão-Júnior, Alceu Afonso; Frade, Marco Andrey Cipriani

2017-09-02

Diabetes can cause serious health complications, which can affect every organ of the body, including the skin. The molecular etiology has not yet been clarified for all diabetic skin conditions. Thus, this study aimed to investigate the changes of diabetes in skin compared to non-diabetic skin in rats. Fifteen days after establishing the diabetic status, skin samples from the dorsum-cervical region were harvested for subsequent analysis of alterations caused by diabetes. Our results demonstrate that diabetes stimulated higher inflammation and oxidative stress in skin, but antioxidant defense levels were lower compared to the non-diabetic group (p skin changes compared to non-diabetic skin in rats. Copyright © 2017 Elsevier Inc. All rights reserved.

Diabetes induces metabolic alterations in dental pulp.

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Leite, Mariana Ferreira; Ganzerla, Emily; Marques, Márcia Martins; Nicolau, José

2008-10-01

Diabetes can interfere in tissue nutrition and can impair dental pulp metabolism. This disease causes oxidative stress in cells and tissues. However, little is known about the antioxidant system in the dental pulp of diabetics. Thus, it would be of importance to study this system in this tissue in order to verify possible alterations indicative of oxidative stress. The aim of this study was to evaluate some parameters of antioxidant system of the dental pulp of healthy (n = 8) and diabetic rats (n = 8). Diabetes was induced by streptozotocin in rats. Six weeks after diabetes induction, a pool of the dental pulp of the 4 incisors of each rat (healthy and diabetic) was used for the determination of total protein and sialic acid concentrations and catalase and peroxidase activities. Data were compared by a Student t test (p pulps from both groups presented similar total protein concentrations and peroxidase activity. Dental pulps of diabetic rats exhibited significantly lower free, conjugated, and total sialic acid concentrations than those of control tissues. Catalase activity in diabetic dental pulps was significantly enhanced in comparison with that of control pulps. The result of the present study is indicative of oxidative stress in the dental pulp caused by diabetes. The increase of catalase activity and the reduction of sialic acid could be resultant of reactive oxygen species production.

Arbutus unedo prevents cardiovascular and morphological alterations in L-NAME-induced hypertensive rats Part I: cardiovascular and renal hemodynamic effects of Arbutus unedo in L-NAME-induced hypertensive rats.

Science.gov (United States)

Afkir, Saida; Nguelefack, Telesphore Benoit; Aziz, Mohamed; Zoheir, Johar; Cuisinaud, Guy; Bnouham, Mohamed; Mekhfi, Hassane; Legssyer, Abdelkhaleq; Lahlou, Saad; Ziyyat, Abderrahim

2008-03-05

Hypertension induced by nitric oxide synthase inhibition is associated with functional abnormalities of the heart and kidney. The aim of the present study was to investigate whether chronic treatment with Arbutus unedo leaf (AuL) or root (AuR) aqueous extracts can prevent these alterations. Six groups of rats were used: control group received tap water; N(G)-nitro-l-arginine methyl-ester (L-NAME) group treated with L-NAME at 40 mg/kg/day; AuL and AuR groups received simultaneously L-NAME (40 mg/kg/day) and Au leaves or roots extract at the same concentration 250 mg/kg/day; l-arginine and enalapril groups received simultaneously L-NAME (40 mg/kg/day) and l-arginine at 50mg/kg/day or enalapril at 15 mg/kg/day. Treatment of rats during 4 weeks with L-NAME caused an increase of the systolic blood pressure (SBP) accompanied by a ventricular hypertrophy, an impairment of endothelium-dependent vasorelaxation, an increase of the cardiac baroreflex sensitivity and a decrease of water, sodium and potassium excretion. The co-administration of AuL or AuR extracts with L-NAME reduces the development of increased SBP, ameliorates the vascular reactivity as well as the baroreflex sensitivity and normalizes the renal function. AuR reduces the ventricular hypertrophy but AuL do not. Enalapril associated with L-NAME reverses the majority of alterations induced by L-NAME while l-arginine only lightly ameliorates the vascular reactivity. These results show that chronic treatment with Arbutus extract regress the development of hypertension and ameliorate cardiovascular and renal functions in NO deficient hypertension.

Repeated cocaine exposure facilitates the expression of incentive motivation and induces habitual control in rats.

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Kimberly H LeBlanc

Full Text Available There is growing evidence that mere exposure to drugs can induce long-term alterations in the neural systems that mediate reward processing, motivation, and behavioral control, potentially causing the pathological pursuit of drugs that characterizes the addicted state. The incentive sensitization theory proposes that drug exposure potentiates the influence of reward-paired cues on behavior. It has also been suggested that drug exposure biases action selection towards the automatic execution of habits and away from more deliberate goal-directed control. The current study investigated whether rats given repeated exposure to peripherally administered cocaine would show alterations in incentive motivation (assayed using the Pavlovian-to-instrumental transfer (PIT paradigm or habit formation (assayed using sensitivity to reward devaluation. After instrumental and Pavlovian training for food pellet rewards, rats were given 6 daily injections of cocaine (15 mg/kg, IP or saline, followed by a 10-d period of rest. Consistent with the incentive sensitization theory, cocaine-treated rats showed stronger cue-evoked lever pressing than saline-treated rats during the PIT test. The same rats were then trained on a new instrumental action with a new food pellet reward before undergoing a reward devaluation testing. Although saline-treated rats exhibited sensitivity to reward devaluation, indicative of goal-directed performance, cocaine-treated rats were insensitive to this treatment, suggesting a reliance on habitual processes. These findings, when taken together, indicate that repeated exposure to cocaine can cause broad alterations in behavioral control, spanning both motivational and action selection processes, and could therefore help explain aberrations of decision-making that underlie drug addiction.

Repeated cocaine exposure facilitates the expression of incentive motivation and induces habitual control in rats.

Science.gov (United States)

LeBlanc, Kimberly H; Maidment, Nigel T; Ostlund, Sean B

2013-01-01

There is growing evidence that mere exposure to drugs can induce long-term alterations in the neural systems that mediate reward processing, motivation, and behavioral control, potentially causing the pathological pursuit of drugs that characterizes the addicted state. The incentive sensitization theory proposes that drug exposure potentiates the influence of reward-paired cues on behavior. It has also been suggested that drug exposure biases action selection towards the automatic execution of habits and away from more deliberate goal-directed control. The current study investigated whether rats given repeated exposure to peripherally administered cocaine would show alterations in incentive motivation (assayed using the Pavlovian-to-instrumental transfer (PIT) paradigm) or habit formation (assayed using sensitivity to reward devaluation). After instrumental and Pavlovian training for food pellet rewards, rats were given 6 daily injections of cocaine (15 mg/kg, IP) or saline, followed by a 10-d period of rest. Consistent with the incentive sensitization theory, cocaine-treated rats showed stronger cue-evoked lever pressing than saline-treated rats during the PIT test. The same rats were then trained on a new instrumental action with a new food pellet reward before undergoing a reward devaluation testing. Although saline-treated rats exhibited sensitivity to reward devaluation, indicative of goal-directed performance, cocaine-treated rats were insensitive to this treatment, suggesting a reliance on habitual processes. These findings, when taken together, indicate that repeated exposure to cocaine can cause broad alterations in behavioral control, spanning both motivational and action selection processes, and could therefore help explain aberrations of decision-making that underlie drug addiction.

Glycyrrhizic Acid Can Attenuate Metabolic Deviations Caused by a High-Sucrose Diet without Causing Water Retention in Male Sprague-Dawley Rats

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Hamish Alexander Fernando

2014-11-01

Full Text Available Glycyrrhizic acid (GA ameliorates many components of the metabolic syndrome, but its potential therapeutic use is marred by edema caused by inhibition of renal 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2. We assessed whether 100 mg/kg per day GA administered orally could promote metabolic benefits without causing edema in rats fed on a high-sucrose diet. Groups of eight male rats were fed on one of three diets for 28 days: normal diet, a high-sucrose diet, or a high-sucrose diet supplemented with GA. Rats were then culled and renal 11β-HSD2 activity, as well as serum sodium, potassium, angiotensin II and leptin levels were determined. Histological analyses were performed to assess changes in adipocyte size in visceral and subcutaneous depots, as well as hepatic and renal tissue morphology. This dosing paradigm of GA attenuated the increases in serum leptin levels and visceral, but not subcutaneous adipocyte size caused by the high-sucrose diet. Although GA decreased renal 11β-HSD2 activity, it did not affect serum electrolyte or angiotensin II levels, indicating no onset of edema. Furthermore, there were no apparent morphological changes in the liver or kidney, indicating no toxicity. In conclusion, it is possible to reap metabolic benefits of GA without edema using the current dosage and treatment time.

Fructose-Drinking Water Induced Nonalcoholic Fatty Liver Disease and Ultrastructural Alteration of Hepatocyte Mitochondria in Male Wistar Rat

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Norshalizah Mamikutty

2015-01-01

Full Text Available Background. Nonalcoholic fatty liver disease (NAFLD is one of the complications of the metabolic syndrome. It encompasses a wide range of disease spectrum from simple steatosis to liver cirrhosis. Structural alteration of hepatic mitochondria might be involved in the pathogenesis of NAFLD. Aims. In the present study, we used a newly established model of fructose-induced metabolic syndrome in male Wistar rats in order to investigate the ultrastructural changes in hepatic mitochondria that occur with fructose consumption and their association with NAFLD pathogenesis. Methods. The concentration of fructose-drinking water (FDW used in this study was 20%. Six male Wistar rats were supplemented with FDW 20% for eight weeks. Body composition and metabolic parameters were measured before and after 8 weeks of FDW 20%. Histomorphology of the liver was evaluated and ultrastructural changes of mitochondria were assessed with transmission electron micrograph. Results. After 8 weeks of fructose consumption, the animals developed several features of the metabolic syndrome. Moreover, fructose consumption led to the development of macrovesicular hepatic steatosis and mitochondrial ultrastructural changes, such as increase in mitochondrial size, disruption of the cristae, and reduction of matrix density. Conclusion. We conclude that in male Wistar rat 8-week consumption of FDW 20% leads to NAFLD likely via mitochondrial structural alteration.

Exercise in rats does not alter hypothalamic AMP-activated protein kinase activity

DEFF Research Database (Denmark)

Andersson, Ulrika; Treebak, Jonas Thue; Nielsen, Jakob Nis

2005-01-01

. In recovery, glucose feeding increased plasma glucose and insulin concentrations whereas ghrelin and PYY decreased to (ghrelin) or below (PPY) resting levels. It is concluded that 1 h of strenuous exercise in rats does not elicit significant changes in hypothalamic AMPK activity despite an increase in plasma...... ghrelin. Thus, changes in energy metabolism during or after exercise are likely not coordinated by changes in hypothalamic AMPK activity.......Recent studies have demonstrated that AMP-activated protein kinase (AMPK) in the hypothalamus is involved in the regulation of food intake. Because exercise is known to influence appetite and cause substrate depletion, it may also influence AMPK in the hypothalamus. Male rats that either rested...

A diet containing the soy phytoestrogen genistein causes infertility in female rats partially deficient in UDP glucuronyltransferase

International Nuclear Information System (INIS)

Seppen, Jurgen

2012-01-01

Soy beans contain genistein, a natural compound that has estrogenic effects because it binds the estrogen receptor with relatively high affinity. Genistein is therefore the most important environmental estrogen in the human diet. Detoxification of genistein is mediated through conjugation by UDP-glucuronyltransferase 1 and 2 (UGT1 and UGT2) isoenzymes. Gunn rats have a genetic deficiency in UGT1 activity, UGT2 activities are not affected. Because our Gunn rats stopped breeding after the animal chow was changed to a type with much higher soy content, we examined the mechanism behind this soy diet induced infertility. Gunn and control rats were fed diets with and without genistein. In these rats, plasma levels of genistein and metabolites, fertility and reproductive parameters were determined. Enzyme assays showed reduced genistein UGT activity in Gunn rats, as compared to wild type rats. Female Gunn rats were completely infertile on a genistein diet, wild type rats were fertile. Genistein diet caused a persistent estrus, lowered serum progesterone and inhibited development of corpora lutea in Gunn rats. Concentrations of total genistein in Gunn and control rat plasma were identical and within the range observed in humans after soy consumption. However, Gunn rat plasma contained 25% unconjugated genistein, compared to 3.6% in control rats. This study shows that, under conditions of reduced glucuronidation, dietary genistein exhibits a strongly increased estrogenic effect. Because polymorphisms that reduce UGT1 expression are prevalent in the human population, these results suggest a cautionary attitude towards the consumption of large amounts of soy or soy supplements. -- Highlights: ► Gunn rats are partially deficient in detoxification by UDP glucuronyltransferases. ► Female Gunn rats are infertile on a soy containing diet. ► Soy contains genistein, a potent phytoestrogen. ► Inefficient glucuronidation of genistein causes female infertility.

A diet containing the soy phytoestrogen genistein causes infertility in female rats partially deficient in UDP glucuronyltransferase

Energy Technology Data Exchange (ETDEWEB)

Seppen, Jurgen, E-mail: j.seppen@amc.uva.nl

2012-11-01

Soy beans contain genistein, a natural compound that has estrogenic effects because it binds the estrogen receptor with relatively high affinity. Genistein is therefore the most important environmental estrogen in the human diet. Detoxification of genistein is mediated through conjugation by UDP-glucuronyltransferase 1 and 2 (UGT1 and UGT2) isoenzymes. Gunn rats have a genetic deficiency in UGT1 activity, UGT2 activities are not affected. Because our Gunn rats stopped breeding after the animal chow was changed to a type with much higher soy content, we examined the mechanism behind this soy diet induced infertility. Gunn and control rats were fed diets with and without genistein. In these rats, plasma levels of genistein and metabolites, fertility and reproductive parameters were determined. Enzyme assays showed reduced genistein UGT activity in Gunn rats, as compared to wild type rats. Female Gunn rats were completely infertile on a genistein diet, wild type rats were fertile. Genistein diet caused a persistent estrus, lowered serum progesterone and inhibited development of corpora lutea in Gunn rats. Concentrations of total genistein in Gunn and control rat plasma were identical and within the range observed in humans after soy consumption. However, Gunn rat plasma contained 25% unconjugated genistein, compared to 3.6% in control rats. This study shows that, under conditions of reduced glucuronidation, dietary genistein exhibits a strongly increased estrogenic effect. Because polymorphisms that reduce UGT1 expression are prevalent in the human population, these results suggest a cautionary attitude towards the consumption of large amounts of soy or soy supplements. -- Highlights: ► Gunn rats are partially deficient in detoxification by UDP glucuronyltransferases. ► Female Gunn rats are infertile on a soy containing diet. ► Soy contains genistein, a potent phytoestrogen. ► Inefficient glucuronidation of genistein causes female infertility.

Altered dopaminergic regulation of the dorsal striatum is able to induce tic-like movements in juvenile rats

Science.gov (United States)

Rizzo, Francesca; Boeckers, Tobias; Schulze, Ulrike

2018-01-01

Motor tics are sudden, repetitive, involuntary movements representing the hallmark behaviors of the neurodevelopmental disease Tourette’s syndrome (TS). The primary cause of TS remains unclear. The initial observation that dopaminergic antagonists alleviate tics led to the development of a dopaminergic theory of TS etiology which is supported by post mortem and in vivo studies indicating that non-physiological activation of the striatum could generate tics. The striatum controls movement execution through the balanced activity of dopamine receptor D1 and D2-expressing medium spiny neurons of the direct and indirect pathway, respectively. Different neurotransmitters can activate or repress striatal activity and among them, dopamine plays a major role. In this study we introduced a chronic dopaminergic alteration in juvenile rats, in order to modify the delicate balance between direct and indirect pathway. This manipulation was done in the dorsal striatum, that had been associated with tic-like movements generation in animal models. The results were movements resembling tics, which were categorized and scored according to a newly developed rating scale and were reduced by clonidine and riluzole treatment. Finally, post mortem analyses revealed altered RNA expression of dopaminergic receptors D1 and D2, suggesting an imbalanced dopaminergic regulation of medium spiny neuron activity as being causally related to the observed phenotype. PMID:29698507

Protective effect of curcumin (Curcuma longa), against aluminium toxicity: Possible behavioral and biochemical alterations in rats.

Science.gov (United States)

Kumar, Anil; Dogra, Samrita; Prakash, Atish

2009-12-28

Aluminium is a potent neurotoxin and has been associated with Alzheimer's disease (AD) causality for decades. Prolonged aluminium exposure induces oxidative stress and increases amyloid beta levels in vivo. Current treatment modalities for AD provide only symptomatic relief thus necessitating the development of new drugs with fewer side effects. The aim of the study was to demonstrate the protective effect of chronic curcumin administration against aluminium-induced cognitive dysfunction and oxidative damage in rats. Aluminium chloride (100 mg/kg, p.o.) was administered to rats daily for 6 weeks. Rats were concomitantly treated with curcumin (per se; 30 and 60 mg/kg, p.o.) daily for a period of 6 weeks. On the 21st and 42nd day of the study behavioral studies to evaluate memory (Morris water maze and elevated plus maze task paradigms) and locomotion (photoactometer) were done. The rats were sacrificed on 43rd day following the last behavioral test and various biochemical tests were performed to assess the extent of oxidative damage. Chronic aluminium chloride administration resulted in poor retention of memory in Morris water maze, elevated plus maze task paradigms and caused marked oxidative damage. It also caused a significant increase in the acetylcholinesterase activity and aluminium concentration in aluminium treated rats. Chronic administration of curcumin significantly improved memory retention in both tasks, attenuated oxidative damage, acetylcholinesterase activity and aluminium concentration in aluminium treated rats (Paluminium-induced cognitive dysfunction and oxidative damage.

Sub-acute nickel exposure impairs behavior, alters neuronal microarchitecture, and induces oxidative stress in rats' brain.

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Ijomone, Omamuyovwi Meashack; Okori, Stephen Odey; Ijomone, Olayemi Kafilat; Ebokaiwe, Azubike Peter

2018-02-26

Nickel (Ni) is a heavy metal with wide industrial uses. Environmental and occupational exposures to Ni are potential risk factors for neurological symptoms in humans. The present study investigated the behavior and histomorphological alterations in brain of rats sub-acutely exposed to nickel chloride (NiCl 2 ) and the possible involvement of oxidative stress. Rats were administered with 5, 10 or 20 mg/kg NiCl 2 via intraperitoneal injections for 21 days. Neurobehavioral assessment was performed using the Y-maze and open field test (OFT). Histomorphological analyses of brain tissues, as well as biochemical determination of oxidative stress levels were performed. Results showed that Ni treatments significantly reduced body weight and food intake. Cognitive and motor behaviors on the Y-maze and OFT, respectively, were compromised following Ni treatments. Administration of Ni affected neuronal morphology in the brain and significantly reduced percentage of intact neurons in both hippocampus and striatum. Additionally, markers of oxidative stress levels and nitric oxide (NO) levels were significantly altered following Ni treatments. These data suggest that compromised behavior and brain histomorphology following Ni exposures is associated with increase in oxidative stress.

Cronobacter sakazakii infection alters serotonin transporter and improved fear memory retention in the rats

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Bhagavathi Sundaram eSivamaruthi

2015-09-01

Full Text Available It is well established that Cronobacter sakazakii infection cause septicemia, necrotizingenterocolitis (NEC and meningitis. In the present study, we tested whether the C. sakazakii infection alter the learning and memory through serotonin transporter (SERT. To investigate the possible effect on SERT, on postnatal day (PND-15, wistar rat pups were administered with single dose of C. sakazakii culture (Infected group: IF; 107 CFU or 100μL of Luria-Bertani broth (LB; Medium Control: MC or without any treatment (Naïve control: NC. All the individuals were subjected to passive avoidance test on PND-30 to test their fear memory. We show that single dose of C. sakazakii infection improved fear memory retention. Subsequently, we show that C. sakazakii infection induced the activation of Toll-like receptor-3 (TLR-3 and heat-shock proteins-90 (Hsp-90. On the other hand, level of serotonin (5-HT and SERT protein was down-regulated. Furthermore, we show that C. sakazakii infection up-regulate microRNA (miR-16 expression. The observed results highlight that C. sakazakii infections was responsible for improved fear memory retention and may have reduced the level of SERT protein, which is possibly associated with the interaction of up-regulated Hsp-90 with SERT protein or miR-16 with SERT mRNA. Taken together, observed results suggest that C. sakazakkii infection alter the fear memory possibly through SERT. Hence, this model may be effective to test the C. sakazakii infection induced changes in synaptic plasticity through SERT and effect of other pharmacological agents against pathogen induced memory disorder.

Specific alteration of rhythm in temperature-stressed rats possess features of abdominal pain in IBS patients

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Yasuo Itomi

2015-09-01

Full Text Available It is known that specific alteration of rhythm in temperature (SART stress produces somatic pain. However, it remains to be investigated whether SART stress induces visceral pain. In this study, we investigated the visceral hypersensitivity in the SART stress model by pharmacological tools and heterotopical nociception. Four-week-old Sprague–Dawley rats were exposed to repeated cold stress. Visceral pain was measured by visceromotor response to colorectal distension, and the effects of alosetron and duloxetine on visceral pain were investigated in SART rats. Heterotopical nociception was given by capsaicin injection into the left forepaw to induce diffuse noxious inhibitory controls (DNIC. SART stress induced visceral hypersensitivity that was sustained at minimum for one week. In pharmacological analysis, alosetron and duloxetine improved SART stress-induced visceral hypersensitivity. Heterotopical nociception induced DNIC in normal conditions, but was disrupted in SART rats. On the other hand, RMCP-II mRNA in distal colon was not affected by SART stress. In conclusion, SART rats exhibit several features of visceral pain in IBS, and may be a useful model for investigating the central modification of pain control in IBS.

Physiological and Histological Alterations in Rats Liver Induced by Sumithion NP 25/2.5 EC, an Insecticide Used in Dengue Fever Vector Control in Jeddah, Saudi Arabia

International Nuclear Information System (INIS)

AlJahdali, Mohammed O.; Bisher, Ameen S. Bin; Zeid, Isam M. Abu

2009-01-01

The hepatotoxicity of Sumithion NP 25/2.5 EC, a new formulated organophosphorous insecticide used in dengue fever vector (Aedes aegypti) control in Jeddah (Saudi Arabia), was studied in albino rats. Both levels of GPT, GOT and ALP, and the combined histological alterations were assessed after treatment. Rats were daily injected intraperitoneally for two and four weeks with 80 and 200 mg/kg of body weight (1/10 and 1/4 of the LD50, respectively). Significant increase in GPT, GOT and ALP levels relative to the increase of treatment dose and duration time was observed. The time factor effect was remarkably noticed in ALP level fluctuation. These results indicate a remarkable defect in the liver functions induced by Sumithion NP 25/2.5 EC. Also, histological alterations in the treated animal's liver were observed including: blood congestion, fatty degeneration, hepatocytes swelling and necrosis. The liver syndrome's intensity correlated with the increase in dose and duration time. The present results could prove the hepatotoxicity of Sumithion NP 25/2.5 EC and its ability to cause severe physiological and histopathological defects in the liver. Therefore, the chemical control of Aedes aegypti must be reduced and other recommended control strategies should be promoted. (author)

Exposure to a glyphosate-based herbicide during pregnancy and lactation induces neurobehavioral alterations in rat offspring.

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Gallegos, Cristina E; Bartos, Mariana; Bras, Cristina; Gumilar, Fernanda; Antonelli, Marta C; Minetti, Alejandra

2016-03-01

The impact of sub-lethal doses of herbicides on human health and the environment is a matter of controversy. Due to the fact that evidence particularly of the effects of glyphosate on the central nervous system of rat offspring by in utero exposure is scarce, the purpose of the present study was to assess the neurobehavioral effects of chronic exposure to a glyphosate-containing herbicide during pregnancy and lactation. To this end, pregnant Wistar rats were exposed through drinking water to 0.2% or 0.4% of a commercial formulation of glyphosate (corresponding to a concentration of 0.65 or 1.30g/L of glyphosate, respectively) during pregnancy and lactation and neurobehavioral alterations in offspring were analyzed. The postnatal day on which each pup acquired neonatal reflexes (righting, cliff aversion and negative geotaxis) and that on which eyes and auditory canals were fully opened were recorded for the assessment of sensorimotor development. Locomotor activity and anxiety levels were monitored via open field test and plus maze test, respectively, in 45- and 90-day-old offspring. Pups exposed to a glyphosate-based herbicide showed early onset of cliff aversion reflex and early auditory canal opening. A decrease in locomotor activity and in anxiety levels was also observed in the groups exposed to a glyphosate-containing herbicide. Findings from the present study reveal that early exposure to a glyphosate-based herbicide affects the central nervous system in rat offspring probably by altering mechanisms or neurotransmitter systems that regulate locomotor activity and anxiety. Copyright © 2015 Elsevier Inc. All rights reserved.

Dearomatized white spirit inhalation exposure causes long-lasting neurophysiological changes in rats

DEFF Research Database (Denmark)

Lund, S. P.; Simonsen, L.; Hass, Ulla

1996-01-01

Dearomatized white spirit inhalation exposure causes long-lasting neurophysioloical changes in rats. NEUROTOXICOL TERATOL 18(1), 67-76, 1996. -Exposure for 6 h per day, 5 days per week, during a period of 6 months to the organic solvent dearomatized white spirit (0, 400, and 800 ppm) was studied ...

Flavonoid-rich fraction of the Monodora tenuifolia seed extract attenuates behavioural alterations and oxidative damage in forced-swim stressed rats.

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Ekeanyanwu, Raphael Chukwuma; Njoku, Obioma Uzoma

2015-03-01

The antidepressant effects of the flavonoid-rich fraction of Monodora tenuifolia seed extract were examined by assessing the extent of attenuation of behavioural alterations and oxidative damage in the rats that were stressed by forced swim test. Compared with the model control group, the altered behavioural parameters were attenuated significantly (P fluoxetine (10 mg·kg(-1)). The flavonoid-rich fraction and fluoxetine improved significantly (P < 0.05) the activities of the antioxidant enzymes such as superoxide dismutase and catalase as well as other biochemical parameters such as reduced glutathione, protein, and nitrite in the brain of the stressed rats. These results suggested that the flavonoid-rich fraction of Monodora tenuifolia seed extract exerted the antidepressant-like effects which could be useful in the management of stress induced disease. Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

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

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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.

Preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats.

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Roy, Abhro Jyoti; Stanely Mainzen Prince, P

2013-10-01

The present study evaluated the preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days and then injected with isoproterenol (100mg/kg body weight) on 8th and 9th day to induce myocardial infarction. Myocardial infarction induced by isoproterenol was indicated by increased level of cardiac sensitive marker and elevated ST-segments in the electrocardiogram. Also, the levels/concentrations of serum and heart cholesterol, triglycerides and free fatty acids were increased in myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high density lipoprotein cholesterol. It also enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase. p-Coumaric acid pretreatment revealed preventive effects on all the biochemical parameters and electrocardiogram studied in myocardial infarcted rats. The in vitro study confirmed the free radical scavenging property of p-coumaric acid. Thus, p-coumaric acid prevented cardiac hypertrophy and alterations in lipids, lipoproteins, and electrocardiogram, by virtue of its antihypertrophic, antilipidemic, and free radical scavenging effects in isoproterenol induced myocardial infarcted rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

Developmental vitamin D deficiency alters MK 801-induced hyperlocomotion in the adult rat: An animal model of schizophrenia.

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Kesby, James P; Burne, Thomas H J; McGrath, John J; Eyles, Darryl W

2006-09-15

Developmental vitamin D (DVD) deficiency has been proposed as a risk factor for schizophrenia. The behavioral phenotype of adult rats subjected to transient low prenatal vitamin D is characterized by spontaneous hyperlocomotion but normal prepulse inhibition of acoustic startle (PPI). The aim of this study was to examine the impact of selected psychotropic agents and one well-known antipsychotic agent on the behavioral phenotype of DVD deplete rats. Control versus DVD deplete adult rats were assessed on holeboard, open field and PPI. In the open field, animals were given MK-801 and/or haloperidol. For PPI, the animals were given apomorphine or MK-801. DVD deplete rats had increased baseline locomotion on the holeboard task and increased locomotion in response to MK-801 compared to control rats. At low doses, haloperidol antagonized the MK-801 hyperactivity of DVD deplete rats preferentially and, at a high dose, resulted in a more pronounced reduction in spontaneous locomotion in DVD deplete rats. DVD depletion did not affect either baseline or drug-mediated PPI response. These results suggest that DVD deficiency is associated with a persistent alteration in neuronal systems associated with motor function but not those associated with sensory motor gating. In light of the putative association between low prenatal vitamin D and schizophrenia, the discrete behavioral differences associated with the DVD model may help elucidate the neurobiological correlates of schizophrenia.

The effects of abnormalities of glucose homeostasis on the expression and binding of muscarinic receptors in cerebral cortex of rats.

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Sherin, Antony; Peeyush, Kumar T; Naijil, George; Nandhu, Mohan Sobhana; Jayanarayanan, Sadanandan; Jes, Paul; Paulose, Cheramadathikudiyil Skaria

2011-01-25

Glucose homeostasis in humans is an important factor for the functioning of nervous system. Both hypo and hyperglycemia contributes to neuronal functional deficit. In the present study, effect of insulin induced hypoglycemia and streptozotocin induced diabetes on muscarinic receptor binding, cholinergic enzymes; AChE, ChAT expression and GLUT3 in the cerebral cortex of experimental rats were analysed. Total muscarinic, muscarinic M(1) receptor showed a significant decrease and muscarinic M(3) receptor subtype showed a significant increased binding in the cerebral cortex of hypoglycemic rats compared to diabetic and control. Real-Time PCR analysis of muscarinic M(1), M(3) receptor subtypes confirmed the receptor binding studies. Immunohistochemistry of muscarinic M(1), M(3) receptors using specific antibodies were also carried out. AChE and GLUT3 expression up regulated and ChAT expression down regulated in hypoglycemic rats compared to diabetic and control rats. Our results showed that hypo/hyperglycemia caused impaired glucose transport in neuronal cells as shown by altered expression of GLUT3. Increased AChE and decreased ChAT expression is suggested to alter cortical acetylcholine metabolism in experimental rats along with altered muscarinic receptor binding in hypo/hyperglycemic rats, impair cholinergic transmission, which subsequently lead to cholinergic dysfunction thereby causing learning and memory deficits. We observed a prominent cholinergic functional disturbance in hypoglycemic condition than in hyperglycemia. Hypoglycemia exacerbated the neurochemical changes in cerebral cortex induced by hyperglycemia. These findings have implications for both therapy and identification of causes contributing to neuronal dysfunction in diabetes. Copyright © 2010 Elsevier B.V. All rights reserved.

Low-dose, Chronic Exposure to Silver Nanoparticles Causes Mild Mitochondrial Alterations in the Liver of Sprague-Dawley Rat

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2014-05-10

of Sprague-Dawley rat CARLOS PALMEIRA CENTRO DE NEUROCIENCIAS E BIOLOGIA CELULAR (CNC) DEPARTAMENTO DE ZOOLOGIA COIMBRA 3000 - 329...CENTRO DE NEUROCIENCIAS E BIOLOGIA CELULAR (CNC) DEPARTAMENTO DE ZOOLOGIA COIMBRA 3000 - 329 PORTUGAL 8. PERFORMING ORGANIZATION REPORT NUMBER

Bifidobacterium breve alters immune function and ameliorates DSS-induced inflammation in weanling rats.

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Izumi, Hirohisa; Minegishi, Mario; Sato, Yohei; Shimizu, Takashi; Sekine, Kazunori; Takase, Mitsunori

2015-10-01

Bifidobacterium breve M-16V (M16V) is a probiotic bacterial strain with a long tradition of use in neonatal intensive care units in some countries. Previous study showed that the effects of M16V administration on gene expression were greater during the weaning period than in the neonatal period and were greater in the colon than in the small intestine and spleen, suggesting that M16V has anti-inflammatory effects. In this study, we evaluated the effects of inflammation during the weaning period and the effects of M16V on normal and inflammatory conditions. From postnatal day (PD) 21 to 34, weanling rats were administered of 2.5 × 10(9) of M16V daily, and colitis was induced by administration of 2% dextran sulfate sodium from PD28 to 35. Colitis severity, immune function, and microbiota were investigated. Colitis caused a reduction in body weight gain, colon shortening, poor nutritional status, anemia, changes in blood and spleen lymphocyte populations, spleen T-cell malfunctions, and alterations in colon microbiota. M16V administration improved some but not all of the changes induced by colitis. M16V could suppress inflammation and, therefore, can be considered a safe strain to use not only during the neonatal period but also the weaning period.

Role of Neurotrophins in Mediating the Effect of Altered Gravity on the Developing Rat Cerebellum.

Science.gov (United States)

Sajdel-Sulkowska, Elizabeth

We previously reported that perinatal exposure to hypergravity resulted in oxidative stress that may contribute to the decrease in Purkinje cell number and the impairment of motor coordination in hypergravity-exposed rat neonates. However, the increase in oxidative stress markers was not uniformly observed in males and females. In the present study we explored the possibility that exposure to hypergravity may result in altered level of neurotrophins, which have been recognized as mediators of both neurodegenerative and neuroprotective mechanisms in the central nervous system. An elevation of neurotrophin-3 (NT-3) has been observed in animal models of hypoxia. To test this hypothesis we compared cerebellar levels of NT-3 between stationary control (SC) and rat neonates exposed perinatally to 1.65 G on a 24-ft centrifuge. The levels of NT-3 were determined by specific ELISA. Preliminary data suggests a 123

Effects of prenatal irradiation with an accelerated heavy-ion beam on postnatal development in rats: II. Further study on neurophysiologic alterations

Science.gov (United States)

Wang, B.; Murakami, M.; Eguchi-Kasai, K.; Nojima, K.; Shang, Y.; Tanaka, K.; Watanabe, K.; Fujita, K.; Moreno, S. G.; Coffigny, H.; Hayata, I.

Organogenesis is a highly radiosensitive period, study of prenatal exposure to high LET heavy ion beams on postnatal development is important for clarifying the radiation risk in space and promoting the evidence-based mechanism research. The effects from heavy ion irradiations are not well studied as those for low LET radiations such as X-rays in this field, even the ground-based investigations remain to be addressed. Using the Heavy Ion Medical Accelerator in Chiba (HIMAC) and Wistar rats, postnatal neurophysiological development in offspring was investigated following exposure of pregnant rats to accelerated neon-ion beams with a LET value of about 30 keV/μm at a dose range from 0.1 to 2.0 Gy on the 15th day of gestation. The age for appearance of four physiologic markers and attainment of five neonatal reflexes, and gain in body weight were monitored. Male offspring were evaluated as young adults using two behavioral tests including open field and hole-board dipping tests. The effects of X-rays at 200 kVp measured for the same biological end points were studied for comparison. For most of the endpoints at early age, significant neurophysiological alteration was observed even in offspring receiving 0.1 Gy of accelerated neon ions but not X-rays. All offspring receiving 2.0 Gy of accelerated neon ions died prior to weaning. Offspring prenatally irradiated with neon ions generally showed higher incidences of prenatal death, increased preweaning mortality, markedly delayed accomplishment in physiological markers and reflexes, significantly lower body weight and reduced ratios of main organ weight to body weight, and altered behavior compared to those exposed to X-rays at doses of 0.1 1.5 Gy. These findings indicate that irradiations with neon ions at 0.1 1.5 Gy on day 15 of gestation caused varied developmental alterations in offspring, and efficient dose leading to the detrimental effects seemed to be lower than that of X-rays.

Biochemical and functional correlates of an increased membrane density of caveolae in hypertrophic rat urinary bladder.

OpenAIRE

Shakirova, Yulia; Swärd, Karl; Uvelius, Bengt; Ekman, Mari

2010-01-01

Organ hypertrophy is often found to be associated with changes in the expression of caveolins and altered density of caveolae in the membrane. A plethora of signalling intermediaries are associated with caveolae and loss of caveolae has profound effects on contractility of the urinary bladder. We hypothesized that smooth muscle hypertrophy caused by bladder outflow obstruction (BOO) might lead to an altered caveola density with consequences for contractile regulation. Rat BOO for 6weeks cause...

Polycystic ovary syndrome resembling histopathological alterations in ovaries from prenatal androgenized female rats

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Wang Fang

2012-05-01

Full Text Available Abstract Background The polycystic ovary syndrome (PCOS affects approximately 6-10% of women of reproductive age and is characterized by chronic anovulation and hyperandrogenism. However, a comprehensive understanding of the mechanisms that dictate androgen overproduction is lacking, which may account for inconsistencies between measures of androgen excess and clinical presentation in individual cases. Methods A rat model of PCOS was established by injecting dehydroepiandrosterone sulfoconjugate (DHEAS into pregnant females. Rats were administered with DHEAS (60 mg/kg/d subcutaneously (s.c. for all 20 days of pregnancy (Group A, or for the first 10 days (Group B, or from day 11 to day 20 (Group C. Controls were administered with injection oil (0.2 ml/day s.c. throughout pregnancy (Group D. The litter rate, abortion rate, and offspring survival rate in each group were recorded. Serum androgen and estrogen were measured and the morphological features of the ovaries were examined by light and electron microscopy in the offspring of each group. Results We found that rats injected with DHEAS throughout pregnancy (group A lost fertility. Rats injected with DHEAS during early pregnancy (group B exhibited more serious aberrations in fertility than both Group C, in which rats were injected with DHEAS during late pregnancy (P  Conclusions Our results indicate that androgen excess during pregnancy can decrease rat fertility. Excess androgen at the early stage of pregnancy causes high reproductive toxicity, leading to abnormality of ovarian morphology and functions in female offspring.

Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia.

Science.gov (United States)

Kesby, James P; Cui, Xiaoying; Burne, Thomas H J; Eyles, Darryl W

2013-01-01

Schizophrenia is a heterogeneous group of disorders with unknown etiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine (DA) neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesized that abnormal DA signaling in the adult patient may result from altered DA signaling during fetal brain development. Environmental and genetic risk factors can be modeled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the etiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD) deficiency. DVD-deficient adult rats display an altered behavioral profile in response to DA releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis, and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters DA metabolism in the developing brain. We speculate such alterations in fetal brain development may change the trajectory of DA neuron ontogeny to induce the behavioral abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in DA ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.

Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia

Directory of Open Access Journals (Sweden)

James P. Kesby

2013-07-01

Full Text Available Schizophrenia is a heterogeneous group of disorders with unknown aetiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesised that abnormal dopamine signalling in the adult patient may result from altered dopamine signalling during foetal brain development. Environmental and genetic risk factors can be modelled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the aetiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD deficiency. DVD-deficient adult rats display an altered behavioural profile in response to dopamine releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters dopamine metabolism in the developing brain. We speculate such alterations in foetal brain development may change the trajectory of dopamine neuron ontogeny to induce the behavioural abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in dopamine ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.

Receptor tyrosine kinase inhibition causes simultaneous bone loss and excess bone formation within growing bone in rats

International Nuclear Information System (INIS)

Nurmio, Mirja; Joki, Henna; Kallio, Jenny; Maeaettae, Jorma A.; Vaeaenaenen, H. Kalervo; Toppari, Jorma; Jahnukainen, Kirsi; Laitala-Leinonen, Tiina

2011-01-01

During postnatal skeletal growth, adaptation to mechanical loading leads to cellular activities at the growth plate. It has recently become evident that bone forming and bone resorbing cells are affected by the receptor tyrosine kinase (RTK) inhibitor imatinib mesylate (STI571, Gleevec (registered) ). Imatinib targets PDGF, ABL-related gene, c-Abl, c-Kit and c-Fms receptors, many of which have multiple functions in the bone microenvironment. We therefore studied the effects of imatinib in growing bone. Young rats were exposed to imatinib (150 mg/kg on postnatal days 5-7, or 100 mg/kg on postnatal days 5-13), and the effects of RTK inhibition on bone physiology were studied after 8 and 70 days (3-day treatment), or after 14 days (9-day treatment). X-ray imaging, computer tomography, histomorphometry, RNA analysis and immunohistochemistry were used to evaluate bone modeling and remodeling in vivo. Imatinib treatment eliminated osteoclasts from the metaphyseal osteochondral junction at 8 and 14 days. This led to a resorption arrest at the growth plate, but also increased bone apposition by osteoblasts, thus resulting in local osteopetrosis at the osteochondral junction. The impaired bone remodelation observed on day 8 remained significant until adulthood. Within the same bone, increased osteoclast activity, leading to bone loss, was observed at distal bone trabeculae on days 8 and 14. Peripheral quantitative computer tomography (pQCT) and micro-CT analysis confirmed that, at the osteochondral junction, imatinib shifted the balance from bone resorption towards bone formation, thereby altering bone modeling. At distal trabecular bone, in turn, the balance was turned towards bone resorption, leading to bone loss. - Research highlights: → 3-Day imatinib treatment. → Causes growth plate anomalies in young rats. → Causes biomechanical changes and significant bone loss at distal trabecular bone. → Results in loss of osteoclasts at osteochondral junction.

Serotonin antagonists fail to alter MDMA self-administration in rats.

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Schenk, Susan; Foote, Jason; Aronsen, Dane; Bukholt, Natasha; Highgate, Quenten; Van de Wetering, Ross; Webster, Jeremy

2016-09-01

Acute exposure to ±3,4-methylenedioxymethamphetamine (MDMA) preferentially increases release of serotonin (5-HT), and a role of 5-HT in many of the behavioral effects of acute exposure to MDMA has been demonstrated. A role of 5-HT in MDMA self-administration in rats has not, however, been adequately determined. Therefore, the present study measured the effect of pharmacological manipulation of some 5-HT receptor subtypes on self-administration of MDMA. Rats received extensive experience with self-administered MDMA prior to tests with 5-HT ligands. Doses of the 5-HT1A antagonist, WAY 100635 (0.1-1.0mg/kg), 5-HT1B antagonist, GR 127935 (1.0-3.0mg/kg), and the 5-HT2A antagonist, ketanserin (1.0-3.0mg/kg) that have previously been shown to decrease self-administration of other psychostimulants and that decreased MDMA-produced hyperactivity in the present study did not alter MDMA self-administration. Experimenter-administered injections of MDMA (10.0mg/kg, ip) reinstated extinguished drug-taking behavior, but this also was not decreased by any of the antagonists. In contrast, both WAY 100635 and ketanserin, but not GR 127935, decreased cocaine-produced drug seeking in rats that had been trained to self-administered cocaine. The 5-HT1A agonist, 8-OH-DPAT (0.1-1.0mg/kg), but not the 5-HT1B/1A agonist, RU 24969 (0.3-3.0mg/kg), decreased drug-seeking produced by the reintroduction of a light stimulus that had been paired with self-administered MDMA infusions. These findings suggest a limited role of activation of 5-HT1A, 5-HT1B or 5-HT2 receptor mechanisms in MDMA self-administration or in MDMA-produced drug-seeking following extinction. The data suggest, however, that 5-HT1A agonists inhibit cue-induced drug-seeking following extinction of MDMA self-administration and might, therefore, be useful adjuncts to therapies to limit relapse to MDMA use. Copyright © 2016 Elsevier Inc. All rights reserved.

Branched-chain amino acids alter neurobehavioral function in rats

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Coppola, Anna; Wenner, Brett R.; Ilkayeva, Olga; Stevens, Robert D.; Maggioni, Mauro; Slotkin, Theodore A.; Levin, Edward D.

2013-01-01

Recently, we have described a strong association of branched-chain amino acids (BCAA) and aromatic amino acids (AAA) with obesity and insulin resistance. In the current study, we have investigated the potential impact of BCAA on behavioral functions. We demonstrate that supplementation of either a high-sucrose or a high-fat diet with BCAA induces anxiety-like behavior in rats compared with control groups fed on unsupplemented diets. These behavioral changes are associated with a significant decrease in the concentration of tryptophan (Trp) in brain tissues and a consequent decrease in serotonin but no difference in indices of serotonin synaptic function. The anxiety-like behaviors and decreased levels of Trp in the brain of BCAA-fed rats were reversed by supplementation of Trp in the drinking water but not by administration of fluoxetine, a selective serotonin reuptake inhibitor, suggesting that the behavioral changes are independent of the serotonergic pathway of Trp metabolism. Instead, BCAA supplementation lowers the brain levels of another Trp-derived metabolite, kynurenic acid, and these levels are normalized by Trp supplementation. We conclude that supplementation of high-energy diets with BCAA causes neurobehavioral impairment. Since BCAA are elevated spontaneously in human obesity, our studies suggest a potential mechanism for explaining the strong association of obesity and mood disorders. PMID:23249694

Circadian Clock Protein Content and Daily Rhythm of Locomotor Activity Are Altered after Chronic Exposure to Lead in Rat

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Sabbar, Mariam; Dkhissi-Benyahya, Ouria; Benazzouz, Abdelhamid; Lakhdar-Ghazal, Nouria

2017-01-01

Lead exposure has been reported to produce many clinical features, including parkinsonism. However, its consequences on the circadian rhythms are still unknown. Here we aimed to examine the circadian rhythms of locomotor activity following lead intoxication and investigate the mechanisms by which lead may induce alterations of circadian rhythms in rats. Male Wistar rats were injected with lead or sodium acetate (10 mg/kg/day, i.p.) during 4 weeks. Both groups were tested in the “open field” to quantify the exploratory activity and in the rotarod to evaluate motor coordination. Then, animals were submitted to continuous 24 h recordings of locomotor activity under 14/10 Light/dark (14/10 LD) cycle and in complete darkness (DD). At the end of experiments, the clock proteins BMAL1, PER1-2, and CRY1-2 were assayed in the suprachiasmatic nucleus (SCN) using immunohistochemistry. We showed that lead significantly reduced the number of crossing in the open field, impaired motor coordination and altered the daily locomotor activity rhythm. When the LD cycle was advanced by 6 h, both groups adjusted their daily locomotor activity to the new LD cycle with high onset variability in lead-intoxicated rats compared to controls. Lead also led to a decrease in the number of immunoreactive cells (ir-) of BMAL1, PER1, and PER2 without affecting the number of ir-CRY1 and ir-CRY2 cells in the SCN. Our data provide strong evidence that lead intoxication disturbs the rhythm of locomotor activity and alters clock proteins expression in the SCN. They contribute to the understanding of the mechanism by which lead induce circadian rhythms disturbances. PMID:28970786

Diallyl tetrasulfide improves cadmium induced alterations of acetylcholinesterase, ATPases and oxidative stress in brain of rats

International Nuclear Information System (INIS)

Pari, Leelavinothan; Murugavel, Ponnusamy

2007-01-01

Cadmium (Cd) is a neurotoxic metal, which induces oxidative stress and membrane disturbances in nerve system. The garlic compound diallyl tetrasulfide (DTS) has the cytoprotective and antioxidant activity against Cd induced toxicity. The present study was carried out to investigate the efficacy of DTS in protecting the Cd induced changes in the activity of acetylcholinesterase (AChE), membrane bound enzymes, lipid peroxidation (LPO) and antioxidant status in the brain of rats. In rats exposed to Cd (3 mg/kg/day subcutaneously) for 3 weeks, a significant (P + K + -ATPase, Mg 2+ -ATPase and Ca 2+ -ATPase) were observed in brain tissue. Oral administration of DTS (40 mg/kg/day) with Cd significantly (P < 0.05) diminished the levels of LPO and protein carbonyls and significantly (P < 0.05) increased the activities of ATPases, antioxidant enzymes, GSH and TSH in brain. These results indicate that DTS attenuate the LPO and alteration of antioxidant and membrane bound enzymes in Cd exposed rats, which suggest that DTS protects the brain function from toxic effects of Cd

Transcriptional profiling of rat white adipose tissue response to 2,3,7,8-tetrachlorodibenzo-ρ-dioxin

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Houlahan, Kathleen E.; Prokopec, Stephenie D.; Sun, Ren X. [Informatics and Bio-Computing Program, Ontario Institute for Cancer Research, Toronto (Canada); Moffat, Ivy D. [Department of Pharmacology & Toxicology, University of Toronto, Toronto (Canada); Lindén, Jere [Department of Veterinary Biosciences, University of Helsinki, Helsinki (Finland); Lensu, Sanna [Department of Biology of Physical Activity, University of Jyväskylä, Jyväskylä (Finland); Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Okey, Allan B. [Department of Pharmacology & Toxicology, University of Toronto, Toronto (Canada); Pohjanvirta, Raimo, E-mail: raimo.pohjanvirta@helsinki.fi [Department of Food Hygiene and Environmental Health, University of Helsinki, Helsinki (Finland); Boutros, Paul C., E-mail: Paul.Boutros@oicr.on.ca [Informatics and Bio-Computing Program, Ontario Institute for Cancer Research, Toronto (Canada); Department of Pharmacology & Toxicology, University of Toronto, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada)

2015-10-15

Polychlorinated dibenzodioxins are environmental contaminants commonly produced as a by-product of industrial processes. The most potent of these, 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD), is highly lipophilic, leading to bioaccumulation. White adipose tissue (WAT) is a major site for energy storage, and is one of the organs in which TCDD accumulates. In laboratory animals, exposure to TCDD causes numerous metabolic abnormalities, including a wasting syndrome. We therefore investigated the molecular effects of TCDD exposure on WAT by profiling the transcriptomic response of WAT to 100 μg/kg of TCDD at 1 or 4 days in TCDD-sensitive Long-Evans (Turku/AB; L-E) rats. A comparative analysis was conducted simultaneously in identically treated TCDD-resistant Han/Wistar (Kuopio; H/W) rats one day after exposure to the same dose. We sought to identify transcriptomic changes coinciding with the onset of toxicity, while gaining additional insight into later responses. More transcriptional responses to TCDD were observed at 4 days than at 1 day post-exposure, suggesting WAT shows mostly secondary responses. Two classic AHR-regulated genes, Cyp1a1 and Nqo1, were significantly induced by TCDD in both strains, while several genes involved in the immune response, including Ms4a7 and F13a1 were altered in L-E rats alone. We compared genes affected by TCDD in rat WAT and human adipose cells, and observed little overlap. Interestingly, very few genes involved in lipid metabolism exhibited altered expression levels despite the pronounced lipid mobilization from peripheral fat pads by TCDD in L-E rats. Of these genes, the lipolysis-associated Lpin1 was induced slightly over 2-fold in L-E rat WAT on day 4. - Highlights: • Exposure to TCDD causes wasting syndrome in L-E rats but not in H/W rats. • We examined the transcriptome of TCDD-treated L-E and H/W rat white adipose tissue. • L-E WAT demonstrated altered abundance of several genes involved in immune response. • Few

Investigations on the effects of polychlorinated biphenyls on the function and structure of the thyroid gland of adult and perinatal rats

International Nuclear Information System (INIS)

Collins, W.T. Jr.

1979-01-01

Recent evidence indicates that PCB may cause alterations in thyroid structure and thyroxine metabolism. The administration of PCB to rats results in an enlargement of the thyroid gland, lowered serum thyroxine concentration, and increased conjugation and excretion of thyroxine-glucuronide in the bile. These findings suggest that some of the metabolic alterations produced by intoxication with PCB may be related to alterations in thyroid structure and function. Therefore, the objectives of this investigation were: (a) to evaluate the acute, subchronic and delayed effects of PCB on the structure and function of the thyroid gland in adult Osborne-Mendel rats; (b) to compare the changes produced by PCB with those produced by iodide excess and deficiency, and thyrotropin and thyroxine administration; (c) to investigate the fine structural changes and hormonal alterations in thyroid glands of perinatal rats exposed in utero and by the milk to PCB; and (d) to determine the alterations in the biliary excretion of 125 I-thyroxine and fine structural changes in thyroid glands of the glucuronyltransferase deficient homozygous Gunn rat exposed to PCB

Induced-hypercholesterolemia as a probable cause of alterations in ...

African Journals Online (AJOL)

Methods: The telemetry technique was used to investigate the cardiovascular dysfunctions in induced hypercholesterolemia in Wistar Kyoto (WKY) rats. Methods for this investigation include: inducing hypercholesterolemic condition in Wistar Kyoto rats through diet; measuring the blood cholesterol levels of the experimental ...

High intraocular pressure produces learning and memory impairments in rats.

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Yuan, Yuxiang; Chen, Zhiqi; Li, Lu; Li, Xing; Xia, Qian; Zhang, Hong; Duan, Qiming; Zhao, Yin

2017-11-15

Primary open angle glaucoma (POAG) is a leading cause of irreversible blindness worldwide. Previous MRI studies have revealed that POAG can be associated with alterations in hippocampal function. Thus, the aim of this study was to investigate a relationship between chronic high intraocular pressure (IOP) and hippocampal changes in a rat model. We used behavioural tests to assess learning and memory ability, and additionally investigated the hippocampal expression of pathological amyloid beta (Aβ), phospho-tau, and related pathway proteins. Chronic high IOP impaired learning and memory in rats and concurrently increased Aβ and phospho-tau expression in the hippocampus by altering the activation of different kinase (GSK-3β, BACE1) and phosphatase (PP2A) proteins in the hippocampus. This study provides novel evidence for the relationship between high IOP and hippocampal alterations, especially in the context of learning and memory. Copyright © 2017 Elsevier B.V. All rights reserved.

Antioxidant-Rich Fraction of Urtica dioica Mediated Rescue of Striatal Mito-Oxidative Damage in MPTP-Induced Behavioral, Cellular, and Neurochemical Alterations in Rats.

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Bisht, Rohit; Joshi, Bhuwan Chandra; Kalia, Ajudhiya Nath; Prakash, Atish

2017-09-01

Parkinson's disease (PD) having a complex and multi-factorial neuropathology includes mainly the degeneration of the dopaminergic nigrostriatal pathway, which is a cumulative effect of depleted endogenous antioxidant enzymes, increased oxidative DNA damage, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. The present study was designed to investigate the neuroprotective effect of a potent antioxidant from Urtica dioica in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism. MPTP was administered intranigrally for the induction of PD in male Wistar rats. Behavioral alterations were assessed in between the study period. Animals were sacrificed immediately after behavioral session, and different biochemical, cellular, and neurochemical parameters were measured. Intranigrally repeated administration of MPTP showed significant impairment of motor co-ordination and marked increase of mito-oxidative damage and neuroinflammation in rats. Intranigral MPTP significantly decreases the dopamine and its metabolites with impairment of dopaminergic cell density in rat brain. However, post-treatment with the potent antioxidant fraction of Urtica dioica Linn. (UD) (20, 40, 80 mg/kg) improved the motor function, mito-oxidative defense alteration significantly and dose dependently in MPTP-treated rats. In addition, the potent antioxidant fraction of UD attenuated the pro-inflammatory cytokines (TNF-α and IL-β) and restored the level of dopamine and its metabolites in MPTP-induced PD in rats. Moreover, minocycline (30 mg/kg) with lower dose of UD (20 mg/kg) had significantly potentiated the protective effect of minocycline as compared to its effect with other individual drug-treated groups. In conclusion, Urtica dioica protected the dopaminergic neurons probably by reducing mito-oxidative damage, neuroinflammation, and cellular alteration along with enhanced neurotrophic potential. The above results revealed that the antioxidant rich

Housing in Pyramid Counteracts Neuroendocrine and Oxidative Stress Caused by Chronic Restraint in Rats

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M. Surekha Bhat

2007-01-01

Full Text Available The space within the great pyramid and its smaller replicas is believed to have an antistress effect. Research has shown that the energy field within the pyramid can protect the hippocampal neurons of mice from stress-induced atrophy and also reduce neuroendocrine stress, oxidative stress and increase antioxidant defence in rats. In this study, we have, for the first time, attempted to study the antistress effects of pyramid exposure on the status of cortisol level, oxidative damage and antioxidant status in rats during chronic restraint stress. Adult female Wistar rats were divided into four groups as follows: normal controls (NC housed in home cage and left in the laboratory; restrained rats (with three subgroups subject to chronic restraint stress by placing in a wire mesh restrainer for 6 h per day for 14 days, the restrained controls (RC having their restrainers kept in the laboratory; restrained pyramid rats (RP being kept in the pyramid; and restrained square box rats (RS in the square box during the period of restraint stress everyday. Erythrocyte malondialdehyde (MDA and plasma cortisol levels were significantly increased and erythrocyte-reduced glutathione (GSH levels, erythrocyte glutathione peroxidase (GSH-Px and superoxide dismutase (SOD activities were significantly decreased in RC and RS rats as compared to NC. However, these parameters were maintained to near normal levels in RP rats which showed significantly decreased erythrocyte MDA and plasma cortisol and significantly increased erythrocyte GSH levels, erythrocyte GSH-Px and SOD activities when compared with RS rats. The results showed that housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats.

Influence of ovarian hormones on development of ingestive responding to alterations in fatty acid oxidation in female rats

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Swithers, Susan E.; McCurley, Melissa; Hamilton, Erica; Doerflinger, Alicia

2008-01-01

Adult male rats have been demonstrated to increase food intake in response to administration of drugs that interfere with oxidation of fatty acids (e.g. methyl palmoxirate and mercaptoacetate [MA]), effects that are larger in animals maintained on a high-fat diet. In contrast, while administration of MA has been reported to stimulate food intake in pre-pubertal female rats, food intake is not stimulated by MA in adult female rats. Instead, administration of MA to adult females results in changes in reproductive behavior and physiology. The present experiments were designed to examine the effects of administration of MA on food intake in adult female rats. The results demonstrated that, as previously reported, food intake was stimulated by MA in adult male rats on low-fat and high-fat diets, but food intake in was not stimulated by MA in gonadally-intact adult female rats on either low-fat or high-fat diet. Further, MA did not stimulate food intake in female rats ovariectomized as adults. However, when females were ovariectomized prior to the onset of puberty (postnatal day 25 – 28), food intake was stimulated by administration of MA in adulthood. Finally, cyclic injections of 17-β-estradiol benzoate given to females ovariectomized prior to the onset of puberty abolished the stimulatory effects of MA on food intake in adult females. Taken together, the data suggest that exposure to estrogens during the time of puberty in female rats can persistently alter adult ingestive responding to signals related to changes in energy utilization. PMID:18586247

Alteration of gastrointestinal transit time in the rat after bile duct cannulation surgery

International Nuclear Information System (INIS)

Ayres, P.H.; Medinsky, M.A.; Muggenburg, B.A.; Bond, J.A.

1985-01-01

Alteration of gastrointestinal (GI) transit time could affect the bioavailability of a toxicant if the toxicant is absorbed in the GI tract. The effect of surgery on GI transit time was investigated using radiographic imaging of barium during passage through the GI tract of the rat. Bile duct cannulation surgery delayed transit of barium to over 18 h, whereas in the normal animal, transit required approximately 6 h. GI transit time was only moderately affected by laparotomy after an 18-h postsurgery recovery period. These results suggest that the gastrointestinal absorption of orally administered toxicants could be affected by bile duct cannulation. 3 references, 1 figure, 1 table

The inhibition of nitric oxide-activated poly(ADP-ribose) synthetase attenuates transsynaptic alteration of spinal cord dorsal horn neurons and neuropathic pain in the rat.

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Mao, J; Price, D D; Zhu, J; Lu, J; Mayer, D J

1997-09-01

Transsynaptic alteration of spinal cord dorsal horn neurons characterized by hyperchromatosis of cytoplasm and nucleoplasm (so-called 'dark' neurons) occurs in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the common sciatic nerve. The incidence of dark neurons in CCI rats has been proposed to be mediated by glutamate-induced neurotoxicity. In the present study, we examined whether the inhibition of the nitric oxide (NO)-activated poly(ADP-ribose) synthetase (PARS), a nuclear enzyme critical to glutamate-induced neurotoxicity, would both reduce the incidence of dark neurons and attenuate behavioral manifestations of neuropathic pain in CCI rats. Dark neurons were observed bilaterally (with ipsilateral predominance) within the spinal cord dorsal horn, particularly in laminae I-II, of rats 8 days after unilateral sciatic nerve ligation as compared to sham operated rats. The number of dark neurons in the dorsal horn was dose-dependently reduced in CCI rats receiving once daily intrathecal (i.t.) treatment with the PARS inhibitor benzamide (200 or 400 nmol, but not 100 nmol benzamide or saline) for 7 days. Consistent with the histological improvement, thermal hyperalgesia, mechanical hyperalgesia, and low threshold mechano-allodynia also were reliably reduced in CCI rats treated with either 200 or 400 nmol benzamide. Neither dark neurons nor neuropathic pain behaviors were reliably affected by i.t. administration of either 800 nmol novobiocin (a mono(ADP-ribose) synthetase) or 800 nmol benzoic acid (the backbone structure of benzamide), indicating a selective effect of benzamide. Intrathecal treatment with an NO synthase inhibitor NG-nitro-L-arginine methyl ester (40 nmol, but not its inactive D-isomer) utilizing the same benzamide treatment regimen resulted in similar reductions of both dark neurons and neuropathic pain behaviors in CCI rats. These results provide, for the first time, in vivo evidence indicating that benzamide is

[Alterations of glial fibrillary acidic protein in rat brain after gamma knife irradiation].

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Ma, Z M; Jiang, B; Ma, J R

2001-08-28

To study glial fibrillary acidic protein (GFAP) immunoreactivity in different time and water content of the rat brain treated with gamma knife radiotherapy and to understand the alteration course of the brain lesion after a single high dose radiosurgical treatment. In the brains of the normal rats were irradiated by gamma knife with 160 Gy-high dose. The irradiated rats were then killed on the 1st day, 7th day, 14th day, and 28th day after radiotherapy, respectively. The positive cells of GFAP in brain tissue were detected by immunostaining; the water content of the brain tissue was measured by microgravimetry. The histological study of the irradiated brain tissue was performed with H.E. and examined under light microscope. The numbers of GFAP-positive astrocytes began to increase on the 1st day after gamma knife irradiation. It was enlarged markedly in the number and size of GFAP-stained astrocytes over the irradiated areas. Up to the 28th day, circumscribed necrosis foci (4 mm in diameter) was seen in the central area of the target. In the brain tissue around the necrosis, GFAP-positive astrocytes significantly increased (P gravity in the irradiated brain tissue the 14th and 28th day after irradiation. The results suggest that GFAP can be used as a marker for the radiation-induced brain injury. The brain edema and disruption of brain-blood barrier can be occurred during the acute stage after irradiation.

Low level postnatal methylmercury exposure in vivo alters developmental forms of short-term synaptic plasticity in the visual cortex of rat

International Nuclear Information System (INIS)

Dasari, Sameera; Yuan, Yukun

2009-01-01

Methylmercury (MeHg) has been previously shown to affect neurotransmitter release. Short-term synaptic plasticity (STP) is primarily related to changes in the probability of neurotransmitter release. To determine if MeHg affects STP development, we examined STP forms in the visual cortex of rat following in vivo MeHg exposure. Neonatal rats received 0 (0.9% NaCl), 0.75 or 1.5 mg/kg/day MeHg subcutaneously for 15 or 30 days beginning on postnatal day 5, after which visual cortical slices were prepared for field potential recordings. In slices prepared from rats treated with vehicle, field excitatory postsynaptic potentials (fEPSPs) evoked by paired-pulse stimulation at 20-200 ms inter-stimulus intervals showed a depression (PPD) of the second fEPSP (fEPSP2). PPD was also seen in slices prepared from rats after 15 day treatment with 0.75 or 1.5 mg/kg/day MeHg. However, longer duration treatment (30 days) with either dose of MeHg resulted in paired-pulse facilitation (PPF) of fEPSP2 in the majority of slices examined. PPF remained observable in slices prepared from animals in which MeHg exposure had been terminated for 30 days after completion of the initial 30 day MeHg treatment, whereas slices from control animals still showed PPD. MeHg did not cause any frequency- or region-preferential effect on STP. Manipulations of [Ca 2+ ] e or application of the GABA A receptor antagonist bicuculline could alter the strength and polarity of MeHg-induced changes in STP. Thus, these data suggest that low level postnatal MeHg exposure interferes with the developmental transformation of STP in the visual cortex, which is a long-lasting effect.

The rat intervertebral disk degeneration pain model: relationships between biological and structural alterations and pain.

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Kim, Jae-Sung; Kroin, Jeffrey S; Li, Xin; An, Howard S; Buvanendran, Asokumar; Yan, Dongyao; Tuman, Kenneth J; van Wijnen, Andre J; Chen, Di; Im, Hee-Jeong

2011-01-01

Degeneration of the interverterbral disk is as a cause of low-back pain is increasing. To gain insight into relationships between biological processes, structural alterations and behavioral pain, we created an animal model in rats. Disk degeneration was induced by removal of the nucleus pulposus (NP) from the lumbar disks (L4/L5 and L5/L6) of Sprague Dawley rats using a 0.5-mm-diameter microsurgical drill. The degree of primary hyperalgesia was assessed by using an algometer to measure pain upon external pressure on injured lumbar disks. Biochemical and histological assessments and radiographs of injured disks were used for evaluation. We investigated therapeutic modulation of chronic pain by administering pharmaceutical drugs in this animal model. After removal of the NP, pressure hyperalgesia developed over the lower back. Nine weeks after surgery we observed damaged or degenerated disks with proteoglycan loss and narrowing of disk height. These biological and structural changes in disks were closely related to the sustained pain hyperalgesia. A high dose of morphine (6.7 mg/kg) resulted in effective pain relief. However, high doses of pregabalin (20 mg/kg), a drug that has been used for treatment of chronic neuropathic pain, as well as the anti-inflammatory drugs celecoxib (50 mg/kg; a selective inhibitor of cyclooxygenase 2 (COX-2)) and ketorolac (20 mg/kg; an inhibitor of COX-1 and COX-2), did not have significant antihyperalgesic effects in our disk injury animal model. Although similarities in gene expression profiles suggest potential overlap in chronic pain pathways linked to disk injury or neuropathy, drug-testing results suggest that pain pathways linked to these two chronic pain conditions are mechanistically distinct. Our findings provide a foundation for future research on new therapeutic interventions that can lead to improvements in the treatment of patients with back pain due to disk degeneration.

Running wheel training does not change neurogenesis levels or alter working memory tasks in adult rats

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Cesar A. Acevedo-Triana

2017-05-01

Full Text Available Background Exercise can change cellular structure and connectivity (neurogenesis or synaptogenesis, causing alterations in both behavior and working memory. The aim of this study was to evaluate the effect of exercise on working memory and hippocampal neurogenesis in adult male Wistar rats using a T-maze test. Methods An experimental design with two groups was developed: the experimental group (n = 12 was subject to a forced exercise program for five days, whereas the control group (n = 9 stayed in the home cage. Six to eight weeks after training, the rats’ working memory was evaluated in a T-maze test and four choice days were analyzed, taking into account alternation as a working memory indicator. Hippocampal neurogenesis was evaluated by means of immunohistochemistry of BrdU positive cells. Results No differences between groups were found in the behavioral variables (alternation, preference index, time of response, time of trial or feeding, or in the levels of BrdU positive cells. Discussion Results suggest that although exercise may have effects on brain structure, a construct such as working memory may require more complex changes in networks or connections to demonstrate a change at behavioral level.

Prenatal noise and restraint stress interact to alter exploratory behavior and balance in juvenile rats, and mixed stress reverses these effects.

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Badache, Soumeya; Bouslama, Slim; Brahmia, Oualid; Baïri, Abdel Madjid; Tahraoui, Abdel Krim; Ladjama, Ali

2017-05-01

We aimed to investigate in adolescent rats the individual and combined effects of prenatal noise and restraint stress on balance control, exploration, locomotion and anxiety behavior. Three groups of pregnant rats were exposed to daily repeated stress from day 11 to day 19 of pregnancy: 3 min noise (Noise Stress, NS); 10 min restraint (restraint stress, RS); or 3 min noise followed by 10 min restraint (mixed stress, MS). On postnatal days (PND) 44, 45 and 46, four groups of male rats (Control, NS, RS:, MS; 16 rats each), were tested as follows: (1) beam walking (BW), (2) open field (OF) and (3) elevated plus maze (EPM). Our results show that the NS group had significantly impaired balance control, locomotion and both horizontal and vertical exploration (p time in EPM open arms: p time to complete BW: p < .05). Hence, combined prenatal stressors exert non-additive effects on locomotion, exploration and balance control, but induce greater anxiety through additive effects. Terminal plasma ACTH concentration was increased by prenatal stress, especially noise, which group had the largest adrenal glands. Overall, contrary to expectation, combined prenatal stressors can interact to increase anxiety level, but diminish alteration of exploration, locomotion and impaired balance control, which were strongly induced by noise stress. Lay summary: Experience of stress in pregnancy can have negative effects on the offspring that are long-lasting. Here, we used laboratory rats to see whether repeated episodes of exposure to loud noise or preventing free movement, alone or together, during pregnancy had different effects on behaviors of the adolescent offspring. Using standard tests, we found the prenatal stresses caused the offspring to be anxious, and not to balance when moving around as well as normal offspring; the degree of impairment depended on the type of stress - loud noise exposure had the greatest effects, but if the stresses were combined the effects

Neuronal Rat Brain Damage Caused by Endogenous and Exogenous Hyperthermia

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Mustafa Aydın

2012-03-01

Full Text Available OBJECTIVE: Hyperthermia may induce pathologic alterations within body systems and organs including brain. In this study, neuronal effects of endogenous and exogenous hyperthermia (41°C were studied in rats. METHODS: The endogenous hyperthermia (41°C was induced by lipopolysaccharide and the exogenous by an (electric heater. Possible neuronal damage was evaluated by examining healthy, apoptotic and necrotic cells, and heat shock proteins (HSP 27, HSP 70 in the cerebral cortex, cerebellum and hypothalamus RESULTS: At cellular level, when all neuronal tissues are taken into account; (i a significant increase in the necrotic cells was observed in the both groups (p0.05. CONCLUSION: The neural tissue of brain can show different degree of response to hyperthermia. But we can conclude that endogenous hyperthermia is more harmful to central nervous system than exogenous hyperthermia

Low-protein diet does not alter reproductive, biochemical, and hematological parameters in pregnant Wistar rats

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M.A.V. Barros

2018-05-01

Full Text Available The aim of this study was to investigate the reproductive, biochemical, and hematological outcomes of pregnant rats exposed to protein restriction. Wistar rat dams were fed a control normal-protein (NP, 17% protein, n=8 or a low-protein (LP, 8% protein, n=14 diet from the 1st to the 20th day of pregnancy. On the 20th day, the clinical signs of toxicity were evaluated. The pregnant rats were then anesthetized and blood samples were collected for biochemical-hematological analyses, and laparotomy was performed to evaluate reproductive parameters. No sign of toxicity, or differences (P>0.05 in body weight gain and biochemical parameters (urea, creatinine, albumin, globulin, and total protein between NP and LP pregnant dams were observed. Similarly, hematological data, including red blood cell count, white blood cell count, hemoglobin, hematocrit, red blood cell distribution width (coefficient of variation, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, % lymphocytes, absolute lymphocyte count, platelet count, and mean platelet volume were similar (P>0.05 at the end of pregnancy. Reproductive parameters (the dam-offspring relationship, ovary mass, placenta mass, number of corpora lutea, implantation index, resorption index, and the pre- and post-implantation loss rates were also not different (P>0.05 between NP and LP pregnant dams. The present data showed that a protein-restricted diet during pregnancy did not alter reproductive, biochemical, and hematological parameters and seems not to have any toxic effect on pregnant Wistar rats.

Omega-3 Fatty Acid Enriched Chevon (Goat Meat Lowers Plasma Cholesterol Levels and Alters Gene Expressions in Rats

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Mahdi Ebrahimi

2014-01-01

Full Text Available In this study, control chevon (goat meat and omega-3 fatty acid enriched chevon were obtained from goats fed a 50% oil palm frond diet and commercial goat concentrate for 100 days, respectively. Goats fed the 50% oil palm frond diet contained high amounts of α-linolenic acid (ALA in their meat compared to goats fed the control diet. The chevon was then used to prepare two types of pellets (control or enriched chevon that were then fed to twenty-male-four-month-old Sprague-Dawley rats (n=10 in each group for 12 weeks to evaluate their effects on plasma cholesterol levels, tissue fatty acids, and gene expression. There was a significant increase in ALA and docosahexaenoic acid (DHA in the muscle tissues and liver of the rats fed the enriched chevon compared with the control group. Plasma cholesterol also decreased (P<0.05 in rats fed the enriched chevon compared to the control group. The rat pellets containing enriched chevon significantly upregulated the key transcription factor PPAR-γ and downregulated SREBP-1c expression relative to the control group. The results showed that the omega-3 fatty acid enriched chevon increased the omega-3 fatty acids in the rat tissues and altered PPAR-γ and SREBP-1c genes expression.

Omega-3 fatty acid enriched chevon (goat meat) lowers plasma cholesterol levels and alters gene expressions in rats.

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Ebrahimi, Mahdi; Rajion, Mohamed Ali; Meng, Goh Yong; Soleimani Farjam, Abdoreza

2014-01-01

In this study, control chevon (goat meat) and omega-3 fatty acid enriched chevon were obtained from goats fed a 50% oil palm frond diet and commercial goat concentrate for 100 days, respectively. Goats fed the 50% oil palm frond diet contained high amounts of α-linolenic acid (ALA) in their meat compared to goats fed the control diet. The chevon was then used to prepare two types of pellets (control or enriched chevon) that were then fed to twenty-male-four-month-old Sprague-Dawley rats (n = 10 in each group) for 12 weeks to evaluate their effects on plasma cholesterol levels, tissue fatty acids, and gene expression. There was a significant increase in ALA and docosahexaenoic acid (DHA) in the muscle tissues and liver of the rats fed the enriched chevon compared with the control group. Plasma cholesterol also decreased (P < 0.05) in rats fed the enriched chevon compared to the control group. The rat pellets containing enriched chevon significantly upregulated the key transcription factor PPAR-γ and downregulated SREBP-1c expression relative to the control group. The results showed that the omega-3 fatty acid enriched chevon increased the omega-3 fatty acids in the rat tissues and altered PPAR-γ and SREBP-1c genes expression.

Prior methylphenidate self-administration alters the subsequent reinforcing effects of methamphetamine in rats.

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Baladi, Michelle G; Nielsen, Shannon M; Umpierre, Anthony; Hanson, Glen R; Fleckenstein, Annette E

2014-12-01

Methylphenidate (MPD) is clinically effective in treating the symptoms of attention-deficit hyperactivity disorder; however, its relatively widespread availability has raised public health concerns on nonmedical use of MPD among certain adult populations. Most preclinical studies investigate whether presumed therapeutically relevant doses of MPD alter sensitivity to the reinforcing effects of other drugs, but it remains unclear whether doses of MPD likely exceeding therapeutic relevance impact the subsequent reinforcing effects of drugs. To begin to address this question, the effect of prior MPD self-administration (0.56 mg/kg/infusion) on the subsequent reinforcing effects of methamphetamine (METH, 0.032 or 0.1 mg/kg/infusion) was investigated in male Sprague-Dawley rats. For comparison, it was also determined whether prior experimenter-administered MPD, injected daily at a presumed therapeutically relevant dose (2 mg/kg), altered the subsequent reinforcing effects of METH. Results indicated that, under the current conditions, only a history of MPD self-administration increased sensitivity to the subsequent reinforcing effects of METH. Furthermore, MPD did not impact food-maintained responding, suggesting that the effect of MPD might be specific to drug reinforcers. These data suggest that short-term, nonmedical use of MPD might alter the positive reinforcing effects of METH in a manner relevant to vulnerability to drug use in humans.

Impact of ginger aqueous extract on carbimazole induced testicular degenerative alterations and oxidative stress in albino rats

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Saber Abdel-Rahman Sakr

2017-04-01

Full Text Available Objective: To evaluate the effect of ginger (Zingiber officinale aqueous extract, a natural herb, with antioxidant properties, on testicular toxicity and oxidative stress induced by the antithyroid drug carbimazole in albino rats. Methods: Four groups of male albino rats were used. Group I served as control. Group II rats were treated with ginger aqueous extract (24 mg/mL. Group III rats were given orally carbimazole (1.35 mg/kg bw. Group IV rats were given carbimazole and ginger extract. Animals were sacrificed and their testes were removed and stained with H&E for histological examination. Sperms were collected from epididymis for detection of sperm head abnormalities. Immunohistochemical expression of PCNA and Bax was detected in the testes. MDA, CAT and GSH were measured in the sera. Results: Treating rats with carbimazole revealed significant alterations in the tissue of testis including decreased seminiferous epithelium height, decreased diameter of seminiferous tubule and changes in the spermatogenic layers arrangement. Intertubular hemorrhage and congested blood vessels were noted. An increase in sperm head abnormalities was recorded. Decreased cell proliferation was reflected by a decrease in PCNA expression, while the increase in apoptotic rate was accompanied with an increase in Bax expression. Oxidative stress was demonstrated by an increase in malondialdehyde and decrease in activity of catalase and glutathione. Combined treatment of carbimazole and aqueous ginger extract led to an improvement in histological, morphometrical, immunohistochemical changes and oxidative stress induced by carbimazole. Conclusions: The ameliorative effects of ginger extract could be due to its antioxidant properties.

Alteration of gene expression profiles in skeletal muscle of rats exposed to microgravity during a spaceflight

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Taylor, Wayne E.; Bhasin, Shalender; Lalani, Rukhsana; Datta, Anuj; Gonzalez-Cadavid, Nestor F.

2002-01-01

To clarify the mechanism of skeletal muscle wasting during spaceflights, we investigated whether intramuscular gene expression profiles are affected, by using DNA microarray methods. Male rats sent on the 17-day NASA STS-90 Neurolab spaceflight were sacrificed 24 hours after return to earth (MG group). Ground control rats were maintained for 17 days in flight-simulated cages (CS group). Spaceflight induced a 19% and 23% loss of tibialis anterior and gastrocnemius muscle mass, respectively, as compared to ground controls. Muscle RNA was analyzed by the Clontech Atlas DNA expression array in four rats, with two MG/ CS pairs for the tibialis anterior, and one pair for the gastrocnemius. Alterations in gene expression were verified for selected genes by reverse-transcription PCR. In both muscles of MG rats, mRNAs for 12 genes were up-regulated by over 2-fold, and 38 were down-regulated compared to controls. There was inhibition of genes for cell proliferation and growth factor cascades, including cell cycle genes and signal transduction proteins, such as p21 Cip1, retinoblastoma (Rb), cyclins G1/S, -E and -D3, MAP kinase 3, MAD3, and ras related protein RAB2. These data indicate that following exposure to microgravity, there is downregulation of genes involved in regulation of muscle satellite cell replication.

Evaluation of the water disinfection by-product dichloroacetonitrile-induced biochemical, oxidative, histopathological, and mitochondrial functional alterations: Subacute oral toxicity in rats.

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Dong, Ying; Li, Fang; Shen, Haijun; Lu, Rongzhu; Yin, Siqi; Yang, Qi; Li, Zhuangfa; Wang, Suhua

2018-03-01

Dichloroacetonitrile (DCAN), an emerging nitrogenous disinfection by-product, is more genotoxic and cytotoxic than the currently regulated carbonaceous disinfection by-products such as haloacetic acids. Few mechanistic studies have been conducted on the hepatic and renal toxicities of DCAN. This study examined the clinical biochemical, hematological, histopathological, oxidative, and mitochondrial functional alterations to evaluate the systematic toxicity after subacute oral exposure of 11 or 44 mg/kg/day in rats for 28 days. Body and spleen weights were lower, and organ-to-body weight ratios of the liver and kidney were higher in rats administered 44-mg/kg DCAN than in controls. The activities of serum alanine aminotransferase and alkaline phosphatase, and concentrations of blood serum urea nitrogen and retinol-binding protein were increased in rats administered 44-mg/kg DCAN compared with those of controls, thereby indicating hepatic and renal damage in this group. This was confirmed by histopathological alterations, including hepatic sinus dilation, extensive hemorrhage, vacuolar degeneration in the liver and glomerulus hemorrhage, and renal tubular swelling, in DCAN-exposed rats. Exposure to 44-mg/kg DCAN induced hepatic oxidative damage shown by the significant increase in malonaldehyde levels, a poisonous product of lipid peroxidation. Exposure to 44-mg/kg DCAN significantly increased hepatic glutathione content and mitochondrial bioenergy as noted by the elevation of mitochondrial membrane potential and cytochrome c oxidase activity, which might be attributed to compensatory pathophysiologic responses to DCAN-induced hepatic mitochondrial damage.

Alterations in rat cardiac myosin isozymes induced by whole-body irradiation are prevented by 3,5,3'-L-triiodothyronine

International Nuclear Information System (INIS)

Litten, R.Z.; Fein, H.G.; Gainey, G.T.; Walden, T.L.; Smallridge, R.C.

1990-01-01

Changes in cardiac myosin isozymes and serum thyroid hormone levels were investigated in rats following 10 Gy whole-body gamma irradiation. The percent beta-myosin heavy chain increased from 21.3 ± 1.8 to 28.1 ± 6.8 (NS) at 3-day postirradiation, 37.7 ± 1.9 (P less than .001) at 6-day postirradiation, and 43.8 ± 3.3 (P less than .001) at 9-day postirradiation. Along with the change in myosin isozymes was a significant 53% decrease (P less than .001) in the serum thyroxine (T4) level by day 3 postirradiation, remaining depressed through day 9 postirradiation. The serum 3,5,3'-triiodothyronine (T3) level, however, was normal until day 9, when significant depression was also observed. In contrast, the thyroid-stimulating hormone (TSH) level was significantly increased by fourfold at day 3, returning to near normal values by day 9 postirradiation. Daily injections of physiological doses of T3 (0.3 microgram/100 g body weight) prevented the change in the myosin isozymes following whole-body irradiation. Daily pharmacological injections of T3 (3.0 micrograms/100 g body weight) to the irradiated rats produced a further decrease in the percent beta-myosin heavy chain (below control values) indicating tissue hyperthyroidism. Thus, this study suggests that the change in myosin isozymes following whole-body irradiation is caused by an alteration in thyroid hormone activity

Alteration of NPY and Y1 receptor in dorsomedial and ventromedial areas of hypothalamus in anorectic tumor-bearing rats.

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Chance, William T; Xiao, Chun; Dayal, Ramesh; Sheriff, Sulaiman

2007-02-01

Although previous studies have implicated NPY in the etiology of experimental cancer anorexia, the results have been difficult to interpret. Studies have suggested that although NPY level and message were decreased in the dorsomedial hypothalamic area (DMA), they were elevated in the ventromedial hypothalamic area (VMA). To better assess specific intra-area alterations of NPY, Y(1) receptor (Y(1) R), and agouti-related peptide (AgRP) in TB rats, we used radioimmunoassay, quantitative real-time RT-PCR, and immunohistochemistry. We found that NPY and AgRP mRNA were elevated significantly in whole hypothalamus of anorectic TB rats, while Y(1) R mRNA was decreased. Based on two replicates of four pooled samples each, both NPY and AgRP mRNA appeared to be elevated in the VMA of anorectic TB rats, while only AgRP exhibited a similar increase in the DMA. Levels of NPY were elevated in the VMA of both TB and pair-fed (PF) rats, but in the DMA only PF rats exhibited a significant NPY increase. NPY and Y(1) R immunohistochemistry revealed reduced NPY staining in PVN and ARC nucleus of TB and PF rats. Y(1) R immunostaining was also reduced in the ARC and PVN of TB rats, while PF rats exhibited elevated immunostaining in the PVN. These results continue to implicate dysfunction of NPY feeding systems in experimental cancer anorexia and suggest down-regulation of Y(1) R receptors as well as possible problems in NPY translation.

Endothelin mechanisms in altered thyroid states in the rat.

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Rebello, S; Thompson, E B; Gulati, A

1993-06-11

Endothelin (ET) and its receptor characteristics were studied in hyper- and hypo-thyroid states in the rats. Hyperthyroidism was induced by daily administration of thyroxine (0.1 mg/kg i.p.) for 8 weeks, while hypothyrodism was induced by daily administration of methimazole (10 mg/kg i.p.) for 8 weeks. The chronic administration of thyroxine to rats decreased their rate of gain of body weight, increased serum T3 and T4 concentration, blood pressure and heart rate. The chronic administration of methimazole decreased the rate of gain of body weight, serum T3 and T4 concentration, blood pressure and heart rate as compared to vehicle-treated control. Plasma ET-1 levels were found to be similar in control and methimazole-treated rats, while the levels were found to be significantly (P < 0.002) increased in thyroxine-treated rats as compared to control rats. Binding studies showed that [125I]ET-1 bound to a single, high affinity binding site in the cerebral cortex, hypothalamus and pituitary. The density (Bmax) and the affinity (Kd) of [125I]ET-1 binding in the cerebral cortex and hypothalamus were found to be similar in control, methimazole- and thyroxine-treated rats. The pituitary of thyroxine-treated rats showed a decrease in the binding (34.3% decrease in the density) of [125I]ET-1 as compared to control rats. No difference was observed in the binding of [125I]ET-1 to pituitary membranes from control and methimazole-treated rats. Competition studies showed that the IC50 and Ki values of ET-3 for [125]ET-1 binding were about 8 to 11 times higher than ET-1 in cerebral cortex, hypothalamus and pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)

Noise exposure of immature rats can induce different age-dependent extra-auditory alterations that can be partially restored by rearing animals in an enriched environment.

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Molina, S J; Capani, F; Guelman, L R

2016-04-01

It has been previously shown that different extra-auditory alterations can be induced in animals exposed to noise at 15 days. However, data regarding exposure of younger animals, that do not have a functional auditory system, have not been obtained yet. Besides, the possibility to find a helpful strategy to restore these changes has not been explored so far. Therefore, the aims of the present work were to test age-related differences in diverse hippocampal-dependent behavioral measurements that might be affected in noise-exposed rats, as well as to evaluate the effectiveness of a potential neuroprotective strategy, the enriched environment (EE), on noise-induced behavioral alterations. Male Wistar rats of 7 and 15 days were exposed to moderate levels of noise for two hours. At weaning, animals were separated and reared either in standard or in EE cages for one week. At 28 days of age, different hippocampal-dependent behavioral assessments were performed. Results show that rats exposed to noise at 7 and 15 days were differentially affected. Moreover, EE was effective in restoring all altered variables when animals were exposed at 7 days, while a few were restored in rats exposed at 15 days. The present findings suggest that noise exposure was capable to trigger significant hippocampal-related behavioral alterations that were differentially affected, depending on the age of exposure. In addition, it could be proposed that hearing structures did not seem to be necessarily involved in the generation of noise-induced hippocampal-related behaviors, as they were observed even in animals with an immature auditory pathway. Finally, it could be hypothesized that the differential restoration achieved by EE rearing might also depend on the degree of maturation at the time of exposure and the variable evaluated, being younger animals more susceptible to environmental manipulations. Copyright © 2016 Elsevier B.V. All rights reserved.

Functional disconnection of the orbitofrontal cortex and basolateral amygdala impairs acquisition of a rat gambling task and disrupts animals' ability to alter decision-making behavior after reinforcer devaluation.

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Zeeb, Fiona D; Winstanley, Catharine A

2013-04-10

An inability to adjust choice preferences in response to changes in reward value may underlie key symptoms of many psychiatric disorders, including chemical and behavioral addictions. We developed the rat gambling task (rGT) to investigate the neurobiology underlying complex decision-making processes. As in the Iowa Gambling task, the optimal strategy is to avoid choosing larger, riskier rewards and to instead favor options associated with smaller rewards but less loss and, ultimately, greater long-term gain. Given the demonstrated importance of the orbitofrontal cortex (OFC) and basolateral amygdala (BLA) in acquisition of the rGT and Iowa Gambling task, we used a contralateral disconnection lesion procedure to assess whether functional connectivity between these regions is necessary for optimal decision-making. Disrupting the OFC-BLA pathway retarded acquisition of the rGT. Devaluing the reinforcer by inducing sensory-specific satiety altered decision-making in control groups. In contrast, disconnected rats did not update their choice preference following reward devaluation, either when the devalued reward was still delivered or when animals needed to rely on stored representations of reward value (i.e., during extinction). However, all rats exhibited decreased premature responding and slower response latencies after satiety manipulations. Hence, disconnecting the OFC and BLA did not affect general behavioral changes caused by reduced motivation, but instead prevented alterations in the value of a specific reward from contributing appropriately to cost-benefit decision-making. These results highlight the role of the OFC-BLA pathway in the decision-making process and suggest that communication between these areas is vital for the appropriate assessment of reward value to influence choice.

Alterations in the Interplay between Neurons, Astrocytes and Microglia in the Rat Dentate Gyrus in Experimental Models of Neurodegeneration

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Daniele Lana

2017-09-01

Full Text Available The hippocampus is negatively affected by aging and neurodegenerative diseases leading to impaired learning and memory abilities. A diverse series of progressive modifications in the intercellular communication among neurons, astrocytes and microglia occur in the hippocampus during aging or inflammation. A detailed understanding of the neurobiological modifications that contribute to hippocampal dysfunction may reveal new targets for therapeutic intervention. The current study focussed on the interplay between neurons and astroglia in the Granule Layer (GL and the Polymorphic Layer (PL of the Dentate Gyrus (DG of adult, aged and LPS-treated rats. In GL and PL of aged and LPS-treated rats, astrocytes were less numerous than in adult rats. In GL of LPS-treated rats, astrocytes acquired morphological features of reactive astrocytes, such as longer branches than was observed in adult rats. Total and activated microglia increased in the aged and LPS-treated rats, as compared to adult rats. In the GL of aged and LPS-treated rats many neurons were apoptotic. Neurons decreased significantly in GL and PL of aged but not in rats treated with LPS. In PL of aged and LPS-treated rats many damaged neurons were embraced by microglia cells and were infiltrated by branches of astrocyte, which appeared to be bisecting the cell body, forming triads. Reactive microglia had a scavenging activity of dying neurons, as shown by the presence of neuronal debris within their cytoplasm. The levels of the chemokine fractalkine (CX3CL1 increased in hippocampal homogenates of aged rats and rats treated with LPS, and CX3CL1 immunoreactivity colocalized with activated microglia cells. Here we demonstrated that in the DG of aged and LPS-treated rats, astrocytes and microglia cooperate and participate in phagocytosis/phagoptosis of apoptotic granular neurons. The differential expression/activation of astroglia and the alteration of their intercommunication may be responsible for

Acetate causes alcohol hangover headache in rats.

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Christina R Maxwell

2010-12-01

Full Text Available The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache.We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats.Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia, followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate increased nociceptive behaviors suggesting that acetate, not acetaldehyde, accumulation results in hangover-like hypersensitivity in our model. Since adenosine accumulation is a result of acetate formation, we administered an adenosine antagonist that blocked hypersensitivity.Our study shows that acetate contributes to hangover headache. These findings provide insight into the mechanism of hangover headache and the mechanism of headache induction.

Renal alterations in prediabetic rats with periodontitis

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Andersen, Carla Cruvinel Pontes; Holmstrup, Palle; Buschard, Karsten

2008-01-01

BACKGROUND: Periodontitis was shown to have an impact on glucose levels in prediabetic and diabetic rats. The Zucker fatty rat (ZFR) is a well-characterized model of prediabetes presenting with impaired glucose tolerance, hyperinsulinemia, dyslipidemia, and moderate hypertension. The aim...... IValpha1, fibronectin, and nephrin. Urinary albumin excretion and creatinine clearance were also evaluated. RESULTS: In prediabetic ZFRs, periodontitis was associated with kidney hypertrophy (P = 0.03) and a tendency for increased glomerular volume (P = 0.06). In lean littermates, elevated fibronectin m...

The CNTF-derived peptide mimetic Cintrofin attenuates spatial-learning deficits in a rat post-status epilepticus model

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Russmann, Vera; Seeger, Natalie; Zellinger, Christina

2013-01-01

Ciliary neurotrophic growth factor is considered a potential therapeutic agent for central nervous system diseases. We report first in vivo data of the ciliary neurotrophic growth factor peptide mimetic Cintrofin in a rat post-status epilepticus model. Cintrofin prevented long-term alterations...... in the number of doublecortin-positive neuronal progenitor cells and attenuated the persistence of basal dendrites. In contrast, Cintrofin did neither affect acute status epilepticus-associated alterations in hippocampal cell proliferation and neurogenesis nor reveal any relevant effect on seizure activity....... Whereas status epilepticus caused a significant disturbance in spatial learning in reversed peptide-treated rats, the performance of Cintrofin-treated rats did not differ from controls. The study confirms that Cintrofin comprises an active sequence mimicking effects of its parent molecule. While the data...

Bladder instillation of Escherichia coli lipopolysaccharide alters the muscle contractions in rat urinary bladder via a protein kinase C-related pathway

International Nuclear Information System (INIS)

Weng, T.I.; Chen, W.J.; Liu, S.H.

2005-01-01

Uropathogenic Escherichia coli is a common cause of urinary tract infection. We determined the effects of intravesical instillation of E. coli lipopolysaccharide (LPS, endotoxin) on muscle contractions, protein kinase C (PKC) translocation, and inducible nitric oxide synthase (iNOS) expression in rat urinary bladder. The contractions of the isolated rat detrusor muscle evoked by electrical field stimulations were measured short-term (1 h) or long-term (24 h) after intravesical instillation of LPS. One hour after LPS intravesical instillation, bladder PKC-α translocation from cytosolic fraction to membrane fraction and endothelial (e)NOS protein was elevated, and detrusor muscle contractions were significantly increased. PKC inhibitors chelerythrine and Ro32-0432 inhibited this LPS-enhanced contractile response. Application of PKC activator β-phorbol-12,13-dibutyrate enhanced the muscle contractions. Three hours after intravesical instillation of LPS, iNOS mRNA was detected in the bladder. Immunoblotting study also demonstrated that the induction of iNOS proteins is detected in bladder in which LPS was instilled. 24 h after intravesical instillation of LPS, PKC-α translocation was impaired in the bladder; LPS did not affect PKC-δ translocation. Muscle contractions were also decreased 24 h after LPS intravesical instillation. Aminoguanidine, a selective iNOS inhibitor, blocked the decrease in PKC-α translocation and detrusor contractions induced by LPS. These results indicate that there are different mechanisms involved in the alteration of urinary bladder contractions after short-term and long-term treatment of LPS; an iNOS-regulated PKC signaling may participate in causing the inhibition of muscle contractions in urinary bladder induced by long-term LPS treatment

Gestational Diabetes Alters Offspring DNA Methylation Profiles in Human and Rat: Identification of Key Pathways Involved in Endocrine System Disorders, Insulin Signaling, Diabetes Signaling, and ILK Signaling.

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Petropoulos, Sophie; Guillemin, Claire; Ergaz, Zivanit; Dimov, Sergiy; Suderman, Matthew; Weinstein-Fudim, Liza; Ornoy, Asher; Szyf, Moshe

2015-06-01

Gestational diabetes is associated with risk for metabolic disease later in life. Using a cross-species approach in rat and humans, we examined the hypothesis that gestational diabetes during pregnancy triggers changes in the methylome of the offspring that might be mediating these risks. We show in a gestation diabetes rat model, the Cohen diabetic rat, that gestational diabetes triggers wide alterations in DNA methylation in the placenta in both candidate diabetes genes and genome-wide promoters, thus providing evidence for a causal relationship between diabetes during pregnancy and DNA methylation alterations. There is a significant overlap between differentially methylated genes in the placenta and the liver of the rat offspring. Several genes differentially methylated in rat placenta exposed to maternal diabetes are also differentially methylated in the human placenta of offspring exposed to gestational diabetes in utero. DNA methylation changes inversely correlate with changes in expression. The changes in DNA methylation affect known functional gene pathways involved in endocrine function, metabolism, and insulin responses. These data provide support to the hypothesis that early-life exposures and their effects on metabolic disease are mediated by DNA methylation changes. This has important diagnostic and therapeutic implications.

A cafeteria diet alters the decision making strategy and metabolic markers in Sprague-Dawley male rats

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Virtuoso, Alessandro; Forkman, Björn; Sarruf, David A.

2018-01-01

of completion of a task, both of which can be influenced by the physiological changes induced by obesity. Here we assess the effects of an energy rich diet (Cafeteria Diet, CAF) on the performance of male Sprague-Dawley rats in the Decision Making paradigm, an operant conditioning task using water...... as a reinforcer and based on the patch depletion paradigm of optimal foraging in a test that is independent from motivation and time budget. As expected, CAF diet resulted in increased body weight and circulating leptin and insulin levels. Our results show that the decision rule of rats fed a CAF is altered......Consumption of diets rich in refined sugar and saturated fat has been linked with development of mild cognitive impairment and dementia in humans. Most cognitive paradigms used in biomedical research to investigate the relationship between obesity and cognition rely on food motivation and speed...

Alterations in NMDA receptor expression during retinal degeneration in the RCS rat.

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Gründer, T; Kohler, K; Guenther, E

2001-01-01

To determine how a progressive loss of photoreceptor cells and the concomitant loss of glutamatergic input to second-order neurons can affect inner-retinal signaling, glutamate receptor expression was analyzed in the Royal College of Surgeons (RCS) rat, an animal model of retinitis pigmentosa. Immunohistochemistry was performed on retinal sections of RCS rats and congenic controls between postnatal (P) day 3 and the aged adult (up to P350) using specific antibodies against N-methyl-D-aspartate (NMDA) subunits. All NMDA subunits (NR1, NR2A-2D) were expressed in control and dystrophic retinas at all ages, and distinct patterns of labeling were found in horizontal cells, subpopulations of amacrine cells and ganglion cells, as well as in the outer and inner plexiform layer (IPL). NRI immunoreactivity in the inner plexiform layer of adult control retinas was concentrated in two distinct bands, indicating a synaptic localization of NMDA receptors in the OFF and ON signal pathways. In the RCS retina, these bands of NRI immunoreactivity in the IPL were much weaker in animals older than P40. In parallel, NR2B immunoreactivity in the outer plexiform layer (OPL) of RCS rats was always reduced compared to controls and vanished between P40 and P120. The most striking alteration observed in the degenerating retina, however, was a strong expression of NRI immunoreactivity in Müller cell processes in the inner retina which was not observed in control animals and which was present prior to any visible sign of photoreceptor degeneration. The results suggest functional changes in glutamatergic receptor signaling in the dystrophic retina and a possible involvement of Müller cells in early processes of this disease.

α-Lipoic Acid Mitigates Arsenic-Induced Hematological Abnormalities in Adult Male Rats

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Sonali Ghosh

2017-05-01

Full Text Available Background: Arsenic toxicity is a major global health problem and exposure via contaminated drinking water has been associated with hematological and other systemic disorders. The present investigation has been conducted in adult male rats to evaluate the protective ability of α-lipoic acid (ALA against such hematological disorders. Methods: Twenty-four adult male Wister rats (b.wt.130±10g were grouped and accordingly group I (control received the normal diet, group II (treated was given arsenic orally for 28 consecutive days as arsenic trioxide (3 mg/kgbw/rat/day whereas group III (supplemented received the same dose of arsenic along with ALA (25 mg/kgbw/rat/day as oral supplement. Hematological profile, plasma oxidant/antioxidant status, and erythrocyte morphology were assessed. Statistical analysis was done by one-way ANOVA using SPSS software (version 16.0. Results: Arsenic exposure caused reduction of erythrocyte (P=0.021, leucocyte (P<0.001, and hemoglobin (P=0.031 associated with echinocytic transformation as evidenced by light and scanning electron microscopic studies. The other significantly altered parameters include increased mean corpuscular volume (P=0.041 and lymphocytopenia (P<0.001 with insignificant neutropenia and eosinophilia. Altered serum oxidative balance as evidenced by decreased TAS (P<0.001 and increased TOS (P<0.001 with OSI (P<0.001 was also noted. The dietary supplementation of ALA has a beneficial effect against the observed (P<0.05 arsenic toxicities. It brings about the protection by restoring the hematological redox and inflammatory status near normal in treated rats. Arsenic-induced morphological alteration of erythrocytes was also partially attenuated by ALA supplementation. Conclusion: It is concluded that arsenicosis is associated with hematological alterations and ALA co-supplementation can partially alleviate these changes in an experimental male rat model.

Oral Supplementation of Melatonin Protects against Fibromyalgia-Related Skeletal Muscle Alterations in Reserpine-Induced Myalgia Rats.

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Favero, Gaia; Trapletti, Valentina; Bonomini, Francesca; Stacchiotti, Alessandra; Lavazza, Antonio; Rodella, Luigi Fabrizio; Rezzani, Rita

2017-06-29

Fibromyalgia is a chronic syndrome characterized by widespread musculoskeletal pain and an extensive array of other symptoms including disordered sleep, fatigue, depression and anxiety. Important factors involved in the pathogenic process of fibromyalgia are inflammation and oxidative stress, suggesting that ant-inflammatory and/or antioxidant supplementation might be effective in the management and modulation of this syndrome. Recent evidence suggests that melatonin may be suitable for this purpose due to its well known ant-inflammatory, antioxidant and analgesic effects. Thus, in the current study, the effects of the oral supplementation of melatonin against fibromyalgia-related skeletal muscle alterations were evaluated. In detail, 90 Sprague Dawley rats were randomly treated with reserpine, to reproduce the pathogenic process of fibromyalgia and thereafter they received melatonin. The animals treated with reserpine showed moderate alterations at hind limb skeletal muscles level and had difficulty in moving, together with significant morphological and ultrastructural alterations and expression of inflammatory and oxidative stress markers in the gastrocnemius muscle. Interestingly, melatonin, dose and/or time dependently, reduced the difficulties in spontaneous motor activity and the musculoskeletal morphostructural, inflammatory, and oxidative stress alterations. This study suggests that melatonin in vivo may be an effective tool in the management of fibromyalgia-related musculoskeletal morphofunctional damage.

Anthocyanin-rich extract from Hibiscus sabdariffa calyx counteracts UVC-caused impairments in rats.

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Ozkol, Hatice Uce; Koyuncu, Ismail; Tuluce, Yasin; Dilsiz, Nihat; Soral, Sinan; Ozkol, Halil

2015-01-01

Ultraviolet radiation (UV) was reported to cause oxidative stress. Hibiscus sabdariffa L. (Malvaceae) calyx is commonly used in traditional Asian and African medicines and possesses strong antioxidant capacity due to its anthocyanin (ANTH) content. This study researched the possible protective role of Hibiscus sabdariffa calyx extract (HSCE) in UVC exposure of rats. Levels of serum enzymes, renal function tests, and some oxidant/antioxidant biomarkers of skin, lens, and retina tissues were monitored. Rats were exposed to UVC 4 h daily for 40 d and simultaneously received HSCE containing 2.5, 5, and 10 mg doses of ANTH in drinking water. Significant (p < 0.05) increases in the levels of serum aminotransferases, lactate dehydrogenase, urea, creatinine, and uric acid were noted after UVC exposure. In skin, lens, and retina tissues, total oxidant status, oxidative stress index, lipid peroxidation, and protein oxidation escalated markedly (p < 0.05) whereas total antioxidant status, reduced glutathione, and superoxide dismutase decreased dramatically (p < 0.05) related to UVC. Co-administration of HSCE with each ANTH dose significantly (p < 0.05) reversed aforementioned parameters (except total oxidant status) almost in all tissues. The LD50 of HSCE in rats was determined to be above 5000 mg/kg. Our data revealed that HSCE has a remarkable potential to counteract UVC-caused impairments, probably through its antioxidant and free radical-defusing effects. Therefore, HSCE could be useful against some cutaneous and ocular diseases in which UV and oxidative stress have a role in the etiopathogenesis.

Alteration of the digestive motility linked with radiation-induced inflammatory processes in rats; Alterations de la motricite digestive associees aux processus inflammatoires induits par les rayonnements ionisants chez le rat

Energy Technology Data Exchange (ETDEWEB)

Picard, C

2000-12-01

Exposure to ionizing radiation, whether accidental or for medical reasons, may lead to gastro-intestinal injury, characterized by nausea, vomiting, diarrhea and abdominal cramps. The aetiology of radiation-induced diarrhea remains to date unclear. In this study, we have investigated the acute effects of a 10 Gy abdominal irradiation on rat digestive functions. The objective of the first study was to evaluate the role of sensory afferent neurons, capsaicin-sensitive, on morphological changes and the inflammatory response following exposure. Three days after irradiation, we observed an inflammatory response characterized by neutrophils infiltration and mast cells de-granulation. No effect of capsaicin pre-treatment was seen on these parameters. However, neutrophils infiltration was increased as early as one day after irradiation in capsaicin-treated rats. No difference in severity of diarrhea was observed after denervation nor in morphological changes. These data demonstrate that abdominal irradiation results in diarrhea concomitant with an inflammatory response, and that sensory innervation does not play a major protective role. The objective of the rest of the work was in the first instance to characterize radiation-induced alterations of intestinal and colonic motility leading to diarrhea and secondly to evaluate the role of serotonin in such disorders. Perturbations in intestinal (MMC) and colonic (LSB) motor profiles were observed from the first day onwards. Migrating motor complexes (MMC) were completely disrupted at three days at the same time as the onset of diarrhea. In addition to inhibition of LSB, colonic fluid absorptive capacity was decreased and serotonin colonic tissue levels were increased three days after irradiation. Radiation-induced diarrhea was reduced by treatment with an antagonist of 5-HT{sub 3} receptors, granisetron, as were alterations of colonic motility and serotonin tissue levels. However, this treatment did not significantly ameliorate

Alteration in neonatal nutrition causes perturbations in hypothalamic neural circuits controlling reproductive function.

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Caron, Emilie; Ciofi, Philippe; Prevot, Vincent; Bouret, Sebastien G

2012-08-15

It is increasingly accepted that alterations of the early life environment may have lasting impacts on physiological functions. In particular, epidemiological and animal studies have indicated that changes in growth and nutrition during childhood and adolescence can impair reproductive function. However, the precise biological mechanisms that underlie these programming effects of neonatal nutrition on reproduction are still poorly understood. Here, we used a mouse model of divergent litter size to investigate the effects of early postnatal overnutrition and undernutrition on the maturation of hypothalamic circuits involved in reproductive function. Neonatally undernourished females display attenuated postnatal growth associated with delayed puberty and defective development of axonal projections from the arcuate nucleus to the preoptic region. These alterations persist into adulthood and specifically affect the organization of neural projections containing kisspeptin, a key neuropeptide involved in pubertal activation and fertility. Neonatal overfeeding also perturbs the development of neural projections from the arcuate nucleus to the preoptic region, but it does not result in alterations in kisspeptin projections. These studies indicate that alterations in the early nutritional environment cause lasting and deleterious effects on the organization of neural circuits involved in the control of reproduction, and that these changes are associated with lifelong functional perturbations.

Ayahuasca Alters Structural Parameters of the Rat Aorta.

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Pitol, Dimitrius L; Siéssere, Selma; Dos Santos, Rafael G; Rosa, Maria L N M; Hallak, Jaime E C; Scalize, Priscilla H; Pereira, Bruno F; Iyomasa, Melina M; Semprini, Marisa; Riba, Jordi; Regalo, Simone C H

2015-07-01

Ayahuasca is a hallucinogenic brew traditionally used by Northwestern Amazonian indigenous groups for therapeutic purposes. It is prepared by the decoction of Banisteriopsis caapi with the leaves of Psychotria viridis. Banisteriopsis caapi contains β-carbolines that are inhibitors of monoamine oxidase and P. viris is rich in dimethyltryptamine, a 5-HT(1A/2A/2C) agonist. Acute ayahuasca administration produces moderate cardiovascular effects in healthy volunteers, but information regarding long-term use is lacking. This study investigated the effects of ayahuasca (2-4 mL/kg) in the rat aorta after acute and chronic (14 days) administration. Ayahuasca caused flattening and stretching of vascular smooth muscle cells and changes in the arrangement and distribution of collagen and elastic fibers. Chronic treatment with the higher dose significantly increased media thickness and the ratio of media thickness to lumen diameter. More research is needed on the cardiovascular function of long-term ayahuasca consumers.

Promoting effects of phenobarbital on the enzyme-altered foci induced by intrahepatic γ-ray-irradiation in the rat liver

International Nuclear Information System (INIS)

Ida, Katsuya; Nakamura, Satoshi; Muro, Hiroyuki; Takai, Michikatsu; Kaneko, Masao

1995-01-01

Radiation-induced carcinogenesis of the rat liver using iridium-192 seeds as an intrahepatic radioactive source was studied by enzyme histochemical means. Rats were divided into six groups according to various combinations of one or two iridium-192 or stainless steel seeds and whether they were given a diet containing 0.05% phenobarbital (PB) or a basal diet (BD). Each group were sacrificed at 20, 40, and 60 weeks after intrahepatic insertion of the iridium-192 or stainless steel seeds. γ-Glutamyl transpeptidase (GGT), glucose-6-phosphatase (G6Pase), and adenosine triphosphatase (ATPase) were stained in the liver tissues, and GGT-positive foci were quantified. Liver neoplasm was not evident, but enzyme-altered foci (EAF) were induced by γ-ray irradiation. At every point (20, 40, and 60 weeks) after the insertion of the seeds, the GGT-positive area was larger in the rats given PB than those given BD. Moreover, despite the iridium-192 radioactivity decay, EAF developed continuously in the rats given PB, and persisted in those given BD from 40 to 60 weeks after insertion. These results indicated that phenobarbital promotes the development of EAF initiated by irradiation, as it promotes the process of chemical carcinogenesis in the rat liver. (author)

Low glucose utilization and neurodegenerative changes caused by sodium fluoride exposure in rat's developmental brain.

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Jiang, Chunyang; Zhang, Shun; Liu, Hongliang; Guan, Zhizhong; Zeng, Qiang; Zhang, Cheng; Lei, Rongrong; Xia, Tao; Wang, Zhenglun; Yang, Lu; Chen, Yihu; Wu, Xue; Zhang, Xiaofei; Cui, Yushan; Yu, Linyu; Wang, Aiguo

2014-03-01

Fluorine, a toxic and reactive element, is widely prevalent throughout the environment and can induce toxicity when absorbed into the body. This study was to explore the possible mechanisms of developmental neurotoxicity in rats treated with different levels of sodium fluoride (NaF). The rats' intelligence, as well as changes in neuronal morphology, glucose absorption, and functional gene expression within the brain were determined using the Morris water maze test, transmission electron microscopy, small-animal magnetic resonance imaging and Positron emission tomography and computed tomography, and Western blotting techniques. We found that NaF treatment-impaired learning and memory in these rats. Furthermore, NaF caused neuronal degeneration, decreased brain glucose utilization, decreased the protein expression of glucose transporter 1 and glial fibrillary acidic protein, and increased levels of brain-derived neurotrophic factor in the rat brains. The developmental neurotoxicity of fluoride may be closely associated with low glucose utilization and neurodegenerative changes.

Autonomic control of the heart is altered in Sprague-Dawley rats with spontaneous hydronephrosis

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Arnold, Amy C.; Shaltout, Hossam A.; Gilliam-Davis, Shea; Kock, Nancy D.

2011-01-01

The renal medulla plays an important role in cardiovascular regulation, through interactions with the autonomic nervous system. Hydronephrosis is characterized by substantial loss of renal medullary tissue. However, whether alterations in autonomic control of the heart are observed in this condition is unknown. Thus we assessed resting hemodynamics and baroreflex sensitivity (BRS) for control of heart rate in urethane/chloralose-anesthetized Sprague-Dawley rats with normal or hydronephrotic kidneys. While resting arterial pressure was similar, heart rate was higher in rats with hydronephrosis (290 ± 12 normal vs. 344 ± 11 mild/moderate vs. 355 ± 13 beats/min severe; P hydronephrosis, with no differences in measures of indirect sympathetic activity among conditions. As a secondary aim, we investigated whether autonomic dysfunction in hydronephrosis is associated with activation of the renin-angiotensin system (RAS). There were no differences in circulating angiotensin peptides among conditions, suggesting that the impaired autonomic function in hydronephrosis is independent of peripheral RAS activation. A possible site for angiotensin II-mediated BRS impairment is the solitary tract nucleus (NTS). In normal and mild/moderate hydronephrotic rats, NTS administration of the angiotensin II type 1 receptor antagonist candesartan significantly improved the BRS, suggesting that angiotensin II provides tonic suppression to the baroreflex. In contrast, angiotensin II blockade produced no significant effect in severe hydronephrosis, indicating that at least within the NTS baroreflex suppression in these animals is independent of angiotensin II. PMID:21460193

[A study on the role of vascular endothelial growth factor in emphysema of rat caused by smog exposure].

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Chen, Jin-long; Ran, Pi-xin

2003-11-01

To explore the role of vascular endothelial growth factor (VEGF) in emphysema of rat caused by smog exposure. Thirty-six 12-week male rats were randomly divided into 2 groups: a smog exposure group (S group), and a normal control group (N group). S group rats were randomly subdivided into 3 groups: S(1) group, S(2) group, S(3) group, which were exposed to smog for 2 weeks, 4 weeks, 8 weeks, respectively; N group rats were randomly subdivided into 3 groups: N(1) group, N(2) group, N(3) group, which were raised in normal oxygen condition for 0 week, 4 weeks, 8 weeks, respectively. The expressions of VEGF mRNA and VEGF protein and kinase-insert domain containing receptor (KDR) protein were determined by reverse transcription-polymerase chain reaction (RT-PCR) and modified SABC immunohistochemistry assay separately. The pathological change in smog exposure rat lung was determined by HE staining. MLI and MAN were determined as an index of emphysema. Variance analysis, nonparametric analysis and correlate analysis were conducted in SPSS 10.0. (1) There were airway inflammation in S group rat lungs, and an early-emphysema-like change in S(3) group rat lungs: MAN in S(3) group was significantly decreased compared with N(3) group, MLI in S(3) group was significantly increased compared with N(3) group (P 0.05). (3) VEGF protein expression in alveolar epithelium and bronchial epithelium had a positive correlation with MAN (r = 0.43, r = 0.37, P Smog exposure decrease the expression of VEGF and KDR in rat lung. VEGF might involve in the pathology of emphysema caused by smog exposure.

Dietary soya protein improves intra-myocardial lipid deposition and altered glucose metabolism in a hypertensive, dyslipidaemic, insulin-resistant rat model.

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Oliva, María E; Creus, Agustina; Ferreira, María R; Chicco, Adriana; Lombardo, Yolanda B

2018-01-01

This study investigates the effects of replacing dietary casein by soya protein on the underlying mechanisms involved in the impaired metabolic fate of glucose and lipid metabolisms in the heart of dyslipidaemic rats chronically fed (8 months) a sucrose-rich (62·5 %) diet (SRD). To test this hypothesis, Wistar rats were fed an SRD for 4 months. From months 4 to 8, half the animals continued with the SRD and the other half were fed an SRD in which casein was substituted by soya. The control group received a diet with maize starch as the carbohydrate source. Compared with the SRD-fed group, the following results were obtained. First, soya protein significantly (Psoya protein significantly increased (Psoya protein upon the altered pathways of glucose and lipid metabolism in the heart muscle of this rat model.

Excipient-mediated alteration in drug bioavailability in the rat depends on the sex of the animal.

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Mai, Yang; Afonso-Pereira, Francisco; Murdan, Sudaxshina; Basit, Abdul W

2017-09-30

The pharmaceutical excipient, polyethylene glycol 400 (PEG 400), unexpectedly alters the bioavailability of the BCS class III drug ranitidine in a sex-dependent manner. As ranitidine is a substrate for the efflux transporter P-glycoprotein (P-gp), we hypothesized that the sex-related influence could be due to interactions between PEG 400 and P-gp. In this study, we tested this hypothesis by: i) measuring the influence of PEG 400 on the oral bioavailability of another P-gp substrate (ampicillin) and of a non-P-gp substrate (metformin); and ii) measuring the effect of PEG 400 on drug bioavailability in the presence of a P-gp inhibitor (cyclosporine A) in male and female rats. We found that PEG 400 significantly increased (pbioavailability of ampicillin (the P-gp substrate) in male rats, but not in female ones. In contrast, PEG 400 had no influence on the bioavailability of the non-P-gp substrate, metformin in male or female rats. Inhibition of P-gp by oral pre-treatment with cyclosporine A increased the bioavailability of the P-gp substrates (ampicillin and ranitidine) in males and females (pbioavailability of metformin in either male or female rats. These results prove the hypothesis that the sex-specific effect of PEG 400 on the bioavailability of certain drugs is due to the interaction of PEG 400 with the efflux transporter P-gp. Copyright © 2017 Elsevier B.V. All rights reserved.

Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo

International Nuclear Information System (INIS)

Herrmann, Julia E.; Heale, Jason; Bieraugel, Mike; Ramos, Meg; Fisher, Robyn L.; Vickers, Alison E.M.

2014-01-01

Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100 μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24 h. In this in vivo rat study (0.5 mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48 h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in an apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70 kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1α, Il-1β, IL-6 and TNFα in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices. - Highlights: • Human response to isoproterenol induced cardiac injury evaluated in heart slices. • Isoproterenol altered apoptosis, energy, inflammation and remodeling pathways. • Human model verified by comparison to rat heart slices and rat heart in vivo. • Human and rat respond to isoproterenol

Botulinum toxin injection causes hyper-reflexia and increased muscle stiffness of the triceps surae muscle in the rat

DEFF Research Database (Denmark)

Pingel, Jessica; Wienecke, Jacob; Lorentzen, Jakob

2016-01-01

Botulinum toxin is used to diminish spasticity and reduce the risk of development of contractures. Here, we investigated changes in muscle stiffness caused by reflex activity or elastic muscle properties following botulinum toxin injection in the triceps surae muscle in rats. Forty-four rats...... received injection of botulinum toxin in the left triceps surae muscle. Control measurements were performed on the non-injected contralateral side in all rats. Acute experiments were performed 1, 2, 4 and 8 weeks following injection. The triceps surae muscle was dissected free, the Achilles tendon was cut...... and attached to a muscle puller. The resistance of the muscle to stretches of different amplitudes and velocities was systematically investigated. Reflex mediated torque was normalized to the maximal muscle force (Mmax) evoked by supramaximal stimulation of the tibial nerve. Botulinum toxin injection caused...

Increase of long-term 'diabesity' risk, hyperphagia, and altered hypothalamic neuropeptide expression in neonatally overnourished 'small-for-gestational-age' (SGA rats.

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Karen Schellong

Full Text Available BACKGROUND: Epidemiological data have shown long-term health adversity in low birth weight subjects, especially concerning the metabolic syndrome and 'diabesity' risk. Alterations in adult food intake have been suggested to be causally involved. Responsible mechanisms remain unclear. METHODS AND FINDINGS: By rearing in normal (NL vs. small litters (SL, small-for-gestational-age (SGA rats were neonatally exposed to either normal (SGA-in-NL or over-feeding (SGA-in-SL, and followed up into late adult age as compared to normally reared appropriate-for-gestational-age control rats (AGA-in-NL. SGA-in-SL rats displayed rapid neonatal weight gain within one week after birth, while SGA-in-NL growth caught up only at juvenile age (day 60, as compared to AGA-in-NL controls. In adulthood, an increase in lipids, leptin, insulin, insulin/glucose-ratio (all p<0.05, and hyperphagia under normal chow as well as high-energy/high-fat diet, modelling modern 'westernized' lifestyle, were observed only in SGA-in-SL as compared to both SGA-in-NL and AGA-in-NL rats (p<0.05. Lasercapture microdissection (LMD-based neuropeptide expression analyses in single neuron pools of the arcuate hypothalamic nucleus (ARC revealed a significant shift towards down-regulation of the anorexigenic melanocortinergic system (proopiomelanocortin, Pomc in SGA-in-SL rats (p<0.05. Neuropeptide expression within the orexigenic system (neuropeptide Y (Npy, agouti-related-peptide (Agrp and galanin (Gal was not significantly altered. In essence, the 'orexigenic index', proposed here as a neuroendocrine 'net-indicator', was increased in SGA-in-SL regarding Npy/Pomc expression (p<0.01, correlated to food intake (p<0.05. CONCLUSION: Adult SGA rats developed increased 'diabesity' risk only if exposed to neonatal overfeeding. Hypothalamic malprogramming towards decreased anorexigenic activity was involved into the pathophysiology of this neonatally acquired adverse phenotype. Neonatal overfeeding

Gastric dysregulation induced by microinjection of 6-OHDA in the substantia nigra pars compacta of rats is determined by alterations in the brain-gut axis.

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Toti, Luca; Travagli, R Alberto

2014-11-15

Idiopathic Parkinson's disease (PD) is a late-onset, chronic, and progressive motor dysfunction attributable to loss of nigrostriatal dopamine neurons. Patients with PD experience significant gastrointestinal (GI) issues, including gastroparesis. We aimed to evaluate whether 6-hydroxy-dopamine (6-OHDA)-induced degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) induces gastric dysmotility via dysfunctions of the brain-gut axis. 6-OHDA microinjection into the SNpc induced a >90% decrease in tyrosine hydroxylase-immunoreactivity (IR) on the injection site. The [13C]-octanoic acid breath test showed a delayed gastric emptying 4 wk after the 6-OHDA treatment. In control rats, microinjection of the indirect sympathomimetic, tyramine, in the dorsal vagal complex (DVC) decreased gastric tone and motility; this inhibition was prevented by the fourth ventricular application of either a combination of α1- and α2- or a combination of D1 and D2 receptor antagonists. Conversely, in 6-OHDA-treated rats, whereas DVC microinjection of tyramine had reduced effects on gastric tone or motility, DVC microinjection of thyrotropin-releasing hormone induced a similar increase in motility as in control rats. In 6-OHDA-treated rats, there was a decreased expression of choline acetyl transferase (ChAT)-IR and neuronal nitric oxide synthase (NOS)-IR in DVC neurons but an increase in dopamine-β-hydroxylase-IR in the A2 area. Within the myenteric plexus of the esophagus, stomach, and duodenum, there were no changes in the total number of neurons; however, the percentage of NOS-IR neurons increased, whereas that of ChAT-IR decreased. Our data suggest that the delayed gastric emptying in a 6-OHDA rat model of PD may be caused by neurochemical and neurophysiological alterations in the brain-gut axis. Copyright © 2014 the American Physiological Society.

High-protein diet improves sensitivity to cholecystokinin and shifts the cecal microbiome without altering brain inflammation in diet-induced obesity in rats.

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Wang, Lixin; Jacobs, Jonathan P; Lagishetty, Venu; Yuan, Pu-Qing; Wu, Shuping V; Million, Mulugeta; Reeve, Joseph R; Pisegna, Joseph R; Taché, Yvette

2017-10-01

High-protein diet (HPD) curtails obesity and/or fat mass, but it is unknown whether it reverses neuroinflammation or alters glucose levels, CCK sensitivity, and gut microbiome in rats fed a Western diet (WD)-induced obesity (DIO). Male rats fed a WD (high fat and sugar) for 12 wk were switched to a HPD for 6 wk. Body composition, food intake, meal pattern, sensitivity to intraperitoneal CCK-8S, blood glucose, brain signaling, and cecal microbiota were assessed. When compared with a normal diet, WD increased body weight (9.3%) and fat mass (73.4%). CCK-8S (1.8 or 5.2 nmol/kg) did not alter food intake and meal pattern in DIO rats. Switching to a HPD for 6 wk reduced fat mass (15.7%) with a nonsignificantly reduced body weight gain, normalized blood glucose, and decreased feeding after CCK-8S. DIO rats on the WD or switched to a HPD showed comparable microbial diversity. However, in HPD versus WD rats, there was enrichment of 114 operational taxonomic units (OTUs) and depletion of 188 OTUs. Of those, Akkermansia muciniphila (enriched on a HPD), an unclassified Clostridiales, a member of the RF39 order, and a Phascolarctobacterium were significantly associated with fat mass. The WD increased cytokine expression in the hypothalamus and dorsal medulla that was unchanged by switching to HPD. These data indicate that HPD reduces body fat and restores glucose homeostasis and CCK sensitivity, while not modifying brain inflammation. In addition, expansion of cecal Akkermansia muciniphila correlated to fat mass loss may represent a potential peripheral mechanism of HPD beneficial effects.

Impairment of cognitive function and synaptic plasticity associated with alteration of information flow in theta and gamma oscillations in melamine-treated rats.

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Xiaxia Xu

Full Text Available Changes of neural oscillations at a variety of physiological rhythms are effectively associated with cognitive performance. The present study investigated whether the directional indices of neural information flow (NIF could be used to symbolize the synaptic plasticity impairment in hippocampal CA3-CA1 network in a rat model of melamine. Male Wistar rats were employed while melamine was administered at a dose of 300 mg/kg/day for 4 weeks. Behavior was measured by the Morris water maze(MWMtest. Local field potentials (LFPs were recorded before long-term potentiation (LTP induction. Generalized partial directed coherence (gPDC and phase-amplitude coupling conditional mutual information (PAC_CMI were used to measure the unidirectional indices in both theta and low gamma oscillations (LG, ~ 30-50 Hz. Our results showed that melamine induced the cognition deficits consistent with the reduced LTP in CA1 area. Phase locking values (PLVs showed that the synchronization between CA3 and CA1 in both theta and LG rhythms was reduced by melamine. In both theta and LG rhythms, unidirectional indices were significantly decreased in melamine treated rats while a similar variation trend was observed in LTP reduction, implying that the effects of melamine on cognitive impairment were possibly mediated via profound alterations of NIF on CA3-CA1 pathway in hippocampus. The results suggested that LFPs activities at these rhythms were most likely involved in determining the alterations of information flow in the hippocampal CA3-CA1 network, which might be associated with the alteration of synaptic transmission to some extent.

Hormonal evaluation of T4 and T3 through radioimmunoassay in younglings of rats with hypothyroidism

International Nuclear Information System (INIS)

Silveira, M.F.G.; Silva, I.M.S.; Pereira, S.S.L.; Souza, G.M.L.; Carvalho, E.F.M.B.; Cavalcante, C.V.G.; Lima Filho, G.L.; Catanho, M.T.J.A.

2000-01-01

The onset of fetal thyroid function occurs about 17-18 days after conception in the rat. The maternal hypothyroidism which occurs during gestation provokes alteration in the rat after birth. Due to this alteration, we decided to analyze the hormonal modification in the newborn rats. The hypothyroidism was induced in normal dams, which were being treated for 7 days with MMI (in the concentration of 0,03% in drinking water) before mating. Another dam group which was submitted to an induction of hypothyroidism maintained the treatment with MMI for 13 days during gestation. The hormones were assessed by radioimmunoassay technique. It was seen that the rats which were born from hypothyroid dams suffered alterations on its T 4 and T 3 hormone levels concerning to 10, 30 and 60 days after birth. There was also modifications on their weight and size. The growth is affected throughout post-natal life by thyroid hormones, which has a facilitator influence on growth hormone economy, as opposed to the inhibitory effects on TSH economy. The administration of MMI bars the fetal thyroid gland function, causing a decrease of both T 4 and T 3 levels, even after the birth, indicating that the maternal hypothyroidism influences on the post-natal life of the rat. (author)

Alterations in the neural circuits from peripheral afferents to the spinal cord: possible implications for diabetic polyneuropathy in streptozotocin-induced type 1 diabetic rats

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Zhen-Zhen eKou

2014-01-01

Full Text Available Diabetic polyneuropathy (DPN presents as a wide variety of sensorimotor symptoms and affects approximately 50% of diabetic patients. Changes in the neural circuits may occur in the early stages in diabetes and are implicated in the development of DPN. Therefore, we aimed to detect changes in the expression of isolectin B4 (IB4, the marker for nonpeptidergic unmyelinated fibers and their cell bodies and calcitonin gene-related peptide (CGRP, the marker for peptidergic fibers and their cell bodies in the dorsal root ganglion (DRG and spinal cord of streptozotocin (STZ-induced type 1 diabetic rats showing alterations in sensory and motor function. We also used cholera toxin B subunit (CTB to show the morphological changes of the myelinated fibers and motor neurons. STZ-induced diabetic rats exhibited hyperglycemia, decreased body weight gain, mechanical allodynia and impaired locomotor activity. In the DRG and spinal dorsal horn, IB4-labeled structures decreased, but both CGRP immunostaining and CTB labeling increased from day 14 to day 28 in diabetic rats. In spinal ventral horn, CTB labeling decreased in motor neurons in diabetic rats. Treatment with intrathecal injection of insulin at the early stages of DPN could alleviate mechanical allodynia and impaired locomotor activity in diabetic rats. The results suggest that the alterations of the neural circuits between spinal nerve and spinal cord via the DRG and ventral root might be involved in DPN.

Alteration of tricarboxylic acid cycle metabolism in rat brain slices by halothane

International Nuclear Information System (INIS)

Cheng, S.C.; Brunner, E.A.

1978-01-01

Metabolism of [2- 14 C] pyruvate, [1- 14 C] acetate and [5- 14 C] citrate in rat cerebral cortex slices was studied in the presence of halothane. Metabolites assayed include acetylcholine (ACh), citrate, glutamate, glutamineγ-aminobutyrate (GABA) and aspartate. The trichloroacetic acid soluble extract, the trichloracetic acid insoluble precipitate and its lipid extract were also studied. In control experiments, pyruvate preferentially labelled ACh, citrate, glutamate, GABA and aspartate. Acetate labelled ACh, but to a lesser extent than pyruvate. Acetate also labelled lipids and glutamine. Citrate labelled lipids but not ACh and served as a preferential precursor for glutamine. These data support a three-compartment model for cerebral tricarboxylic acid cycle metabolism. Halothane caused increases in GABA and aspartate contents and a decrease in ACh content. It has no effect on the contents of citrate, glutamate and glutamine. Halothane preferentially inhibited the metabolic transfer of radioactivity from pyruvate into almost all metabolites, an effect probably not related to pyruvate permeability. This is interpreted as halothane depression of the large metabolic compartment which includes the nerve endings. Halothane increased the metabolic transfer of radioactivity from acetate into lipids but did not alter such a transfer into the trichloroacetic acid extract. Halothane increased the metabolic transfer of radioactivity from citrate into the trichloroacetic acid precipitate, lipids and especially glutamine. Transfer of citrate radioactivity into GABA was somewhat decreased. The differential effects of halothane on acetate and citrate utilization suggest that the small metabolic compartment should be subdivided. Therefore, at least three metabolic compartments are demonstrated. Halothane did not interfere with the dicarboxylic acid portion of the tricarboxylic acid cycle. (author)

Transcriptional dysregulation causes altered modulation of inhibition by haloperidol.

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Brady, Lillian J; Bartley, Aundrea F; Li, Qin; McMeekin, Laura J; Hablitz, John J; Cowell, Rita M; Dobrunz, Lynn E

2016-12-01

Many neuropsychiatric and neurodevelopmental disorders such as schizophrenia and autism involve interneuron transcriptional dysregulation. The transcriptional coactivator PGC-1α regulates gene expression in GABAergic interneurons, which are important for regulating hippocampal network activity. Genetic deletion of PGC-1α causes a decrease in parvalbumin expression, similar to what is observed in schizophrenia postmortem tissue. Our lab has previously shown that PGC-1α -/- mice have enhanced GABAergic inhibition onto CA1 pyramidal cells, which increases the inhibition/excitation (I/E) ratio, alters hippocampal circuit function, and impairs hippocampal dependent behavior. The typical antipsychotic haloperidol, a dopamine receptor antagonist with selectivity for D2-like receptors, has previously been shown to increase excitation in the CA1 region of hippocampus. We therefore tested whether haloperidol could normalize the I/E balance in CA1 of PGC-1α -/- mice, potentially improving circuit function and behavior. Surprisingly, we discovered instead that interneuron transcriptional dysregulation caused by loss of PGC-1α alters the effects of haloperidol on hippocampal synaptic transmission and circuit function. Acute administration of haloperidol causes disinhibition in CA1 and decreases the I/E ratio onto CA1 pyramidal cells in slices from PGC-1α +/+ mice, but not PGC-1α -/- mice. The spread of activity in CA1, assessed by voltage sensitive dye imaging, is increased by haloperidol in slices from PGC-1α +/+ mice; however haloperidol decreases the spread of activity in slices from PGC-1α -/- mice. Haloperidol increased the power of hippocampal gamma oscillation in slices from PGC-1α +/+ mice but reduced the power of gamma oscillations in slices from PGC-1α -/- mice. Nest construction, an innate hippocampal-dependent behavior, is inhibited by haloperidol in PGC-1α +/+ mice, but not in PGC-1α -/- mice, which already have impaired nest building. The effects of

Exposure to 16O-particle radiation causes aging-like decrements in rats through increased oxidative stress, inflammation and loss of autophagy.

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Poulose, Shibu M; Bielinski, Donna F; Carrihill-Knoll, Kirsty; Rabin, Bernard M; Shukitt-Hale, Barbara

2011-12-01

Exposing young rats to particles of high energy and charge (HZE particles), a ground-based model for exposure to cosmic rays, enhances indices of oxidative stress and inflammation, disrupts the functioning of neuronal communication, and alters cognitive behaviors. Even though exposure to HZE particles occurs at low fluence rates, the cumulative effects of long-term exposure result in molecular changes similar to those seen in aged animals. In the present study, we assessed markers of autophagy, a dynamic process for intracellular degradation and recycling of toxic proteins and organelles, as well as stress and inflammatory responses, in the brains of Sprague-Dawley rats irradiated at 2 months of age with 5 and 50 cGy and 1 Gy of ionizing oxygen particles ((16)O) (1000 MeV/n). Compared to nonirradiated controls, exposure to (16)O particles significantly inhibited autophagy function in the hippocampus as measured by accumulation of ubiquitin inclusion bodies such as P62/SQSTM1, autophagosome marker microtubule-associated protein 1 beta light chain 3 (MAP1B-LC3), beclin1 and proteins such as mammalian target of rapamycin (mTOR). The molecular changes measured at short (36 h) and long (75 days) intervals after (16)O-particle exposure indicate that the loss of autophagy function occurred shortly after exposure but was recovered via inhibition of mTOR. However, HZE-particle radiation caused significant sustained loss of protein kinase C alpha (PKC-α), a key G protein modulator involved in neuronal survival and functions of neuronal trophic factors. Exposure to (16)O particles also caused substantial increases in the levels of nuclear factor kappa B (NF-κB) and glial fibrillary acidic protein (GFAP), indicating glial cell activation 75 days after exposure. This is the first report to show the molecular effects of (16)O-particle radiation on oxidative stress, inflammation and loss of autophagy in the brain of young rats.

Whey protein hydrolysate enhances HSP90 but does not alter HSP60 and HSP25 in skeletal muscle of rats.

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Carolina Soares Moura

Full Text Available Whey protein hydrolysate (WPH intake has shown to increase HSP70 expression. The aim of the present study was to investigate whether WPH intake would also influences HSP90, HSP60 and HSP25 expression, as well as associated parameters. Forty-eight male Wistar rats were divided into sedentary (unstressed and exercised (stressed groups, and were fed with three different sources of protein: whey protein (WP, whey protein hydrolysate (WPH and casein (CAS as a control, based on the AIN93G diet for 3 weeks. WPH intake increased HSP90 expression in both sedentary and exercised animals compared to WP or CAS, however no alteration was found from exercise or diet to HSP60 or HSP25. Co-chaperone Aha1 and p-HSF1 were also increased in the exercised animals fed with WPH in comparison with WP or CAS, consistent with enhanced HSP90 expression. VEGF and p-AKT were increased in the WPH exercised group. No alteration was found in BCKDH, PI3-Kinase (p85, GFAT, OGT or PGC for diet or exercise. The antioxidant system GPx, catalase and SOD showed different responses to diet and exercise. The data indicate that WPH intake enhanced factors related to cell survival, such as HSP90 and VEGF, but does not alter HSP60 or HSP25 in rat skeletal muscle.

CNS development under altered gravity: cerebellar glial and neuronal protein expression in rat neonates exposed to hypergravity

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Nguon, K.; Li, G.-H.; Sajdel-Sulkowska, E. M.

2004-01-01

The future of space exploration depends on a solid understanding of the developmental process under microgravity, specifically in relation to the central nervous system (CNS). We have previously employed a hypergravity paradigm to assess the impact of altered gravity on the developing rat cerebellum [Exp. Biol. Med. 226 (2000) 790]. The present study addresses the molecular mechanisms involved in the cerebellar response to hypergravity. Specifically, the study focuses on the expression of selected glial and neuronal cerebellar proteins in rat neonates exposed to hypergravity (1.5 G) from embryonic day (E)11 to postnatal day (P)6 or P9 (the time of maximal cerebellar changes) comparing them against their expression in rat neonates developing under normal gravity. Proteins were analyzed by quantitative Western blots of cerebellar homogenates; RNA analysis was performed in the same samples using quantitative PCR. Densitometric analysis of Western blots suggested a reduction in glial (glial acidic protein, GFAP) and neuronal (neuronal cell adhesion moiecule, NCAM-L1, synaptophysin) proteins, but the changes in individual cerebellar proteins in hypergravity-exposed neonates appeared both age- and gender-specific. RNA analysis suggested a reduction in GFAP and synaptophysin mRNAs on P6. These data suggest that exposure to hypergravity may interfere with the expression of selected cerebellar proteins. These changes in protein expression may be involved in mediating the effect of hypergravity on the developing rat cerebellum.

Food restriction causes low bone strength and microarchitectural deterioration in exercised growing male rats.

Science.gov (United States)

Hattori, Satoshi; Park, Jong-Hoon; Agata, Umon; Oda, Masaya; Higano, Michito; Aikawa, Yuki; Akimoto, Takayuki; Nabekura, Yoshiharu; Yamato, Hideyuki; Ezawa, Ikuko; Omi, Naomi

2014-01-01

The pathogenesis of bone disorders in young male athletes has not been well understood. We hypothesized that bone fragility is caused by low energy availability, due to insufficient food intake and excessive exercise energy expenditure in young male athletes. To examine this hypothesis, we investigated the influence of food restriction on bone strength and bone morphology in exercised growing male rats, using three-point bending test, dual-energy X-ray absormetry, and micro-computed tomography. Four-week-old male Sprague-Dawley rats were divided randomly into the following groups: the control (Con) group, exercise (Ex) group, food restriction (R) group, and food restriction plus exercise (REx) group after a 1-wk acclimatization period. Thirty-percent food restriction in the R and REx groups was carried out in comparison with that in the Con group. Voluntary running exercise was performed in the Ex and REx groups. The experimental period lasted 13 wk. At the endpoint of this experiment, the bone strength of the femurs and tibial BMD in the REx group were significantly lower than those in the Con group. Moreover, trabecular bone volume and cortical bone volume in the REx group were also significantly lower than those in the Con group. These findings indicate that food restriction causes low bone strength and microarchitectural deterioration in exercised growing male rats.

Prenatal exposure to aflatoxin B1: developmental, behavioral, and reproductive alterations in male rats

Science.gov (United States)

Supriya, Ch.; Reddy, P. Sreenivasula

2015-06-01

studies revealed a significant decrease in the mating index in experimental rats with an increase in the pre- and post-implantation losses in rats mated with prenatal AfB1-exposed males, indicating poor male reproductive performance. These results indicate that in utero exposure to AfB1 severely compromised postnatal development of neonatal rats, and caused a delay in testes descent and reduction in steroidogenesis and spermatogenesis that were accomplished by suppressed reproduction at adulthood.

Epidermal growth factor inhibits rat pancreatic cell proliferation, causes acinar cell hypertrophy, and prevents caerulein-induced desensitization of amylase release.

Science.gov (United States)

Morisset, J; Larose, L; Korc, M

1989-06-01

The in vivo effects of epidermal growth factor (EGF) on pancreatic growth and digestive enzyme concentrations were compared with the actions of the pancreatic secretagogue caerulein in the adult rat. EGF (10 micrograms/kg BW) did not alter pancreatic weight or protein content. However, this concentration of EGF inhibited [3H]thymidine incorporation into DNA by 44%, decreased DNA content by 20%, and increased the concentrations of amylase, chymotrypsinogen, and protein by 106%, 232%, and 42%, respectively. Pancreatic acini prepared from EGF-treated rats exhibited a characteristic secretory response to caerulein that was superimposable to that obtained in acini from saline-treated rats. In both groups of acini half-maximal and maximal stimulation of amylase release occurred at approximately 5 pM and 50 pM caerulein, respectively. In contrast to EGF, caerulein (1 microgram/kg BW) increased pancreatic weight by 29% and protein content by 59%, and enhanced [3H]thymidine incorporation into DNA by 70%. Although caerulein increased the concentrations of pancreatic amylase and chymotrypsinogen by 38% and 297%, respectively, pancreatic acini prepared from caerulein-treated rats were less sensitive to the actions of caerulein in vitro when compared with acini from control rats. Indeed, the EC50 was shift from 4.8 pM to 9.8 pM after 4 days of treatment. EGF potentiated the actions of caerulein on pancreatic weight, protein content, and chymotrypsinogen concentration, and prevented the caerulein-induced alteration in the secretory responsiveness of the acinar cell. Conversely, caerulein reversed the inhibitory effect of EGF on thymidine incorporation. These findings suggest that EGF may modulate the trophic effects of certain gastrointestinal hormones, and may participate in the regulation of pancreatic exocrine function in vivo.

Alteration of the digestive motility linked with radiation-induced inflammatory processes in rats

International Nuclear Information System (INIS)

Picard, C.

2000-12-01

Exposure to ionizing radiation, whether accidental or for medical reasons, may lead to gastro-intestinal injury, characterized by nausea, vomiting, diarrhea and abdominal cramps. The aetiology of radiation-induced diarrhea remains to date unclear. In this study, we have investigated the acute effects of a 10 Gy abdominal irradiation on rat digestive functions. The objective of the first study was to evaluate the role of sensory afferent neurons, capsaicin-sensitive, on morphological changes and the inflammatory response following exposure. Three days after irradiation, we observed an inflammatory response characterized by neutrophils infiltration and mast cells de-granulation. No effect of capsaicin pre-treatment was seen on these parameters. However, neutrophils infiltration was increased as early as one day after irradiation in capsaicin-treated rats. No difference in severity of diarrhea was observed after denervation nor in morphological changes. These data demonstrate that abdominal irradiation results in diarrhea concomitant with an inflammatory response, and that sensory innervation does not play a major protective role. The objective of the rest of the work was in the first instance to characterize radiation-induced alterations of intestinal and colonic motility leading to diarrhea and secondly to evaluate the role of serotonin in such disorders. Perturbations in intestinal (MMC) and colonic (LSB) motor profiles were observed from the first day onwards. Migrating motor complexes (MMC) were completely disrupted at three days at the same time as the onset of diarrhea. In addition to inhibition of LSB, colonic fluid absorptive capacity was decreased and serotonin colonic tissue levels were increased three days after irradiation. Radiation-induced diarrhea was reduced by treatment with an antagonist of 5-HT 3 receptors, granisetron, as were alterations of colonic motility and serotonin tissue levels. However, this treatment did not significantly ameliorate

Iron deficiency alters megakaryopoiesis and platelet phenotype independent of thrombopoietin.

Science.gov (United States)

Evstatiev, Rayko; Bukaty, Adam; Jimenez, Kristine; Kulnigg-Dabsch, Stefanie; Surman, Lidia; Schmid, Werner; Eferl, Robert; Lippert, Kathrin; Scheiber-Mojdehkar, Barbara; Kvasnicka, Hans Michael; Khare, Vineeta; Gasche, Christoph

2014-05-01

Iron deficiency is a common cause of reactive thrombocytosis, however, the exact pathways have not been revealed. Here we aimed to study the mechanisms behind iron deficiency-induced thrombocytosis. Within few weeks, iron-depleted diet caused iron deficiency in young Sprague-Dawley rats, as reflected by a drop in hemoglobin, mean corpuscular volume, hepatic iron content and hepcidin mRNA in the liver. Thrombocytosis established in parallel. Moreover, platelets produced in iron deficient animals displayed a higher mean platelet volume and increased aggregation. Bone marrow studies revealed subtle alterations that are suggestive of expansion of megakaryocyte progenitors, an increase in megakaryocyte ploidy and accelerated megakaryocyte differentiation. Iron deficiency did not alter the production of hematopoietic growth factors such as thrombopoietin, interleukin 6 or interleukin 11. Megakaryocytic cell lines grown in iron-depleted conditions exhibited reduced proliferation but increased ploidy and cell size. Our data suggest that iron deficiency increases megakaryopoietic differentiation and alters platelet phenotype without changes in megakaryocyte growth factors, specifically TPO. Iron deficiency-induced thrombocytosis may have evolved to maintain or increase the coagulation capacity in conditions with chronic bleeding. Copyright © 2014 Wiley Periodicals, Inc.

Alterations in rat cardiac myosin isozymes induced by whole-body irradiation are prevented by 3,5,3'-L-triiodothyronine

Energy Technology Data Exchange (ETDEWEB)

Litten, R.Z.; Fein, H.G.; Gainey, G.T.; Walden, T.L.; Smallridge, R.C. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

1990-01-01

Changes in cardiac myosin isozymes and serum thyroid hormone levels were investigated in rats following 10 Gy whole-body gamma irradiation. The percent beta-myosin heavy chain increased from 21.3 {plus minus} 1.8 to 28.1 {plus minus} 6.8 (NS) at 3-day postirradiation, 37.7 {plus minus} 1.9 (P less than .001) at 6-day postirradiation, and 43.8 {plus minus} 3.3 (P less than .001) at 9-day postirradiation. Along with the change in myosin isozymes was a significant 53% decrease (P less than .001) in the serum thyroxine (T4) level by day 3 postirradiation, remaining depressed through day 9 postirradiation. The serum 3,5,3'-triiodothyronine (T3) level, however, was normal until day 9, when significant depression was also observed. In contrast, the thyroid-stimulating hormone (TSH) level was significantly increased by fourfold at day 3, returning to near normal values by day 9 postirradiation. Daily injections of physiological doses of T3 (0.3 microgram/100 g body weight) prevented the change in the myosin isozymes following whole-body irradiation. Daily pharmacological injections of T3 (3.0 micrograms/100 g body weight) to the irradiated rats produced a further decrease in the percent beta-myosin heavy chain (below control values) indicating tissue hyperthyroidism. Thus, this study suggests that the change in myosin isozymes following whole-body irradiation is caused by an alteration in thyroid hormone activity.

Altered expression of miRNAs in the uterus from a letrozole-induced rat PCOS model.

Science.gov (United States)

Li, Chunjin; Chen, Lu; Zhao, Yun; Chen, Shuxiong; Fu, Lulu; Jiang, Yanwen; Gao, Shan; Liu, Zhuo; Wang, Fengge; Zhu, Xiaoling; Rao, Jiahui; Zhang, Jing; Zhou, Xu

2017-01-20

Polycystic ovary syndrome (PCOS) causes female subfertility with ovarian disorders and may be associated with increased rate of early-pregnancy failure. Rat PCOS models were established using letrozole to understand the uterine pathogenesis of PCOS. The differential expression of microRNAs (miRNAs) was observed in rat uterus with PCOS. After estrous cycles were disrupted, significantly abnormal ovarian morphology and hormone level were observed in rats with PCOS. A total of 148 miRNAs differentially expressed were identified in the uterus from the letrozole-induced rat model compared with the control. These miRNAs included 111 upregulated miRNAs and 37 downregulated miRNAs. The differential expression of miR-484, miR-375-3p, miR-324-5p, and miR-223-3p was further confirmed by quantitative reverse transcription polymerase chain reaction. Bioinformatic analysis showed that these four miRNAs were predicted to regulate a large number of genes with different functions. Pathway analysis supported that target genes of miRNAs were involved in insulin secretion and signaling pathways, such as wnt, AMPK, PI3K-Akt, and Ras. These data indicated that miRNAs differentially expressed in rat uterus with PCOS may be associated with PCOS pathogenesis in the uterus. Our findings can help clarify the mechanism of uterine defects in PCOS. Copyright © 2016. Published by Elsevier B.V.

d-limonene ameliorates diabetes and its complications in streptozotocin-induced diabetic rats.

Science.gov (United States)

Bacanlı, Merve; Anlar, Hatice Gül; Aydın, Sevtap; Çal, Tuğbagül; Arı, Nuray; Ündeğer Bucurgat, Ülkü; Başaran, A Ahmet; Başaran, Nurşen

2017-12-01

It is known that diabetes causes some complications including alterations in lipid profile, hepatic enzyme levels but also it causes oxidative stress. Limonene, a major component of Citrus oils, has important health beneficial effects in lowering the level of oxidative stress due to its antioxidant activity. The aim of this study was to investigate the effects of D-limonene on streptozotocin (STZ)-induced diabetes in Wistar albino rats. For this purpose, DNA damage was evaluated by alkaline comet assay. Changes in the activities of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GSHPx) and the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), total glutathione (GSH), malondialdehyde (MDA), insulin, total bilirubin and BCA protein, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT), high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol and triglyceride were also evaluated. D-limonene treatment was found to significantly decrease DNA damage, GR enzyme activities and MDA levels and significantly increase GSH levels and CAT, SOD and GSH-Px enzyme activities and altered lipid and liver enzyme parameters in diabetic rats. According to our results, it seems that D-limonene might have a role in the prevention of the complication of diabetes in rats. Copyright © 2017 Elsevier Ltd. All rights reserved.

The upright posture improves plantar stepping and alters responses to serotonergic drugs in spinal rats.

Science.gov (United States)

Sławińska, Urszula; Majczyński, Henryk; Dai, Yue; Jordan, Larry M

2012-04-01

Recent studies on the restoration of locomotion after spinal cord injury have employed robotic means of positioning rats above a treadmill such that the animals are held in an upright posture and engage in bipedal locomotor activity. However, the impact of the upright posture alone, which alters hindlimb loading, an important variable in locomotor control, has not been examined. Here we compared the locomotor capabilities of chronic spinal rats when placed in the horizontal and upright postures. Hindlimb locomotor movements induced by exteroceptive stimulation (tail pinching) were monitored with video and EMG recordings. We found that the upright posture alone significantly improved plantar stepping. Locomotor trials using anaesthesia of the paws and air stepping demonstrated that the cutaneous receptors of the paws are responsible for the improved plantar stepping observed when the animals are placed in the upright posture.We also tested the effectiveness of serotonergic drugs that facilitate locomotor activity in spinal rats in both the horizontal and upright postures. Quipazine and (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) improved locomotion in the horizontal posture but in the upright posture either interfered with or had no effect on plantar walking. Combined treatment with quipazine and 8-OH-DPAT at lower doses dramatically improved locomotor activity in both postures and mitigated the need to activate the locomotor CPG with exteroceptive stimulation. Our results suggest that afferent input from the paw facilitates the spinal CPG for locomotion. These potent effects of afferent input from the paw should be taken into account when interpreting the results obtained with rats in an upright posture and when designing interventions for restoration of locomotion after spinal cord injury.

Pomegranate Alleviates Oxidative Damage and Neurotransmitter Alterations in Rats Brain Exposed to Aluminum Chloride and/or Gamma Radiation

International Nuclear Information System (INIS)

Said, U.Z.; EL-Tahawey, N.A.; Elassal, A.A.; Elsayed, E.M.; Shousha, W.Gh.

2013-01-01

Aluminum and gamma radiation, both are potent neurotoxins and have been implicated in many human neuro degenerative diseases. The present study was designed to investigate the role of pomegranate in alleviating oxidative damage and alteration of neurotransmitters in the brain of rats exposed to aluminum chloride (AlCl 3 ), and/or gamma radiation (IR). The results revealed that rats whole body exposed to γ- rays, (1 Gy/week up to 4 Gy), and/or administered aluminum chloride (35 mg/kg body weight), via gavages for 4 weeks, resulted in brain tissue damage, featuring by significant increase of the level of thiobarbituric acid reactive substances (TBARS), and advanced oxidation protein products (AOPP), associated with significant decrease of superoxide dismutase (SOD) and catalase (CAT) activities, as well as glutathione (GSH) content indicating occurrence of oxidative stress. A significant decrease of serotonin (5-HT) level associated with a significant increase of 5-hydroxyindole acetic acid (5-HIAA), in addition to a significant decrease in dopamine (DA), norepinephrine (NE) and epinephrine (EPI) contents recorded at the 1st, 7th and 14th day post-irradiation, indicating alterations in the metabolism of brain monoamines. On the other hand, the results exhibited that, supplementation of rats with pomegranate, via gavages, at a dose of 3 ml /kg body weight/ day, for 4 weeks along with AlCl 3 with or without radiation has significantly ameliorated the changes occurred in the mentioned parameters and the values returned close to the normal ones. It could be concluded that pomegranate, by its antioxidant constituents might antagonize brain oxidative damage and minimize the severity of aluminum (Al), and/or radiation-induced neurotransmitters disorders

Hypothyroidism in the adult rat causes incremental changes in brain-derived neurotrophic factor, neuronal and astrocyte apoptosis, gliosis, and deterioration of postsynaptic density.

Science.gov (United States)

Cortés, Claudia; Eugenin, Eliseo; Aliaga, Esteban; Carreño, Leandro J; Bueno, Susan M; Gonzalez, Pablo A; Gayol, Silvina; Naranjo, David; Noches, Verónica; Marassi, Michelle P; Rosenthal, Doris; Jadue, Cindy; Ibarra, Paula; Keitel, Cecilia; Wohllk, Nelson; Court, Felipe; Kalergis, Alexis M; Riedel, Claudia A

2012-09-01

Adult hypothyroidism is a highly prevalent condition that impairs processes, such as learning and memory. Even though tetra-iodothyronine (T(4)) treatment can overcome the hypothyroidism in the majority of cases, it cannot fully recover the patient's learning capacity and memory. In this work, we analyzed the cellular and molecular changes in the adult brain occurring with the development of experimental hypothyroidism. Adult male Sprague-Dawley rats were treated with 6-propyl-2-thiouracil (PTU) for 20 days to induce hypothyroidism. Neuronal and astrocyte apoptosis were analyzed in the hippocampus of control and hypothyroid adult rats by confocal microscopy. The content of brain-derived neurotrophic factor (BDNF) was analyzed using enzyme-linked immunosorbent assay (ELISA) and in situ hybridization. The glutamatergic synapse and the postsynaptic density (PSD) were analyzed by electron microscopy. The content of PSD proteins like tyrosine receptor kinase B (TrkB), p75, and N-methyl-D-aspartate receptor (NMDAr) were analyzed by immunoblot. We observed that the hippocampus of hypothyroid adult rats displayed increased apoptosis levels in neurons and astrocyte and reactive gliosis compared with controls. Moreover, we found that the amount of BDNF mRNA was higher in the hippocampus of hypothyroid rats and the content of TrkB, the receptor for BDNF, was reduced at the PSD of the CA3 region of hypothyroid rats, compared with controls. We also observed that the glutamatergic synapses from the stratum radiatum of CA3 from hypothyroid rats, contained thinner PSDs than control rats. This observation was in agreement with a reduced content of NMDAr subunits at the PSD in hypothyroid animals. Our data suggest that adult hypothyroidism affects the hippocampus by a mechanism that alters the composition of PSD, reduces neuronal and astrocyte survival, and alters the content of the signaling neurotrophic factors, such as BDNF.

The effects of a single memantine treatment on behavioral alterations associated with binge alcohol exposure in neonatal rats.

Science.gov (United States)

Idrus, Nirelia M; McGough, Nancy N H; Spinetta, Michael J; Thomas, Jennifer D; Riley, Edward P

2011-01-01

The third trimester in human fetal development represents a critical time of brain maturation referred to as the "brain growth spurt". This period occurs in rats postnatally, and exposure to ethanol during this time can increase the risk of impairments on a variety of cognitive and motor tasks. It has been proposed that one potential mechanism for the teratogenic effects of ethanol is NMDA receptor-mediated excitotoxicity during periods of ethanol withdrawal. In neonatal rats, antagonism of NMDA receptors during ethanol withdrawal, with drugs such as MK-801 and eliprodil, has been shown to mitigate some of the behavioral deficits induced by developmental ethanol exposure. The current study examined whether memantine, an NMDA receptor antagonist and a drug used clinically in Alzheimer's patients, would attenuate impairments associated with binge ethanol exposure in neonatal rats. On postnatal day 6, rats were exposed to 6 g/kg ethanol via intubation with controls receiving an isocaloric maltose dextrin solution. Twenty-one hours following the ethanol binge, rats received intraperitoneal injections of memantine at 0, 10, 15, or 20 mg/kg. Ethanol's teratogenic effects were assessed using multiple behavioral tasks: open field activity, parallel bars and spatial discrimination reversal learning. Ethanol-treated rats were overactive in the open field and were impaired on both reversal learning and motor performance. Administration of 15 or 20 mg/kg memantine during withdrawal significantly attenuated ethanol's adverse effects on motor coordination, but did not significantly alter activity levels or improve the spatial learning deficits associated with neonatal alcohol exposure. These results indicate that a single memantine administration during ethanol withdrawal can mitigate motor impairments but not spatial learning impairments or overactivity observed following a binge ethanol exposure during development in the rat. Copyright © 2011 Elsevier Inc. All rights reserved.

Acute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II Diabetes

Science.gov (United States)

Abstract for Society of Toxicology, March 22-25, 2015, San Diego, CAAcute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II DiabetesS.J. Snow1,3, D. Miller2, V. Bass2, M. Schladweiler3, A. Ledbetter3, J. Richards3, C...

Modifications of thyroid hormones secretion and production in newborn rats from hyperthyroic dams

International Nuclear Information System (INIS)

Silveira, M.F.G.; Neves, E.S.S.; Neves, S.R.S.; Catanho, M.T.J.A.

1997-01-01

The onset of fetal thyroid function occurs about 17-18 days after conception in the rat. The maternal hyperthyroidism which occurs during gestation provokes alterations in the rat after its birth; due to this alterations, we decided to analyze the metabolic and hormonal modification in the newborn rats. The hyperthyroidism was induced in normal dams, which were being trated for 2 days with T4 2mg (thyroxine per 100g body wt/day) before mating. Another dam group which was submitted to an inducement of hyperthyroidism maintained the treatment with T4 and six day after gestation were being treated for 9 days. It was seen that the rat which was born from hyperthyroic dams suffered alterations on its T4 and T3 hormone levels concerning the days 10, 20 and 30 after birth. T4 e T3 were performed with Immu chem cooted tube - I 125 RIA KIT .The administration of T4 affected the fetal thyroid function gland to, causing a decrease of both T4 and T3 levels, as was also modifications on their weight and size, even after the birth, indicating that the maternal hyperthyroidism influences on the post-natal life of the rat. The growth is affected throught post-natal life by thyroid hormones, which have a facilitatory influence on GH economy, as opposed to the inhibitory effects on TSH economy. (author). 12 refs., 4 figs

Restraint stress impairs glucose homeostasis through altered insulin ...

African Journals Online (AJOL)

The study investigated the potential alteration in the level of insulin and adiponectin, as well as the expression of insulin receptors (INSR) and glucose transporter 4 GLUT-4 in chronic restraint stress rats. Sprague-Dawley rats were randomly divided into two groups: the control group and stress group in which the rats were ...

Protective Efficacy of Emodin against γ-Rays Induced Acute Hepatorenal Injury in Rats

International Nuclear Information System (INIS)

Ibrahim, S.I.; Lotfi, S.A.

2011-01-01

Emodin(C 16 H 12 O 5 ), an active principle extracted from Rheum palmatum. Its protective effect was evaluated against γ-rays-induced biochemical alterations in rats. The purpose of recent study is to demonstrate protective efficacy of emodin against γ-rays induced acute hepatorenal injury in rats.γ -irradiation (6 Gy) caused significant elevation in the release of serum alanine and aspartate transaminases, (ALT and AST), alkaline phosphatase (SALP), lactate dehydrogenase (LDH), bilirubin (Br) and glucose (Gu) with concomitant decrease in haemoglobin (Hb) after 24 h of its exposure. Toxicant exposure intensified the lipid peroxidation (LPO, measured as MDA units), total cholesterol (TC) and activity of acid phosphatase (TAC) and altered glutathione status (GSH), activities of adenosine triphosphatase (ATP), alkaline phosphatase (TALP), glutamate dehydrogenase (GDH) as well as major cellular constituents; total proteins (TP) and glycogen (Gn) in liver and kidney, compared to control measures. Emodin, oral treatment, significantly lessened the toxicity by protecting γ-rays-induced alterations in various blood and tissue biochemical variables, compared to irradiated groups. Thus, the study concluded that emodin at a dose of 40 mg/ kg body wt possesses optimum hepatorenal protective ability in γ-irradiated toxicant rats

Ethanol concentration-dependent alterations in gene expression during acute binge drinking in the HIV-1 transgenic rat.

Science.gov (United States)

Sarkar, Sraboni; Chang, Sulie L

2013-07-01

Binge drinking of high ethanol (EtOH) concentration beverages is common among young adults and can be a risk factor for exposure to sexually transmitted diseases, including HIV-1. We used a novel noninfectious HIV-1 transgenic (HIV-1Tg) rat model that mimics HIV-1 patients in terms of altered immune responses and deficits in cognitive learning and memory to investigate EtOH concentration-dependent effects on 48 alcohol-modulated genes during binge EtOH administration. HIV-1Tg and control F344 rats were administered water, 8% EtOH, or 52% EtOH by gavage (i.g.) for 3 days (2.0 g/kg/d). Two hours after final treatment, blood, liver, and spleen were collected from each animal. Serum blood EtOH concentration (BEC) was measured, and gene expression in the liver and spleen was determined using a specifically designed PCR array. The BEC was significantly higher in the 52% EtOH-treated HIV-1Tg rats compared with the 8% EtOH group; however, the BEC was higher in the 8% EtOH-treated control rats compared with the 52% EtOH group. There was no change in expression of the EtOH metabolism-related genes, Adh1, Adh4, and Cyp2e1, in either the 8 or 52% EtOH-treated HIV-1Tg rats, whereas expression of those genes was significantly higher in the liver of the 52% EtOH control rats, but not in the 8% EtOH group. In the HIV-1Tg rats, expression of the GABAA , metabotropic glutamate, and dopamine neurotransmitter receptor genes was significantly increased in the spleen of the 52% EtOH group, but not in the 8% EtOH group, whereas no change was observed in those genes in either of the control groups. Our data indicate that, in the presence of HIV-1 infection, EtOH concentration-dependent binge drinking can have significantly different molecular effects. Copyright © 2013 by the Research Society on Alcoholism.

ENPP1 Mutation Causes Recessive Cole Disease by Altering Melanogenesis.

Science.gov (United States)

Chourabi, Marwa; Liew, Mei Shan; Lim, Shawn; H'mida-Ben Brahim, Dorra; Boussofara, Lobna; Dai, Liang; Wong, Pui Mun; Foo, Jia Nee; Sriha, Badreddine; Robinson, Kim Samirah; Denil, Simon; Common, John Ea; Mamaï, Ons; Ben Khalifa, Youcef; Bollen, Mathieu; Liu, Jianjun; Denguezli, Mohamed; Bonnard, Carine; Saad, Ali; Reversade, Bruno

2018-02-01

Cole disease is a genodermatosis of pigmentation following a strict dominant mode of inheritance. In this study, we investigated eight patients affected with an overlapping genodermatosis after recessive inheritance. The patients presented with hypo- and hyperpigmented macules over the body, resembling dyschromatosis universalis hereditaria in addition to punctuate palmoplantar keratosis. By homozygosity mapping and whole-exome sequencing, a biallelic p.Cys120Arg mutation in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) was identified in all patients. We found that this mutation, like those causing dominant Cole disease, impairs homodimerization of the ENPP1 enzyme that is mediated by its two somatomedin-B-like domains. Histological analysis revealed structural and molecular changes in affected skin that were likely to originate from defective melanocytes because keratinocytes do not express ENPP1. Consistently, RNA-sequencing analysis of patient-derived primary melanocytes revealed alterations in melanocyte development and in pigmentation signaling pathways. We therefore conclude that germline ENPP1 cysteine-specific mutations, primarily affecting the melanocyte lineage, cause a clinical spectrum of dyschromatosis, in which the p.Cys120Arg allele represents a recessive and more severe form of Cole disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Does inflammation induced by ultraviolet B and heat rekindling alter pain-related behaviour in rats?

Science.gov (United States)

Smith, Melissa; Taylor, Collette; Weerasinghe, Nirosha; Koutsikou, Stella; Lumb, Bridget; Murrell, Jo

2016-09-01

To investigate whether induction of the ultraviolet B and heat rekindling (UVB/HR) model alters burrowing behaviour in rats. Randomized, blinded, prospective experimental study. Sixteen adult male Wistar rats weighing 250-300 g. In the UVB/HR group (n = 8), UV irradiation was delivered to the heel area of the right plantar pelvic limb paw at a dose of 1000 mJ cm(-2) , using a narrow-band UVB light source. Twenty-four hours later, heat rekindling was performed by placement of a feedback-controlled thermode set at a constant temperature of 45 °C over the area of UVB irradiation for 5 minutes. Both interventions were carried out under pentobarbital anaesthesia. The 'sham' group (n = 8) was anaesthetized only. In the burrowing test, rats were housed singly for 2 hours in cages furnished with a burrow filled with sand. The amount of sand remaining in the burrow after 2 hours was weighed and the amount displaced from the burrow calculated. The burrowing test was carried out for two consecutive days prior to UVB irradiation (day 0), on day 1 prior to HR, on days 2 and 3 after UVB exposure and at equivalent time points in the sham group. Rats in the sham group burrowed means (SD) of 2429 (73) g and 2358 (124) g of sand on days -2 and 3, respectively, while those in the UVB/HR group burrowed 2460 (26) and 2419 (58) g on days -2 and 3, respectively. There was no significant effect of treatment on the amount of sand burrowed at any time point. Pain associated with UVB/HR model induction is below the threshold required to affect rat burrowing behaviour and therefore questions the face validity of UVB/HR as a translational model of inflammatory pain. © 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

RNaseT2 knockout rats exhibit hippocampal neuropathology and deficits in memory.

Science.gov (United States)

Sinkevicius, Kerstin W; Morrison, Thomas R; Kulkarni, Praveen; Cagliostro, Martha K Caffrey; Iriah, Sade; Malmberg, Samantha; Sabrick, Julia; Honeycutt, Jennifer A; Askew, Kim L; Trivedi, Malav; Ferris, Craig F

2018-05-10

RNASET2 deficiency in humans is associated with infant cystic leukoencephalopathy, which causes psychomotor impairment, spasticity, and epilepsy. A zebrafish mutant model suggests that loss of RNASET2 function leads to neurodegeneration due to the accumulation of non-degraded RNA in the lysosomes. The goal of this study was to characterize the first rodent model of RNASET2 deficiency. The brains of 3- and 12-month-old RNaseT2 knockout rats were studied using multiple magnetic resonance imaging modalities and behavioral tests. While T1 and T2 weighted images of RNaseT2 knockout rats exhibited no evidence of cystic lesions, the prefrontal cortex and hippocampal complex were enlarged in knockout animals. Diffusion weighted imaging showed altered anisotropy and putative gray matter changes in the hippocampal complex of the RNaseT2 knockout rats. Immunohistochemistry for glial fibrillary acidic protein (GFAP) showed the presence of hippocampal neuroinflammation. Decreased levels of lysosome-associated membrane protein 2 (LAMP2) and elevated acid phosphatase and β-N-Acetylglucosaminidase (NAG) activities indicated that the RNASET2 knockout rats likely had altered lysosomal function and potential defects in autophagy. Object recognition tests confirmed the RNaseT2 knockout rats exhibited memory deficits. However, the Barnes maze, and balance beam and rotarod tests, indicated there were no differences in spatial memory or motor impairments, respectively. Overall, patients with RNASET2 deficiency exhibited a more severe neurodegeneration phenotype than was observed in the RNaseT2 knockout rats. However, the vulnerability of the knockout rat hippocampus as evidenced by neuroinflammation, altered lysosomal function, and cognitive defects indicates this is still a useful in vivo model to study RNASET2 function. © 2018. Published by The Company of Biologists Ltd.

Early brain connectivity alterations and cognitive impairment in a rat model of Alzheimer's disease.

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Muñoz-Moreno, Emma; Tudela, Raúl; López-Gil, Xavier; Soria, Guadalupe

2018-02-07

Animal models of Alzheimer's disease (AD) are essential to understanding the disease progression and to development of early biomarkers. Because AD has been described as a disconnection syndrome, magnetic resonance imaging (MRI)-based connectomics provides a highly translational approach to characterizing the disruption in connectivity associated with the disease. In this study, a transgenic rat model of AD (TgF344-AD) was analyzed to describe both cognitive performance and brain connectivity at an early stage (5 months of age) before a significant concentration of β-amyloid plaques is present. Cognitive abilities were assessed by a delayed nonmatch-to-sample (DNMS) task preceded by a training phase where the animals learned the task. The number of training sessions required to achieve a learning criterion was recorded and evaluated. After DNMS, MRI acquisition was performed, including diffusion-weighted MRI and resting-state functional MRI, which were processed to obtain the structural and functional connectomes, respectively. Global and regional graph metrics were computed to evaluate network organization in both transgenic and control rats. The results pointed to a delay in learning the working memory-related task in the AD rats, which also completed a lower number of trials in the DNMS task. Regarding connectivity properties, less efficient organization of the structural brain networks of the transgenic rats with respect to controls was observed. Specific regional differences in connectivity were identified in both structural and functional networks. In addition, a strong correlation was observed between cognitive performance and brain networks, including whole-brain structural connectivity as well as functional and structural network metrics of regions related to memory and reward processes. In this study, connectivity and neurocognitive impairments were identified in TgF344-AD rats at a very early stage of the disease when most of the pathological hallmarks

Lead Exposure Impairs Hippocampus Related Learning and Memory by Altering Synaptic Plasticity and Morphology During Juvenile Period.

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Wang, Tao; Guan, Rui-Li; Liu, Ming-Chao; Shen, Xue-Feng; Chen, Jing Yuan; Zhao, Ming-Gao; Luo, Wen-Jing

2016-08-01

Lead (Pb) is an environmental neurotoxic metal. Pb exposure may cause neurobehavioral changes, such as learning and memory impairment, and adolescence violence among children. Previous animal models have largely focused on the effects of Pb exposure during early development (from gestation to lactation period) on neurobehavior. In this study, we exposed Sprague-Dawley rats during the juvenile stage (from juvenile period to adult period). We investigated the synaptic function and structural changes and the relationship of these changes to neurobehavioral deficits in adult rats. Our results showed that juvenile Pb exposure caused fear-conditioned memory impairment and anxiety-like behavior, but locomotion and pain behavior were indistinguishable from the controls. Electrophysiological studies showed that long-term potentiation induction was affected in Pb-exposed rats, and this was probably due to excitatory synaptic transmission impairment in Pb-exposed rats. We found that NMDA and AMPA receptor-mediated current was inhibited, whereas the GABA synaptic transmission was normal in Pb-exposed rats. NR2A and phosphorylated GluR1 expression decreased. Moreover, morphological studies showed that density of dendritic spines declined by about 20 % in the Pb-treated group. The spine showed an immature form in Pb-exposed rats, as indicated by spine size measurements. However, the length and arborization of dendrites were unchanged. Our results suggested that juvenile Pb exposure in rats is associated with alterations in the glutamate receptor, which caused synaptic functional and morphological changes in hippocampal CA1 pyramidal neurons, thereby leading to behavioral changes.

Administration of exercise-conditioned plasma alters muscle catalase kinetics in rat: An argument for in vivo-like Km instead of in vitro-like Vmax

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Aristidis S. Veskoukis

2018-05-01

Full Text Available Maximal velocity (Vmax is a well established biomarker for the assessment of tissue redox status. There is scarce evidence, though, that it does not probably reflect sufficiently in vivo tissue redox profile. Instead, the Michaelis constant (Km could more adequately image tissue oxidative stress and, thus, be a more physiologically relevant redox biomarker. Therefore, the aim of the present study was to side-by-side compare Vmax and Km of an antioxidant enzyme after implementing an in vivo set up that induces alterations in tissue redox status. Forty rats were divided into two groups including rats injected with blood plasma originating from rats that had previously swam until exhaustion and rats injected with blood plasma originating from sedentary rats. Tail-vein injections were performed daily for 21 days. Catalase Vmax and Km measured in gastrocnemius muscle were increased after administration of the exercise-conditioned plasma, denoting enhancement of the enzyme activity but impairment of its affinity for the substrate, respectively. These alterations are potential adaptations stimulated by the administered plasma pointing out that blood is an active fluid capable of regulating tissue homeostasis. Our findings suggest that Km adequately reflects in vivo modifications of skeletal muscle catalase and seems to surpass Vmax regarding its physiological relevance and biological interpretation. In conclusion, Km can be regarded as an in vivo-like biomarker that satisfactorily images the intracellular environment, as compared to Vmax that could be aptly parallelized with a biomarker that describes tissue oxidative stress in an in vitro manner.

Modelled microgravity alters the Na+, K+-ATPase activity in rat heart homogenates

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Peana, Alessandra T.; Pippia, Proto; Paci, Silvia; Tognacini, Christina; Assaretti, Anna Rita; Meloni, Antonietta M.; Galleri, Grazia; Bernardini, Federico

2005-08-01

This study was aimed at establishing whether modeled microgravity conditions, created in a three-dimensional clinostat (Random Positioning Machine, RPM), influence the membrane-associated Na+, K+- and Mg2+- ATPase activities in heart homogenates from rats (ex- posed to RPM for 48 hours). The experimental data indicate that modeled low g significantly decreased the total ATPase (p<0.01) and Na+, K+ -ATPase activities (p<0.05) with no change of the Mg2+-ATPase activity, compared to the respective rat control groups (ground). This Na+, K+- pump inhibition could cause a digital- like effect in response to several modifications of many physiological processes even if this inhibition might also be causally related to the physiological environment induced by RPM. The exact mechanism by which total A TPase and Na+, K+ -A TPase activities decrease in response to RPM conditions remains to be established. We cannot rule out that a reduced intracellular ATP production, previously demonstrated in other cellular systems submitted to modeled microgravity conditions, could be responsible for the effects reported here.

3. Impact of altered gravity on CNS development and behavior in male and female rats

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Sajdel-Sulkowska, E. M.; Nguon, K.; Ladd, B.; Sulkowski, V. A.; Sulkowski, Z. L.; Baxter, M. G.

The present study examined the effect of altered gravity on CNS development. Specifically, we compared neurodevelopment, behavior, cerebellar structure and protein expression in rat neonates exposed perinatally to hypergravity. Pregnant Sprague-Dawley rats were exposed to 1.5G-1.75G hypergravity on a 24-ft centrifuge starting on gestational day (G) 10, through giving birth on G22/G23, and nursing their offspring through postnatal day (P) 21. Cerebellar mass on P6 was decreased in 1.75G-exposed male pups by 27.5 percent; in 1.75G-exposed female pups it was decreased by 22.5 percent. The observed cerebellar changes were associated with alterations in neurodevelopment and motor behavior. Exposure to hypergravity impaired performance on the following neurocognitive tests: (1) righting time on P3 was more than doubled in 1.75G-exposed rats and the effect appeared more pronounced in female pups, (2) startle response on P10 was delayed in both male and female HG pups; HG pups were one-fifth as likely to respond to a clapping noise as SC pups, and (3) performance on a rotorod on P21 was decreased in HG pups; the duration of the stay on rotorod recorded for HG pups of both sexes was one tenth of the SC pups. Furthermore, Western blot analysis of selected cerebellar proteins suggested gender-specific changes in glial and neuronal proteins. On P6, GFAP expression was decreased by 59.2 percent in HG males, while no significant decrease was observed in female cerebella. Synaptophysin expression was decreased in HG male neonates by 29.9 percent and in HG female neonates by 20.7 percent as compared to its expression in SC cerebella. The results of this experiment suggest that perinatal exposure to hypergravity affects cerebellar development and behavior differently in male and female neonates. If one accepts that hypergravity is a good paradigm to study the effect of microgravity on the CNS, and since males and females were shown to respond differently to hypergravity, it can be

Vinpocetine and Vitamin E Modulates Some Biochemical Alterations Induced by Exposure to Ionizing Radiation and Chloropyrifos in Rats

International Nuclear Information System (INIS)

Kamal El-Dein, E.M.; Abd El-Azime, A.SH.

2013-01-01

Acapi-Cav is a well balanced and well tolerated formula containing vinpocetine and vitamin E. The objective of this study was to investigate the effect of vinpocetine and vitamin E on the oxidative stress, electrolytes and monoamines level in rats exposed to ionizing radiation (gamma rays), chloropyrifos (CPF) as well as rats exposed to a combination of gamma rays and CPF. Irradiation was performed by whole body exposure of rats to 8 Gy delivered at 1 Gy every 4 days. CPF was administered to rats by oral gavages at a dose of 3.6 mg/kg body weight ( 1/10 LD50 ) daily for 30 days. Vinpocetine and vitamin E were administered to rats by oral gavages at a dose of 20 mg/kg body weight daily during 7 days before starting the experiment and continued during the period of exposure to gamma rays and/or CPF. The results revealed significant increase of malondialdehyde (MDA) level associated with a significant decrease of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in the blood of rats exposed to gamma rays and/or CPF indicating oxidative stress. The levels of serum electrolytes (sodium Na + , potassium K + , calcium Ca ++ and magnesium Mg) showed significant decrease. Serum dopamine (DA) level was decreased and norepinephrine (NE) was increased while epinephrine (EPI) showed non-significant change. The level of serum monoamine oxidase (MAO) showed significant increase. The administration of vinpocetine and vitamin E to rats exposed to gamma rays and/or CPF significantly reduced the amount of MDA which associated with an increase in the level of antioxidants and significant improvement was recorded for electrolytes level. The results demonstrated that vinpocetine and vitamin E significantly attenuated the increase of MAO and induced significant amelioration in the level of monoamines. It could be concluded that vinpocetine and vitamin E might protect the body from oxidative damage and electrolytes and monoamines alterations in rats exposed to gamma rays

Correlation between dopamine receptor D2 expression and presence of abnormal involuntary movements in Wistar rats with hemiparkinsonism and dyskinesia.

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Caro Aponte, P A; Otálora, C A; Guzmán, J C; Turner, L F; Alcázar, J P; Mayorga, E L

2018-03-07

Parkinson's disease (PD) is characterised by motor alterations, which are commonly treated with L-DOPA. However, long-term L-DOPA use may cause dyskinesia. Although the pathogenic mechanism of L-DOPA-induced dyskinesia is unclear, the condition has been associated with alterations in dopamine receptors, among which D2 receptors (D2R) have received little attention. This study aims to: (i)develop and standardise an experimental model of L-DOPA-induced dyskinesia in rats with hemiparkinsonism; and (ii)evaluate the correlation between D2R expression and presence of abnormal involuntary movements (AIM). We allocated 21 male Wistar rats into 3 groups: intact controls, lesioned rats (with neurotoxin 6-OHDA), and dyskinetic rats (injected with L-DOPA for 19 days). Sensorimotor impairment was assessed with behavioural tests. Dyskinetic rats gradually developed AIMs during the treatment period; front leg AIMs were more severe and locomotor AIMs less severe (Pde Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Melatonin Alleviates Liver Apoptosis in Bile Duct Ligation Young Rats.

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Sheen, Jiunn-Ming; Chen, Yu-Chieh; Hsu, Mei-Hsin; Tain, You-Lin; Huang, Ying-Hsien; Tiao, Mao-Meng; Li, Shih-Wen; Huang, Li-Tung

2016-08-20

Bile duct ligation (BDL)-treated rats display cholestasis and liver damages. The potential protective activity of melatonin in young BDL rats in terms of apoptosis, mitochondrial function, and endoplasmic reticulum (ER) homeostasis has not yet been evaluated. Three groups of young male Sprague-Dawley rats were used: one group received laparotomy (Sham), a second group received BDL for two weeks (BDL), and a third group received BDL and intraperitoneal melatonin (100 mg/day) for two weeks (BDL + M). BDL group rats showed liver apoptosis, increased pro-inflamamtory mediators, caspases alterations, anti-apoptotic factors changes, and dysfunction of ER homeostasis. Melatonin effectively reversed apoptosis, mainly through intrinsic pathway and reversed ER stress. In addition, in vitro study showed melatonin exerted its effect mainly through the melatonin 2 receptor (MT2) in HepG2 cells. In conclusion, BDL in young rats caused liver apoptosis. Melatonin rescued the apoptotic changes via the intrinsic pathway, and possibly through the MT2 receptor. Melatonin also reversed ER stress induced by BDL.

Agomelatine's effect on circadian locomotor rhythm alteration and depressive-like behavior in 6-OHDA lesioned rats.

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Souza, Leonardo C; Martynhak, Bruno J; Bassani, Taysa B; Turnes, Joelle de M; Machado, Meira M; Moura, Eric; Andreatini, Roberto; Vital, Maria A B F

2018-05-01

Parkinson's disease (PD) patients often suffer from circadian locomotor rhythms impairment and depression, important non-motor symptoms. It is known that toxin-based animal models of PD can reproduce these features. In a 6-hydroxydopamine (6-OHDA) intranigral model, we first investigated the possible disturbances on circadian rhythms of locomotor activity. The rats were divided into 6-OHDA and Sham groups. After a partial dopaminergic lesion, the 6-OHDA group showed slight alterations in different circadian locomotor rhythms parameters. In a second experiment, we hypothesized agomelatine, an melatoninergic antidepressant with potential to resynchronize disturbed rhythms, could prevent neuronal damage and rhythm alterations in the same 6-OHDA model. The animals were divided into four groups: 6-OHDA+vehicle, 6-OHDA+ago, Sham+vehicle and 6-OHDA+ago. However, the treated animals (agomelatine 50 mg/kg for 22 days) showed an impaired rhythm robustness, and agomelatine did not induce significant changes in the other circadian parameters nor neuroprotection. Finally, in a third experiment, we examined the effects of agomelatine in the 6-OHDA model regarding depressive-like behavior, evaluated by sucrose preference test. The animals were also divided into four groups: 6-OHDA+vehicle, 6-OHDA+ago, Sham+vehicle and 6-OHDA+ago. The toxin infused animals showed a decrease in sucrose preference in comparison with the vehicle infused animals, however, agomelatine did not prevent this decrease. Our findings indicate that agomelatine worsened circadian locomotor rhythm and was not able to reverse the depressive-like behavior of rats in the 6-OHDA PD model. Copyright © 2018. Published by Elsevier Inc.

Effects of an onion by-product on bioactivity and safety markers in healthy rats.

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Roldán-Marín, Eduvigis; Krath, Britta N; Poulsen, Morten; Binderup, Mona-Lise; Nielsen, Tom H; Hansen, Max; Barri, Thaer; Langkilde, Søren; Cano, M Pilar; Sánchez-Moreno, Concepción; Dragsted, Lars O

2009-12-01

Onions are excellent sources of bioactive compounds including fructo-oligosaccharides (FOS) and polyphenols. An onion by-product was characterised in order to be developed as a potentially bioactive food ingredient. Our main aim was to investigate whether the potential health and safety effects of this onion by-product were shared by either of two derived fractions, an extract containing the onion FOS and polyphenols and a residue fraction containing mainly cell wall materials. We report here on the effects of feeding these products on markers of potential toxicity, protective enzymes and gut environment in healthy rats. Rats were fed during 4 weeks with a diet containing the products or a control feed balanced in carbohydrate. The onion by-product and the extract caused anaemia as expected in rodents for Allium products. No other toxicity was observed, including genotoxicity. Glutathione reductase (GR) and glutathione peroxidase (GPx1) activities in erythrocytes increased when rats were fed with the onion extract. Hepatic gene expression of Gr, Gpx1, catalase, 5-aminolevulinate synthase and NAD(P)H:quinone oxidoreductase was not altered in any group of the onion fed rats. By contrast, gamma-glutamate cysteine ligase catalytic subunit gene expression was upregulated but only in rats given the onion residue. The onion by-products as well as the soluble and insoluble fractions had prebiotic effects as evidenced by decreased pH, increased butyrate production and altered gut microbiota enzyme activities. In conclusion, the onion by-products have no in vivo genotoxicity, may support in vivo antioxidative defence and alter the functionality of the rat gut microbiota.

Methionine metabolism after portacaval shunt in the rat

International Nuclear Information System (INIS)

Benjamin, L.E.; Steele, R.D.

1985-01-01

The effect of portacaval shunt (PCS) on methionine metabolism in the rat was investigated. Male Sprague-Dawley rats were subjected to PCS and maintained on an 18% casein diet. Growth curves of operated rats were similar to controls. PCS rats excreted more urinary 35 SO 4 and less [ 35 S]taurine than controls after intraperitoneal injection of 0.3 mmol/100 g [ 35 S]methionine or [ 35 S]cysteine. Total urinary taurine excretion was similar in PCS and control rats after a methionine or cysteine load; however, under basal conditions PCS rats had higher urinary taurine levels than controls, indicating that PCS may cause the taurine pool to be expanded. Hepatic methionine, S-adenosylmethionine, and cysteine pools were significantly decreased in PCS rats, while S-adenosylhomocysteine levels were unchanged. Relative rates of transsulfuration in PCS and control rats were studied by following the decrease in the 3 H-to- 35 S ratio in liver protein after injection of [methyl-3H]methionine and [ 35 S]methionine, and no difference in flux of 35 S from [ 35 S]methionine to [ 35 S]cysteine was found. Similarly, total hepatic activities of methionine adenosyltransferase, cystathionine synthase, and cystathionine gamma-lyase were unchanged in PCS rats. These results indicate that altered methionine metabolism in PCS rats is not explained by changes in conversion of methionine to cysteine via the transsulfuration pathway

Ebselen alters mitochondrial physiology and reduces viability of rat hippocampal astrocytes.

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Santofimia-Castaño, Patricia; Salido, Ginés M; González, Antonio

2013-04-01

The seleno-organic compound and radical scavenger ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) have been extensively employed as an anti-inflammatory and neuroprotective compound. However, its glutathione peroxidase activity at the expense of cellular thiols groups could underlie certain deleterious actions of the compound on cell physiology. In this study, we have analyzed the effect of ebselen on rat hippocampal astrocytes in culture. Cellular viability, the intracellular free-Ca(2+) concentration ([Ca(2+)]c), the mitochondrial free-Ca(2+) concentration ([Ca(2+)]m), and mitochondrial membrane potential (ψm) were analyzed. The caspase-3 activity was also assayed. Our results show that cell viability was reduced by treatment of cells with ebselen, depending on the concentration employed. In the presence of ebselen, we observed an initial transient increase in [Ca(2+)]c that was then followed by a progressive increase to an elevated plateau. We also observed a transient increase in [Ca(2+)]m in the presence of ebselen that returned toward a value over the prestimulation level. The compound induced depolarization of ψm and altered the permeability of the mitochondrial membrane. Additionally, a disruption of the mitochondrial network was observed. Finally, we did not detect changes in caspase-3 activation in response to ebselen treatment. Collectively, these data support the likelihood of ebselen, depending on the concentration employed, reduces viability of rat hippocampal astrocytes via its action on the mitochondrial activity. These may be early effects that do not involve caspase-3 activation. We conclude that, depending on the concentration used, ebselen might exert deleterious actions on astrocyte physiology that could compromise cell function.

Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain

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Elphick Maurice R

2009-07-01

Full Text Available Abstract Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG, and the related compound N-palmitoylethanolamine (PEA, in neuropathic spinal cord. Selective spinal nerve ligation (SNL in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P P P P P

Alterations in the brain adenosine metabolism cause behavioral and neurological impairment in ADA-deficient mice and patients

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Sauer, Aisha V.; Hernandez, Raisa Jofra; Fumagalli, Francesca; Bianchi, Veronica; Poliani, Pietro L.; Dallatomasina, Chiara; Riboni, Elisa; Politi, Letterio S.; Tabucchi, Antonella; Carlucci, Filippo; Casiraghi, Miriam; Carriglio, Nicola; Cominelli, Manuela; Forcellini, Carlo Alberto; Barzaghi, Federica; Ferrua, Francesca; Minicucci, Fabio; Medaglini, Stefania; Leocani, Letizia; la Marca, Giancarlo; Notarangelo, Lucia D.; Azzari, Chiara; Comi, Giancarlo; Baldoli, Cristina; Canale, Sabrina; Sessa, Maria; D’Adamo, Patrizia; Aiuti, Alessandro

2017-01-01

Adenosine Deaminase (ADA) deficiency is an autosomal recessive variant of severe combined immunodeficiency (SCID) caused by systemic accumulation of ADA substrates. Neurological and behavioral abnormalities observed in ADA-SCID patients surviving after stem cell transplantation or gene therapy represent an unresolved enigma in the field. We found significant neurological and cognitive alterations in untreated ADA-SCID patients as well as in two groups of patients after short- and long-term enzyme replacement therapy with PEG-ADA. These included motor dysfunction, EEG alterations, sensorineural hypoacusia, white matter and ventricular alterations in MRI as well as a low mental development index or IQ. Ada-deficient mice were significantly less active and showed anxiety-like behavior. Molecular and metabolic analyses showed that this phenotype coincides with metabolic alterations and aberrant adenosine receptor signaling. PEG-ADA treatment corrected metabolic adenosine-based alterations, but not cellular and signaling defects, indicating an intrinsic nature of the neurological and behavioral phenotype in ADA deficiency. PMID:28074903

Altered blood-brain barrier permeability in rats with prehepatic portal hypertension turns to normal when portal pressure is lowered

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Eizayaga, Francisco; Scorticati, Camila; Prestifilippo, Juan P; Romay, Salvador; Fernandez, Maria A; Castro, José L; Lemberg, Abraham; Perazzo, Juan C

2006-01-01

AIM: To study the blood-brain barrier integrity in prehepatic portal hypertensive rats induced by partial portal vein ligation, at 14 and 40 d after ligation when portal pressure is spontaneously normalized. METHODS: Adult male Wistar rats were divided into four groups: Group I: Sham14d , sham operated; Group II: PH14d , portal vein stenosis; (both groups were used 14 days after surgery); Group III: Sham40d, Sham operated and Group IV: PH40d Portal vein stenosis (Groups II and IV used 40 d after surgery). Plasma ammonia, plasma and cerebrospinal fluid protein and liver enzymes concentrations were determined. Trypan and Evans blue dyes, systemically injected, were investigated in hippocampus to study blood-brain barrier integrity. Portal pressure was periodically recorded. RESULTS: Forty days after stricture, portal pressure was normalized, plasma ammonia was moderately high, and both dyes were absent in central nervous system parenchyma. All other parameters were reestablished. When portal pressure was normalized and ammonia level was lowered, but not normal, the altered integrity of blood-brain barrier becomes reestablished. CONCLUSION: The impairment of blood-brain barrier and subsequent normalization could be a mechanism involved in hepatic encephalopathy reversibility. Hemodynamic changes and ammonia could trigger blood-brain barrier alterations and its reestablishment. PMID:16552803

Increased Oxidative Stress and Imbalance in Antioxidant Enzymes in the Brains of Alloxan-Induced Diabetic Rats

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Luciane B. Ceretta

2012-01-01

Full Text Available Diabetes Mellitus (DM is associated with pathological changes in the central nervous system (SNC as well as alterations in oxidative stress. Thus, the main objective of this study was to evaluate the effects of the animal model of diabetes induced by alloxan on memory and oxidative stress. Diabetes was induced in Wistar rats by using a single injection of alloxan (150 mg/kg, and fifteen days after induction, the rats memory was evaluated through the use of the object recognition task. The oxidative stress parameters and the activity of antioxidant enzymes, superoxide dismutase (SOD, and catalase (CAT were measured in the rat brain. The results showed that diabetic rats did not have alterations in their recognition memory. However, the results did show that diabetic rats had increases in the levels of superoxide in the prefrontal cortex, and in thiobarbituric acid reactive species (TBARS production in the prefrontal cortex and in the amygdala in submitochondrial particles. Also, there was an increase in protein oxidation in the hippocampus and striatum, and in TBARS oxidation in the striatum and amygdala. The SOD activity was decreased in diabetic rats in the striatum and amygdala. However, the CAT activity was increased in the hippocampus taken from diabetic rats. In conclusion, our findings illustrate that the animal model of diabetes induced by alloxan did not cause alterations in the animals’ recognition memory, but it produced oxidants and an imbalance between SOD and CAT activities, which could contribute to the pathophysiology of diabetes.

Dioxin-induced acute cardiac mitochondrial oxidative damage and increased activity of ATP-sensitive potassium channels in Wistar rats

International Nuclear Information System (INIS)

Pereira, Susana P.; Pereira, Gonçalo C.; Pereira, Cláudia V.; Carvalho, Filipa S.; Cordeiro, Marília H.; Mota, Paula C.; Ramalho-Santos, João; Moreno, António J.; Oliveira, Paulo J.

2013-01-01

The environmental dioxin 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is classified as a Group 1 human carcinogen and teratogenic agent. We hypothesize that TCDD-induced oxidative stress may also interfere with mitochondrial ATP-sensitive potassium channels (mitoKATP), which are known to regulate and to be regulated by mitochondrial redox state. We investigated the effects of an acute treatment of male Wistar rats with TCDD (50 μg/kg i.p.) and measured the regulation of cardiac mitoKATP. While the function of cardiac mitochondria was slightly depressed, mitoKATP activity was 52% higher in animals treated with TCDD. The same effects were not observed in liver mitochondria isolated from the same animals. Our data also shows that regulation of mitochondrial ROS production by mitoKATP activity is different in both groups. To our knowledge, this is the first report to show that TCDD increases mitoKATP activity in the heart, which may counteract the increased oxidative stress caused by the dioxin during acute exposure. -- Highlights: •Acute TCDD treatment of Wistar rats causes cardiac oxidative stress. •Acute TCDD treatment causes cardiac mitochondrial alterations. •Mitochondrial liver vs. heart alterations are distinct. •TCDD treatment resulted in altered activity of cardiac mitochondrial K-ATP channels. -- Dioxin alters the regulation of cardiac mitochondrial ATP-sensitive potassium channels and disturbs mitochondrial physiology

Carbonated soft drinks induce oxidative stress and alter the expression of certain genes in the brains of Wistar rats.

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El-Terras, Adel; Soliman, Mohamed Mohamed; Alkhedaide, Adel; Attia, Hossam Fouad; Alharthy, Abdullah; Banaja, Abdel Elah

2016-04-01

In Saudi Arabia, the consumption of carbonated soft drinks is common and often occurs with each meal. Carbonated soft drink consumption has been shown to exhibit effects on the liver, kidney and bone. However, the effects of these soft drinks on brain activity have not been widely examined, particularly at the gene level. Therefore, the current study was conducted with the aim of evaluating the effects of chronic carbonated soft drink consumption on oxidative stress, brain gene biomarkers associated with aggression and brain histology. In total, 40 male Wistar rats were divided into four groups: Group 1 served as a control and was provided access to food and water ad libitum; and groups 2‑4 were given free access to food and carbonated soft drinks only (Cola for group 2, Pepsi for group 3 and 7‑UP for group 4). Animals were maintained on these diets for 3 consecutive months. Upon completion of the experimental period, animals were sacrificed and serological and histopathological analyses were performed on blood and tissues samples. Reverse transcription‑polymerase chain reaction was used to analyze alterations in gene expression levels. Results revealed that carbonated soft drinks increased the serum levels of malondialdehyde (MDA). Carbonated soft drinks were also observed to downregulate the expression of antioxidants glutathione reductase (GR), catalase and glutathione peroxidase (GPx) in the brain when compared with that in the control rats. Rats administered carbonated soft drinks also exhibited decreased monoamine oxidase A (MAO‑A) and acetylcholine esterase (AChE) serum and mRNA levels in the brain. In addition, soft drink consumption upregulated mRNA expression of dopamine D2 receptor (DD2R), while 5-hydroxytryptamine transporter (5‑HTT) expression was decreased. However, following histological examination, all rats had a normal brain structure. The results of this study demonstrated that that carbonated soft drinks induced oxidative stress and

Alterations in sulfur and nitrogen metabolism in rats with portacaval shunts

International Nuclear Information System (INIS)

Benjamin, L.E.

1985-01-01

The effect of portacaval shunt (PCS) on methionine and cysteine metabolism was investigated. PCS rats excreted more urinary [ 35 S]sulfate and less [ 35 S]taurine than controls after injection of [ 35 S]methionine of [ 35 S]cysteine. Total urinary taurine excretion was unchanged. Under basal conditions PCS rats excreted more taurine than controls. Relative rates of transsulfuration in PCS and control rats were studied, and no difference in flux of 35 S from methionine to cysteine was found. Total hepatic activities of three transsulfuration pathway enzymes were also unchanged after PCS. In contrast, hepatic activities of three cysteine-oxidizing enzymes were depressed after PCS, suggesting that changes in hepatic metabolism after PCS are selective. PCS rats fed a high (60%) casein diet ate less and took longer to recover their preoperative body weight than controls. All PCS rats had higher plasma ammonia and urinary orotic acid levels than controls. Increasing dietary protein elevated plasma ammonia and urinary orotic acid to a greater extent in PCS rats. After injection of [ 35 S]methionine or [ 35 S]cysteine, urinary 35 S and [ 35 S]sulfate excretion increased and [ 35 S]taurine an total taurine excretion decreased in all rats fed 60% casein, but the effect was greater in PCS rats. Changes in cysteine sulfinate decarboxylase activity in rats fed a high protein diet was examined. Activity decreased 95% in rats fed diets containing between 18 and 75% casein. The effect was observed after feeding a 60% casein diet for 2 days and was reversed when rats were refed an 18% casein diet

Cross-fostering does not alter the neurochemistry or behavior of spontaneously hypertensive rats

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Russell Vivienne A

2009-06-01

Full Text Available Abstract Background Attention-deficit/hyperactivity disorder (ADHD is a highly heritable developmental disorder resulting from complex gene-gene and gene-environment interactions. The most widely used animal model, the spontaneously hypertensive rat (SHR, displays the major symptoms of ADHD (deficits in attention, impulsivity and hyperactivity and has a disturbance in the noradrenergic system when compared to control Wistar-Kyoto rats (WKY. The aim of the present study was to determine whether the ADHD-like characteristics of SHR were purely genetically determined or dependent on the gene-environment interaction provided by the SHR dam. Methods SHR/NCrl (Charles River, USA, WKY/NCrl (Charles River, USA and Sprague Dawley rats (SD/Hsd, Harlan, UK were bred at the University of Cape Town. Rat pups were cross-fostered on postnatal day 2 (PND 2. Control rats remained with their birth mothers to serve as a reference for their particular strain phenotype. Behavior in the open-field and the elevated-plus maze was assessed between PND 29 and 33. Two days later, rats were decapitated and glutamate-stimulated release of [3H]norepinephrine was determined in prefrontal cortex and hippocampal slices. Results There was no significant effect of "strain of dam" but there was a significant effect of "pup strain" on all parameters investigated. SHR pups travelled a greater distance in the open field, spent a longer period of time in the inner zone and entered the inner zone of the open-field more frequently than SD or WKY. SD were more active than WKY in the open-field. WKY took longer to enter the inner zone than SHR or SD. In the elevated-plus maze, SHR spent less time in the closed arms, more time in the open arms and entered the open arms more frequently than SD or WKY. There was no difference between WKY and SD behavior in the elevated-plus maze. SHR released significantly more [3H]norepinephrine in response to glutamate than SD or WKY in both hippocampus

Alterations in protein transport events in rat liver after estrogen treatment

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Goldsmith, M.A.; Jones, A.L.; Underdown, B.J.; Schiff, J.M.

1987-01-01

The effects of 17α-ethynylestradiol (EE) treatment on the hepatic processing of rat polymeric immunoglobulin A (IgA) and human asialoorosomucoid (ASOr) were studied. After 5 days of treatment with EE (5 mg/kg) or solvent alone, male rats were anesthetized and injected with tracer doses of the test proteins. Bile flow rates had been reduced by >60% in the EE-treated animals. A previously reported radiolabeling strategy was used to monitor both the transport of intact protein to bile and the degradation of protein in lysosomes. Transport of intact IgA to bile was reduced by 43%, with transport peaking 27 min later in EE-treated animals compared with controls. There was a corresponding impairment of uptake of labeled IgA from blood. EE induced no kinetic change in the uptake or processing of ASOr. However, there was an increase in the proportion of ASOr reaching bile intact from 3% to 15-23% of the injected dose. The data indicate that EE disables the transport pathway for IgA and causes a partial change in the routing of ASOr after endocytosis in favor of direct transport to the bile canaliculus. These findings may have implications for the importance of membrane composition in protein transport events

Organophosphate pesticides-induced changes in the redox status of rat tissues and protective effects of antioxidant vitamins.

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Mishra, Vibhuti; Srivastava, Nalini

2015-04-01

Organophosphates (OPs) pesticides are among the most toxic synthetic chemicals purposefully added in the environment. The common use of OP insecticides in public health and agriculture results in an environmental pollution and a number of acute and chronic poisoning events. Present study was aimed to evaluate the potential of monocrotophos and quinalphos to effect the redox status and glutathione (GSH) homeostasis in rat tissues and find out whether antioxidant vitamins have some protection on the pesticide-induced alterations. The results showed that these pesticides alone or in combination, caused decrease in the levels of GSH and the corresponding increase in the levels of GSSG, decreasing the GSH/GSSG ratio. The results also showed that NADPH/NADP(+) and NADH/NAD(+) ratios were decreased in the liver and brain of rats on exposure with mococrotophos, quinalphos, and their mixture. These pesticides, alone or in combination, caused alterations in the activities of GSH reductase and glucose-6-phosphate dehydrogenase in the rat tissues. However, the expression of the GSH recycling enzymes did not show significant alterations as compared to control. From the results, it can be concluded that these pesticides generate oxidative stress but their effects were not synergistic when given together and prior feeding of antioxidant vitamins tend to reduce the toxicities of these pesticides. Copyright © 2013 Wiley Periodicals, Inc.

Perinatal intermittent hypoxia alters γ-aminobutyric acid: a receptor levels in rat cerebellum.

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Pae, Eung-Kwon; Yoon, Audrey J; Ahuja, Bhoomika; Lau, Gary W; Nguyen, Daniel D; Kim, Yong; Harper, Ronald M

2011-12-01

Perinatal hypoxia commonly causes brain injury in infants, but the time course and mechanisms underlying the preferential male injury are unclear. Intermittent hypoxia disturbs cerebellar γ-aminobutyric (GABA)-A receptor profiles during the perinatal period, possibly responding to transient excitatory processes associated with GABA(A) receptors. We examined whether hypoxic insults were particularly damaging to the male rodent cerebellum during a specific developmental time window. We evaluated cerebellar injury and GABA(A) receptor profiles following 5-h intermittent hypoxia (IH: 20.8% and 10.3% ambient oxygen, switched every 240s) or room-air control in groups of male and female rat pups on postnatal d 1-2, wk 1, or wk 3. The cerebella were harvested and compared between groups. The mRNA levels of GABA(A) receptors α6, normalized to a house-keeping gene GAPDH, and assessed using real-time reverse-transcriptase PCR assays were up-regulated by IH at wk 1, more extensively in male rats, with sex influencing the regulatory time-course. In contrast, GABA(A) α6 receptor protein expression levels, assessed using Western blot assays, reached a nadir at wk 1 in both male and female rats, possibly indicating involvement of a post-transcriptional mechanism. The extent of cerebellar damage and level of apoptosis, assessed by DNA fragmentation, were greatest in the wk 3 IH-exposed group. The findings suggest partial protection for female rats against early hypoxic insult in the cerebellum, and that down-regulation of GABA(A) receptors, rather than direct neural injury assessed by DNA fragmentation may modify cerebellar function, with potential later motor and other deficits. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

A High-Fat Diet Causes Impairment in Hippocampal Memory and Sex-Dependent Alterations in Peripheral Metabolism

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Erica L. Underwood

2016-01-01

Full Text Available While high-fat diets are associated with rising incidence of obesity/type-2 diabetes and can induce metabolic and cognitive deficits, sex-dependent comparisons are rarely systematically made. Effects of exclusive consumption of a high-fat diet (HFD on systemic metabolism and on behavioral measures of hippocampal-dependent memory were compared in young male and female LE rats. Littermates were fed from weaning either a HFD or a control diet (CD for 12 wk prior to testing. Sex-different effects of the HFD were observed in classic metabolic signs associated with type-2 diabetes. Males fed the HFD became obese, and had elevated fasted blood glucose levels, elevated corticosterone, and impaired glucose-tolerance, while females on the HFD exhibited only elevated corticosterone. Regardless of peripheral metabolism alteration, rats of both sexes fed the HFD were equally impaired in a spatial object recognition memory task associated with impaired hippocampal function. While the metabolic changes reported here have been characterized previously in males, the set of diet-induced effects observed here in females are novel. Impaired memory can have significant cognitive consequences, over the short-term and over the lifespan. A significant need exists for comparative research into sex-dependent differences underlying obesity and metabolic syndromes relating systemic, cognitive, and neural plasticity mechanisms.

Long Lasting Microvascular Tone Alteration in Rat Offspring Exposed In Utero to Maternal Hyperglycaemia.

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Emilie Vessières

Full Text Available Epidemiologic studies have demonstrated that cardiovascular risk is not only determined by conventional risk factors in adulthood, but also by early life events which may reprogram vascular function. To evaluate the effect of maternal diabetes on fetal programming of vascular tone in offspring and its evolution during adulthood, we investigated vascular reactivity of third order mesenteric arteries from diabetic mother offspring (DMO and control mother offspring (CMO aged 3 and 18 months. In arteries isolated from DMO the relaxation induced by prostacyclin analogues was reduced in both 3- and 18-month old animals although endothelium (acetylcholine-mediated relaxation was reduced in 18-month old DMO only. Endothelium-independent (sodium nitroprusside relaxation was not affected. Pressure-induced myogenic tone, which controls local blood flow, was reduced in 18-month old CMO compared to 3-month old CMO. Interestingly, myogenic tone was maintained at a high level in 18-month old DMO even though agonist-induced vasoconstriction was not altered. These perturbations, in 18-months old DMO rats, were associated with an increased pMLC/MLC, pPKA/PKA ratio and an activated RhoA protein. Thus, we highlighted perturbations in the reactivity of resistance mesenteric arteries in DMO, at as early as 3 months of age, followed by the maintenance of high myogenic tone in older rats. These modifications are in favour of excessive vasoconstrictor tone. These results evidenced a fetal programming of vascular functions of resistance arteries in adult rats exposed in utero to maternal diabetes, which could explain a re-setting of vascular functions and, at least in part, the occurrence of hypertension later in life.

Delayed maturation and altered proliferation within the rat rostral migratory stream following maternal deprivation

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K. Lievajova

2011-10-01

Full Text Available The objective of this study was to investigate whether stressful experience during early postnatal period may influence morphological characteristics of the rat neurogenic pathway – the rostral migratory stream (RMS and proliferation of neuronal precursors in three successive areas of the RMS: in the vertical arm, the elbow and the horizontal arm. To induce stress, the pups were subjected to repeated maternal deprivation during the first postnatal week after birth. Brains were analyzed at the seventh postnatal day. The controls matched the age of maternally deprived animals. Observation of hematoxylin-eosin stained sections showed that maternal deprivation did not affect the general morphological appearance of the RMS. The shape of the RMS of maternally deprived rats resembles the RMS of control animals. Maternal deprivation caused slight, not significant increase in the RMS thickness in comparison with control rats. Significant difference between the control and maternally deprived rats concerns the olfactory ventricle. While in seven days old control rats the olfactory ventricle is completely closed, in maternally deprived rats of the same age the olfactory ventricle was regularly visible as a narrow lumen at the axis of the RMS horizontal arm. This finding indicates delayed maturation of the migratory pathway as a consequence of stress. Proliferation activity has been assessed by immunoreactivity of the endogenous cell cycle protein Ki-67. The results of Ki-67 immunohistochemistry showed that seven days’ maternal separation for 3 h daily induces significant quantitative changes in the number of proliferating cells within the RMS. The response of Ki-67-positive cells to stress differed in individual part of the RMS, with a marked decrease in the vertical arm and a significant increase in the elbow, suggesting heterogeneity of neural stem cells along the RMS; while in the RMS vertical arm the number of dividing cells significantly decreased

Atrazine-induced reproductive tract alterations after transplacental and/or lactational exposure in male Long-Evans rats

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Rayner, Jennifer L.; Enoch, Rolondo R.; Wolf, Douglas C.; Fenton, Suzanne E.

2007-01-01

Studies showed that early postnatal exposure to the herbicide atrazine (ATR) delayed preputial separation (PPS) and increased incidence of prostate inflammation in adult Wistar rats. A cross-fostering paradigm was used in this study to determine if gestational exposure to ATR would also result in altered puberty and reproductive tissue effects in the male rat. Timed-pregnant Long-Evans (LE) rats were dosed by gavage on gestational days (GD) 15-19 with 100 mg ATR/kg body weight (BW) or 1% methylcellulose (controls, C). On postnatal day (PND)1, half litters were cross-fostered, creating 4 treatment groups; C-C, ATR-C, C-ATR, and ATR-ATR (transplacental-milk as source, respectively). On PND4, male offspring in the ATR-ATR group weighed significantly less than the C-C males. ATR-ATR male pups had significantly delayed preputial separation (PPS). BWs at PPS for C-ATR and ATR-ATR males were reduced by 6% and 9%, respectively, from that of C-C. On PND120, lateral prostate weights of males in the ATR-ATR group were significantly increased over C-C. Histological examination of lateral and ventral prostates identified an increased distribution of inflammation in the lateral prostates of C-ATR males. By PND220, lateral prostate weights were significantly increased for ATR-C and ATR-ATR, but there were no significant changes in inflammation in either the lateral or ventral prostate. These results suggest that in LE rats, gestational ATR exposure delays PPS when male offspring suckle an ATR dam, but leads to increased lateral prostate weight via transplacental exposure alone. Inflammation present at PND120 does not increase in severity with time

Development of an Assay Based on the Effects of PGBx on the Isolated Perfused Rat Heart and Rat Skeletal Muscle.

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1980-09-01

had no effect on discphe- nol induced alterations in spontaneous heart rate, but did appear to prevent the increase in coronary flow caused by...Phosphorylase a i -24 activity was also the same in each of the groups examined (Table 2-4). DISCUSSION The ability of PGBx to prevent 2,4-dinitrophenol-induced...euthyroid and hyperthyroid rats. Eur. J. Pharmac. 19, 12-17. Aronson, C. E. and Serlick, E. R. (1977a) Effects of chlorpromazine on the isolated

Administration of exercise-conditioned plasma alters muscle catalase kinetics in rat: An argument for in vivo-like Km instead of in vitro-like Vmax.

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Veskoukis, Aristidis S; Paschalis, Vassilis; Kyparos, Antonios; Nikolaidis, Michalis G

2018-05-01

Maximal velocity (V max ) is a well established biomarker for the assessment of tissue redox status. There is scarce evidence, though, that it does not probably reflect sufficiently in vivo tissue redox profile. Instead, the Michaelis constant (K m ) could more adequately image tissue oxidative stress and, thus, be a more physiologically relevant redox biomarker. Therefore, the aim of the present study was to side-by-side compare V max and K m of an antioxidant enzyme after implementing an in vivo set up that induces alterations in tissue redox status. Forty rats were divided into two groups including rats injected with blood plasma originating from rats that had previously swam until exhaustion and rats injected with blood plasma originating from sedentary rats. Tail-vein injections were performed daily for 21 days. Catalase V max and K m measured in gastrocnemius muscle were increased after administration of the exercise-conditioned plasma, denoting enhancement of the enzyme activity but impairment of its affinity for the substrate, respectively. These alterations are potential adaptations stimulated by the administered plasma pointing out that blood is an active fluid capable of regulating tissue homeostasis. Our findings suggest that K m adequately reflects in vivo modifications of skeletal muscle catalase and seems to surpass V max regarding its physiological relevance and biological interpretation. In conclusion, K m can be regarded as an in vivo-like biomarker that satisfactorily images the intracellular environment, as compared to V max that could be aptly parallelized with a biomarker that describes tissue oxidative stress in an in vitro manner. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Transcriptomic responses of the liver and adipose tissues to altered carbohydrate-fat ratio in diet: an isoenergetic study in young rats.

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Tanaka, Mitsuru; Yasuoka, Akihito; Shimizu, Manae; Saito, Yoshikazu; Kumakura, Kei; Asakura, Tomiko; Nagai, Toshitada

2017-01-01

To elucidate the effects of altered dietary carbohydrate and fat balance on liver and adipose tissue transcriptomes, 3-week-old rats were fed three kinds of diets: low-, moderate-, and high-fat diets (L, M, and H) containing a different ratio of carbohydrate-fat (C-F) (65:15, 60:20, and 35:45 in energy percent, respectively). The rats consumed the diets for 9 weeks and were subjected to biochemical and DNA microarray analyses. The rats in the H-group exhibited lower serum triacylglycerol (TG) levels but higher liver TG and cholesterol content than rats in the L-group. The analysis of differentially expressed genes (DEGs) between each group (L vs M, M vs H, and L vs H) in the liver revealed about 35% of L vs H DEGs that were regulated in the same way as M vs H DEGs, and most of the others were L- vs H-specific. Gene ontology analysis of these L vs H DEGs indicated that those related to fatty acid synthesis and circadian rhythm were enriched. Interestingly, about 30% of L vs M DEGs were regulated in a reverse way compared with L vs H and M vs H DEGs. These reversed liver DEGs included M-up/H-down genes ( Sds for gluconeogenesis from amino acids) and M-down/H-up genes ( Gpd2 for gluconeogenesis from glycerol, Agpat9 for TG synthesis, and Acot1 for beta-oxidation). We also analyzed L vs H DEGs in white (WAT) and brown (BAT) adipose tissues and found that both oxidation and synthesis of fatty acids were inhibited in these tissues. These results indicate that the alteration of dietary C-F balance differentially affects the transcriptomes of metabolizing and energy-storing tissues.

[Relationship between PMI and relative expression of myocardial various RNAs in rats died of different causes].

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Lü, Ye-Hui; Zhang, Heng; Pan, Hui; Ma, Kai-Jun; Li, Wen-Can; Chen, Wen-Feng; Jiang, Jie-Qing'; Xue, Ai-Min; Zhang, Ping; Wang, Hui-Jun; Chen, Long

2014-02-01

To observe the changes of relative expression of myocardial various RNAs in rats died of different causes and their relationship with PMI. The rat models were established in which the rats were sacrificed by broken neck, asphyxia, and hemorrhagic shock. Total RNAs were extracted from myocardium. The quantitative real time PCR was used to calculate threshold cycle values of RNAs including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), beta-actin, inducible nitric oxide synthase (iNOS), hypoxia-inducible factor-1 (HIF-1), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and U6 small nuclear RNA (U6 snRNA) and to study the changes of the relative expressions of various indexes with PMI. U6 snRNA with stable expression level could be used as appropriate internal control. In the early PMI, the relative expression of GAPDH, HIF-1, iNOS, TNF-alpha, and IL-6 more characteristically increased in groups of asphyxia and hemorrhagic shock than in group of broken neck, but the quantity of beta-actin decreased in all groups. In the late PMI, all the relative expressions significantly declined in correlation with the degradation of RNA. The characteristic changes of each RNA expression can be used as references to estimate PMI in deaths by different causes.

Traumatic brain injury causes an FK506-sensitive loss and an overgrowth of dendritic spines in rat forebrain.

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Campbell, John N; Register, David; Churn, Severn B

2012-01-20

Traumatic brain injury (TBI) causes both an acute loss of tissue and a progressive injury through reactive processes such as excitotoxicity and inflammation. These processes may worsen neural dysfunction by altering neuronal circuitry beyond the focally-damaged tissue. One means of circuit alteration may involve dendritic spines, micron-sized protuberances of dendritic membrane that support most of the excitatory synapses in the brain. This study used a modified Golgi-Cox technique to track changes in spine density on the proximal dendrites of principal cells in rat forebrain regions. Spine density was assessed at 1 h, 24 h, and 1 week after a lateral fluid percussion TBI of moderate severity. At 1 h after TBI, no changes in spine density were observed in any of the brain regions examined. By 24 h after TBI, however, spine density had decreased in ipsilateral neocortex in layer II and III and dorsal dentate gyrus (dDG). This apparent loss of spines was prevented by a single, post-injury administration of the calcineurin inhibitor FK506. These results, together with those of a companion study, indicate an FK506-sensitive mechanism of dendritic spine loss in the TBI model. Furthermore, by 1 week after TBI, spine density had increased substantially above control levels, bilaterally in CA1 and CA3 and ipsilaterally in dDG. The apparent overgrowth of spines in CA1 is of particular interest, as it may explain previous reports of abnormal and potentially epileptogenic activity in this brain region.

Alteration of Na-K pump activity in supersensitive rat caudal artery following 6-hydroxydopamine (6-OHDA) treatment

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Wong, S.K.; Foley, D.H.

1986-01-01

Contractile response and the Na-K pump activity, measured as ouabain-sensitive 86 Rb-uptake, were determined in caudal artery strips of rats pretreated with 6-OHDA. At 6-7 days after 6-OHDA treatment, the potencies of norepinephrine and serotonin in causing contraction of rat caudal artery were significantly increased by 2.3 - and 1.7 - fold respectively. There was, however, no change in maximum contractile response to either agent. Treatment with 6-OHDA also reduced endogenous catecholamine content of the caudal artery to 7% of the control. Analysis of ouabain-inhibitable 86 Rb-uptake of rat caudal artery by the double-reciprocal plots showed that both the rate of 86 Rb-uptake and the affinity for rubidium were depressed after 6-OHDA treatment. The results indicate that 6-OHDA induced supersensitivity in the rat caudal artery is associated with a decrease in the Na-K pump activity. These data provide additional support to the concept that inhibition of the Na-K pump may result in partial depolarization of the cell membrane which leads to supersensitivity of smooth muscle to excitatory drugs

Postnatal growth velocity modulates alterations of proteins involved in metabolism and neuronal plasticity in neonatal hypothalamus in rats born with intrauterine growth restriction.

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Alexandre-Gouabau, Marie-Cécile F; Bailly, Emilie; Moyon, Thomas L; Grit, Isabelle C; Coupé, Bérengère; Le Drean, Gwenola; Rogniaux, Hélène J; Parnet, Patricia

2012-02-01

Intrauterine growth restriction (IUGR) due to maternal protein restriction is associated in rats with an alteration in hypothalamic centers involved in feeding behaviour. In order to gain insight into the mechanism of perinatal maternal undernutrition in the brain, we used proteomics approach to identify hypothalamic proteins that are altered in their expression following protein restriction in utero. We used an animal model in which restriction of the protein intake of pregnant rats (8% vs. 20%) produces IUGR pups which were randomized to a nursing regimen leading to either rapid or slow catch-up growth. We identified several proteins which allowed, by multivariate analysis, a very good discrimination of the three groups according to their perinatal nutrition. These proteins were related to energy-sensing pathways (Eno 1, E(2)PDH, Acot 1 and Fabp5), redox status (Bcs 1L, PrdX3 and 14-3-3 protein) or amino acid pathway (Acy1) as well as neurodevelopment (DRPs, MAP2, Snca). In addition, the differential expressions of several key proteins suggested possible shunts towards ketone-body metabolism and lipid oxidation, providing the energy and carbon skeletons necessary to lipogenesis. Our results show that maternal protein deprivation during pregnancy only (IUGR with rapid catch-up growth) or pregnancy and lactation (IUGR with slow postnatal growth) modulates numerous metabolic pathways resulting in alterations of hypothalamic energy supply. As several of these pathways are involved in signalling, it remains to be determined whether hypothalamic proteome adaptation of IUGR rats in response to different postnatal growth rates could also interfere with cerebral plasticity or neuronal maturation. Copyright © 2012 Elsevier Inc. All rights reserved.

Repeated nicotine exposure enhances reward-related learning in the rat.

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Olausson, Peter; Jentsch, J David; Taylor, Jane R

2003-07-01

Repeated exposure to addictive drugs causes neuroadaptive changes in cortico-limbic-striatal circuits that may underlie alterations in incentive-motivational processes and reward-related learning. Such drug-induced alterations may be relevant to drug addiction because enhanced incentive motivation and increased control over behavior by drug-associated stimuli may contribute to aspects of compulsive drug-seeking and drug-taking behaviors. This study investigated the consequences of repeated nicotine treatment on the acquisition and performance of Pavlovian discriminative approach behavior, a measure of reward-related learning, in male rats. Water-restricted rats were trained to associate a compound conditioned stimulus (tone+light) with the availability of water (the unconditioned stimulus) in 15 consecutive daily sessions. In separate experiments, rats were repeatedly treated with nicotine (0.35 mg/kg, s.c.) either (1) prior to the onset of training, (2) after each daily training session was completed (ie postsession injections), or (3) received nicotine both before the onset of training as well as after each daily training session. In this study, all nicotine treatment schedules increased Pavlovian discriminative approach behavior and, thus, prior repeated exposure to nicotine, repeated postsession nicotine injections, or both, facilitated reward-related learning.

Reproduction and evaluation of a rat model of inhalation lung injury caused by black gunpowder smog

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Yi-fan LIU

2013-09-01

Full Text Available Objective　To reproduce and evaluate a rat model of inhalation lung injury caused by black gunpowder smog. Methods　The smog composition was analyzed and a rat model of inhalation lung injury was reproduced. Forty two healthy male Wistar rats were randomly divided into normal control (NC group and 1h, 2h, 6h, 24h, 48h and 96h after inhalation group (n=6. The arterial blood gas, wet to dry weight ratio (W/D of lung, leukocyte count, and protein concentration in broncho-alveolar lavage fluid (BALF were determined. Macroscopic and microscopic changes in lung tissue were observed. Results　The composition of black gunpowder smog was composed mainly of CO2 and CO, and their concentrations remained stable within 12 minutes. Smog inhalation caused a significant hypoxemia, the concentration of blood COHb reached a peak value 1h, and the W/D of lung reached peak value 2h after inhalation (P<0.05. The amount of leukocytes and content of protein in BALF increased significantly within 24h after inhalation (P<0.05. Histopathological observation showed diffuse hemorrhage, edema and inflammatory cell infiltration in lung tissue as manifestations of acute lung injury, and the injury did not recover at 96h after inhalation. Conclusion　The rat model of inhalation lung injury can be reproduced using black gunpowder smog, and it has the advantages of its readiness for reproduction, reliability and stability, and it could be used for the experiment of inhalation injury in a battlefield environment.

SURVEY OF HOUSE RAT INTESTINAL PARASITES FROM SURABAYA DISTRICT, EAST JAVA, INDONESIA THAT CAN CAUSE OPPORTUNISTIC INFECTIONS IN HUMANS.

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Prasetyo, R H

2016-03-01

The purpose of this study was to investigate the prevalence of house rat zoonotic intestinal parasites from Surabaya District, East Java, Indonesia that have the potential to cause opportunistic infection in humans. House rat fecal samples were collected from an area of Surabaya District with a dense rat population during May 2015. Intestinal parasites were detected microscopically using direct smear of feces stained with Lugol's iodine and modified Ziehl-Neelsen stains. The fecal samples were also cultured for Strongyloides stercoralis. Ninety-eight house rat fecal samples were examined. The potential opportunistic infection parasite densities found in those samples were Strongyloides stercoralis in 53%, Hymenolepis nana in 42%, Cryptosporidium spp in 33%, and Blastocystis spp in 6%. This is the first report of this kind in Surabaya District. Measures need to be taken to control the house rat population in the study area to reduce the risk of the public health problem. Keywords: zoonotic intestinal parasites, opportunistic infection, house rat, densely populated area, Indonesia

An imbalance between apoptosis and proliferation contributes to follicular persistence in polycystic ovaries in rats

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Neme Leandro G

2009-07-01

Full Text Available Abstract Background Cystic ovarian disease is an important cause of infertility that affects bovine, ovine, caprine and porcine species and even human beings. Alterations in the ovarian micro-environment of females with follicular cysts could alter the normal processes of proliferation and programmed cell death in ovarian cells. Thus, our objective was to evaluate apoptosis and proliferation in ovarian cystic follicles in rats in order to investigate the cause of cystic follicle formation and persistence. Methods We compared the number of in situ apoptotic cells by TUNEL assay, expression of active caspase-3 and members of Bcl-2 family by immunohistochemistry; and cell proliferation by the expression of the proliferation markers: PCNA and Ki-67. Results The proliferation index was low in granulosa of tertiary and cystic follicles of light exposed rats when compared with tertiary follicles of control animals, while in theca interna only cystic follicles presented low proliferation index when compared with tertiary follicles (p Conclusion These results show that the combination of weak proliferation indices and low apoptosis observed in follicular cysts, could explain the cause of the slow growth of cystic follicles and the maintenance of a static condition without degeneration, which leads to their persistence. These alterations may be due to structural and functional modifications that take place in these cells and could be related to hormonal changes in animals with this condition.

Learning and memory alterations are associated with hippocampal N-acetylaspartate in a rat model of depression as measured by 1H-MRS.

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Guangjun Xi

Full Text Available It is generally accepted that cognitive processes, such as learning and memory, are affected in depression. The present study used a rat model of depression, chronic unpredictable mild stress (CUMS, to determine whether hippocampal volume and neurochemical changes were involved in learning and memory alterations. A further aim was to determine whether these effects could be ameliorated by escitalopram treatment, as assessed with the non-invasive techniques of structural magnetic resonance imaging (MRI and magnetic resonance spectroscopy (MRS. Our results demonstrated that CUMS had a dramatic influence on spatial cognitive performance in the Morris water maze task, and CUMS reduced the concentration of neuronal marker N-acetylaspartate (NAA in the hippocampus. These effects could be significantly reversed by repeated administration of escitalopram. However, neither chronic stress nor escitalopram treatment influenced hippocampal volume. Of note, the learning and memory alterations of the rats were associated with right hippocampal NAA concentration. Our results indicate that in depression, NAA may be a more sensitive measure of cognitive function than hippocampal volume.

The genotoxicity and systemic toxicity of a pharmaceutical effluent in Wistar rats may involve oxidative stress induction

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Grace O. Adeoye

2015-01-01

Full Text Available There is scarcity of information on the possible mechanisms of pharmaceutical effluent induced genotoxicity and systemic toxicity. This study investigated the genotoxicity and systemic toxicity of a pharmaceutical effluent in Wistar rats. Rats were orally treated with 5–50% concentrations of the effluent for 28 days. At post-exposure, blood, liver, kidney and bone marrow cells were examined for alterations in serum biochemical parameters and hematological indices, histopathological lesions and micronucleated polychromatic erythrocytes formation (MNPCE. The effluent caused concentration independent significant (p < 0.05 alterations in aspartate (AST and alanine (ALT aminotransferases, superoxide dismutase (SOD, catalase (CAT, malondialdehyde (MDA, total and direct bilirubin and creatinine. There was reduction in red blood count (RBC, hemoglobin concentration (HGB, platelets, percentage hematocrit (HCT, white blood count (WBC and mean corpuscle hemoglobin (MCH except mean corpuscle hemoglobin concentration (MCHC, which increased in the treated rats. Histopathological lesions observed in the liver and kidney of the effluent treated rats were thinning of the hepatic cord, kuffer cell hyperplasia, vacuolation of the hepatocytes and renal cells, multifocal inflammatory changes, necrosis and congestion of the renal blood vessels and central vein. MNPCE significantly increase in the bone marrow of the treated rats compared to the negative control. The concentration of some toxic metals and anions in the effluent were above standard permissible limits. These findings showed that the pharmaceutical effluent caused somatic DNA damage and systemic toxicity in rats may involve induction of oxidative stress, suggesting environmental contamination and health risks in wildlife and humans.

Moringa oleifera extract (Lam) attenuates Aluminium phosphide-induced acute cardiac toxicity in rats.

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Gouda, Ahmed S; El-Nabarawy, Nagla A; Ibrahim, Samah F

2018-01-01

Moringa oleifera extract (Lam) has many antioxidant and protective properties. Objective: to investigate the antioxidant activities of Lam in counteracting the high oxidative stress caused by acute sub-lethal aluminium phosphide (AlP) intoxication in rat heart. These activities will be detected by histopathological examination and some oxidative stress biomarkers. a single sub-lethal dose of Alp (2 mg/kg body weight) was administered orally, and Lam was given orally at a dose (100 mg/kg body weight) one hour after receiving AlP to rats. aluminium phosphide caused significant cardiac histopathological changes with a significant increase in malondialdehyde (MDA); lipid peroxidation marker; and a significant depletion of antioxidant enzymes (catalase and glutathione reductase). However, treatment with Lam protected efficiently the cardiac tissue of intoxicated rats by increasing antioxidants levels with slight decreasing in MDA production compared to untreated group. This study suggested that Moringa oleifera extract could possibly restore the altered cardiac histopathology and some antioxidant power in AlP intoxicated rats, and it could even be used as adjuvant therapy against AlP-induced cardiotoxicity.

Alterations by peroxisome proliferators of acyl composition of hepatic phosphatidylcholine in rats, mice and guinea-pigs. Role of stearoyl-CoA desaturase.

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Kawashima, Y; Hirose, A; Kozuka, H

1986-01-01

Rats, mice and guinea-pigs were administered p-chlorophenoxyisobutyric acid (clofibric acid) or 2,2'-(decamethylenedithio)diethanol (tiadenol). The treatments of rats and mice with either clofibric acid or tiadenol increased markedly the activities of stearoyl-CoA desaturase, palmitoyl-CoA chain elongation, 1-acylglycerophosphate (1-acyl-GP) acyltransferase and 1-acylglycerophosphocholine (1-acyl-GPC) acyltransferase, but not 2-acylglycerophosphocholine (2-acyl-GPC) acyltransferase in liver microsomes. The treatment of guinea-pigs with clofibric acid did not cause any change in the activities of these enzymes. The treatment of guinea-pigs with tiadenol caused a slight, but significant, increase in the activities of 1-acyl-GP acyltransferase and 1-acyl-GPC acyltransferase. The treatment of rats and mice with either clofibric acid or tiadenol increased markedly the proportion of 18:1 and decreased greatly the proportion of 18:0 in liver microsomal phosphatidylcholine. However, there is a considerable difference in the effects of the two peroxisome proliferators on the composition of polyunsaturated fatty acids in phosphatidylcholine between rats and mice. The treatment of guinea-pigs with either of the two peroxisome proliferators caused no change in acyl composition of phosphatidylcholine. The possible role of stearoyl-CoA desaturation in the regulation of acyl composition of phosphatidylcholine was discussed. PMID:2874791

Hypothyroidism Causes Endoplasmic Reticulum Stress in Adult Rat Hippocampus: A Mechanism Associated with Hippocampal Damage

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Alejandra Paola Torres-Manzo

2018-01-01

Full Text Available Thyroid hormones (TH are essential for hippocampal neuronal viability in adulthood, and their deficiency causes hypothyroidism, which is related to oxidative stress events and neuronal damage. Also, it has been hypothesized that hypothyroidism causes a glucose deprivation in the neuron. This study is aimed at evaluating the temporal participation of the endoplasmic reticulum stress (ERE in hippocampal neurons of adult hypothyroid rats and its association with the oxidative stress events. Adult Wistar male rats were divided into euthyroid and hypothyroid groups. Thyroidectomy with parathyroid gland reimplementation caused hypothyroidism at three weeks postsurgery. Oxidative stress, redox environment, and antioxidant enzyme markers, as well as the expression of the ERE through the pathways of PERK, ATF6, and IRE1, were evaluated at the 3rd and 4th weeks postsurgery. We found a rise in ROS and nitrite production; also, catalase increased and glutathione peroxidase diminished their activities. These events promote an enhancement of the lipoperoxidation, as well as of γ-GT, myeloperoxidase, and caspase 3 activities. With respect to ERE, there were ATF6, IRE1, and GADD153 overexpressions with a reduction in mitochondrial activity and GSH2/GSSG ratio. We conclude that the endoplasmic reticulum stress might play a pivotal role in the activation of hypothyroidism-induced hippocampal cell death.

Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth-restricted rats

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Goodspeed, Danielle; Seferovic, Maxim D.; Holland, William; Mcknight, Robert A.; Summers, Scott A.; Branch, D. Ware; Lane, Robert H.; Aagaard, Kjersti M.

2015-01-01

Intrauterine growth restriction (IUGR) confers heritable alterations in DNA methylation, rendering risk of adult metabolic syndrome (MetS). Because CpG methylation is coupled to intake of essential nutrients along the one-carbon pathway, we reasoned that essential nutrient supplementation (ENS) may abrogate IUGR-conferred multigenerational MetS. Pregnant Sprague-Dawley rats underwent bilateral uterine artery ligation causing IUGR in F1. Among the F2 generation, IUGR lineage rats were underweight at birth (6.7 vs. 8.0 g, P 30% elevated, P 5-fold less central fat mass, normal hepatic glucose efflux, and >70% reduced circulating triglycerides and very-LDLs compared with IUGR control-fed F2 offspring (P intrauterine growth-restricted rats. PMID:25395450

A Free-Choice High-Fat High-Sugar Diet Alters Day-Night Per2 Gene Expression in Reward-Related Brain Areas in Rats.

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Blancas-Velazquez, Aurea Susana; Unmehopa, Unga A; Eggels, Leslie; Koekkoek, Laura; Kalsbeek, Andries; Mendoza, Jorge; la Fleur, Susanne E

2018-01-01

Under normal light-dark conditions, nocturnal rodents consume most of their food during the dark period. Diets high in fat and sugar, however, may affect the day-night feeding rhythm resulting in a higher light phase intake. In vitro and in vivo studies showed that nutrients affect clock-gene expression. We therefore hypothesized that overconsuming fat and sugar alters clock-gene expression in brain structures important for feeding behavior. We determined the effects of a free-choice high-fat high-sugar (fcHFHS) diet on clock-gene expression in rat brain areas related to feeding and reward and compared them with chow-fed rats. Consuming a fcHFHS diet for 6 weeks disrupted day-night differences in Per2 mRNA expression in the nucleus accumbens (NAc) and lateral hypothalamus but not in the suprachiasmatic nucleus, habenula, and ventral tegmental area. Furthermore, short-term sugar drinking, but not fat feeding, upregulates Per2 mRNA expression in the NAc. The disruptions in day-night differences in NAc Per2 gene expression were not accompanied by altered day-night differences in the mRNA expression of peptides related to food intake. We conclude that the fcHFHS diet and acute sugar drinking affect Per2 gene expression in areas involved in food reward; however, this is not sufficient to alter the day-night pattern of food intake.

Ultrastructural alterations in adult Schistosoma mansoni caused by artemether

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Shuhua Xiao

2002-07-01

Full Text Available Progress has been made over the last decade with the development and clinical use of artemether as an agent against major human schistosome parasites. The tegument has been identified as a key target of artemether, implying detailed studies on ultrastructural damage induced by this compound. We performed a temporal examination, employing a transmission electron microscope to assess the pattern and extent of ultrastructural alterations in adult Schistosoma mansoni harboured in mice treated with a single dose of 400 mg/kg artemether. Eight hours post-treatment, damage to the tegument and subtegumental structures was seen. Tegumental alterations reached a peak 3 days after treatment and were characterized by swelling, fusion of distal cytoplasma, focal lysis of the tegumental matrix and vacuolisation. Tubercles and sensory organelles frequently degenerated or collapsed. Typical features of subtegumental alterations, including muscle fibres, syncytium and parenchyma tissues, were focal or extensive lysis, vacuolisation and degeneration of mitochondria. Severe alterations were also observed in gut epithelial cells and vitelline cells of female worms. Our findings of artemether-induced ultrastructural alterations in adult S. mansoni confirm previous results obtained with juvenile S. mansoni and S. japonicum of different ages.

Altered Potassium Ion Channel Function as a Possible Mechanism of Increased Blood Pressure in Rats Fed Thermally Oxidized Palm Oil Diets.

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Nkanu, Etah E; Owu, Daniel U; Osim, Eme E

2017-12-27

Intake of thermally oxidized palm oil leads to cytotoxicity and alteration of the potassium ion channel function. This study investigated the effects of fresh and thermally oxidized palm oil diets on blood pressure and potassium ion channel function in blood pressure regulation. Male Wistar rats were randomly divided into three groups of eight rats. Control group received normal feed; fresh palm oil (FPO) and thermally oxidized palm oil (TPO) groups were fed a diet mixed with 15% (weight/weight) fresh palm oil and five times heated palm oil, respectively, for 16 weeks. Blood pressure was measured; blood samples, hearts, and aortas were collected for biochemical and histological analyses. Thermally oxidized palm oil significantly elevated basal mean arterial pressure (MAP). Glibenclamide (10 -5 mmol/L) and tetraethylammonium (TEA; 10 -3 mmol/L) significantly raised blood pressure in TPO compared with FPO and control groups. Levcromakalim (10 -6 mmol/L) significantly (p palm oil increases MAP probably due to the attenuation of adenosine triphosphate-sensitive potassium (K ATP ) and large-conductance calcium-dependent potassium (BK Ca ) channels, tissue peroxidation, and altered histological structures of the heart and blood vessels.

Chronic Stress Induces Structural Alterations in Splenic Lymphoid Tissue That Are Associated with Changes in Corticosterone Levels in Wistar-Kyoto Rats

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María Eugenia Hernandez

2013-01-01

Full Text Available Major depressive disorder patients present chronic stress and decreased immunity. The Wistar-Kyoto rat (WKY is a strain in which the hypothalamic-pituitary-adrenal axis is overactivated. To determine whether chronic stress induces changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male rats were subject to restraint stress (3 h daily, chemical stress (hydrocortisone treatment, 50 mg/Kg weight, mixed stress (restraint plus hydrocortisone, or control treatment (without stress for 1, 4, and 7 weeks. The serum corticosterone levels by RIA and spleens morphology were analyzed. Corticosterone levels as did the structure, size of the follicles and morphology of the parenchyma (increase in red pulp in the spleen, varied depending on time and type of stressor. These changes indicate that chronic stress alters the immune response in the spleen in WKY rats by inducing morphological changes, explaining in part the impaired immunity that develops in organisms that are exposed to chronic stress.

Hyperproteic diet and pregnancy of rat.

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Greco, A M; Sticchi, R; Gambardella, P; D'Aponte, D; Ferrante, P

1986-01-01

We have studied the effects of a purified diet enriched with animal protein (casein 40%, lactalbumin 20%) on different stages of rat pregnancy. We observed that hyperproteic diet, especially when administered from the first day of pregnancy, induces morphological alterations of liver, adrenal cortex, heart and kidney. Moreover, haematic dosages, carried out on 15th day of pregnancy, have shown moderate but significant increase of glucose and triglycerides and significant decrease of circulating aldosterone and corticosterone as well. Finally an early administration of hyperproteic diet causes less numerous litters and high mortality rate at birth.

Prenatal exposure to BPA alters the epigenome of the rat mammary gland and increases the propensity to neoplastic development.

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Eugen Dhimolea

Full Text Available Exposure to environmental estrogens (xenoestrogens may play a causal role in the increased breast cancer incidence which has been observed in Europe and the US over the last 50 years. The xenoestrogen bisphenol A (BPA leaches from plastic food/beverage containers and dental materials. Fetal exposure to BPA induces preneoplastic and neoplastic lesions in the adult rat mammary gland. Previous results suggest that BPA acts through the estrogen receptors which are detected exclusively in the mesenchyme during the exposure period by directly altering gene expression, leading to alterations of the reciprocal interactions between mesenchyme and epithelium. This initiates a long sequence of altered morphogenetic events leading to neoplastic transformation. Additionally, BPA induces epigenetic changes in some tissues. To explore this mechanism in the mammary gland, Wistar-Furth rats were exposed subcutaneously via osmotic pumps to vehicle or 250 µg BPA/kg BW/day, a dose that induced ductal carcinomas in situ. Females exposed from gestational day 9 to postnatal day (PND 1 were sacrificed at PND4, PND21 and at first estrus after PND50. Genomic DNA (gDNA was isolated from the mammary tissue and immuno-precipitated using anti-5-methylcytosine antibodies. Detection and quantification of gDNA methylation status using the Nimblegen ChIP array revealed 7412 differentially methylated gDNA segments (out of 58207 segments, with the majority of changes occurring at PND21. Transcriptomal analysis revealed that the majority of gene expression differences between BPA- and vehicle-treated animals were observed later (PND50. BPA exposure resulted in higher levels of pro-activation histone H3K4 trimethylation at the transcriptional initiation site of the alpha-lactalbumin gene at PND4, concomitantly enhancing mRNA expression of this gene. These results show that fetal BPA exposure triggers changes in the postnatal and adult mammary gland epigenome and alters gene

Branched-chain amino acid-rich diet improves skeletal muscle wasting caused by cigarette smoke in rats.

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Tomoda, Koichi; Kubo, Kaoru; Hino, Kazuo; Kondoh, Yasunori; Nishii, Yasue; Koyama, Noriko; Yamamoto, Yoshifumi; Yoshikawa, Masanori; Kimura, Hiroshi

2014-04-01

Cigarette smoke induces skeletal muscle wasting by a mechanism not yet fully elucidated. Branched-chain amino acids (BCAA) in the skeletal muscles are useful energy sources during exercise or systemic stresses. We investigated the relationship between skeletal muscle wasting caused by cigarette smoke and changes in BCAA levels in the plasma and skeletal muscles of rats. Furthermore, the effects of BCAA-rich diet on muscle wasting caused by cigarette smoke were also investigated. Wistar Kyoto (WKY) rats that were fed with a control or a BCAA-rich diet were exposed to cigarette smoke for four weeks. After the exposure, the skeletal muscle weight and BCAA levels in plasma and the skeletal muscles were measured. Cigarette smoke significantly decreased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles, while a BCAA-rich diet increased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles that had decreased by cigarette smoke exposure. In conclusion, skeletal muscle wasting caused by cigarette smoke was related to the decrease of BCAA levels in the skeletal muscles, while a BCAA-rich diet may improve cases of cigarette smoke-induced skeletal muscle wasting.

Oxcarbazepine causes neurocyte apoptosis and developing brain damage by triggering Bax/Bcl-2 signaling pathway mediated caspase 3 activation in neonatal rats.

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Song, Y; Zhong, M; Cai, F-C

2018-01-01

Anti-epileptic drugs (AEDs) are the main methods for treatment of neonatal seizures; however, a few AEDs may cause developing brain damage of neonate. This study aims to investigate effects of oxcarbazepine (OXC) on developing brain damage of neonatal rats. Both of neonatal and adult rats were divided into 6 groups, including Control, OXC 187.5 mg/kg, OXC 281.25 mg/kg, OXC 375 mg/kg group, LEV and PHT group. Body weight and brain weight were evaluated. Hematoxylin and eosin (HE) and Nissl staining were used to observe neurocyte morphology and Nissl bodies, respectively. Apoptosis was examined using TUNEL assay, and caspase 8 activity was evaluated using spectrophotometer method. Cytochrome C-release was evaluated using flow cytometry. Western blot was used to examine Bax and Bcl-2 expression. OXC 375 mg/kg treatment significantly decreased brain weight compared to Control group in neonatal rats (P5 rats) (pOxcarbazepine at a concentration of 281.25 mg/kg or more causes neurocyte apoptosis and developing brain damage by triggering Bax/Bcl-2 signaling pathway mediated caspase 3 activation in neonatal rats.

Effects of exposure to cigarette smoke prior to pregnancy in diabetic rats

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Damasceno Débora C

2011-08-01

Full Text Available Abstract Background The purpose of this study was to evaluate the effects of cigarette smoke exposure before pregnancy on diabetic rats and their offspring development. Methods Diabetes was induced by streptozotocin and cigarette smoke exposure was conducted by mainstream smoke generated by a mechanical smoking device and delivered into a chamber. Diabetic female Wistar rats were randomly distributed in four experimental groups (n minimum = 13/group: nondiabetic (ND and diabetic rats exposed to filtered air (D, diabetic rats exposed to cigarette smoke prior to and into the pregnancy period (DS and diabetic rats exposed to cigarette smoke prior to pregnancy period (DSPP. At day 21 of pregnancy, rats were killed for maternal biochemical determination and reproductive outcomes. Results The association of diabetes and cigarette smoke in DSPP group caused altered glycemia at term, reduced number of implantation and live fetuses, decreased litter and maternal weight, increased pre and postimplantation loss rates, reduced triglyceride and VLDL-c concentrations, increased levels of thiol groups and MDA. Besides, these dams presented increased SOD and GSH-Px activities. However, the increased antioxidant status was not sufficient to prevent the lipid peroxidation observed in these animals. Conclusion Despite the benefits stemming from smoking interruption during the pregnancy of diabetic rats, such improvement was insufficient to avoid metabolic alterations and provide an adequate intrauterine environment for embryofetal development. Therefore, these results suggest that it is necessary to cease smoking extensive time before planning pregnancy, since stopping smoking only when pregnancy is detected may not contribute effectively to fully adequate embryofetal development.

PREGNANCY LOSS IN THE F344 RAT CAUSED BY BROMODICHLOROMETHANE: EFFECTS ON SERUM LUTEINIZING HORMONE LEVELS

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PREGNANCY LOSS IN THE F344 RAT CAUSED BY BROMODICHLOROMETHANE: EFFECTS ON SERUM LUTEINIZING HORMONE LEVELS Bielmeier1, S.R., D.S. Best2, and M.G. Narotsky2; 1University of North Carolina at Chapel Hill, Curriculum in Toxicology, 2Reproductive Toxicology Division, U.S. Enviro...

Hypoxic Living and Exercise Training Alter Adipose Tissue Leptin/Leptin Receptor in Rats

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Yingli Lu

2016-11-01

Full Text Available Background: Hypobaric hypoxia results in weight loss in obese individuals, and exercise training is advocated for the treatment of obesity and its related metabolic dysfunctions. The purpose of this study was to investigate the effects of hypoxic living and exercise training on obesity and adipose tissue leptin/leptin receptor in dietary-induced obese rats. Methods: One hundred and thirty high-fat diet fed Sprague-Dawley rats were assigned into one of the following groups (n=10 each: control, sedentary hypoxic living for 1 to 4 weeks (SH1, SH2, SH3, and SH4, living and exercise training in normoxic conditions for 1 to 4 weeks (TN1, TN2, TN3, and TN4, and living and exercise training in hypoxic conditions for 1 to 4 weeks (TN1, TN2, TN3, and TN4. Epididymal adipose tissue expression levels of leptin and leptin receptor were determined. Results: Compared to hypoxic living and living and exercise training in normoxic conditions, living and exercise training in hypoxic conditions for 3-4 weeks resulted in lower Lee index (P<0.05 to P<0.01, and higher expression of leptin and leptin receptor (P<0.05 to P<0.01 in adipose tissue. Conclusion: In a rodent model of altitude training, living and exercise training in hypoxic conditions resulted in greater alterations in obesity and adipose tissue leptin/leptin receptor than hypoxic living alone and living and exercise training in normoxic conditions.

Acute and chronic ethanol intake: effects on spatial and non-spatial memory in rats.

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García-Moreno, Luis M; Cimadevilla, Jose M

2012-12-01

Abusive alcohol consumption produces neuronal damage and biochemical alterations in the mammal brain followed by cognitive disturbances. In this work rats receiving chronic and acute alcohol intake were evaluated in a spontaneous delayed non-matching to sample/position test. Chronic alcohol-treated rats had free access to an aqueous ethanol solution as the only available liquid source from the postnatal day 21 to the end of experiment (postnatal day 90). Acute alcoholic animals received an injection of 2 g/kg ethanol solution once per week. Subjects were evaluated in two tests (object recognition and spatial recognition) based on the spontaneous delayed non-matching to sample or to position paradigm using delays of 1 min, 15 min and 60 min. Results showed that chronic and acute alcohol intake impairs the rats' performance in both tests. Moreover, chronic alcohol-treated rats were more altered than acute treated animals in both tasks. Our results support the idea that chronic and acute alcohol administration during postnatal development caused widespread brain damage resulting in behavioral disturbances and learning disabilities. Copyright © 2012 Elsevier Inc. All rights reserved.

Litter size reduction accentuates maternal care and alters behavioral and physiological phenotypes in rat adult offspring.

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Enes-Marques, Silvia; Giusti-Paiva, Alexandre

2018-01-27

Maternal behavior has a substantial impact on the behavioral, endocrine, and neural development of the pups. This study investigated the effect of altering the neonatal nutritional environment by modifying the litter size on maternal care and anxiety- and fear-like behaviors in rats during adulthood. On postnatal day (PND) 2, litters were adjusted to a small litter (SL) size of three pups per dam or normal litter (NL) size of 12 pups per dam. Maternal behaviors were scored daily during lactation (PND2-21). The weight gain, food intake, adiposity, and biochemical landmarks of offspring rats were evaluated. On PND60, performances in the open field, elevated plus-maze (EPM), and fear conditioning test were measured. The reduction of the litter size enhanced maternal care in lactating rats, increasing the arched-back posture and licking pups. SL offspring exhibited accelerated weight gain, hyperphagia, increased visceral fat mass, dyslipidemia, and hyperleptinemia in adulthood. The SL offspring of both sexes showed an increase in the anti-thigmotactic effect in the open field, an intact anxious-phenotype in the EPM, and a decrease in the time spent freezing during the fear-conditioning test, compared to NL. The neonatal environment as determined by litter size plays a crucial role in programming the adult metabolic phenotype as well as behavioral responses to stressful stimuli, with an impact on anxiety-like and fear behaviors. These behavioral changes in offspring may be, at least in part, a result of increased maternal care.

PhyloChip microarray analysis reveals altered gastrointestinal microbial communities in a rat model of colonic hypersensitivity

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Nelson, T.A.; Holmes, S.; Alekseyenko, A.V.; Shenoy, M.; DeSantis, T.; Wu, C.H.; Andersen, G.L.; Winston, J.; Sonnenburg, J.; Pasricha, P.J.; Spormann, A.

2010-12-01

Irritable bowel syndrome (IBS) is a chronic, episodic gastrointestinal disorder that is prevalent in a significant fraction of western human populations; and changes in the microbiota of the large bowel have been implicated in the pathology of the disease. Using a novel comprehensive, high-density DNA microarray (PhyloChip) we performed a phylogenetic analysis of the microbial community of the large bowel in a rat model in which intracolonic acetic acid in neonates was used to induce long lasting colonic hypersensitivity and decreased stool water content and frequency, representing the equivalent of human constipation-predominant IBS. Our results revealed a significantly increased compositional difference in the microbial communities in rats with neonatal irritation as compared with controls. Even more striking was the dramatic change in the ratio of Firmicutes relative to Bacteroidetes, where neonatally irritated rats were enriched more with Bacteroidetes and also contained a different composition of species within this phylum. Our study also revealed differences at the level of bacterial families and species. The PhyloChip is a useful and convenient method to study enteric microflora. Further, this rat model system may be a useful experimental platform to study the causes and consequences of changes in microbial community composition associated with IBS.

Aconitine-induced Ca2+ overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats

International Nuclear Information System (INIS)

Sun, Gui-bo; Sun, Hong; Meng, Xiang-bao; Hu, Jin; Zhang, Qiang; Liu, Bo; Wang, Min; Xu, Hui-bo; Sun, Xiao-bo

2014-01-01

Aconitine is a major bioactive diterpenoid alkaloid with high content derived from herbal aconitum plants. Emerging evidence indicates that voltage-dependent Na + channels have pivotal roles in the cardiotoxicity of aconitine. However, no reports are available on the role of Ca 2+ in aconitine poisoning. In this study, we explored the importance of pathological Ca 2+ signaling in aconitine poisoning in vitro and in vivo. We found that Ca 2+ overload lead to accelerated beating rhythm in adult rat ventricular myocytes and caused arrhythmia in conscious freely moving rats. To investigate effects of aconitine on myocardial injury, we performed cytotoxicity assay in neonatal rat ventricular myocytes (NRVMs), as well as measured lactate dehydrogenase level in the culture medium of NRVMs and activities of serum cardiac enzymes in rats. The results showed that aconitine resulted in myocardial injury and reduced NRVMs viability dose-dependently. To confirm the pro-apoptotic effects, we performed flow cytometric detection, cardiac histology, transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. The results showed that aconitine stimulated apoptosis time-dependently. The expression analysis of Ca 2+ handling proteins demonstrated that aconitine promoted Ca 2+ overload through the expression regulation of Ca 2+ handling proteins. The expression analysis of apoptosis-related proteins revealed that pro-apoptotic protein expression was upregulated, and anti-apoptotic protein BCL-2 expression was downregulated. Furthermore, increased phosphorylation of MAPK family members, especially the P-P38/P38 ratio was found in cardiac tissues. Hence, our results suggest that aconitine significantly aggravates Ca 2+ overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase. - Highlights: • Aconitine-induced Ca 2+ overload causes arrhythmia in rats

Ketamine differentially restores diverse alterations of neuroligins in brain regions in a rat model of neuropathic pain-induced depression.

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Pan, Wei; Zhang, Guang-Fen; Li, Hui-Hui; Ji, Mu-Huo; Zhou, Zhi-Qiang; Li, Kuan-Yu; Yang, Jian-Jun

2018-07-04

Depression is present in a large proportion of patients suffering from chronic pain, and yet the underlying mechanisms remain to be elucidated. Neuroligins (NLs), as a family of cell-adhesion proteins, are involved in synaptic formation and have been linked to various neuropsychiatric disorders. Here, we studied the alterations in NL1 and NL2 in the medial prefrontal cortex (mPFC), the anterior cingulate cortex (ACC), and the hippocampus in a rat model of neuropathic pain-induced depression, and whether ketamine, a rapid and robust antidepressant, could restore these abnormalities. In the present study, we found that spared nerve injury induced significant mechanical allodynia and subsequent depressive-like symptoms, along with decreased NL1 and increased NL2 in the mPFC, decreased NL1 in the ACC, and decreased NL2 in the hippocampus. In addition, brain-derived neurotrophic factor (BDNF) was reduced in these brain regions. It is noteworthy that ketamine (10 mg/kg) relieved neuropathic pain-induced depressive behaviors and restored alterations of BDNF and NLs in the mPFC and the hippocampus at 24 h and 72 h after the administration of ketamine, but only restored BDNF in the ACC. In conclusion, NLs showed diverse changes in different brain regions in the rat model of neuropathic pain-induced depression, which could be reversed differentially by the administration of ketamine.

Patterns of blood pressure variability in normotensive and hypertensive rats

DEFF Research Database (Denmark)

Holstein-Rathlou, N H; He, J; Wagner, A J

1995-01-01

We sought patterns in mean arterial pressure of normotensive rats and alterations in chronic hypertension. Pressure was recorded for 4-6 days by telemetry from conscious, unrestrained rats and sampled digitally at 3 Hz, using normotensive Sprague-Dawley rats, spontaneously hypertensive rats (SHR)...... the day; less pronounced in 2K,1C; and not detectable in SHR. There are regular patterns of blood pressure fluctuations and specific modifications to the patterns by different forms of hypertension.......We sought patterns in mean arterial pressure of normotensive rats and alterations in chronic hypertension. Pressure was recorded for 4-6 days by telemetry from conscious, unrestrained rats and sampled digitally at 3 Hz, using normotensive Sprague-Dawley rats, spontaneously hypertensive rats (SHR...

Botulinum toxin injection causes hyper-reflexia and increased muscle stiffness of the triceps surae muscle in the rat.

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Pingel, Jessica; Wienecke, Jacob; Lorentzen, Jakob; Nielsen, Jens Bo

2016-12-01

Botulinum toxin is used with the intention of diminishing spasticity and reducing the risk of development of contractures. Here, we investigated changes in muscle stiffness caused by reflex activity or elastic muscle properties following botulinum toxin injection in the triceps surae muscle in rats. Forty-four rats received injection of botulinum toxin in the left triceps surae muscle. Control measurements were performed on the noninjected contralateral side in all rats. Acute experiments were performed, 1, 2, 4, and 8 wk following injection. The triceps surae muscle was dissected free, and the Achilles tendon was cut and attached to a muscle puller. The resistance of the muscle to stretches of different amplitudes and velocities was systematically investigated. Reflex-mediated torque was normalized to the maximal muscle force evoked by supramaximal stimulation of the tibial nerve. Botulinum toxin injection caused severe atrophy of the triceps surae muscle at all time points. The force generated by stretch reflex activity was also strongly diminished but not to the same extent as the maximal muscle force at 2 and 4 wk, signifying a relative reflex hyperexcitability. Passive muscle stiffness was unaltered at 1 wk but increased at 2, 4, and 8 wk (P botulinum toxin causes a relative increase in reflex stiffness, which is likely caused by compensatory neuroplastic changes. The stiffness of elastic elements in the muscles also increased. The data are not consistent with the ideas that botulinum toxin is an efficient antispastic medication or that it may prevent development of contractures. Copyright © 2016 the American Physiological Society.

Multiple toxic doses of methamphetamine alter neurotensin concentrations in various region of the rat brain

International Nuclear Information System (INIS)

Hanson, G.R.; Merchant, K.; Gibb, J.W.; Letter, A.A.

1986-01-01

The authors have previously reported that multiple high doses of methamphetamine (METH) alter neuronal monoamine metabolism and release. Recently, Hokfelt et al. showed that neurotensin, a tridecapeptide, has neurotransmitter properties which may be involved with DA neuronal activity. In the present study they investigated the possible effects of METH on the CNS neurotensin system. Five doses of METH (15 mg/kg) were administered every 6 h; control and treated rats were sacrificed 18 h after the last dose and concentrations of neurotensin-like immuno-reactivity (NTLI) were measured by radioimmunoassay. NTLI was elevated 200-300% in the nucleus accumbens, neostriatum, and substantia nigra; 30-40% increases in NTLI were measured in the hippocampus and hypothalamus. No change was observed in amygdala, A-10 or periaqueductal gray. In contrast to the above measured areas, the frontal lobe and olfactory bulb showed decreases of 25-35%. These findings demonstrate that METH treatment alters the activities of several CNS neurotensin systems, possibly due to the influence of this drug on DA pathways. The variability in the type and magnitude of these responses suggests that DA and neurotensin systems interact by more than one mechanism

Subthalamic nucleus high-frequency stimulation restores altered electrophysiological properties of cortical neurons in parkinsonian rat.

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Bertrand Degos

Full Text Available Electrophysiological recordings performed in parkinsonian patients and animal models have confirmed the occurrence of alterations in firing rate and pattern of basal ganglia neurons, but the outcome of these changes in thalamo-cortical networks remains unclear. Using rats rendered parkinsonian, we investigated, at a cellular level in vivo, the electrophysiological changes induced in the pyramidal cells of the motor cortex by the dopaminergic transmission interruption and further characterized the impact of high-frequency electrical stimulation of the subthalamic nucleus, a procedure alleviating parkinsonian symptoms. We provided evidence that a lesion restricted to the substantia nigra pars compacta resulted in a marked increase in the mean firing rate and bursting pattern of pyramidal neurons of the motor cortex. These alterations were underlain by changes of the electrical membranes properties of pyramidal cells including depolarized resting membrane potential and increased input resistance. The modifications induced by the dopaminergic loss were more pronounced in cortico-striatal than in cortico-subthalamic neurons. Furthermore, subthalamic nucleus high-frequency stimulation applied at parameters alleviating parkinsonian signs regularized the firing pattern of pyramidal cells and restored their electrical membrane properties.

Aromatase deficiency causes altered expression of molecules critical for calcium reabsorption in the kidneys of female mice *.

NARCIS (Netherlands)

Oz, O.K.; Hajibeigi, A.; Howard, K.; Cummins, C.L.; Abel, M. van; Bindels, R.J.M.; Word, R.A.; Kuro-o, M.; Pak, C.Y.; Zerwekh, J.E.

2007-01-01

Kidney stones increase after menopause, suggesting a role for estrogen deficiency. ArKO mice have hypercalciuria and lower levels of calcium transport proteins, whereas levels of the klotho protein are elevated. Thus, estrogen deficiency is sufficient to cause altered renal calcium handling.

Cigarette smoke regulates VEGFR2-mediated survival signaling in rat lungs

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Stevenson Christopher S

2010-02-01

Full Text Available Abstract Background Vascular endothelial growth factor (VEGF and VEGF receptor 2 (VEGFR2-mediated survival signaling is critical to endothelial cell survival, maintenance of the vasculature and alveolar structure and regeneration of lung tissue. Reduced VEGF and VEGFR2 expression in emphysematous lungs has been linked to increased endothelial cell death and vascular regression. Previously, we have shown that CS down-regulated the VEGFR2 and its downstream signaling in mouse lungs. However, the VEGFR2-mediated survival signaling in response to oxidants/cigarette smoke (CS is not known. We hypothesized that CS exposure leads to disruption of VEGFR2-mediated endothelial survival signaling in rat lungs. Methods Adult male Sprague-Dawley rats were exposed CS for 3 days, 8 weeks and 6 months to investigate the effect of CS on VEGFR2-mediated survival signaling by measuring the Akt/PI3-kinase/eNOS downstream signaling in rat lungs. Results and Discussion We show that CS disrupts VEGFR2/PI3-kinase association leading to decreased Akt and eNOS phosphorylation. This may further alter the phosphorylation of the pro-apoptotic protein Bad and increase the Bad/Bcl-xl association. However, this was not associated with a significant lung cell death as evidenced by active caspase-3 levels. These data suggest that although CS altered the VEGFR2-mediated survival signaling in the rat lungs, but it was not sufficient to cause lung cell death. Conclusion The rat lungs exposed to CS in acute, sub-chronic and chronic levels may be representative of smokers where survival signaling is altered but was not associated with lung cell death whereas emphysema is known to be associated with lung cell apoptosis.

Alterations in glucose kinetics induced by pentobarbital anesthesia

International Nuclear Information System (INIS)

Lang, C.H.; Bagby, G.J.; Spitzer, J.J.

1986-01-01

Pentobarbital is a common anesthetic agent used in animal research that is known to alter sympathetic function and may also affect carbohydrate metabolism. The in vivo effects of iv pentobarbital on glucose homeostasis were studied in chronically catheterized fasted rats. Whole body glucose kinetics, assessed by the constant iv infusion of [6- 3 H]- and [U- 14 C]-glucose, were determined in all rats in the conscious state. Thereafter, glucose metabolism was followed over the next 4 hr in 3 subgroups of rats; conscious, anesthetized with body temperature maintained, and anesthetized with body temperature not maintained. Hypothermia (a 5 0 C decrease) developed spontaneously in anesthetized rats kept at ambient temperature (22 0 C). No differences were seen in MABP and heart rate between conscious and normothermic anesthetized rats; however, hypothermic anesthetized rats showed a decrease in MABP (20%) and heart rate (35%). Likewise, plasma glucose and lactate concentrations, the rate of glucose appearance (Ra), recycling and metabolic clearance (MCR) did not differ between conscious and normothermic anesthetized animals. In contrast, hypothermic anesthetized rats showed a 50% reduction in plasma lactate, a 40% drop in glucose Ra, and a 30-40% decrease in glucose recycling and MCR. Thus, pentobarbital does not appear to alter in vivo glucose kinetics, compared to unanesthetized controls, provided that body temperature is maintained

Studies on alterations of the 86-rubidium efflux from rat pancreatic islets caused by thiol and thiol oxidants

International Nuclear Information System (INIS)

Wahl, M.A.

1983-01-01

The following findings were revealed by this study: 1) Oxidation-reduction (redox) of the intracellular system of glutathione influences the potassium efflux by way of an increase in the 86-rubidium efflux brought about by the oxidation of intracellular thiols. 2) The 86-rubidium efflux is not subject to change by oxidation of extracellular thiols located in the membrane, nor can it in any way be influenced by reduced glutathione of exogenous origin. 3) The potassium efflux from rat pancreatic islets, being generally known to trigger the electric activities of the beta-cell, is controlled by the oxidation-reduction of intracellular thiols rather than by that of extracellular thiols. (TRV) [de

Functional and structural alterations of epithelial barrier properties of rat ileum following X-irradiation

International Nuclear Information System (INIS)

Dublineau, I.; Lebrun, F.; Grison, S.; Griffiths, N.M.

2004-01-01

Irradiation of the digestive system leads to alterations of the small intestine. We have characterized the disruption of the barrier integrity in rat ileum from 1 to 14 days following irradiation ranging from 6 to 12 Gy. The intestinal permeability to 14 C-mannitol and 3 H-dextran 70,000 was measured in vitro in Ussing chambers. In parallel to these functional studies, immunohistochemical analyses of junctional proteins (ZO-1 and β-catenin) of ileal epithelium were performed by confocal microscopy. Irradiation with 10 Gy induced a marked decrease in epithelial tissue resistance at three days and a fivefold increase in mannitol permeability, without modifications of dextran permeability. A disorganization of the localization for ZO-1 and β-catenin was also observed. At 7 days after irradiation, we observed a recovery of the organization of junctional proteins in parallel to a return of intestinal permeability to control value. In addition to these time-dependent effects, a gradual effect on epithelial integrity of the radiation doses was observed 3 days after irradiation. This study shows a disruption of the integrity of the intestinal barrier in rat ileum following abdominal X-irradiation, depending on the time postirradiation and on the delivered dose. The loss of barrier integrity was characterized by a disorganization of proteins of tight and adherent junctions, leading to increased intestinal permeability to mannitol. (author)

Alterations on the morphology, nitric oxide synthesis and activity of platelets reproduced in rats as possible biomarkers for depression are reversed by fluoxetine.

Science.gov (United States)

González-Trujano, María Eva; Alvarado-Vásquez, Noé; Mendoza-Sotelo, José; López, Guadalupe; Estrada-Camarena, Erika; Martínez-Mota, Lucia; Moreno, Julia

2012-08-01

Biochemical markers associated with the prognosis of depression in humans are being described in the literature, whereas experimental studies in animal models in search for antidepressant strategies are lacking. The aim of this study was to evaluate platelet morphology, platelet activity and nitric oxide (NO) synthesis as possible biomarkers of depressive-like behavior by using FST alone and in the presence of fluoxetine. Naïve rats were compared to those receiving vehicle or fluoxetine at 10mg/kg i.p. in acute, subchronic and chronic administration in the FST. After behavioral assessment, platelets were isolated from blood samples and analyzed by flow cytometry to determine the platelet mitochondrial membrane potential and NO synthesis. In addition, HPLC and electron microscopy were used to examine 5-HT and tryptophan levels and morphology of platelets, respectively. Rats receiving vehicle and exposed to FST showed depressive-like behavior at all the times tested; after chronic FST rats showed a similar pattern of alteration in platelet morphology and in the studied as possible biochemical markers as those previously recognized in depressive humans. Depressive-like behavior in rats exposed to FST was prevented in the presence of fluoxetine administration at all the times tested and associated with the prevention of alterations in platelet morphology, platelet activity and NO synthesis, and/or in 5-HT concentrations. The results of the present study suggest that platelet function and morphology might be relevant markers for the prognosis of depression and the search for functional treatments. Besides, the relevance of FST as model to study this psychiatric illness is reinforced. Copyright © 2012 Elsevier Inc. All rights reserved.

Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

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Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Jong Seok [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); National Institute of Biological Resources, Incheon (Korea, Republic of); Kim, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Yu-Na; Kim, Min-Chul [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Animal and Plant Quarantine Agency, Gyeonggi-do, Gimcheon, Gyeongsangbukdo (Korea, Republic of); Cho, Minkyoung [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Kang, Sang-Moo, E-mail: skang24@gsu.edu [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States)

2016-07-15

A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

International Nuclear Information System (INIS)

Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin; Lee, Jong Seok; Kim, Yu-Jin; Lee, Yu-Na; Kim, Min-Chul; Cho, Minkyoung; Kang, Sang-Moo

2016-01-01

A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

Effects of environmental enrichment on the activity of the amygdala in micrencephalic rats exposed to a novel open field.

Science.gov (United States)

Matsuda, Wakoto; Ehara, Ayuka; Nakadate, Kazuhiko; Yoshimoto, Kanji; Ueda, Shuichi

2018-01-01

Environmental enrichment (EE) mediates recovery from sensory, motor, and cognitive deficits and emotional abnormalities. In the present study, we examined the effects of EE on locomotor activity and neuronal activity in the amygdala in control and methylazoxymethanol acetate (MAM)-induced micrencephalic rats after challenge in a novel open field. Control rats housed in EE (CR) showed reduced locomotor activity compared to rats housed in a conventional cage (CC), whereas hyperactivity was seen in MAM rats housed in a conventional cage (MC) and in MAM rats housed in EE (MR). Novel open field exposure in both CC and MC resulted in a marked increase in Fos expression in the anterior and posterior parts of the basolateral amygdaloid nucleus, basomedial nucleus, and medial nucleus, whereas these increases in expression were not observed in CR. The effect of EE on Fos expression in the amygdala was different in MR exposed to a novel open field compared to CR. Furthermore, we observed a quite different pattern of Fos expression in the central nucleus of the amygdala between control and MAM rats. The present results suggest that neuronal activity in the amygdala that responds to anxiety is altered in MAM rats, especially when the rats are reared in EE. These alterations may cause behavioral differences between control and MAM rats. © 2017 Japanese Teratology Society.

Alterations in the K-ras and p53 genes in rat lung tumors

Energy Technology Data Exchange (ETDEWEB)

Belinsky, S.A.; Swafford, D.S.; Finch, G.L.; Mitchell, C.E. [Inhalation Toxicology Research Institute, Albuquerque, NM (United States)] [and others

1997-06-01

Activation of the K-ras protooncogene and inactivation of the p53 tumor suppressor gene are events common to many types of human cancers. Molecular epidemiology studies have associated mutational profiles in these genes with specific exposures. The purpose of this paper is to review investigations that have examined the role of the K-ras and p53 genes in lung tumors induced in the F344 rat by mutagenic and nonmutagenic exposures. Mutation profiles within the K-ras and p53 genes, if present in rat lung tumors, would help to define some of the molecular mechanisms underlying cancer induction by various environmental agents. Pulmonary adenocarcinomas or squamous cell carcinomas were induced by tetranitromethane (TNM), 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK), beryllium metal, plutonium-239, X-ray, diesel exhaust, or carbon black. These agents were chosen because the tumors they produced could arise via different types of DNA damage. Mutation of the K-ras gene was determined by approaches that included DNA transfection, direct sequencing, mismatch hybridization, and restriction fragment length polymorphism analysis. The frequency for mutation of the K-ras gene was exposure dependent. The transition mutations formed could have been derived from deamination of cytosine. Alteration in the p53 gene was assessed by immunohistochemical analysis for p53 protein and single-strand conformation polymorphism (SSCP) analysis of exons 4 to 9. None of the 93 adenocarinomas examined was immunoreactive toward the anti-p53 antibody CM1. In contrast, 14 of 71 squamous cell carcinomas exhibited nuclear p53 immunoreactivity with no correlation to type of exposure. However, SSCP analysis only detected mutations in 2 of 14 squamous cell tumors that were immunoreactive, suggesting that protein stabilization did not stem from mutations within the p53 gene. Thus, the p53 gene does not appear to be involved in the genesis of most rat lung tumors. 2 figs., 2 tabs., 48 refs.

Diffusion MRI and MR spectroscopy reveal microstructural and metabolic brain alterations in chronic mild stress exposed rats: A CMS recovery study.

Science.gov (United States)

Khan, Ahmad Raza; Hansen, Brian; Wiborg, Ove; Kroenke, Christopher D; Jespersen, Sune Nørhøj

2018-02-15

Chronic mild stress (CMS) induced depression elicits several debilitating symptoms and causes a significant economic burden on society. High variability in the symptomatology of depression poses substantial impediment to accurate diagnosis and therapy outcome. CMS exposure induces significant metabolic and microstructural alterations in the hippocampus (HP), prefrontal cortex (PFC), caudate-putamen (CP) and amygdala (AM), however, recovery from these maladaptive changes are limited and this may provide negative effects on the therapeutic treatment and management of depression. The present study utilized anhedonic rats from the unpredictable CMS model of depression to study metabolic recovery in the ventral hippocampus (vHP) and microstructural recovery in the HP, AM, CP, and PFC. The study employed 1 H MR spectroscopy ( 1 H MRS) and in-vivo diffusion MRI (d-MRI) at the age of week 18 (week 1 post CMS exposure) week 20 (week 3 post CMS) and week 25 (week 8 post CMS exposure) in the anhedonic group, and at the age of week 18 and week 22 in the control group. The d-MRI data have provided an array of diffusion tensor metrics (FA, MD, AD, and RD), and fast kurtosis metrics (MKT, W L and W T ). CMS exposure induced a significant metabolic alteration in vHP, and significant microstructural alterations were observed in the HP, AM, and PFC in comparison to the age match control and within the anhedonic group. A significantly high level of N-acetylaspartate (NAA) was observed in vHP at the age of week 18 in comparison to age match control and week 20 and week 25 of the anhedonic group. HP and AM showed significant microstructural alterations up to the age of week 22 in the anhedonic group. PFC showed significant microstructural alterations only at the age of week 18, however, most of the metrics showed significantly higher value at the age of week 20 in the anhedonic group. The significantly increased NAA concentration may indicate impaired catabolism due to astrogliosis or

Furan induced ovarian damage in non-diabetic and diabetic rats and cellular protective role of lycopene.

Science.gov (United States)

Uçar, Semra; Pandir, Dilek

2017-11-01

In our work, furan, lycopene, and furan + lycopene treatments were applied to non-diabetic and diabetic female rats via gavage. Ovarian tissue alterations with histopathology, immunohistochemistry, malondialdehyde levels, oxidative stress parameters such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and harmful effect on ovarian tissue DNA were evaluated in all groups for 28 days. Furan caused the changes histological, ovarian cell's DNA structure, malondialdehyde levels, antioxidant enzymes activities as in a statistically significant manner in each group. Useful effect of lycopene was determined both in non-diabetic and diabetic treatment groups against furan according to the used experimental parameters. Although some histopathological alterations were seen in diabetic and non-diabetic/diabetic plus furan-treated group's ovarians, lycopene restored these variations near to normal levels in furan + lycopene treated groups for in 28 days. Additionally, the results of our immunohistochemical analysis and alterations of the oxidative stress parameters results also supported these findings. Our result confirms that lycopene has protective effect and significantly altered diabetes and furan-induced toxicity in the rat ovarian tissue.

Maternal hyperthyroidism alters the pattern of expression of cardiac renin-angiotensin system components in rat offspring.

Science.gov (United States)

Lino, Caroline A; Shibata, Caroline E R; Barreto-Chaves, Maria Luiza M

2014-03-01

Changes in perinatal environment can lead to physiological, morphological, or metabolic alterations in adult life. It is well known that thyroid hormones (TH) are critical for the development, growth, and maturation of organs and systems. In addition, TH interact with the renin-angiotensin system (RAS), and both play a critical role in adult cardiovascular function. The objective of this study was to evaluate the effect of maternal hyperthyroidism on cardiac RAS components in pups during development. From gestational day nine (GD9), pregnant Wistar rats received thyroxine (T4, 12 mg/l in tap water; Hyper group) or vehicle (control group). Dams and pups were killed on GD18 and GD20. Serum concentrations of triiodothyronine (T3) and T4 were higher in the Hyper group than in the control group dams. Cardiac hypertrophy was observed in Hyper pups on GD20. Cardiac angiotensin-converting enzyme (ACE) activity was significantly lower in Hyper pups on both GD18 and GD20, but there was no difference in Ang I/Ang II levels. Ang II receptors expression was higher in the Hyper pup heart on GD18. Maternal hyperthyroidism is associated with alterations in fetal development and altered pattern of expression in RAS components, which in addition to cardiac hypertrophy observed on GD20 may represent an important predisposing factor to cardiovascular diseases in adult life.

Effects of nanoparticle zinc oxide on emotional behavior and trace elements homeostasis in rat brain.

Science.gov (United States)

Amara, Salem; Slama, Imen Ben; Omri, Karim; El Ghoul, Jaber; El Mir, Lassaad; Rhouma, Khemais Ben; Abdelmelek, Hafedh; Sakly, Mohsen

2015-12-01

Over recent years, nanotoxicology and the potential effects on human body have grown in significance, the potential influences of nanosized materials on the central nervous system have received more attention. The aim of this study was to determine whether zinc oxide (ZnO) nanoparticles (NPs) exposure cause alterations in emotional behavior and trace elements homeostasis in rat brain. Rats were treated by intraperitoneal injection of ZnO NPs (20-30 nm) at a dose of 25 mg/kg body weight. Sub -: acute ZnO NPs treatment induced no significant increase in the zinc content in the homogenate brain. Statistically significant decreases in iron and calcium concentrations were found in rat brain tissue compared to control. However, sodium and potassium contents remained unchanged. Also, there were no significant changes in the body weight and the coefficient of brain. In the present study, the anxiety-related behavior was evaluated using the plus-maze test. ZnO NPs treatment modulates slightly the exploratory behaviors of rats. However, no significant differences were observed in the anxious index between ZnO NP-treated rats and the control group (p > 0.05). Interestingly, our results demonstrated minimal effects of ZnO NPs on emotional behavior of animals, but there was a possible alteration in trace elements homeostasis in rat brain. © The Author(s) 2012.

HIV-1 transgenic rats develop T cell abnormalities

International Nuclear Information System (INIS)

Reid, William; Abdelwahab, Sayed; Sadowska, Mariola; Huso, David; Neal, Ashley; Ahearn, Aaron; Bryant, Joseph; Gallo, Robert C.; Lewis, George K.; Reitz, Marvin

2004-01-01

HIV-1 infection leads to impaired antigen-specific T cell proliferation, increased susceptibility of T cells to apoptosis, progressive impairment of T-helper 1 (Th1) responses, and altered maturation of HIV-1-specific memory cells. We have identified similar impairments in HIV-1 transgenic (Tg) rats. Tg rats developed an absolute reduction in CD4 + and CD8 + T cells able to produce IFN-γ following activation and an increased susceptibility of T cells to activation-induced apoptosis. CD4 + and CD8 + effector/memory (CD45RC - CD62L - ) pools were significantly smaller in Tg rats compared to non-Tg controls, although the converse was true for the naieve (CD45RC + CD62L + ) T cell pool. Our interpretation is that the HIV transgene causes defects in the development of T cell effector function and generation of specific effector/memory T cell subsets, and that activation-induced apoptosis may be an essential factor in this process

MicroRNA expression in rat brain exposed to repeated inescapable shock: differential alterations in learned helplessness vs. non-learned helplessness.