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Sample records for chronically exposed rats

  1. Proteomic analysis of liver in rats chronically exposed to fluoride.

    Directory of Open Access Journals (Sweden)

    Heloísa Aparecida Barbosa da Silva Pereira

    Full Text Available Fluoride (F is a potent anti-cariogenic element, but when ingestion is excessive, systemic toxicity may be observed. This can occur as acute or chronic responses, depending on both the amount of F and the time of exposure. The present study identified the profile of protein expression possibly associated with F-induced chronic hepatotoxicity. Weanling male Wistar rats (three-weeks old were divided into three groups and treated with drinking water containing 0, 5 or 50 mg/L F for 60 days (n=6/group. At this time point, serum and livers were collected for F analysis, which was done using the ion-sensitive electrode, after hexamethyldisiloxane-facilitated diffusion. Livers were also submitted to histological and proteomic analyses (2D-PAGE followed by LC-MS/MS. Western blotting was done for confirmation of the proteomic data A dose-response was observed in serum F levels. In the livers, F levels were significantly increased in the 50 mg/L F group compared to groups treated with 0 and 5 mg/L F. Liver morphometric analysis did not reveal alterations in the cellular structures and lipid droplets were present in all groups. Proteomic quantitative intensity analysis detected 33, 44, and 29 spots differentially expressed in the comparisons between control vs. 5 mg/L F, control vs. 50 mg/L F, and 5 mg/L vs. 50 mg/L F, respectively. From these, 92 proteins were successfully identified. In addition, 18, 1, and 5 protein spots were shown to be exclusive in control, 5, and 50 mg/L F, respectively. Most of proteins were related to metabolic process and pronounced alterations were seen for the high-F level group. In F-treated rats, changes in the apolipoprotein E (ApoE and GRP-78 expression may account for the F-induced toxicity in the liver. This can contribute to understanding the molecular mechanisms underlying hepatoxicity induced by F, by indicating key-proteins that should be better addressed in future studies.

  2. Effect of acetaminophen administration to rats chronically exposed to depleted uranium

    International Nuclear Information System (INIS)

    The extensive use of depleted uranium (DU) in both civilian and military applications results in the increase of the number of human beings exposed to this compound. We previously found that DU chronic exposure induces the expression of CYP enzymes involved in the metabolism of xenobiotics (drugs). In order to evaluate the consequences of these changes on the metabolism of a drug, rats chronically exposed to DU (40 mg/l) were treated by acetaminophen (APAP, 400 mg/kg) at the end of the 9-month contamination. Acetaminophen is considered as a safe drug within the therapeutic range but in the case of overdose or in sensitive animals, hepatotoxicity and nephrotoxicity could occur. In the present work, plasma concentration of APAP was higher in the DU group compared to the non-contaminated group. In addition, administration of APAP to the DU-exposed rats increased plasma ALT (p < 0.01) and AST (p < 0.05) more rapidly than in the control group. Nevertheless, no histological alteration of the liver was observed but renal injury characterized by incomplete proximal tubular cell necrosis was higher for the DU-exposed rats. Moreover, in the kidney, CYP2E1 gene expression, an important CYP responsible for APAP bioactivation and toxicity, is increased (p < 0.01) in the DU-exposed group compared to the control group. In the liver, CYP's activities were decreased between control and DU-exposed rats. These results could explain the worse elimination of APAP in the plasma and confirm our hypothesis of a modification of the drug metabolism following a DU chronic contamination

  3. Possible cause for altered spatial cognition of prepubescent rats exposed to chronic radiofrequency electromagnetic radiation.

    Science.gov (United States)

    Narayanan, Sareesh Naduvil; Kumar, Raju Suresh; Karun, Kalesh M; Nayak, Satheesha B; Bhat, P Gopalakrishna

    2015-10-01

    The effects of chronic and repeated radiofrequency electromagnetic radiation (RFEMR) exposure on spatial cognition and hippocampal architecture were investigated in prepubescent rats. Four weeks old male Wistar rats were exposed to RF-EMR (900 MHz; SAR-1.15 W/kg with peak power density of 146.60 μW/cm(2)) for 1 h/day, for 28 days. Followed by this, spatial cognition was evaluated by Morris water maze test. To evaluate the hippocampal morphology; H&E staining, cresyl violet staining, and Golgi-Cox staining were performed on hippocampal sections. CA3 pyramidal neuron morphology and surviving neuron count (in CA3 region) were studied using H&E and cresyl violet stained sections. Dendritic arborization pattern of CA3 pyramidal neuron was investigated by concentric circle method. Progressive learning abilities were found to be decreased in RF-EMR exposed rats. Memory retention test performed 24 h after the last training revealed minor spatial memory deficit in RF-EMR exposed group. However, RF-EMR exposed rats exhibited poor spatial memory retention when tested 48 h after the final trial. Hirano bodies and Granulovacuolar bodies were absent in the CA3 pyramidal neurons of different groups studied. Nevertheless, RF-EMR exposure affected the viable cell count in dorsal hippocampal CA3 region. RF-EMR exposure influenced dendritic arborization pattern of both apical and basal dendritic trees in RF-EMR exposed rats. Structural changes found in the hippocampus of RF-EMR exposed rats could be one of the possible reasons for altered cognition.

  4. Chronic exercise training versus acute endurance exercise in reducing neurotoxicity in rats exposed to lead acetate

    Institute of Scientific and Technical Information of China (English)

    Mohammad Shahandeh; Valiollah Dabidi Roshan; Somayeh Hosseinzadeh; Soleiman Mahjoub; Vaginak Sarkisian

    2013-01-01

    After intraperitoneal injection of 20 mg/kg lead acetate, rats received 8 weeks of treadmill exercise (15–22 m/min, 25–64 minutes) and/or treadmill exercise at 1.6 km/h until exhaustion. The markers related to neurotoxicity were measured by enzyme-linked immunosorbent assay method. 8 weeks of treadmill exercise significantly increased brain-derived neurotrophic factor level in the hippocampus (P = 0.04) and plasma level of total antioxidant capacity of rats exposed to lead acetate (P < 0.001), and significantly decreased plasma level of malondialdehyde (P < 0.001). Acute exercise only decreased the hippocampal malondialdehyde level (P = 0.09) and increased brain-derived neurotrophic factor level in the hippocampus (P = 0.66). Acute exercise also enhanced the total antioxidant capacity in rats exposed to lead acetate, insignificantly (P = 0.99). These findings suggest that chronic treadmill exercise can significantly decrease neurotoxicity and alleviate oxidative stress in rats exposed to lead acetate. However, acute endurance exercise was not associated with these beneficial effects.

  5. Chronic exercise training versus acute endurance exercise in reducing neurotoxicity in rats exposed to lead acetate.

    Science.gov (United States)

    Shahandeh, Mohammad; Roshan, Valiollah Dabidi; Hosseinzadeh, Somayeh; Mahjoub, Soleiman; Sarkisian, Vaginak

    2013-03-15

    After intraperitoneal injection of 20 mg/kg lead acetate, rats received 8 weeks of treadmill exercise (15-22 m/min, 25-64 minutes) and/or treadmill exercise at 1.6 km/h until exhaustion. The markers related to neurotoxicity were measured by enzyme-linked immunosorbent assay method. 8 weeks of treadmill exercise significantly increased brain-derived neurotrophic factor level in the hippocampus (P = 0.04) and plasma level of total antioxidant capacity of rats exposed to lead acetate (P exercise only decreased the hippocampal malondialdehyde level (P = 0.09) and increased brain-derived neurotrophic factor level in the hippocampus (P = 0.66). Acute exercise also enhanced the total antioxidant capacity in rats exposed to lead acetate, insignificantly (P = 0.99). These findings suggest that chronic treadmill exercise can significantly decrease neurotoxicity and alleviate oxidative stress in rats exposed to lead acetate. However, acute endurance exercise was not associated with these beneficial effects. PMID:25206718

  6. Adiponectin alleviates contractile dysfunction of genioglossus in rats exposed to chronic intermittent hypoxia

    Institute of Scientific and Technical Information of China (English)

    WANG Wen-jing; LU Gan; DING Ning; HUANG Han-peng; DING Wen-xiao; ZHANG Xi-long

    2013-01-01

    Background Genioglossal dysfuntion takes an important role in pathogenesis of obstructive sleep apnea hypopnea syndrome (OSAHS) in which chronic intermittent hypoxia (CIH) is the major pathological origin.Recent studies have suggested genioglossal injury induced by CIH might be improved by adiponectin.The aim of this study was to investigate the effects of adiponectin on genioglossus contractile properties in rats exposed to CIH.Methods Thirty-nine healthy male Wistar rats were randomly divided into three groups:normal control (NC),CIH and adiponectin supplement (CIH+Ad) with 13 rats in each.Rats in NC were kept breathing normal air,while rats in CIH and CIH+Ad experienced the same CIH environment eight hours per day for 35 successive days.Rats in CIH+Ad were given intravenous adiponectin of 10 μg twice a week for 30 successive days.Rats in the NC and CIH were injected with normal saline as a control.After 35 days' CIH exposure,the levels of serum adiponectin and genioglossus contractile properties were compared.Results Serum adiponectin level was significantly lower in CIH than in NC (1210 ng/ml vs.2236 ng/ml).Serum adiponectin level in CIH+Ad (1844 ng/ml) was significantly higher than CIH but lower than NC.Twitch tension,time to peak tension,half relaxation time and tetanic tension were significantly lower in CIH than NC and improved in CIH+Ad.All mean tetanic fatigue indices decreased more rapidly in the first 20 seconds than during the subsequent 100 seconds.Tetanic fatigue indices in NC and CIH+Ad were significantly higher compared to CIH.Conclusions CIH could lead to hypoadiponectinaemia,impaired genioglossus contractile properties and decreased fatigue resistance in rats.Such changes could be partially offset by supplementation of adiponectin.

  7. Excretion of 14C-labeled cyanide in rats exposed to chronic intake of potassium cyanide

    International Nuclear Information System (INIS)

    The excretion of an acute dose of 14C-labeled cyanide in urine, feces, and expired air was studied in rats exposed to daily intake of unlabeled KCN in the diet for 6 weeks. Urinary excretion was the main route of elimination of cyanide carbon in these rats, accounting for 83% of the total excreted radioactivity in 12 hr and 89% of the total excreted radioactivity in 24 hr. The major excretion metabolite of cyanide in urine was thiocyanate, and this metabolite accounted for 71 and 79% of the total urinary activity in 12 hr and 24 hr, respectively. The mean total activity excreted in expired air after 12 hr was only 4%, and this value did not change after 24 hr. Of the total activity in expired air in 24 hr, 90% was present as carbon dioxide and 9% as cyanide. When these results were compared with those observed for control rats, it was clear that the mode of elimination of cyanide carbon in both urine and breath was not altered by the chronic intake of cyanide

  8. Paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats

    Directory of Open Access Journals (Sweden)

    Khedr LH

    2015-11-01

    Full Text Available Lobna H Khedr, Noha N Nassar, Ezzeldin S El-Denshary, Ahmed M Abdel-tawab 1Department of Pharmacology, Faculty of Pharmacy, Misr International University, 2Department of Pharmacology, Faculty of Pharmacy, Cairo University, 3Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt Abstract: The molecular mechanisms underlying stress-induced depression have not been fully outlined. Hence, the current study aimed at testing the link between behavioral changes in chronic mild stress (CMS model and changes in hippocampal energy metabolism and the role of paroxetine (PAROX in ameliorating these changes. Male Wistar rats were divided into three groups: vehicle control, CMS-exposed rats, and CMS-exposed rats receiving PAROX (10 mg/kg/day intraperitoneally. Sucrose preference, open-field, and forced swimming tests were carried out. Corticosterone (CORT was measured in serum, while adenosine triphosphate and its metabolites, cytosolic cytochrome-c (Cyt-c, caspase-3 (Casp-3, as well as nitric oxide metabolites (NOx were measured in hippocampal tissue homogenates. CMS-exposed rats showed a decrease in sucrose preference as well as body weight compared to control, which was reversed by PAROX. The latter further ameliorated the CMS-induced elevation of CORT in serum (91.71±1.77 ng/mL vs 124.5±4.44 ng/mL, P<0.001 as well as the changes in adenosine triphosphate/adenosine diphosphate (3.76±0.02 nmol/mg protein vs 1.07±0.01 nmol/mg protein, P<0.001. Furthermore, PAROX reduced the expression of Cyt-c and Casp-3, as well as restoring NOx levels. This study highlights the role of PAROX in reversing depressive behavior associated with stress-induced apoptosis and changes in hippocampal energy metabolism in the CMS model of depression. Keywords: rats, CMS, hippocampus, paroxetine, apoptosis, adenine nucleotides, cytochrome-c, caspase-3

  9. In vitro neuronal and vascular responses to 5-HT in rats chronically exposed to MDMA

    OpenAIRE

    Cannon, Dara M; Keenan, Alan K; Guiry, Patrick J; Buon, Christophe; Baird, Alan W; Gethin J. McBean

    2001-01-01

    This study examined the effects of chronic exposure of rats to 3,4-methylenedioxymethamphetamine (MDMA) on [3H]5-hydroxytryptamine ([3H]5-HT) re-uptake into purified rat brain synaptosomes, 5-HT-induced isometric contraction of aortic rings and [3H]5-HT re-uptake into rat aorta.Rats were administered MDMA (20 mg kg−1 i.p.) twice daily over 4 days. One, 7, 14 or 21 days post treatment, whole brain synaptosomes and descending thoracic aortic rings were prepared for investigation.Chronic MDMA tr...

  10. Proximal renal tubular injury in rats sub-chronically exposed to low fluoride concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Cárdenas-González, Mariana C.; Del Razo, Luz M. [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); Barrera-Chimal, Jonatan [Unidad de Fisiología Molecular, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D. F., México (Mexico); Jacobo-Estrada, Tania [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); López-Bayghen, Esther [Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); and others

    2013-11-01

    Fluoride is usually found in groundwater at a very wide range of concentration between 0.5 and 25 ppm. At present, few studies have assessed the renal effects of fluoride at environmentally relevant concentrations. Furthermore, most of these studies have used insensitive and nonspecific biomarkers of kidney injury. The aim of this study was to use early and sensitive biomarkers to evaluate kidney injury after fluoride exposure to environmentally relevant concentrations. Recently weaned male Wistar rats were exposed to low (15 ppm) and high (50 ppm) fluoride concentrations in drinking water for a period of 40 days. At the end of the exposure period, kidney injury biomarkers were measured in urine and renal mRNA expression levels were assessed by real time RT-PCR. Our results showed that the urinary kidney injury molecule (Kim-1), clusterin (Clu), osteopontin (OPN) and heat shock protein 72 excretion rate significantly increased in the group exposed to the high fluoride concentration. Accordingly, fluoride exposure increased renal Kim-1, Clu and OPN mRNA expression levels. Moreover, there was a significant dose-dependent increase in urinary β-2-microglobulin and cystatin-C excretion rate. Additionally, a tendency towards a dose dependent increase of tubular damage in the histopathological light microscopy findings confirmed the preferential impact of fluoride on the tubular structure. All of these changes occurred at early stages in which, the renal function was not altered. In conclusion using early and sensitive biomarkers of kidney injury, we were able to found proximal tubular alterations in rats sub-chronically exposed to fluoride. - Highlights: • Exposure to low concentrations of fluoride induced proximal tubular injury • Increase in urinary Kim-1, Clu, OPN and Hsp72 in 50 ppm fluoride-exposed group • Increase in urinary B2M and CysC in 15 and 50 ppm fluoride-exposed groups • Fluoride exposure increased renal Kim, Clu and OPN mRNA expression levels.

  11. Chronic exercise training versus acute endurance exercise in reducing neurotoxicity in rats exposed to lead acetate☆

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    Shahandeh, Mohammad; Roshan, Valiollah Dabidi; Hosseinzadeh, Somayeh; Mahjoub, Soleiman; Sarkisian, Vaginak

    2013-01-01

    After intraperitoneal injection of 20 mg/kg lead acetate, rats received 8 weeks of treadmill exercise (15–22 m/min, 25–64 minutes) and/or treadmill exercise at 1.6 km/h until exhaustion. The markers related to neurotoxicity were measured by enzyme-linked immunosorbent assay method. 8 weeks of treadmill exercise significantly increased brain-derived neurotrophic factor level in the hippocampus (P = 0.04) and plasma level of total antioxidant capacity of rats exposed to lead acetate (P < 0.001)...

  12. Electroconvulsive stimulation reverses anhedonia and cognitive impairments in rats exposed to chronic mild stress

    DEFF Research Database (Denmark)

    Henningsen, K; Woldbye, D P D; Wiborg, O

    2013-01-01

    Electroconvulsive therapy remains the most effective treatment for depression including a fast onset of action. However, this therapeutic approach suffers from some potential drawbacks. In the acute phase this includes amnesia. Electroconvulsive stimulation (ECS) has previously been shown...... to reverse a depression-like state in the chronic mild stress model of depression (CMS), but the effect of ECS on cognition has not previously been investigated. In this study the CMS model was used to induce a depressive-like condition in rats. The study was designed to investigate the acute effect of ECS...... treatment on working memory and the chronic effect of repeated ECS treatments on depression-like behavior and working memory. The results indicated that, in the acute phase, ECS treatment induced a working memory deficit in healthy controls unexposed to stress, while repeated treatments reversed stress...

  13. Oxidative damage and histopathological changes in lung of rat chronically exposed to nicotine alone or associated to ethanol.

    Science.gov (United States)

    Dhouib, H; Jallouli, M; Draief, M; Bouraoui, S; El-Fazâa, S

    2015-12-01

    Smoking is the most important preventable risk factor of chronic obstructive pulmonary disease and lung cancer. This study was designed to investigate oxidative damage and histopathological changes in lung tissue of rats chronically exposed to nicotine alone or supplemented with ethanol. Twenty-four male Wistar rats divided into three groups were used for the study. The nicotine group received nicotine (2.5mg/kg/day); the nicotine-ethanol group was given simultaneously same dose of nicotine plus ethanol (0.2g/kg/day), while the control group was administered only normal saline (1 ml/kg/day). The treatment was administered by subcutaneous injection once daily for a period of 18 weeks. Chronic nicotine administration alone or combined to ethanol caused a significant increase in malondialdehyde (MDA) level, superoxide dismutase (SOD) activity and catalase (CAT) activity in lung tissue compared to control rats suggesting an oxidative damage. However, these increases were mostly prominent in nicotine group. The histopathological examination of lung tissue of rats in both treated groups revealed many alterations in the pulmonary structures such as emphysema change (disappearance of the alveolar septa, increased irregularity and size of air sacs) and marked lymphocytic infiltration in perivascular and interstitial areas. However, the changes characterized in the nicotine group (pulmonary congestion, hemorrhage into alveoli and interstitial areas, edema) were more drastic than those observed in the nicotine-ethanol group, and they can be attributed to a significant degree of capillary endothelial permeability and microvascular leak. Conversely, the ethanol supplementation caused an appearance of fatty change and fibrosis in pulmonary tissue essentially due to a metabolism of ethanol. Finally, the lung damage illustrated in nicotine group was more severe than that observed in the nicotine-ethanol group. We conclude that the combined administration of nicotine and ethanol

  14. Oxidative damage and histopathological changes in lung of rat chronically exposed to nicotine alone or associated to ethanol.

    Science.gov (United States)

    Dhouib, H; Jallouli, M; Draief, M; Bouraoui, S; El-Fazâa, S

    2015-12-01

    Smoking is the most important preventable risk factor of chronic obstructive pulmonary disease and lung cancer. This study was designed to investigate oxidative damage and histopathological changes in lung tissue of rats chronically exposed to nicotine alone or supplemented with ethanol. Twenty-four male Wistar rats divided into three groups were used for the study. The nicotine group received nicotine (2.5mg/kg/day); the nicotine-ethanol group was given simultaneously same dose of nicotine plus ethanol (0.2g/kg/day), while the control group was administered only normal saline (1 ml/kg/day). The treatment was administered by subcutaneous injection once daily for a period of 18 weeks. Chronic nicotine administration alone or combined to ethanol caused a significant increase in malondialdehyde (MDA) level, superoxide dismutase (SOD) activity and catalase (CAT) activity in lung tissue compared to control rats suggesting an oxidative damage. However, these increases were mostly prominent in nicotine group. The histopathological examination of lung tissue of rats in both treated groups revealed many alterations in the pulmonary structures such as emphysema change (disappearance of the alveolar septa, increased irregularity and size of air sacs) and marked lymphocytic infiltration in perivascular and interstitial areas. However, the changes characterized in the nicotine group (pulmonary congestion, hemorrhage into alveoli and interstitial areas, edema) were more drastic than those observed in the nicotine-ethanol group, and they can be attributed to a significant degree of capillary endothelial permeability and microvascular leak. Conversely, the ethanol supplementation caused an appearance of fatty change and fibrosis in pulmonary tissue essentially due to a metabolism of ethanol. Finally, the lung damage illustrated in nicotine group was more severe than that observed in the nicotine-ethanol group. We conclude that the combined administration of nicotine and ethanol

  15. The Alteration and Significance of Surfactant Protein A in Rats Chronically Exposed to Cigarette Smoke

    Institute of Scientific and Technical Information of China (English)

    Qiongjie HU; Huilan ZHANG; Shengdao XIONG; Xuemei SHI; Yongjian XU; Zhenxiang ZHANG; Guohua ZHEN; Jianping ZHAO

    2008-01-01

    In order to confirm the alteration and significance of cigarette smoke exposure on SP-A in rats, 20 Wistar rats were assigned randomly to two groups: an N group (n=10), and an S group (n=10). The ultra-structural change was observed by electron microscopy. The number of cells positive for SPA was by immunohistochemically measured. The mRNA expression in the lung tissues was deter-mined by reverse transcription polymerase chain reaction (RT-PCR). The number of cells positive for SPA of the S group (0.52±0.05) was lower than that of the N group (0.72±0.06) (P<0.05). The lev-els of mRNA of SPA in the lung tissues of the S group (0.3522±0.0512) was significantly lower than that of the N group (0.4432±0.05628) (P<0.05). It is concluded that cigarette smoke alone decreased the level of SP-A and that might have an important effect on surfactant metabolism and the host deense functions of surfactant in the peripheral airways, which might play a crucial role in the devel-opment of chronic obstructive lung disease.

  16. Proteomic analysis of kidney in rats chronically exposed to monosodium glutamate.

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    Amod Sharma

    Full Text Available Chronic monosodium glutamate (MSG intake causes kidney dysfunction and renal oxidative stress in the animal model. To gain insight into the renal changes induced by MSG, proteomic analysis of the kidneys was performed.Six week old male Wistar rats were given drinking water with or without MSG (2 mg/g body weight, n = 10 per group for 9 months. Kidneys were removed, frozen, and stored at -75°C. After protein extraction, 2-D gel electrophoresis was performed and renal proteome profiles were examined with Colloidal Coomassie Brilliant Blue staining. Statistically significant protein spots (ANOVA, p<0.05 with 1.2-fold difference were excised and analyzed by LC-MS. Proteomic data were confirmed by immunohistochemistry and Western blot analyses.The differential image analysis showed 157 changed spots, of which 71 spots were higher and 86 spots were lower in the MSG-treated group compared with those in the control group. Eight statistically significant and differentially expressed proteins were identified: glutathione S-transferase class-pi, heat shock cognate 71 kDa, phosphoserine phosphatase, phosphoglycerate kinase, cytosolic glycerol-3-phosphate dehydrogenase, 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase, α-ketoglutarate dehydrogenase and succinyl-CoA ligase.The identified proteins are mainly related to oxidative stress and metabolism. They provide a valuable clue to explore the mechanism of renal handling and toxicity on chronic MSG intake.

  17. Neoplastic and life-span effects of chronic exposure to tritium. II. Rats exposed in utero

    International Nuclear Information System (INIS)

    A study was conducted to determine the effects on neoplasia incidence and life-span of exposure in utero to a major environmental radionuclide. Sprague-Dawley rats were continuously exposed to tritiated water (HTO) from conception through birth in doses of 0, 1, 10, 50, and 100 μCi HTO/ml body water. HTO administration was terminated at birth. Calculated cumulative doses during gestation were approximately 0, 6.6, 66, 330, and 660 rads of total body irradiation. Under these exposure conditions, the two highest doses resulted in sterile offspring. Animals surviving through 30 days postnatally were defined as the study population and observed until their deaths. Intrauterine exposures to doses up to 66 rads had no significant effects on either sex with respect to lifespan, overall neoplasia incidence, incidence rate, or onset of mammary fibroadenomas. Females exposed to 330 or 660 rads were sterile and had lower incidence rates of mammary fibroadenomas than did controls; at 660 rads females had a lower incidence of overall neoplasia and reduced mean lifespans. Sterile male offspring had reduced mean longevity after irradiation at 660 rads. Regardless of dose group, females had significantly higher incidences of neoplasia and longer life-spans than males

  18. Apomorphine induced conditioned place preference and sensitization is greater in rats exposed to unpredictable chronic mild stress.

    Science.gov (United States)

    Kanwal, Sumera; Ikram, Huma; Farhan, Muhammad; Haleem, Darakhshan Jabeen

    2015-11-01

    CNS stimulants are the class of the drugs that may be used to get relief from depression. Apomorphine is a D1 and D2 receptor agonist with a CNS stimulatory effect used for the treatment of Parkinson's disease is also abused. Although many drugs of abuse produce tolerance and dependence. Long term use of pshycostimulants produce reverse tolerance described as sensitization. These drugs also have a number of other beneficial effects but their therapeutic use is limited because of abuse potential. Conditioned place preference (CPP) test is used to monitor the reinforcing effect of drugs of abuse. Stress is an important factor that precipitates and potentiates addictive effects of different drugs of abuse. The present study was designed to investigate the addictive effect of apomorphine (1mg/kg) in rats previously exposed to repeated unpredictable chronic mild stress for 10 days (animal model of depression). Results from present study illustrate that unpredictable chronic mild stress potentiates the reinforcing effects of apomorphine as the number of entries and the time spent in the CPP compartment associated with drug administration is increased. Motor activity was taken as a parameter for behavioral sensitization which is induced by repeated administration of apomorphine, monitored as the number of cage crossings in light compartment of the CPP apparatus, also increased. PMID:26639488

  19. The impacts of swimming exercise on hippocampal expression of neurotrophic factors in rats exposed to chronic unpredictable mild stress.

    Science.gov (United States)

    Jiang, Pei; Dang, Rui-Li; Li, Huan-De; Zhang, Li-Hong; Zhu, Wen-Ye; Xue, Ying; Tang, Mi-Mi

    2014-01-01

    Depression is associated with stress-induced neural atrophy in limbic brain regions, whereas exercise has antidepressant effects as well as increasing hippocampal synaptic plasticity by strengthening neurogenesis, metabolism, and vascular function. A key mechanism mediating these broad benefits of exercise on the brain is induction of neurotrophic factors, which instruct downstream structural and functional changes. To systematically evaluate the potential neurotrophic factors that were involved in the antidepressive effects of exercise, in this study, we assessed the effects of swimming exercise on hippocampal mRNA expression of several classes of the growth factors (BDNF, GDNF, NGF, NT-3, FGF2, VEGF, and IGF-1) and peptides (VGF and NPY) in rats exposed to chronic unpredictable mild stress (CUMS). Our study demonstrated that the swimming training paradigm significantly induced the expression of BDNF and BDNF-regulated peptides (VGF and NPY) and restored their stress-induced downregulation. Additionally, the exercise protocol also increased the antiapoptotic Bcl-xl expression and normalized the CUMS mediated induction of proapoptotic Bax mRNA level. Overall, our data suggest that swimming exercise has antidepressant effects, increasing the resistance to the neural damage caused by CUMS, and both BDNF and its downstream neurotrophic peptides may exert a major function in the exercise related adaptive processes to CUMS. PMID:25477997

  20. The Impacts of Swimming Exercise on Hippocampal Expression of Neurotrophic Factors in Rats Exposed to Chronic Unpredictable Mild Stress

    Directory of Open Access Journals (Sweden)

    Pei Jiang

    2014-01-01

    Full Text Available Depression is associated with stress-induced neural atrophy in limbic brain regions, whereas exercise has antidepressant effects as well as increasing hippocampal synaptic plasticity by strengthening neurogenesis, metabolism, and vascular function. A key mechanism mediating these broad benefits of exercise on the brain is induction of neurotrophic factors, which instruct downstream structural and functional changes. To systematically evaluate the potential neurotrophic factors that were involved in the antidepressive effects of exercise, in this study, we assessed the effects of swimming exercise on hippocampal mRNA expression of several classes of the growth factors (BDNF, GDNF, NGF, NT-3, FGF2, VEGF, and IGF-1 and peptides (VGF and NPY in rats exposed to chronic unpredictable mild stress (CUMS. Our study demonstrated that the swimming training paradigm significantly induced the expression of BDNF and BDNF-regulated peptides (VGF and NPY and restored their stress-induced downregulation. Additionally, the exercise protocol also increased the antiapoptotic Bcl-xl expression and normalized the CUMS mediated induction of proapoptotic Bax mRNA level. Overall, our data suggest that swimming exercise has antidepressant effects, increasing the resistance to the neural damage caused by CUMS, and both BDNF and its downstream neurotrophic peptides may exert a major function in the exercise related adaptive processes to CUMS.

  1. Anti-inflammatory effects of naringin in chronic pulmonary neutrophilic inflammation in cigarette smoke-exposed rats

    OpenAIRE

    Nie, YC; Wu, H.; Li, PB; Luo, YL; Long, K.; Xie, LM; Shen, JG; Su, WW

    2012-01-01

    Naringin, a well-known flavanone glycoside of grapefruit and citrus fruits, was found to be as an effective anti-inflammatory compound in our previous lipopolysaccharide-induced acute lung injury mouse model via blockading activity of nuclear factor κB. The current study sought to explore the anti-inflammatory effects of naringin on chronic pulmonary neutrophilic inflammation in cigarette smoke (CS)-induced rats. Seventy Sprague-Dawley rats were randomly divided into seven groups to study the...

  2. Changes in the structure and function of the kidney of rats chronically exposed to cadmium. I. Biochemical and histopathological studies

    Energy Technology Data Exchange (ETDEWEB)

    Brzoska, Malgorzata M.; Moniuszko-Jakoniuk, Janina [Department of Toxicology, Medical University of Bialystok, Mickiewicza 2c str., 15-222, Bialystok (Poland); Kaminski, Marcin; Supernak-Bobko, Dorota [Department of Histology and Embryology, Silesian School of Medicine, Medykow 20, 40-752, Katowice-Ligota (Poland); Zwierz, Krzysztof [Department of Pharmaceutical Biochemistry, Medical University of Bialystok, Mickiewicza 2A, 15-222, Bialystok (Poland)

    2003-06-01

    We have created an experimental model using rats intoxicated with Cd administered in drinking water at the concentration of 5 or 50 mg Cd/l for 6, 12 and 24 weeks. The degree of kidney damage was evaluated biochemically and histopathologically. Sensitive biomarkers of Cd-induced proximal tubular injury such as urinary total N-acetyl-{beta}-d-glucosaminidase (NAG-T) and its isoenzyme B (NAG-B), and alkaline phosphatase (ALP) were used. Cd content in the kidney increased with the level and duration of exposure leading to dose- and time-dependent structural and functional renal failure. In rats exposed to 5 mg Cd/l, first symptoms of injury of the main tubules of long and short nephrons (structural damage to epithelial cells, increased urinary activities of NAG-T and NAG-B) were noted after 12 weeks of the experiment. The damage occurred at a low kidney Cd concentration amounting to 4.08{+-}0.33 {mu}g/g wet weight (mean {+-}SE) and a urinary concentration of 4.31{+-}0.28 {mu}g/g creatinine. On exposure to 50 mg Cd/l, damage to the main tubules (blurred structure of tubular epithelium, atrophy of brush border, partial fragmentation of cells with release of nuclei into tubular lumen as well as increased urinary activities of NAG-T, NAG-B and ALP) was already evident after 6 week s with the kidney Cd concentration of 24.09{+-}1.72 {mu}g/g wet weight. In rats exposed to 50 mg Cd/l, a lack of regular contour of glomeruli was noted after 12 weeks, whereas after 24 weeks thickening of capillary vessels and widening of filtering space were evident. After 24 weeks of exposure to Cd, increased urea concentration in the serum with simultaneous decrease in its level in the urine, indicating decreased clearance of urea, and increased excretion of total protein were observed, but endogenous creatinine clearance remained unaffected. At the lower exposure, symptoms of structural, but not functional, damage to the glomeruli were also evident after 24 weeks of the experiment. Our

  3. Social stress exacerbates the aversion to painful experiences in rats exposed to chronic pain: The role of the locus coeruleus

    OpenAIRE

    Bravo, Lidia; Alba-Delgado, Cristina; Torres-Sanchez, Sonia; Micó, Juan Antonio; Neto, Fani L; Berrocoso, Esther

    2013-01-01

    Stressful experiences seem to negatively influence pain perception through as yet unknown mechanisms. As the noradrenergic locus coeruleus (LC) nucleus coordinates many components of the stress response, as well as nociceptive transmission, we evaluated whether the sensory and affective dimension of chronic neuropathic pain worsens in situations of stress due to adaptive changes of LC neurons. Accordingly, male rats were socially isolated for 5 weeks, and in the last 2 weeks, neuropathic pain...

  4. The effect of protein kinase C on voltage-gated potassium channel in pulmonary artery smooth muscle cells from rats exposed to chronic hypoxia

    Institute of Scientific and Technical Information of China (English)

    张永昶; 倪望; 张珍祥; 徐永健

    2004-01-01

    Background Chronic hypoxia can cause pulmonary hypertension and pulmonary heart disease with high mortality.The signal transduction pathway of protein kinase C (PKC) plays an important role in chronic pulmonary hypertension. So it is necessary to investigate the effect of PKC on voltage-gated potassium (K+) channels in pulmonary artery smooth muscle cells of rats exposed to chronic hypoxia.Methods Male Wistar rats were randomly divided into a control group (group A) and a chronic hypoxia group (group B). Group B received hypoxia [oxygen concentration (10±1)%] eight hours per day for four consecutive weeks. Single pulmonary artery smooth muscle cells were obtained using an acute enzyme separation method. Conventional whole cell patch clamp technique was used to record resting membrane potential, membrane capacitance and voltage-gated K+ currents. The changes in voltage-gated K+ currents before and after applying paramethoxyamphetamine (PMA) (500 nmol/L), an agonist of PKC, and PMA plus carbohydrate mixture of glucose, fructose and xylitol (GFX) (30 nmol/L), an inhibitor of PKC, were compared between the two groups. Results The resting membrane potential in group B was significantly lower than that of group A: -(29.0±4.8) mV (n=18) vs -(42.5±4.6) mV (n=35) (P0.05). The voltage-gated K+ currents were significantly inhibited by PMA in group A, and this effect was reversed by GFX. However, the voltage-gated K+ currents in group B were not affected by PMA.Conclusions The resting membrane potential and voltage-gated K+ currents in pulmonary artery smooth muscle cells from rats exposed to chronic hypoxia decreased significantly. It seems that PKC has different effects on the voltage-gated K+ currents of pulmonary artery smooth muscle cells under different conditions.

  5. The effects of reboxetine treatment on depression-like behavior, brain neurotrophins, and ERK expression in rats exposed to chronic mild stress.

    Science.gov (United States)

    First, Maya; Gil-Ad, Irit; Taler, Michal; Tarasenko, Igor; Novak, Nurit; Weizman, Abraham

    2013-05-01

    Chronic mild stress (CMS) in rats is an established rodent depression model. Antidepressants attenuate the depression-like symptoms and prevent the biochemical changes caused by stress. In the present study, we examined the effect of CMS and the selective norepinephrine reuptake inhibitor (NRI) reboxetine (REB) treatment on behavioral parameters in rats and on hippocampal and cortical neurotrophic factors. Male Sprague Dawley rats were exposed for 5 weeks to a variety of mild stressors. REB (5 mg/kg/i.p.) was daily injected to half of the stressed and unstressed groups. Animal behavior following CMS was tested using the Morris Water Maze (MWM) cognitive paradigm and by monitoring sucrose intake and weight gain. After 5 weeks of CMS, stressed rats showed decreased sucrose intake, and REB treatment normalized this decrease. CMS reduced hippocampal brain-derived neurotrophic factor (BDNF) levels, and REB treatment reversed this alteration and increased BDNF receptor (TrkB) levels. REB elevated hippocampal extracellular signal-regulated kinase (ERK) phosphorylation of both stressed and unstressed rats. In conclusion, our study shows that BDNF, its receptor TrkB, and ERK participate in the neurobiological response to chronic stress and in the molecular and cellular activities of REB in the hippocampus.

  6. Long-term health effects in hamsters and rats exposed chronically to man-made vitreous fibers

    Energy Technology Data Exchange (ETDEWEB)

    Smith, D.M.; Ortiz, L.W.; Archuleta, R.F.; Johnson, N.F.

    1986-01-01

    Rats and hamsters were exposed to several types of airborne man-made vitreous fibers. Exposure protocols were ''nose-only'' 6 h a day, 5 d a week for 24 m with surviving animals maintained for the rest of their lives. Challenge aerosols consisted of 4 types of fibrous glass, 1 refractory ceramic fiber (RCF), and 1 mineral wool fiber. UICC crocidolite asbestos and clean air served as positive and negative controls for the inhalation groups. Groups of additional controls were unmanipulated caged animals, intraperitoneally (IP) injected animals, and intratracheally (IT) instilled animals. Animals, after their deaths, were examined macroscopically and microscopically. Fiber lung burdens were significant for the inhalation exposures and related to the mean diameters of the fibrous challenge aerosols. The inhalation exposures with MMVF did not result in any adverse effects except for a mesothelioma of the lung in 1 hamster exposed to the RCF, not a statistically significant finding. Consistent with other reported work, abdominal mesotheliomas were induced in the groups of hamsters and rats injected IP with 0.45-micron mean diameter fibrous glass, RCF, and crocidolite asbestos. With IT instillations, primary lung tumors were found only in hamsters and rats receiving UICC crocidolite; no lung tumors occurred in animals instilled IT with 2 types of MMVF. 28 refs., 2 figs., 18 tabs.

  7. Effect of epimedium pubescen flavonoid on bone mineral status and bone turnover in male rats chronically exposed to cigarette smoke

    Directory of Open Access Journals (Sweden)

    Gao Shu-guang

    2012-06-01

    Full Text Available Abstract Background Epimedii herba is one of the most frequently used herbs in formulas that are prescribed for the treatment of osteoporosis in China and its main constituent is Epimedium pubescen flavonoid (EPF. However, it is unclear whether EPF during chronic exposure to cigarette smoke may have a protective influence on the skeleton. The present study investigated the effect of EPF on bone mineral status and bone turnover in a rat model of human relatively high exposure to cigarette smoke. Methods Fifty male Wistar rats were randomized into five groups: controls, passive smoking groups and passive smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day in drinking water for 4 months. A rat model of passive smoking was prepared by breeding male rats in a cigarette-smoking box. Bone mineral content (BMC, bone mineral density (BMD, bone turnover markers, bone histomorphometric parameters and biomechanical properties were examined. Results Smoke exposure decreased BMC and BMD, increased bone turnover (inhibited bone formation and stimulated its resorption, affected bone histomorphometry (increased trabecular separation and osteoclast surface per bone surface; decreased trabecular bone volume, trabecular thickness, trabecular number, cortical thickness, bone formation rate and osteoblast surface per bone surface, and reduced mechanical properties. EPF supplementation during cigarette smoke exposure prevented smoke-induced changes in bone mineral status and bone turnover. Conclusion The results suggest that EPF can prevent the adverse effects of smoke exposure on bone by stimulating bone formation and inhibiting bone turnover and bone resorption.

  8. Two-Year Chronic Bioassay study of Rats Exposed to a 1.6 GHz Radiofrequency Signal.

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Larry E.; Sheen, David M.; Wilson, Bary W.; Grumbein, Sondra L.; Creim, Jeffrey A.; Sasser, Lyle B.

    2004-08-06

    The purpose of this study was to determine whether long-term exposure to a 1.6 GHz radiofrequency (RF) field would affect the incidence of cancer in Fischer 344 rats. Thirty-six timed-pregnant rats were randomly assigned to each of three treatment groups: two groups exposed to a far-field RF Iridium signal and a third group that was sham exposed. Exposures were chosen such that the brain SAR in the fetuses was 0.16 W/kg. Whole-body far-field exposures were initiated at 19 days of gestation and continued at 2 h/day, 7 days/week for dams and pups after parturition until weaning ({approx}23 days old). The offspring (700) of these dams were selected, 90 males and 90 females for each near-field treatment group, with SAR levels in the brain calculated to be as follows: (1) 1.6 W/kg, (2) 0.16 W/kg and (3) near-field sham controls with an additional 80 males and 80 females as shelf controls. Confining, head-first, near-field exposures of 2 h/day, 5 days/week were initiated when the offspring were 36 + 1 days old and continued until the rats were 2 years old. No statistically significant differences were observed among treatment groups for number of live pups/litter, survival index and weaning weights, nor were there differences in clinical signs or neoplastic lesions among the treatment groups. The percentages of animals surviving at the end of the near-field exposure were not different among the male groups. In females a significant decrease in survival time was observed for the case control group.

  9. Evaluation of behavioural and antioxidant activity of Cytisus scoparius Link in rats exposed to chronic unpredictable mild stress

    Directory of Open Access Journals (Sweden)

    Harisudhan Thanukrishnan

    2008-04-01

    Full Text Available Abstract Background Various human diseases have oxidative stress as one of their component. Many herbs have been reported to exhibit properties that combat oxidative stress through their active constituents such as flavonoids, tannins, phenolic compounds etc. Cytisus scoparius (CS Link, (Family: Leguminosae, also called Sarothamnus scoparius, has been shown in invitro experiments to be endowed with anti-diabetic, hypnotic and sedative and antioxidant activity. Therefore this study was carried out to evaluate CS for its anxiolytic, antidepressant and anti-oxidant activity in stressed rats. Methods 60% methanolic extract of CS was quantified for phenolic content by Folin-Ciocalteau's method. Chronic unpredictable mild stress (CMS was employed to induce stress in rats. CS (125 and 250 mg/kg, p.o and diazepam (DZM (2 mg/kg, p.o was administered during the 21 day stress exposure period. Anxiolytic and antidepressant activities of CS were assessed in open field exploratory and behavioural despair paradigms, respectively. Plasma glucose and total lipids; endogenous antioxidant enzymes such as superoxide dismutase (SOD, catalase (CAT; non-enzymic-ascorbic acid and thiobarbituric acid reactive substances (TBARS levels were measured in brain, kidneys and adrenals using standard protocols to assess the effect of CS. Results Total phenolic content of CS was found to be 8.54 ± 0.16% w/w. CMS produced anxiogenic and depressive behaviour in experimental rats with metabolic disturbance. Significant decrease in SOD, CAT levels and increase in lipid peroxidation level was observed in stressed rats. CS administration for 21 days during stress exposure significantly increased the ambulatory behaviour and decreased the freezing time in open field behaviour. In behavioural despair test no significant alteration in the immobility period was observed. CS also improved SOD, CAT, and ascorbic acid level and controlled the lipid peroxidation in different tissues

  10. 7,8-Dihydroxyflavone, a Tropomyosin-Kinase Related Receptor B Agonist, Produces Fast-Onset Antidepressant-Like Effects in Rats Exposed to Chronic Mild Stress

    Science.gov (United States)

    Chang, Hsin-An; Wang, Ying-Hsiu; Tung, Che-Se; Yeh, Chin-Bin

    2016-01-01

    Objective Brain-derived neurotrophic factor (BDNF) and its specific receptor, tropomyosin-related kinase (TrkB), play important roles in treating depression. In this experiment, we examined whether 7,8-dihydroxyflavone, a novel potent TrkB agonist, could reverse the behavioral and biochemical abnormalities induced by the chronic mild stress (CMS) paradigm in rats. Methods SD rats were exposed to a battery of stressors for 56 days. 7,8-dihydroxyflavone (5 and 20 mg/kg) were administered intraperitoneally during the last 28 days of the CMS paradigm. Rats were tested in sucrose consumption test (SCT), forced-swimming test (FST) and elevated T-maze (ETM). Serum corticosterone levels and hippocampal BDNF levels of the rats were measured. Results Four-week CMS on the rats induced their depression-like behavior in SCT. The CMS-reduced sucrose consumption was reversed starting from 7 days after the 7,8-dihydroxyflavone (20 mg/kg) treatment and remained across the subsequent treatment regime. 7,8-dihydroxyflavone, when given at 5 mg/kg for 3 weeks, reduced the immobility time in the FST in the CMS-subjected rats. Additionally, the 4-week treatment with 7,8-dihydroxyflavone (20 mg/kg) attenuated the CMS-induced increase in anxiety-like behavior in the ETM. For the CMS-subjected rats, 7,8-dihydroxyflavone treatment dose-dependently reduced their serum corticosterone levels but increased their hippocampal BDNF levels only at 5 mg/kg. Conclusion 7,8-dihydroxyflavone was beneficial for both depression and anxiety-like behaviors, and may exert fast-onset antidepressant effects. This provides a new insight into the pharmacological management of depression.

  11. Effects of Puerarin on Pulmonary Vascular Remodeling and Protein Kinase C-α in Chronic Cigarette Smoke Exposure Smoke-exposed Rats

    Institute of Scientific and Technical Information of China (English)

    Zhaoxia ZHU; Yongjian XU; Hui ZOU; Zhenxiang ZHANG; Wang NI; Shixin CHEN

    2008-01-01

    In order to investigate the effects of puerarin on pulmonary vascular remodeling and protein kinase C-α (PKC-α) in chronic exposure smoke rats, 54 male Wistar rats were randomly di- vided into 7 groups: control group (C group), smoke exposure groups (S4w group, Saw group), puer- arin groups (P4w group, P8w group), propylene glycol control groups (PC4w group,PC8w group). Rats were exposed to cigarette smoke or air for 4 to 8 weeks. Rats in puerarin groups also received puer- arin. To evaluate vascular remodeling, alpha-smooth muscle actin (α-SM-actin) staining was used to count the percentage of completely muscularised vessels to intraacinar pulmonary arteries (CMA/IAPA) which was determined by morphometric analysis of histological sections. Pulmonary artery smooth muscle cell (PASMC) apoptosis was detected by in situ end labeling technique (TUNEL), and proliferation by proliferating cell nuclear antigen (PCNA) staining. Reverse transcrip- tion-polymerase chain reaction (RT-PCR), immunofluorescence staining and Western blot analysis were done to detect the PKC-α mRNA and protein expression in pulmonary arteries. The results showed that in cigarette smoke-exposed rats the percentage of CMA/IAPA and α-SM-actin expres- sion were increased greatly, PASMC apoptosis was increased and proliferation was markedly in- creased; Apoptosis indices (AI) and proliferation indices (PI) were higher than in C group; AI and PI were correlated with vascular remodeling indices; The expression of PKC-ct mRNA and protein in pulmonary arteries was significantly higher than in C group. In rats treated with puerarin, the per- eentage of CMA/IAPA and cell proliferation was reduced, whereas PASMC apoptosis was increased; The expression levels of PKC-α mRNA and protein were lower than in smoke exposure rats. There was no difference among all these data between S groups and PC groups. These findings suggested that cigarette smoke-induced pulmonary vascular remodeling was most likely an

  12. Changes in the structure and function of the kidney of rats chronically exposed to cadmium. II. histoenzymatic studies

    Energy Technology Data Exchange (ETDEWEB)

    Brzoska, M.M.; Moniuszko-Jakoniuk, J. [Dept. of Toxicology, Medical Univ. of Bialystok, Bialystok (Poland); Kaminski, M.; Dziki, M. [Dept. of Histology and Embryology, Silesian School of Medicine, Katowice-Ligota (Poland)

    2004-04-01

    Early effects of cadmium (Cd) on the structure and function of the kidney were studied in an experimental model using rats intoxicated with Cd at the levels of 5 and 50 mg Cd/1 drinking water. The effect of Cd was evaluated histopathologically and biochemically. Damage to the cellular structures was assessed on the basis of histoenzymatic analyses of the activity and localization of indicator enzymes (succinate dehydrogenase, lactate dehydrogenase, glucose-6-phosphatase, Mg{sup 2+}-dependent adenosine triphosphatase and acid phosphatase). The histochemical observations indicate that Cd causes damage to the organization and function of the nephron. Several structures, i.e. endoplasmic reticulum, mitochondrion, lysosome, cellular and intracellular membrane, as well as their biological functions, i.e. aerobic and anaerobic respiration, transport functions and biochemical processes taking place in the endoplasmic reticulum, were affected. The cytotoxic action of Cd occurs mainly in the tubules and partially also in the glomeruli. The results clearly indicate that Cd damages kidney structurally and functionally even at a relatively low level (5 mg/l) corresponding to human environmental exposure, and they confirm our previous hypothesis that the threshold for the kidney effects of Cd is less than 4.08 {+-} 0.33 {mu}g/g kidney wet weight and higher than 2.40 {+-} 0.15 {mu}g/g. The target for Cd action in the kidney is the tubules (proximal convoluted tubules and straight tubules), and disturbance in their function is the main toxic effect of Cd. Renal glomeruli are also injured, but only partially, whereas in other parts of the nephron the damage is slight. The results, together with observations reported in the first paper of the study, incline us to conclude that humans environmentally exposed to Cd are at risk of tubular damage. (orig.)

  13. Effects of Chronic Administration of Melatonin on Spatial Learning Ability and Long-term Potentiation in Lead-exposed and Control Rats

    Institute of Scientific and Technical Information of China (English)

    XIU-JING CAO; MING WANG; WEI-HENG CHEN; DA-MIAO ZHU; JIA-QI SHE; DI-YUN RUAN

    2009-01-01

    Objective To explore the changes in spatial learning performance and long-term potentiation (LTP) which is recognized as a component of the cellular basis of learning and memory in normal and lead-exposed rats after administration of melatonin (MT) for two months. Methods Experiment was performed in adult male Wistar rats (12 controls, 12 exposed to melatonin treatment, 10 exposed to lead and 10 exposed to lead and melatonin treatment). The lead-exposed rats received 0.2% lead acetate solution from their birth day while the control rats drank tap water. Melatonin (3 mg/kg) or vehicle was administered to the control and lead-exposed rats from the time of their weaning by gastric garage each day for 60 days, depending on their groups. At the age of 81-90 days, all the animals were subjected to Morris water maze test and then used for extracellular recording of LTP in the dentate gyrus (DG) area of the hippocampus in vivo. Results Low dose of melatonin given from weaning for two months impaired LTP in the DG area of hippocampus and induced learning and memory deficit in the control rats. When melatonin was administered over a prolonged period to the lead-exposed rats, it exacerbated LTP impairment, learning and memory deficit induced by lead. Conclusion Melatonin is not suitable for normal and lead-exposed children.

  14. Changes of brain derived neurotrophic factor in hippocampus of chronic lead exposed rats%慢性染铅大鼠海马脑源性神经营养因子的改变

    Institute of Scientific and Technical Information of China (English)

    李积胜; 刘亚华; 杨峰

    2004-01-01

    Objective: To investigate the changes of brain derived neurotrophic factor(BDNF) in hippocampus of chronic lead exposed rats. Methods: Wistar rats were exposed to lead by drinking 0.02%、0.2% lead acetate solution for three months, respectively. Investigate the changes of learning and memory ability by Y-labyrinth experiment, study the changes of BDNF positive neuron in CA1, CA3 and dentate gyrus in hippocampus of rats by immunohistochemistry. Results: BDNF positive neurons distribute everywhere in the hippocampus under normal condition. Compared with the contral group, the number of BDNF positive neurons in the hippocampus subregions were decreased significantly of two different dosage (0.02%, 0.2% ) chronic lead exposed groups( P < 0. 05). Conclusion: These results suggest that the reduction of BDNF positive neuron in hippocampus might be related to the impact of lead on learning and memory.

  15. Acute inhibition of glial cells in the NTS does not affect respiratory and sympathetic activities in rats exposed to chronic intermittent hypoxia.

    Science.gov (United States)

    Costa, Kauê M; Moraes, Davi J A; Machado, Benedito H

    2013-02-16

    Recent studies suggest that neuron-glia interactions are involved in multiple aspects of neuronal activity regulation. In the nucleus tractus solitarius (NTS) neuron-glia interactions are thought to participate in the integration of autonomic responses to physiological challenges. However, it remains to be shown whether NTS glial cells might influence breathing and cardiovascular control, and also if they could be integral to the autonomic and respiratory responses to hypoxic challenges. Here, we investigated whether NTS glia play a tonic role in the modulation of central respiratory and sympathetic activities as well as in the changes in respiratory-sympathetic coupling induced by exposure to chronic intermittent hypoxia (CIH), a model of central autonomic and respiratory plasticity. We show that bilateral microinjections of fluorocitrate (FCt), a glial cell inhibitor, into the caudal and intermediate subnuclei of the NTS did not alter baseline respiratory and sympathetic parameters in in situ preparations of juvenile rats. Similar results were observed in rats previously exposed to CIH. Likewise, CIH-induced changes in respiratory-sympathetic coupling were unaffected by FCt-mediated inhibition. However, microinjection of FCt into the ventral medulla produced changes in respiratory frequency. Our results show that acute glial inhibition in the NTS does not affect baseline respiratory and sympathetic control. Additionally, we conclude that NTS glial cells may not be necessary for the continuous manifestation of sympathetic and respiratory adaptations to CIH. Our work provides evidence that neuron-glia interactions in the NTS do not participate in baseline respiratory and sympathetic control.

  16. Effect of Schizandra chinensis lignans on cell division in the corneal epithelium and tongue of albino rats exposed to chronic cold stress

    International Nuclear Information System (INIS)

    The authors study the possibility of correcting cellular manifestations of disadaptation following chronic exposure to cold stress by means of preparations of Sch. chinensis. The model of chronic stress was cooling male albino rats daily for 1.5 h to a temperature of 28-30 C for 28 days. Since differences between levels of proliferation in intact animals and in the rats receiving 1.9% ethanol solution were absent, values obtained in the group of intact animals are presented in a table as the control. The animals underwent euthanasia 48 hours after the final exposure to the cold. The rats received an injection of tritium-thymidine one hour before sacrifice. It is shown that the results confirm those in previous studies of stimulation of DNA synthesis and mitotic activity in the corneal and lingual epithelium of albino rats during chronic exposure to stress

  17. Differences in behavior associated to anxiety in male and Female rats exposed to a chronic stress protocol: Early maternal separation

    Directory of Open Access Journals (Sweden)

    Duenas Gómez, Zulma Janeth

    2009-06-01

    Full Text Available During the first stages of life, the environment and maternal interactions are essential for normal mammalian neuronal maturity and behavior. In fact, it has been demonstrated that disruption of mother-pup interaction during early life exert long-lasting effects on the development of central nervous, endocrine, and immune systems and behavioral responses. The principal aim of our work was to study the consequences of early maternal separation (EMS on adult male and female anxiety. The behaviors was evaluated using the Elavated Plus-Maze (EPM. Separation procedure was carried out in postnatal days 1 to 21 twice daily: three hours in the morning and three hours in the afternoon. As a control group we used animals that stayed with the mother but were manipulated daily for one minute in the morning and in the afternoon. In postnatal day 22, animals were distributed by sex and then kept in standard lab conditions. Behavioral testing in the EPM was performed at 90/95 days of age. All subjects were videotaped. Records included number of entries, time spent in each arm, and the frequency and time stretching, deeping, rearing, and grooming. Our results showed that separated females have more open arm entries and spent more time there, and exhibit more deeping and less grooming compared to females in the control group and males of the experimental and control group. Thus, based on the anxiolytic profile that female rat shows in the EPM, these data suggest that EMS affects differentially male and female adult rats

  18. Ang Ⅱ type 1 receptor expression in rat aorta exposed to chronic intermittent hypoxia: effects of p38MAPK and ERK1/2 signaling

    Institute of Scientific and Technical Information of China (English)

    SHANG Jin; YANG Yuan-yuan; GUO Xue-ling; LIU Hui-guo

    2013-01-01

    Background Obstructive sleep apnea is a frequent medical condition consisting of repetitive sleep-related episodes of upper air ways obstruction and can lead to hypertension.Ang Ⅱ type 1 receptor (AT1R) played important roles in hypertension since it binds with Ang Ⅱ,controlling salt-water and blood pressure homeostasis.This study explores rat aorta AT1R expression during intermittent hypoxia (IH) and the signaling pathways involved.Methods A rat model and a cell model used a BioSpherix-OxyCycler A84 system and a ProOx C21 system respectively.The arterial blood pressure was recorded by a Nihon Kohden Polygraph System.Immunohistochemic was used to focus and analyze the expression of AT1R in rat aorta.Real-time PCR and Western blotting were used to explore the signaling pathways that participated in AT1R expression.Results In this study,we found that chronic intermittent hypoxia (CIH) induced AT1R transcription which increased the blood pressure in rat aorta compared to normoxia and to sustained hypoxia.The AT1R protein expression in the aorta was similar to the real-time PCR results.We explored the signaling mechanisms involved in the AT1R induction in both rat aorta and the aortic endothelial cells by real-time PCR and Western blotting.Compared to normoxia,CIH increased ERK1 mRNA transcription but not ERK2 or p38MAPK in the aorta; whereas sustained hypoxia (SH) upregulated ERK2 but not ERK1 or p38MAPK mRNA.In cells,IH induced AT1R expression with ERK1/2 phosphorylation but reduced p38MAPKs phosphorylation,whereas SH induced only ERK1/2 phosphorylation.The ERK1/2 inhibitor PD98059 attenuated the IHinduced AT1R increase but the p38MAPK inhibitor SB203580 did not.Conclusions Our results indicate that CIH induced the elevation of rat blood pressure and aorta AT1R expression.Moreover,AT1R expression in IH and sustained hypoxia might be regulated by different signal transduction pathways,highlighting a novel regulatory function through ERK1/2 signaling in IH.

  19. Evaluation of Some Biochemical Parameters and Brain Oxidative Stress in Experimental Rats Exposed Chronically to Silver Nitrate and the Protective Role of Vitamin E and Selenium

    Science.gov (United States)

    Gueroui, Mouna; Kechrid, Zine

    2016-01-01

    Due to undesirable hazardous interactions with biological systems, this investigation was undertaken to evaluate the effect of chronic exposure to silver on certain biochemical and some oxidative stress parameters with histopathological examination of brain, as well as the possible protective role of selenium and/or vitamin E as nutritional supplements. Thirty six male rats were divided into six groups of six each: the first group used as a control group. Group II given both vitamin E (400 mg/kg) of diet and selenium (Se) (1 mg/L) in their drinking water. Group III given silver as silver nitrate (AgNO3) (20 mg/L). Group IV given vitamin E and AgNO3. Group V given both AgNO3 and selenium. Group VI given AgNO3, vitamin E and Se. The animals were in the same exposure conditions for 3 months. According to the results which have been obtained; there was an increase in serum lactate dehydrogenase (LDH), lipase activities and cholesterol level, a decrease in serum total protein, calcium and alkaline phosphatase (ALP) activity in Ag-intoxicated rats. Moreover, the findings showed that Ag+ ions affected antioxidant defense system by decreasing superoxide dismutase (SOD) activity and increasing vitamin E concentration with a high level of malondialdehyde (MDA) in brain tissue. The histological examination also exhibited some nervous tissue alterations including hemorrhage and cytoplasm vacuolization. However, the co-administration of selenium and/or vitamin E ameliorated the biochemical parameters and restored the histological alterations. In conclusion, this study indicated that silver could cause harmful effects in animal body and these effects can be more toxic in high concentrations or prolonged time exposure to this metal. However, selenium and vitamin E act as powerful antioxidants which may exercise adverse effect against the toxicity of this metal.

  20. Effects of pentoxifylline, 7-nitroindazole, and imipramine on tumor necrosis factor-α and indoleamine 2,3-dioxygenase enzyme activity in the hippocampus and frontal cortex of chronic mild-stress-exposed rats

    Directory of Open Access Journals (Sweden)

    Mohamed BMSA

    2013-05-01

    Full Text Available Bassim MSA Mohamed,1,6 Sawsan Aboul-Fotouh,2,5 Eman A Ibrahim,3 Hanan Shehata,4 Amal A Mansour,4 Nemat AZ Yassin,1 Wafaa El-Eraky,1 Ahmed M Abdel-Tawab2,5 1Department of Pharmacology, National Research Centre, Cairo, Egypt; 2Department of Pharmacology, 3Department of Pathology, 4Department of Medical Biochemistry and Molecular Biology, 5Clinical Pharmacology Unit, Ain Shams University, Cairo, Egypt; 6Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada Objectives: This study aimed to investigate the role of tumor necrosis factor (TNF-α and the neuronal nitric oxide synthase enzyme in dysregulation of indoleamine 2,3-dioxygenase (IDO enzyme, and hence serotonin availability in chronic mild stress (CMS, an animal model of depression. Methods: Rats were divided into five groups: two control and CMS-exposed for 6 weeks, and another three groups exposed to CMS and administered pentoxifylline 50 mg/kg/day intraperitoneally, 7-nitroindazole 40 mg/kg/day subcutaneously, or imipramine 20 mg/kg/day intraperitoneally for the previous 3 CMS weeks. Rats were assessed for neurochemical and immunohistochemical abnormalities. Results: Pentoxifylline-, 7-nitroindazole-, and imipramine-treated rats showed amelioration of CMS-induced behavioral deficits that was accompanied by significant reduction in kynurenine/serotonin molar ratio and nitrates/nitrites in frontal cortex and hippocampus. In the pentoxifylline and 7-nitroindazole groups, serum TNF-α was reduced relative to the CMS group (18.54 ± 0.85 and 19.16 ± 1.54 vs 26.20 ± 1.83 pg/mL, respectively; P < 0.05. Exposure to CMS increased TNF-α and IDO immunohistochemical staining scores in both hippocampus and midbrain raphe nuclei. 7-Nitroindazole and pentoxifylline significantly (P < 0.05 reduced TNF-α immunostaining in hippocampus and raphe nuclei, with significant (P < 0.01 reduction of IDO immunostaining in raphe nuclei. Likewise, imipramine reduced TNF

  1. EPITHELIAL INJURY AND INTERSTITIAL FIBROSIS IN THE PROXIMAL ALVEOLAR REGIONS OF RATS CHRONICALLY EXPOSED TO A SIMULATED PATTERN OF URBAN AMBIENT OZONE

    Science.gov (United States)

    Electron microscopic morphometry was used to study the development of lung injury during and after chronic (78 weeks) exposure to a pattern of ozone designed to simulate high urban ambient concentrations that occur in some environments. he dolly exposure regimen consisted of a 1 ...

  2. Enhancement of Latent Inhibition by Chronic Mild Stress in Rats Submitted to Emotional Response Conditioning

    OpenAIRE

    Liana Lins Melo; de Moraes Ferrari, Elenice A.; Nancy Airoldi Teixeira; Guy Sandner

    2003-01-01

    This work evaluated the influence of chronic mild stress on latent inhibition (LI) in rats, using a conditioned emotional response (CER) procedure. Rats were assigned to four groups: a non pre-exposed control group (NPC), a non pre-exposed stressed group (NPS), a preexposed control group (PC), and a pre-exposed stressed group (PS). Stressed animals were submitted to a chronic mild stress (CMS) regimen for three weeks. The off-baseline conditioned emotional response procedure had four phases: ...

  3. The Protective Role of Vitamin C against Histological Changes and Some Biochemical Indices in Liver of Rats Chronically Exposed to Diazinon

    Directory of Open Access Journals (Sweden)

    Walid Ali Abu-Sheir

    2016-07-01

    Full Text Available Background: Diazinon is one of the most toxic organophosphrous pesticides. It is used widely in agriculture and affects the general health and the economy of the human. Toxic effect of Diazinon is due to inhibition of acetylcholine esterase, an enzyme needed for proper nervous system function. This study was designed to investigate the effects of Diazinon on the liver tissue and the expected protective role of vitamin C. Aim of this study: is to evaluate effect of Diazinon and vitamin C on liver of albino rats. Results: data showed a significant increase in liver enzymes AST, ALT in addition to GGT and decreased total proteins and albumin as well as different histological changes caused by the pesticide Diazinon. Using vitamin C caused amelioration in liver structure and function tests, although, all these tests did not return to the normal level. Conclusion: the present study proved that Diazinon has adverse effects on some biochemical parameters and liver functions leading to histological impairment and these effects increase with the increased time of exposure. Meanwhile, supplementation with vitamin C could ameliorate the adverse effects of Diazinon.

  4. Thyroid hormones in chronic heat exposed men

    Science.gov (United States)

    Gertner, A.; Israeli, R.; Lev, A.; Cassuto, Y.

    1983-03-01

    Previous reports have indicated that thyroid gland activity, is depressed in the heat. Total thyroxine (T4) and triiodothyronine (T3) serum levels in 17 workers of the metal work shop at a plant near the Dead Sea and 8 workers in Beer Sheva, Israel were examined. The metal workshop of the plant near the Dead Sea is part of a large chemical plant. The one in Beer Sheva is part of a large construction company. Maintenance work, as well as metal work projects are performed in both workshops. During the work shifts, the workers of the Dead Sea plant were exposed to temperatures ranging from 30 36°C (May Oct.) and 14 21°C (Dec. Feb). In Beer Sheva the range was 25 32°C (June Sept.) and 10 17°C (Dec. Feb.). Total T4 was measured by competitive protein binding and total T3 by radioimmunoassay in blood drawn before work (0700) in July and January. In summer. T4 was higher and T3 was lower for both groups than in winter. The observed summer T3 decrease may result from depressed extrathyroidal conversion of T4 to T3. We conclude that the regulation of energy metabolism in hot climates may be related to extrathyroidal conversion of T4 to T3.

  5. Insulin Expression in Rats Exposed to Cadmium

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objectives To investigate the effects of cadmium exposure on insulin expression in rats. Methods Eighteen adult SD assessed. The levels of cadmium and zinc in pancreas, blood and urine glucose, serum insulin and urine NAG (N-acyetyl-β-glucosaminidase) were determined. The gene expressions of metallothionein (MT) and insulin were also measured,and the oral glucose tolerance tests (OGTT) were carried out. Results The contents of cadmium in pancreas in cadmium-treated rats were higher than that in the control group, which was associated with slight increase of zinc in pancreas.not change significantly after cadmium administration, and the UNAG had no change in Cd-treated group. The gene expression the change of the expression of insulin, MT-Ⅰ and MT-Ⅱ genes. Cadmium can influence the biosynthesis of insulin, but does not induce the release of insulin. The dysfunction of pancreas occurs earlier than that of kidney after administration of cadmium.

  6. Analysis of reproductive function in persons exposed to chronic radiation

    International Nuclear Information System (INIS)

    The purpose of the study was to analyze the reproductive function in individuals exposed to radiation in the riverside villages on the Techa in the Southern Urals. The exposure of the population, numbering 28000, occurred in 1950-1956 as a result of discharges into the river of radioactive wastes from the Mayak facility for processing weapon plutonium. The residents were exposed to chronic radiation, both external and internal. The range of exposure doses to gonads was sufficiently wide: 20-1270 mSv. However, the distribution of doses among the exposed individuals was ununiform, and the proportion of people whose dose was below 120 mGy accounted for 74%. The following characteristics of exposed women were analyzed: menstrual function, outcomes of pregnancy, birth rates, health status for newborns. The analysis of the menstrual function in exposed women showed that in persons exposed in childhood, menarche was registered at the age of 14.3 years, on the average (based on literature sources, menarche is attained at the age of 13 for unexposed population). The mean age at menopause was 47.9 years for exposed women (the respective mean value for Russia is 50.8 years). Pregnancy outcomes were analyzed in 9000 exposed women. The rate of medical and criminal abortions was estimated as 79 per 100 labors. The rate of spontaneous abortions for exposed women was slightly higher, 3.11%, than for controls, 2.30%; these difference, however, were statistically insignificant. The total loss of fetus or neonate (unfavorable outcomes of pregnancy: spontaneous abortions, stillbirths, early neonatal death) was estimated to be 4.58% at zero dose. Exposure to gonads at the dose 1 Sv, estimated using the above-indicated method, yielded 3% of additional unfavorable outcomes of pregnancy. It was shown, based on the analysis of birth rates for the Techa Cohort that they had not undergone any essential changes over the first 25 years of exposure compared to the respective coefficients for

  7. Analysis of reproductive function in persons exposed to chronic radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kossenko, M.M.; Ostroumova, E.V.; Vyushkova, O.V. [Urals Research Center for Radiation Medicine, Chelyabinsk (Russian Federation)

    2000-05-01

    The purpose of the study was to analyze the reproductive function in individuals exposed to radiation in the riverside villages on the Techa in the Southern Urals. The exposure of the population, numbering 28000, occurred in 1950-1956 as a result of discharges into the river of radioactive wastes from the Mayak facility for processing weapon plutonium. The residents were exposed to chronic radiation, both external and internal. The range of exposure doses to gonads was sufficiently wide: 20-1270 mSv. However, the distribution of doses among the exposed individuals was ununiform, and the proportion of people whose dose was below 120 mGy accounted for 74%. The following characteristics of exposed women were analyzed: menstrual function, outcomes of pregnancy, birth rates, health status for newborns. The analysis of the menstrual function in exposed women showed that in persons exposed in childhood, menarche was registered at the age of 14.3 years, on the average (based on literature sources, menarche is attained at the age of 13 for unexposed population). The mean age at menopause was 47.9 years for exposed women (the respective mean value for Russia is 50.8 years). Pregnancy outcomes were analyzed in 9000 exposed women. The rate of medical and criminal abortions was estimated as 79 per 100 labors. The rate of spontaneous abortions for exposed women was slightly higher, 3.11%, than for controls, 2.30%; these difference, however, were statistically insignificant. The total loss of fetus or neonate (unfavorable outcomes of pregnancy: spontaneous abortions, stillbirths, early neonatal death) was estimated to be 4.58% at zero dose. Exposure to gonads at the dose 1 Sv, estimated using the above-indicated method, yielded 3% of additional unfavorable outcomes of pregnancy. It was shown, based on the analysis of birth rates for the Techa Cohort that they had not undergone any essential changes over the first 25 years of exposure compared to the respective coefficients for

  8. Influence of Chronic Stress and Oclusal Interference on Masseter Muscle Pain in Rat

    OpenAIRE

    Simonić-Kocijan, Sunčana; Uhač, Ivone; Braut, Vedrana; Kovač, Zoran; Kovačević Pavičić, Daniela; Fugošić, Vesna; Muhvić Urek, Miranda

    2009-01-01

    This study aimed to investigate the individual effects of chronic stress and occlusal interference, as well as their combined influence on masseter muscle pain. Experiments were performed on 28 male Wistar rats. Animals were submitted to chronic stress procedure, exposed to occlusal interference, or exposed to both mantioned procedures. At the end of the procedure animals were submitted to orofacial formalin test, and nociceptive behavioral response was evaluated. Statisticaly significant dif...

  9. Evaluation of protective effects of fish oil against oxidative damage in rats exposed to methylmercury.

    Science.gov (United States)

    Grotto, Denise; Vicentini, Juliana; Angeli, José Pedro Friedmann; Latorraca, Elder Francisco; Monteiro, Patrícia Alves Pontes; Barcelos, Gustavo Rafael Mazzaron; Somacal, Sabrina; Emanuelli, Tatiana; Barbosa, Fernando

    2011-03-01

    The present study evaluates a possible protective effect of fish oil against oxidative damage promoted by methylmercury (MeHg) in sub-chronically exposed rats. Reduced glutathione peroxidase and catalase enzyme activity and reduced glutathione levels were observed in MeHg-exposed animals compared to controls. Methylmercury exposure was also associated with DNA damage. Administration of fish oil to the methylmercury-exposed animals did not ameliorate enzyme activity or glutathione levels. On the other hand, a significant DNA protective effect (about 30%) was observed with fish oil treatment. There were no differences in the total mercury concentration in rat liver, kidney, heart or brain after MeHg administration with or without fish oil co-administration. Histopathological analyses showed a significant leukocyte infiltration in rat tissues after MeHg exposure, but this effect was significantly reduced after co-administration of fish oil. Taken together, our findings demonstrate oxidative damage even after low-level MeHg exposure and the protective effect of fish oil. This protection seems not to be related to antioxidant defenses or mercury re-distribution in rat tissues. It is probably due to the anti-inflammatory effects of fish oil. PMID:20970192

  10. Brain plasticity of rats exposed to prenatal immobilization stress

    OpenAIRE

    Badalyan B. Yu.; Tumasyan N. V.; Meliksetyan I. B.; Sahakyan I. K.; Abrahamyan S. S.; Galoyan A. A.

    2011-01-01

    Aim. This histochemical and immunohistochemical study was aimed at examining the brain cellular structures of newborn rats exposed to prenatal immobilization (IMO) stress. Methods. Histochemical method on detection of Ca2+-dependent acid phosphatase activity and ABC immunohistochemical technique. Results. Cell structures with radial astrocytes marker GFAP, neuroepithelial stem cell marker gene nestin, stem-cells marker and the hypothalamic neuroprotective proline-rich polypeptide PRP-1 (Galar...

  11. Respiratory plasticity in the behaving rat following chronic intermittent hypoxia.

    Science.gov (United States)

    Edge, Deirdre; Skelly, J Richard; Bradford, Aidan; O'Halloran, Ken D

    2010-01-01

    Chronic intermittent hypoxia (CIH), a feature of obstructive sleep apnoea (OSA) has been shown to have myriad effects on the respiratory control system. The effects on breathing are of great clinical significance for the sleep apnoea patient. We sought to determine the effect of CIH on normoxic ventilation. Both male and female adult Wistar rats were studied due to the evident sex difference in the prevalence of OSA. A role for oxidative stress in respiratory modifications was also explored. Adult male (n = 30) and female (n = 16) rats were exposed to alternating periods of N(2) and O(2) for 90 s each, bringing the ambient oxygen concentration to 5% at nadir (CIH) group. Sham groups were subject to cycles of air/air under identical experimental conditions. A subset of male rats (8 controls, 8 CIH) had free access to water containing 1 mM Tempol (SOD-mimetic) at all times. Treatments were carried out for 8 hours a day for 9 days. Following treatment, normoxic ventilation was assessed by whole body plethysmography in sleeping animals. Baseline normoxic ventilation was increased in both male and female treated rats but this did not achieve statistical significance. However, ventilatory drive (V(T)/Ti) was significantly increased in male rats. Chronic treatment with Tempol abolished this effect. Conversely, CIH had no significant effect on VT/Ti in female rats. Our results indicate subtle effects of intermittent hypoxia on breathing in conscious behaving rats. We speculate the increased ventilatory drive following CIH represents a form a neural plasticity - a ROS dependent phenomenon - with sexual dimorphism. PMID:20217363

  12. Cardiovascular response of rats exposed to 60-Hz electric fields

    Energy Technology Data Exchange (ETDEWEB)

    Hilton, D.I.; Phillips, R.D.

    1980-01-01

    Recently, it has been reported that exposure to high-strength electric fields can influence electrocardiogram (ECG) patterns, heart rates, and blood pressures in various species of animals. Our studies were designed to evaluate these reported effects and to help clarify some of the disagreement present in the literature. Various cardiovascular variables were measured in Sprague-Dawley rats exposed or sham-exposed to 60-Hz electric fields at 80 to 100 kV/m for periods up to four months. No significant differences in heart rates, ECG patterns, blood pressures, or vascular reactivity were observed between exposed and sham-exposed rats after 8 hours, 40 hours, 1 month, or 4 months of exposure. Our studies cannot be directly compared to the work of other investigators because of differences in animal species and electric-field characteristics. However, our failure to detect any cardiovascular changes may have been the result of (1) eliminating secondary field effects such as shocks, audible noise, corona, and ozone; (2) minimizing steady-state microcurrents between the mouth of the animal and watering devices; and (3) minimizing electric-field-induced vibration of the electrodes and animal cages.

  13. Neurobehavioral Assessment of Rats Exposed to Yttrium Nitrate during Development

    Institute of Scientific and Technical Information of China (English)

    LI Chen Xi; MA Chuan; FANG Hai Qin; ZHI Yuan; YU Zhou; XU Hai Bin; JIA Xu Dong

    2015-01-01

    Objective The aim of this study was to assess the effects of yttrium nitrate on neurobehavioral development in Sprague-Dawley rats. Methods Dams were orally exposed to 0, 5, 15, or 45 mg/kg daily of yttrium nitrate from gestation day (GD) 6 to postnatal day (PND) 21. Body weight and food consumption were monitored weekly. Neurobehavior was assessed by developmental landmarks and reflexes, motor activity, hot plate, Rota-rod and cognitive tests. Additionally, brain weights were measured on PND 21 and 70. Results No significant difference was noted among all groups for maternal body weight and food consumption. All yttrium-exposed offspring showed an increase in body weight on PND 21;however, no significant difference in body weight for exposed pups versus controls was observed 2 weeks or more after the yttrium solution was discontinued. The groups given 5 mg/kg daily decreased significantly in the duration of female forelime grip strength and ambulation on PND 13. There was no significant difference between yttrium-exposed offspring and controls with respect to other behavioral ontogeny parameters and postnatal behavioral test results. Conclusion Exposure of rats to yttrium nitrate in concentrations up to 45 mg/kg daily had no adverse effects on their neurobehavioral development.

  14. Brain dysfunctions in Wistar rats exposed to municipal landfill leachates

    Directory of Open Access Journals (Sweden)

    Chibuisi G. Alimba

    2015-12-01

    Full Text Available Brain damage induced by Olusosun and Aba-Eku municipal landfill leachates was investigated in Wistar rats. Male rats were orally exposed to 1–25% concentrations of the leachates for 30 days. Catalase (CAT and superoxide dismutase (SOD activities, and malondialdehyde (MDA concentrations in the brain and serum of rats were evaluated; body and brain weight gain and histopathology were examined. There was significant (p < 0.05 decrease in body weight gain and SOD activity but increase in absolute and relative brain weight gain, MDA concentration and CAT activity in both brain and serum of treated rats. The biochemical parameters, which were more altered in the brain than serum, corroborated the neurologic lesions; neurodegeneration of purkinje cells with loss of dendrites, perineural vacuolations of the neuronal cytoplasm (spongiosis and neuronal necrosis in the brain. The concentrations of Cr, Cu, Pb, As, Cd, Mn, Ni, sulphates, ammonia, chloride and phosphate in the leachate samples were above standard permissible limits. The interactions of the neurotoxic constituents of the leachates induced the observed brain damage in the rats via oxidative damage. This suggests health risk in wildlife and human populations.

  15. Effects of Chronic Central Arginine Vasopressin (AVP on Maternal Behavior in Chronically Stressed Rat Dams

    Directory of Open Access Journals (Sweden)

    Benjamin C. Nephew

    2012-11-01

    Full Text Available Exposure of mothers to chronic stressors during pregnancy or the postpartum period often leads to the development of depression, anxiety, or other related mood disorders. The adverse effects of mood disorders are often mediated through maternal behavior and recent work has identified arginine vasopressin (AVP as a key neuropeptide hormone in the expression of maternal behavior in both rats and humans. Using an established rodent model that elicits behavioral and physiological responses similar to human mood disorders, this study tested the effectiveness of chronic AVP infusion as a novel treatment for the adverse effects of exposure to chronic social stress during lactation in rats. During early (day 3 and mid (day 10 lactation, AVP treatment significantly decreased the latency to initiate nursing and time spent retrieving pups, and increased pup grooming and total maternal care (sum of pup grooming and nursing. AVP treatment was also effective in decreasing maternal aggression and the average duration of aggressive bouts on day 3 of lactation. Central AVP may be an effective target for the development of treatments for enhancing maternal behavior in individuals exposed to chronic social stress.

  16. Effects of Chronic Central Arginine Vasopressin (AVP) on Maternal Behavior in Chronically Stressed Rat Dams

    Science.gov (United States)

    Coverdill, Alexander J.; McCarthy, Megan; Bridges, Robert S.; Nephew, Benjamin C.

    2012-01-01

    Exposure of mothers to chronic stressors during pregnancy or the postpartum period often leads to the development of depression, anxiety, or other related mood disorders. The adverse effects of mood disorders are often mediated through maternal behavior and recent work has identified arginine vasopressin (AVP) as a key neuropeptide hormone in the expression of maternal behavior in both rats and humans. Using an established rodent model that elicits behavioral and physiological responses similar to human mood disorders, this study tested the effectiveness of chronic AVP infusion as a novel treatment for the adverse effects of exposure to chronic social stress during lactation in rats. During early (day 3) and mid (day 10) lactation, AVP treatment significantly decreased the latency to initiate nursing and time spent retrieving pups, and increased pup grooming and total maternal care (sum of pup grooming and nursing). AVP treatment was also effective in decreasing maternal aggression and the average duration of aggressive bouts on day 3 of lactation. Central AVP may be an effective target for the development of treatments for enhancing maternal behavior in individuals exposed to chronic social stress. PMID:24349762

  17. Plasma as an indicator of bone fluoride levels in rats chronically exposed to fluoride Plasma como um indicador dos níveis de flúor no osso em ratos expostos cronicamente ao flúor

    Directory of Open Access Journals (Sweden)

    Juliane Guimarães de Carvalho

    2006-08-01

    Full Text Available OBJECTIVE: This study evaluated the use of plasma, bone surface (periosteal and whole bone as biomarkers of chronic fluoride (F exposure. METHODS: Forty male Wistar rats were assigned to 4 groups (n=10/gr that differed according to the F concentration they received in the drinking water. Groups 1, 2, 3 and 4 received water containing 0 (control, 5, 15, and 50 mg F/L, respectively. The rats were killed at 120 days of age. Plasma and femur were collected and analyzed for fluoride with the ion specific electrode by the direct method or after hexamethyldisiloxane-facilitated diffusion. Data were tested for statistically significant differences by ANOVA and linear regression (pOBJETIVOS: Este estudo avaliou o uso do plasma, superfície óssea e osso total como biomarcadores da exposição crônica ao flúor em ratos. MÉTODOS: Quarenta ratos Wistar machos foram divididos em 4 grupos (n=10/gr que diferiram de acordo com a concentração de flúor presente na água de beber. Os grupos 1, 2, 3 e 4 receberam água contendo 0, 5, 15 e 50 mg F/L, respectivamente. Os ratos foram mortos ao completarem 120 dias. O plasma e os fêmures foram coletados e a concentração de flúor foi analisada com um eletrodo específico pelo método direto para a superfície do fêmur e após difusão facilitada por HMDS para o osso total e o plasma. Os dados foram analisados por ANOVA e regressão linear (p<0,05. RESULTADOS: A média (± EP da concentração de flúor no plasma variou de 0,030±0,006 a 0,187±0,040 (mg/mL. A concentração de flúor na superfície e no osso total variou de 610±103 a 4693±703 e 647±69 a 3439±423 (mg/g, respectivamente. A proporção entre a concentração de flúor na superfície óssea e osso total foi de 0,941, 1,414, 1,173 e 1,377, para os grupos 1, 2, 3 e 4 respectivamente. Para o plasma e osso total, a diferença entre todos os grupos foi estatisticamente significante, exceto para o grupo 2 quando comparado com o grupo 1. Para a

  18. Multiple endocrine disrupting effects in rats perinatally exposed to butylparaben

    DEFF Research Database (Denmark)

    Boberg, Julie; Petersen, Marta Axelstad; Svingen, Terje;

    2016-01-01

    sensitive endpoints, however, remains largely unknown. In this study, time-mated Wistar rats (n=18) were orally exposed to 0, 10, 100 or 500 mg/kg bw/day of butylparaben from gestation day 7 to pup day 22. Several endocrine-sensitive endpoints were adversely affected. In the two highest dose groups......) expression was reduced in prepubertal, but not adult animals exposed to butylparaben. In adult testes, Nr5a1 expression was reduced at all doses, indicating persistent disruption of steroidogenesis. Prostate histology was altered at prepuberty and adult prostate weights were reduced in the high dose group....... Thus, butylparaben exerted endocrine disrupting effects on both male and female offspring. The observed adverse developmental effect on sperm count at the lowest dose is highly relevant to risk assessment, as this is the lowest observed adverse effect level in a study on perinatal exposure...

  19. Low maternal care exacerbates adult stress susceptibility in the chronic mild stress rat model of depression

    DEFF Research Database (Denmark)

    Henningsen, Kim; Dyrvig, Mads; Bouzinova, Elena V;

    2012-01-01

    In the present study we report the finding that the quality of maternal care, in early life, increased the susceptibility to stress exposure in adulthood, when rats were exposed to the chronic mild stress paradigm. Our results indicate that high, as opposed to low maternal care, predisposed rats...... to a differential stress-coping ability. Thus rats fostered by low maternal care dams became more prone to adopt a stress-susceptible phenotype developing an anhedonic-like condition. Moreover, low maternal care offspring had lower weight gain and lower locomotion, with no additive effect of stress. Subchronic...... exposure to chronic mild stress induced an increase in faecal corticosterone metabolites, which was only significant in rats from low maternal care dams. Examination of glucocorticoid receptor exon 17 promoter methylation in unchallenged adult, maternally characterized rats, showed an insignificant...

  20. Diaphragm Muscle Remodeling in a Rat Model of Chronic Intermittent Hypoxia

    OpenAIRE

    Shortt, Christine M.; Fredsted, Anne; Bradford, Aidan; O’Halloran, Ken D.

    2013-01-01

    Respiratory muscle remodeling occurs in human sleep apnea—a common respiratory disorder characterized by chronic intermittent hypoxia (CIH) due to recurrent apnea during sleep. We sought to determine if CIH causes remodeling in rat sternohyoid (upper airway dilator) and diaphragm muscles. Adult male Wistar rats were exposed to CIH (n=8), consisting of 90 sec of hypoxia (5% at the nadir; SaO2 ~80%)/90 sec of normoxia, 8 hr per day, for 7 consecutive days. Sham animals (n=8) were exposed to alt...

  1. Brain plasticity of rats exposed to prenatal immobilization stress

    Directory of Open Access Journals (Sweden)

    Badalyan B. Yu.

    2011-10-01

    Full Text Available Aim. This histochemical and immunohistochemical study was aimed at examining the brain cellular structures of newborn rats exposed to prenatal immobilization (IMO stress. Methods. Histochemical method on detection of Ca2+-dependent acid phosphatase activity and ABC immunohistochemical technique. Results. Cell structures with radial astrocytes marker GFAP, neuroepithelial stem cell marker gene nestin, stem-cells marker and the hypothalamic neuroprotective proline-rich polypeptide PRP-1 (Galarmin, a natural cytokine of a common precursor to neurophysin vasopressin associated glycoprotein have been revealed in several brain regions. Conclusions. Our findings indicate the process of generation of new neurons in response to IMO and PRP-1 involvement in this recovery mechanism, as PRP-1-Ir was detected in the above mentioned cell structures, as well as in the neurons and nerve fibers.

  2. Damage of hippocampal neurons in rats with chronic alcoholism

    Institute of Scientific and Technical Information of China (English)

    Ailin Du; Hongbo Jiang; Lei Xu; Na An; Hui Liu; Yinsheng Li; Ruiling Zhang

    2014-01-01

    Chronic alcoholism can damage the cytoskeleton and aggravate neurological deifcits. However, the effect of chronic alcoholism on hippocampal neurons remains unclear. In this study, a model of chronic alcoholism was established in rats that were fed with 6%alcohol for 42 days. Endog-enous hydrogen sulifde content and cystathionine-beta-synthase activity in the hippocampus of rats with chronic alcoholism were signiifcantly increased, while F-actin expression was decreased. Hippocampal neurons in rats with chronic alcoholism appeared to have a fuzzy nuclear mem-brane, mitochondrial edema, and ruptured mitochondrial crista. These findings suggest that chronic alcoholism can cause learning and memory decline in rats, which may be associated with the hydrogen sulfide/cystathionine-beta-synthase system, mitochondrial damage and reduced expression of F-actin.

  3. The effect of chronic peripheral nesfatin-1 application on blood pressure in normal and chronic restraint stressed rats: related with circulating level of blood pressure regulators.

    Science.gov (United States)

    Ayada, Ceylan; Turgut, Günfer; Turgut, Sebahat; Güçlü, Zuhal

    2015-01-01

    Nesfatin is a peptide secreted by peripheral tissues, central and peripheral nervous system. It is involved in the regulation of homeostasis. Although the effects of nesfatin-1 on nutrition have been studied widely in the literature, the mechanisms of nesfatin-1 action and also relations with other physiological parameters are still not clarified well. We aimed to investigate the effect of peripheral chronic nesfatin-1 application on blood pressure regulation in normal and in rats exposed to restraint immobilization stress. In our study, three month-old male Wistar rats were used. Rats were divided into 4 groups as Control, Stress, Control+Nesfatin-1, Nesfatin-1+Stress. Angiotensinogen, angiotensin converting enzyme 2, angiotensin II, endothelin-1, endothelial nitric oxide synthase, aldosterone, cortisol, nesfatin-1 levels were determined in plasma samples by ELISA. Our results have shown that chronic peripheral nesfatin-1 administration increases blood pressure in normal and in rats exposed to chronic restraint stress. Effect of nesfatin-1 on circulating level of angiotensinogen, angiotensin converting enzyme 2, angiotensin II, endothelin-1, endothelial nitric oxide synthase, aldosterone and cortisol has been identified. We can conclude that elevated high blood pressure after chronic peripheral nesfatin-1 administration in rats exposed to chronic restraint stress may be related to decreased plasma level of endothelial nitric oxide synthase concentration. PMID:25504061

  4. Long-Term Effects of Chronic Oral Ritalin Administration on Cognitive and Neural Development in Adolescent Wistar Kyoto Rats

    OpenAIRE

    Pardey, Margery C.; Kumar, Natasha N.; Goodchild, Ann K.; Clemens, Kelly J.; Homewood, Judi; Cornish, Jennifer L.

    2012-01-01

    The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) often results in chronic treatment with psychostimulants such as methylphenidate (MPH, Ritalin®). With increases in misdiagnosis of ADHD, children may be inappropriately exposed to chronic psychostimulant treatment during development. The aim of this study was to assess the effect of chronic Ritalin treatment on cognitive and neural development in misdiagnosed “normal” (Wistar Kyoto, WKY) rats and in Spontaneously Hypertensive R...

  5. Effect of bacoside A on brain antioxidant status in cigarette smoke exposed rats.

    Science.gov (United States)

    Anbarasi, K; Vani, G; Balakrishna, K; Devi, C S Shyamala

    2006-02-16

    Free radicals mediated oxidative stress has been implicated in the pathogenesis of smoking-related diseases and antioxidant nutrients are reported to prevent the oxidative damage induced by smoking. Therefore, the present study was conducted to evaluate the antioxidant role of bacoside A (triterpenoid saponin isolated from Bacopa monniera) against chronic cigarette smoking induced oxidative damage in rat brain. Adult male albino rats were exposed to cigarette smoke for a period of 12 weeks and simultaneously administered with bacoside A (10 mg/kg b.w./day, p.o.). Antioxidant status of the brain was assessed from the levels of reduced glutathione, vitamin C, vitamin E, and vitamin A and the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. The levels of copper, iron, zinc and selenium in brain and serum ceruloplasmin activity were also measured. Oxidative stress was evident from the diminished levels of both enzymatic and non-enzymatic antioxidants. Alterations in the levels of trace elements with accumulation of copper and iron, and depletion of zinc and selenium were also observed. Bacoside A administration improved the antioxidant status and maintained the levels of trace elements. These results suggest that chronic cigarette smoke exposure enhances oxidative stress, thereby disturbing the tissue defense system and bacoside A protects the brain from the oxidative damage through its antioxidant potential.

  6. Changes of cell factor in bronchoalveolar lavage fluid in rats exposed to silica

    Institute of Scientific and Technical Information of China (English)

    张玮

    2014-01-01

    Objective To investigate the changes in the levels of inflammatory cytokines in bronchoalveolar lavage fluid(BALF)in rats exposed to silica dust.Methods Experimental rats were randomly divided into control group and three experimental groups(doses of dust:15,30,and 60mg/ml),with 42 rats in each group.Each rat in the control group was treated with 1 ml of normal saline by intratracheal instillation,while each rat in the experimental groups was exposed to 1

  7. Effects of SO2 derivatives on sodium currents in acutely isolated rat hippocampal lead-exposed neurons

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    In this study, the effects of acute SO2 derivatives and chronic lead exposure together on sodium cur-rents (INa) were investigated in acutely isolated rat hippocampal neurons by using the whole-cell patch clamp techniques. We found that chronic lead exposure hardly reduced the amplitudes of INa. In the normal condition, sodium current started to appear at around ?70 mV, and reached the peak current at around ?40 mV. After chronic lead exposure, the data changed to ?70 and ?30 mV. After adding SO2 derivatives, the data changed to ?80 and ?40 mV, respectively. SO2 derivatives caused a significant in-crease of INa in hippocampal chronic-lead exposed neurons. Chronic lead exposure induced a right shift of the activation curve and a left shift of the inactivation curve of sodium channels. SO2 derivatives caused negative shifts of the activation and inactivation curves of INa in hippocampal chronic-lead ex-posed neurons. Lead exposure put off the time reaching the peak of INa activation. SO2 derivatives in-creased the time constants of inactivation after lead exposure. The interaction of lead and SO2 deriva-tives with voltage-dependent sodium channels may lead to changes in electrical activity and contribute to worsening the neurotoxicological damage.

  8. Water metabolism in rats subjected to chronic alcohol administration

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Pohl, C.; Bode, J.C.;

    2004-01-01

    AIM: While the diuretic action of acute ingestion of alcohol has been studied extensively, the effect of chronic alcohol consumption has received less attention. The aim of the present study was to investigate the effect of chronic alcohol consumption on the balance of water intake and excretion...... A compared with group C. The changes in water balance induced by chronic alcohol consumption were reversible within a few days when the rats received water instead of 15% alcohol. CONCLUSIONS: Chronic alcohol consumption has an antidiuretic effect in rats. The percentage of total ingested fluid leaving...... the body as hidden water loss increases after alcohol consumption by up to 25-26% over control values....

  9. Hippocampal phosphoproteomics of F344 rats exposed to 1-bromopropane

    International Nuclear Information System (INIS)

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and human. To identify phosphorylated modification on the unrecognized post-translational modifications of proteins and investigate their role in 1-BP-induced neurotoxicity, changes in hippocampal phosphoprotein expression levels were analyzed quantitatively in male F344 rats exposed to 1-BP inhalation at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks. Hippocampal protein extracts were analyzed qualitatively and quantitatively by Pro-Q Diamond gel staining and SYPRO Ruby staining coupled with two-dimensional difference in gel electrophoresis (2D-DIGE), respectively, as well as by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to identify phosphoproteins. Changes in selected proteins were further confirmed by Manganese II (Mn2+)-Phos-tag SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Bax and cytochrome c protein levels were determined by western blotting. Pro-Q Diamond gel staining combined with 2D-DIGE identified 26 phosphoprotein spots (p < 0.05), and MALDI-TOF/MS identified 18 up-regulated proteins and 8 down-regulated proteins. These proteins are involved in the biological process of response to stimuli, metabolic processes, and apoptosis signaling. Changes in the expression of phosphorylated 14-3-3 θ were further confirmed by Mn2+-Phos-tag SDS-PAGE. Western blotting showed overexpression of Bax protein in the mitochondria with down-regulation in the cytoplasm, whereas cytochrome c expression was high in the cytoplasm but low in the mitochondria after 1-BP exposure. Our results suggest that the pathogenesis of 1-BP-induced hippocampal damage involves inhibition of antiapoptosis process. Phosphoproteins identified in this study can potentially serve as biomarkers for 1-BP-induced neurotoxicity. - Highlights: • 1-BP modified hippocampal phosphoproteome in rat and 23 altered proteins were identified. • 1-BP changed phosphorylation of GRP78, 14

  10. Hippocampal phosphoproteomics of F344 rats exposed to 1-bromopropane

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Zhenlie [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Ichihara, Sahoko [Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Oikawa, Shinji [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); Chang, Jie [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Zhang, Lingyi [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510 (Japan); Hu, Shijie [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Huang, Hanlin, E-mail: huanghl@gdoh.org [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Ichihara, Gaku, E-mail: gak@rs.tus.ac.jp [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510 (Japan)

    2015-01-15

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and human. To identify phosphorylated modification on the unrecognized post-translational modifications of proteins and investigate their role in 1-BP-induced neurotoxicity, changes in hippocampal phosphoprotein expression levels were analyzed quantitatively in male F344 rats exposed to 1-BP inhalation at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks. Hippocampal protein extracts were analyzed qualitatively and quantitatively by Pro-Q Diamond gel staining and SYPRO Ruby staining coupled with two-dimensional difference in gel electrophoresis (2D-DIGE), respectively, as well as by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to identify phosphoproteins. Changes in selected proteins were further confirmed by Manganese II (Mn{sup 2+})-Phos-tag SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Bax and cytochrome c protein levels were determined by western blotting. Pro-Q Diamond gel staining combined with 2D-DIGE identified 26 phosphoprotein spots (p < 0.05), and MALDI-TOF/MS identified 18 up-regulated proteins and 8 down-regulated proteins. These proteins are involved in the biological process of response to stimuli, metabolic processes, and apoptosis signaling. Changes in the expression of phosphorylated 14-3-3 θ were further confirmed by Mn{sup 2+}-Phos-tag SDS-PAGE. Western blotting showed overexpression of Bax protein in the mitochondria with down-regulation in the cytoplasm, whereas cytochrome c expression was high in the cytoplasm but low in the mitochondria after 1-BP exposure. Our results suggest that the pathogenesis of 1-BP-induced hippocampal damage involves inhibition of antiapoptosis process. Phosphoproteins identified in this study can potentially serve as biomarkers for 1-BP-induced neurotoxicity. - Highlights: • 1-BP modified hippocampal phosphoproteome in rat and 23 altered proteins were identified. • 1-BP changed phosphorylation

  11. The number of granule cells in rat hippocampus is reduced after chronic mild stress and re-established after chronic escitalopram treatment

    DEFF Research Database (Denmark)

    Jayatissa, Magdalena N; Bisgaard, Christina; West, Mark J;

    2008-01-01

    Stress and depression cause structural changes in the hippocampal formation. Some of these can be reversed by chronic antidepressant treatment. In the present study, we examined the changes in the total number of granule cells and the volume of the granule cell layer after exposing rats to chronic...... changes, indicating a decrease in sensitivity to a reward, were assessed in terms of sucrose consumption. We found a significant 22.4% decrease in the total number of granule cells in the stressed rats. This decrease was reversed in the stressed escitalopram treated rats that responded to the treatment...... shows that the anhedonia-like state in the CMS rats is associated with a reduced number of granule cells. We conclude that escitalopram acts on specific cellular targets during neuronal differentiation and that recovery from anhedonia-like behavior in rats may be the consequence of an escitalopram...

  12. Treadmill exercise does not change gene expression of adrenal catecholamine biosynthetic enzymes in chronically stressed rats

    Directory of Open Access Journals (Sweden)

    LJUBICA GAVRILOVIC

    2013-09-01

    Full Text Available ABSTRACT Chronic isolation of adult animals represents a form of psychological stress that produces sympatho-adrenomedullar activation. Exercise training acts as an important modulator of sympatho-adrenomedullary system. This study aimed to investigate physical exercise-related changes in gene expression of catecholamine biosynthetic enzymes (tyrosine hydroxylase, dopamine-ß-hydroxylase and phenylethanolamine N-methyltransferase and cyclic adenosine monophosphate response element-binding (CREB in the adrenal medulla, concentrations of catecholamines and corticosterone (CORT in the plasma and the weight of adrenal glands of chronically psychosocially stressed adult rats exposed daily to 20 min treadmill running for 12 weeks. Also, we examined how additional acute immobilization stress changes the mentioned parameters. Treadmill running did not result in modulation of gene expression of catecholamine synthesizing enzymes and it decreased the level of CREB mRNA in the adrenal medulla of chronically psychosocially stressed adult rats. The potentially negative physiological adaptations after treadmill running were recorded as increased concentrations of catecholamines and decreased morning CORT concentration in the plasma, as well as the adrenal gland hypertrophy of chronically psychosocially stressed rats. The additional acute immobilization stress increases gene expression of catecholamine biosynthetic enzymes in the adrenal medulla, as well as catecholamines and CORT levels in the plasma. Treadmill exercise does not change the activity of sympatho-adrenomedullary system of chronically psychosocially stressed rats.

  13. Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Sarah M. DeNucci

    2010-01-01

    Full Text Available The finding of more severe steatohepatitis in alcohol fed Long Evans (LE compared with Sprague Dawley (SD and Fisher 344 (FS rats prompted us to determine whether host factors related to alcohol metabolism, inflammation, and insulin/IGF signaling predict proneness to alcohol-mediated liver injury. Adult FS, SD, and LE rats were fed liquid diets containing 0% or 37% (calories ethanol for 8 weeks. Among controls, LE rats had significantly higher ALT and reduced GAPDH relative to SD and FS rats. Among ethanol-fed rats, despite similar blood alcohol levels, LE rats had more pronounced steatohepatitis and fibrosis, higher levels of ALT, DNA damage, pro-inflammatory cytokines, ADH, ALDH, catalase, GFAP, desmin, and collagen expression, and reduced insulin receptor binding relative to FS rats. Ethanol-exposed SD rats had intermediate degrees of steatohepatitis, increased ALT, ADH and profibrogenesis gene expression, and suppressed insulin receptor binding and GAPDH expression, while pro-inflammatory cytokines were similarly increased as in LE rats. Ethanol feeding in FS rats only reduced IL-6, ALDH1–3, CYP2E1, and GAPDH expression in liver. In conclusion, susceptibility to chronic steatohepatitis may be driven by factors related to efficiency of ethanol metabolism and degree to which ethanol exposure causes hepatic insulin resistance and cytokine activation.

  14. Long-Term Effects of Chronic Oral Ritalin Administration on Cognitive and Neural Development in Adolescent Wistar Kyoto Rats

    Directory of Open Access Journals (Sweden)

    Jennifer L. Cornish

    2012-09-01

    Full Text Available The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD often results in chronic treatment with psychostimulants such as methylphenidate (MPH, Ritalin®. With increases in misdiagnosis of ADHD, children may be inappropriately exposed to chronic psychostimulant treatment during development. The aim of this study was to assess the effect of chronic Ritalin treatment on cognitive and neural development in misdiagnosed “normal” (Wistar Kyoto, WKY rats and in Spontaneously Hypertensive Rats (SHR, a model of ADHD. Adolescent male animals were treated for four weeks with oral Ritalin® (2 × 2 mg/kg/day or distilled water (dH2O. The effect of chronic treatment on delayed reinforcement tasks (DRT and tyrosine hydroxylase immunoreactivity (TH-ir in the prefrontal cortex was assessed. Two weeks following chronic treatment, WKY rats previously exposed to MPH chose the delayed reinforcer significantly less than the dH2O treated controls in both the DRT and extinction task. MPH treatment did not significantly alter cognitive performance in the SHR. TH-ir in the infralimbic cortex was significantly altered by age and behavioural experience in WKY and SHR, however this effect was not evident in WKY rats treated with MPH. These results suggest that chronic treatment with MPH throughout adolescence in “normal” WKY rats increased impulsive choice and altered catecholamine development when compared to vehicle controls.

  15. Acute and chronic tramadol administration impair spatial memory in rat

    Science.gov (United States)

    Hosseini-Sharifabad, Ali; Rabbani, Mohammad; Sharifzadeh, Mohammad; Bagheri, Narges

    2016-01-01

    Tramadol hydrochloride, a synthetic opioid, acts via a multiple mechanism of action. Tramadol can potentially change the behavioral phenomena. The present study evaluates the effect of tramadol after single or multiple dose/s on the spatial memory of rat using object recognition task (ORT). Tramadol, 20 mg/kg, was injected intraperitoneally (i.p) as a single dose or once a day for 21 successive days considered as acute or chronic treatment respectively. After treatment, animals underwent two trials in the ORT. In the first trial (T1), animals encountered with two identical objects for exploration in a five-minute period. After 1 h, in the T2 trial, the animals were exposed to a familiar and a nonfamiliar object. The exploration times and frequency of the exploration for any objects were recorded. The results showed that tramadol decreased the exploration times for the nonfamiliar object in the T2 trial when administered either as a single dose (P<0.001) or as the multiple dose (P<0.05) compared to the respective control groups. Both acute and chronic tramadol administration eliminated the different frequency of exploration between the familiar and nonfamiliar objects. Our findings revealed that tramadol impaired memory when administered acutely or chronically. Single dose administration of tramadol showed more destructive effect than multiple doses of tramadol on the memory. The observed data can be explained by the inhibitory effects of tramadol on the wide range of neurotransmitters and receptors including muscarinic, N-methyl D-aspartate, AMPA as well as some second messenger like cAMP and cGMP or its stimulatory effect on the opioid, gama amino butyric acid, dopamine or serotonin in the brain. PMID:27051432

  16. Chronic amphetamine treatment increases striatal calmodulin in rats

    International Nuclear Information System (INIS)

    A radioimmunoassay was developed to measure calmodulin in striatum from rats treated with one dose or repeated injections of amphetamine. Chronic, but not acute, amphetamine treatment resulted in a significant increase in total calmodulin levels in striatal homogenates. This effect may be linked to the behavioral sensitization which develops after chronic amphetamine treatments. (Auth.)

  17. Analysis of emotionality and locomotion in radio-frequency electromagnetic radiation exposed rats.

    Science.gov (United States)

    Narayanan, Sareesh Naduvil; Kumar, Raju Suresh; Paval, Jaijesh; Kedage, Vivekananda; Bhat, M Shankaranarayana; Nayak, Satheesha; Bhat, P Gopalakrishna

    2013-07-01

    In the current study the modulatory role of mobile phone radio-frequency electromagnetic radiation (RF-EMR) on emotionality and locomotion was evaluated in adolescent rats. Male albino Wistar rats (6-8 weeks old) were randomly assigned into the following groups having 12 animals in each group. Group I (Control): they remained in the home cage throughout the experimental period. Group II (Sham exposed): they were exposed to mobile phone in switch-off mode for 28 days, and Group III (RF-EMR exposed): they were exposed to RF-EMR (900 MHz) from an active GSM (Global system for mobile communications) mobile phone with a peak power density of 146.60 μW/cm(2) for 28 days. On 29th day, the animals were tested for emotionality and locomotion. Elevated plus maze (EPM) test revealed that, percentage of entries into the open arm, percentage of time spent on the open arm and distance travelled on the open arm were significantly reduced in the RF-EMR exposed rats. Rearing frequency and grooming frequency were also decreased in the RF-EMR exposed rats. Defecation boli count during the EPM test was more with the RF-EMR group. No statistically significant difference was found in total distance travelled, total arm entries, percentage of closed arm entries and parallelism index in the RF-EMR exposed rats compared to controls. Results indicate that mobile phone radiation could affect the emotionality of rats without affecting the general locomotion.

  18. Chronic Psychological Stress Enhances Nociceptive Processing in the Urinary Bladder in High-Anxiety Rats

    OpenAIRE

    Robbins, M.T.; DeBerry, J.; Ness, T. J

    2007-01-01

    This study sought to determine whether acute and/or chronic psychological stress produce changes in urinary bladder nociception. Female Sprague-Dawley (SD; low/moderate anxiety) or Wistar-Kyoto (WK; high-anxiety) rats were exposed to either an acute (1 day) or a chronic (10 days) water avoidance stress paradigm or a sham stress paradigm. Paw withdrawal thresholds to mechanical and thermal stimuli and fecal pellet output, were quantified at baseline and after the final stress or sham stress ex...

  19. Effects of maternal rats exposed to chronic unpredictable stress before pregnancy on the behaviors and brain monamine of their adult male offspring%母鼠孕前慢性应激对成年雄性子代行为学和脑区单胺递质的影响

    Institute of Scientific and Technical Information of China (English)

    李海红; 张磊; 方泽漫; 吴彩茹; 朱琴; 黄庆军

    2010-01-01

    目的 研究母鼠孕前慢性应激对成年雄性子代行为学和脑内单胺类神经递质的影响.方法 16只成年雌性SD大鼠随机分为正常对照组和慢性不可预见性应激组(CUS),CUS组大鼠每天接受一种应激,共21d,正常对照组不接受任何应激.应激结束后10 d,2组大鼠均与同种SD雄性大鼠合笼,以成年2月龄雄性子代作为研究对象.用糖水消耗实验测量快感缺失,Morris水迷宫检测空间记忆能力,高效液相色谱法测量海马、下丘脑和前额皮质单胺递质的含量.结果 糖水消耗实验示正常对照组子代的糖水消耗量和糖水消耗百分比均显著高于CUS组子代[糖水消耗量:(10.23±4.12)g,(6.48±3.19)g;糖水消耗百分比:(85.43±20.15)%,(60.98±24.65)%](P<0.05).Morris水迷宫检测示2组的逃避潜伏期无差异,但空间探索测试中正常对照组子代[(4.17±2.29)次]穿越平台的次数明显多CUS组子代[(1.64±1.69)次](P<0.05).CUS组子代[(500.17±80.94)ng/g脑组织]下丘脑5-羟色胺的含量低于正常对照组子代[(569.63±50.91)ng/g脑组织](P<0.05),而CUS组子代[(2315.01±1397.12)ng/g脑组织]海马去甲肾上腺素的含量却要高于正常对照组子代[(907.56±207.27)ng/g脑组织](P<0.05).结论 母鼠孕前慢性应激或抑郁会造成成年雄性子代的快感缺失和空间记忆力下降,以及脑内单胺类神经递质异常.%Objective To examine the effects of maternal rats exposed to chronic unpredictable stress before pregnancy on the behaviors and brain monamine of their adult male offspring.Methods Sixteen SD rats were divided into chronic unpredictable stress (CUS) group and controls.CUS rats were exposed to 21 days chronic unpredictable stressors ,and the controls were stress-free.Ten days after the last stressor, all the female rats were caged with sexually experienced males of the same strain.Then we performed the following experiments on the two months male progeny, sucrose consumption

  20. Metabonomic study of rats exposed to cigarette sidestream smoke

    Institute of Scientific and Technical Information of China (English)

    LIAN Wen-liu; SHI Xian-zhe; LUO Jia; REN Feng-lian

    2016-01-01

    A metabonomic approach was undertaken in order to detect urinary endogenous and exogenous metabolites and to evaluate the effects of passive exposure to cigarette sidestream smoke on rats. Urinary samples from three groups of rats were determined including control rats, rats treated with blended cigarettes (nonmenthol cigarettes) and rats treated with menthol cigarettes. The total urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), total 1-hydroxypyrene (1-HOP) and 3-hydroxybenzo[a] pyrene (3-HOBaP) were determined for assessing exposure to cigarette sidestream smoke toxins. Urinary endogenous metabolites in the three groups of rats were also analyzed and the data were processed by chemometrics. Eleven endogenous metabolites were found and identified. Their relative levels were compared among the three groups. The results show that cigarette sidestream smoke has complex effect on rats. Blended cigarette group makes difference to menthol cigarette group in the rats' urinary metabolic changes. Menthol adding to cigarettes has positive and negative effects on rats, respectively. The urinary metabolic profiling of menthol cigarette group is closer to that of control group.

  1. Health status of grandchildren of subjects occupationally exposed to chronic radiation. Communication 3. Disease incidence

    International Nuclear Information System (INIS)

    The morbidity of 1557 grandchildren of subjects occupationally exposed to chronic radiation were analyzed. Three groups were singled out. Group 1 consisted of children whose grandfathers were exposed, group 2 of children grandmothers were exposed and group 3 of children whose both grandparent were exposed. Total morbidity level and morbidity structure for 13 classes of diseases and 60 nosological entities was assessed. The study showed that disease incidence in general, structure by disease and individual nosological entities, the share of frequently falling ill children, and health index in the test group corresponded to those in controls. Reliable differences were observed only for respiratory diseases, at the expense of acute respiratory diseases, which were frequent during the second-third years of life in children whose both grandparents were occupationally exposed to radiation

  2. Psychophysical Evaluation of Achromatic and Chromatic Vision of Workers Chronically Exposed to Organic Solvents

    International Nuclear Information System (INIS)

    The purpose of this paper was to evaluate achromatic and chromatic vision of workers chronically exposed to organic solvents through psychophysical methods. Thirty-one gas station workers (31.5 ± 8.4 years old) were evaluated. Psychophysical tests were achromatic tests (Snellen chart, spatial and temporal contrast sensitivity, and visual perimetry) and chromatic tests (Ishihara's test, color discrimination ellipses, and Farnsworth-Munsell 100 hue test FM100). Spatial contrast sensitivities of exposed workers were lower than the control at spatial frequencies of 20 and 30 cpd whilst the temporal contrast sensitivity was preserved. Visual field losses were found in 10-30 degrees of eccentricity in the solvent exposed workers. The exposed workers group had higher error values of FM100 and wider color discrimination ellipses area compared to the controls. Workers occupationally exposed to organic solvents had abnormal visual functions, mainly color vision losses and visual field constriction

  3. Psychophysical Evaluation of Achromatic and Chromatic Vision of Workers Chronically Exposed to Organic Solvents

    Directory of Open Access Journals (Sweden)

    Eliza Maria da Costa Brito Lacerda

    2012-01-01

    Full Text Available The purpose of this paper was to evaluate achromatic and chromatic vision of workers chronically exposed to organic solvents through psychophysical methods. Thirty-one gas station workers (31.5 ± 8.4 years old were evaluated. Psychophysical tests were achromatic tests (Snellen chart, spatial and temporal contrast sensitivity, and visual perimetry and chromatic tests (Ishihara's test, color discrimination ellipses, and Farnsworth-Munsell 100 hue test—FM100. Spatial contrast sensitivities of exposed workers were lower than the control at spatial frequencies of 20 and 30 cpd whilst the temporal contrast sensitivity was preserved. Visual field losses were found in 10–30 degrees of eccentricity in the solvent exposed workers. The exposed workers group had higher error values of FM100 and wider color discrimination ellipses area compared to the controls. Workers occupationally exposed to organic solvents had abnormal visual functions, mainly color vision losses and visual field constriction.

  4. DETERMINATION OF URINARY TRIVALENT ARSENICALS (MMASIII AND DMASIII) IN INDIVIDUALS CHRONICALLY EXPOSED TO ARSENIC

    Science.gov (United States)

    DETERMINATION OF URINARY TRIVALENT ARSENICALS (MMAsIII and DMAsIII) IN INDIVIDUALS CHRONICALLY EXPOSED TO ARSENIC. L. M. Del Razo1, M. Styblo2, W. R. Cullen3, and D.J. Thomas4. 1Toxicology Section, Cinvestav-IPN, Mexico, D.F., 2Univ. North Carolina, Chapel Hill, NC; 3Uni...

  5. 人参皂苷对慢性应激抑郁模型大鼠行为学及HPA轴、BDNF的影响%Effects of ginsenosides on hypothalamic-pituitary-adrenal function and brain-derived neurotrophic factor in rats exposed to chronic unpredictable mild stress

    Institute of Scientific and Technical Information of China (English)

    刘丽琴; 罗艳; 张瑞睿; 郭建友

    2011-01-01

    Gingseng is commonly used in traditional Chinese medicine community for the treatment of depression-like dis, orders. Ginsenosides is considered to be the major active components of ginseng. Previous studies have demonstrated that ginsenosides produced antidepressant-like action in various mouse models of behavioral despair. The present study aimed to examine whether ginsenosides could affect the chronic unpredictable mild stress (CUMS)-induced depression in rats. The mechanism(s) underlying the antidepressant-like action was investigated by measuring serum corticesterone level, glucocorticoid receptor ( GR), mineralocorticoid receptor (MR) and brain-derived neurotrophic factor (BDNF) mRNA levels in brain tissues. CUMS, being lasted for 6 weeks, caused depression-like behavior in rats, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. Whereas serum corticosterone level was significantly increased in rats exposed to CUMS, expressions of GR mRNA in hippocampus, and BDNF mRNA in hippocampus and frontal cortex, were decreased in CUMS-treated rats. Daily intragastric administration of ginsenosides (12. 5, 25, 50 mg · kg-1) during the six weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS. However, there was no significant difference in MR mRNA level among groups. The results suggest that the antidepressant-like action of ginsenosides is likely mediated by modulating the function of hypothalamic- pituitary -adrenal axis and increasing the expression of BDNF in brain tissues.%目的:探讨人参皂苷对慢性应激所致大鼠抑郁模型的干预作用.方法:通过测定大鼠血清中皮质酮(COR)、糖皮质激素受体(GR)、盐皮质激素受体(MR)和脑组织中神经营养(BDNF)的mRNA表达水平,探讨人参皂苷的抗抑郁机制.结果:与正常组大鼠比较,经过慢性应激6周后大鼠糖水偏好显著下降,强迫游泳测试不动时间

  6. Chronic Pseudomonas aeruginosa lung infection in normal and athymic rats

    DEFF Research Database (Denmark)

    Johansen, H K; Espersen, F; Pedersen, S S;

    1993-01-01

    We have compared a chronic lung infection with Pseudomonas aeruginosa embedded in alginate beads in normal and athymic rats with an acute infection with free live P. aeruginosa bacteria. The following parameters were observed and described: mortality, macroscopic and microscopic pathologic changes......, and antibody responses. The rats challenged with P. aeruginosa alginate beads experienced a generally more severe lung pathology and the antibody responses were more homogeneous with less dispersion as compared to the rats having free live P. aeruginosa bacteria. In general, manifestations were more severe...... in the athymic rats compared to the normal rats. It is, however, notable that the athymic rats developed similar microscopic lung manifestations as the normal rats when given a large number of P. aeruginosa in the beads, with dense accumulation of neutrophil granulocytes and microcolonies comparable...

  7. A chronic inhalation toxicity/oncogenicity study of methylethylketoxime in rats and mice.

    Science.gov (United States)

    Newton, P E; Wooding, W L; Bolte, H F; Derelanko, M J; Hardisty, J F; Rinehart, W E

    2001-12-01

    To evaluate the oncogenic potential of methylethylketoxime (MEKO), CD-1 mice (50/sex/group) and F-344 rats (50/sex/group) were coexposed 6 h/day, 5 days/wk for 18 mo (mice) or 26 mo (rats) via whole-body inhalation exposures to target vapor concentrations of 0, 15, 75, and 375 ppm (actual concentrations of 0, 15 +/- 1, 75 +/- 2, or 374 +/- 10 ppm). Satellite groups of rats and mice (10/sex/group/interval) were exposed for 12 mo (mice) and 3, 12, or 18 mo (rats) to evaluate chronic toxicity. Methyl ethyl ketone (MEK), a possible hydrolysis product of MEKO, was present at less than 1%. Treatment-related effects included increased body weight (male rats only), methemoglobin formation, hematology and clinical chemistry changes, increased liver weight, and increased spleen and testes weights (rats only). A high incidence of cataracts and corneal dystrophy occurred in both control and MEKO-exposed rats, with an earlier appearance and slightly higher incidence for these ocular lesions in MEKO-exposed animals compared to controls. Degenerative and reparative changes of the olfactory epithelium in the nasal turbinates, primarily limited to the dorsal meatus, occurred in both rats (75 and 374 ppm) and mice (15, 75, and 374 ppm). In addition, in the mice, liver changes included increased incidences of pigment in reticuloendothelial cells, centilobular hypertrophy, granulomatous inflammation, and a slightly increased incidence of necrosis (75 and 374 ppm). An increase in hepatocellular carcinomas occurred in male mice at 374 ppm. Additional MEKO-related findings in the rat included congestion of the spleen with pigment in reticuloendothelial cells and extramedullary hematopoiesis and a decreased incidence of lymphoreticular mononuclear cell leukemia. Effects observed in the liver of the rats included decreases in the incidence of both peribiliary fibrosis and hyperplasia/proliferation of the biliary duct, an increase of spongiosis hepatis in males, and an increase in the

  8. Effect of head-only sub-chronic GSM exposure on spatial memory of rats

    International Nuclear Information System (INIS)

    Full text: Introduction: Low power electromagnetic fields (EMF) are suspected to produce deficit memory in rats. The study of Dubreuil et al (2003) showed that a short-term (10-15 days) exposure 'head-only' to GSM 900 MHz radio frequencies does not produce a deficit memory in adult rats. The aim of our experiment was to determine if head-only sub-chronic exposure (2 months) of rats to GSM signal for 45 min at a SAR = 1.5 W/Kg and for 15 min at 6 W/Kg induce deficit in spatial memory of rats in radial maze test. Materials and methods: Exposure system: Animals were placed in Plexiglas rockets with an individual loop antenna placed above the rat's head. Four animals were exposed at the time. Loop antennas were connected to a generator and emitted a GSM signal (900 MHz, pulsed at 217 Hz, 1/8 duty factor) 5 days / week for 8 weeks. Experimental group: 30 Sprague-Dawley male rats were randomly assigned to 5 different groups: a) 6 rats exposed 15 min at SAR = 6 W/Kg; b) 6 rats exposed 45 min at SAR = 1.5 W/g; c) 6 rats sham controls (3 for 5 min and 3 for 45 min, SAR = 0 W/Kg); d) 6 rats without any treatment and manipulation (cage control); e) 6 rats were injected (i.p) S.B.H 0.1 mg/Kg (Sigma Aldrich) as positive control group. Behavioural procedure: The radial maze protocol consists of two consecutive phases: the training task (10 days) and the test task (8 days). In the first phase, rats were trained to visit the 8 arms of the maze without returning to an arm already visited. In the second phase (8 days), a 45-min intra-trial delay was introduced after four visited arms. After the intra-delay, the rat was placed in the maze to finish the test task, which is visiting four other arms he had not visited. During the training task, exposure took place before the behavioural task. During the test task, exposure or sham-exposure took place during the intra-delay. Results and discussion: In all experiments, performance of exposed rats (1.5 and 6 W/Kg) was compared with that of

  9. Effect of ascorbic acid on fatigue of skeletal muscle fibres in long term cold exposed sprague dawley rats

    International Nuclear Information System (INIS)

    On exposure to prolonged cold temperature, the body responds for effective heat production both by shivering and non-shivering thermo genesis. Cold exposure increases the production of reactive oxygen species which influence the sarcoplasmic reticulum Ca/sup ++/ release from the skeletal muscles and affect their contractile properties. The role of ascorbic acid supplementation on force of contraction during fatigue of cold exposed skeletal muscles was evaluated in this study. Method: Ninety healthy, male Sprague Dawley rats were randomly divided into three groups of control, cold exposed, and cold exposed with ascorbic acid 500 mg/L supplementation mixed in drinking water. Group II and III were given cold exposure by keeping their cages in ice-filled tubs for 1 hr/day for one month. After one month, the extensor digitorum longus muscle was dissected out and force of contraction during fatigue in the skeletal muscle fibres was analysed on a computerised data acquisition system. Results: The cold exposed group showed a significant delay in the force of contraction during fatigue of skeletal muscle fibres compared to control group. Group III showed easy fatigability and a better force of contraction than the cold exposed group. Conclusions: Ascorbic acid increases the force of contraction and decreases resistance to fatigue in the muscles exposed to chronic cold. (author)

  10. A study assessing the genotoxicity in rats after chronic oral exposure to a low dose of depleted uranium

    International Nuclear Information System (INIS)

    The aim of this study was to evaluate the potential genotoxicity induced by chronic oral exposure to depleted uranium (DU). Weanling Wistar rats (F0), 50/sex/group, were exposed to DU in food at doses of 0, 4, or 40 mg kg-1 day-1 for four months. They were subsequently mated, resulting in the birth of F1 rats. Fifty F1 weanlings/sex/group were exposed for four months to the same dose levels as their parents. After four months, the uranium content in the tissues, the potential damage to the genetic material, and pathomorphological changes of the testicles were observed in both F0 and F1 rats. The genotoxicity of DU was evaluated by the following methods: sperm abnormality assessment, the bone-marrow micronucleus test, and the comet assay. Uranium content in F1 rats was significantly higher than that in F0 rats in both the kidney and ovary (p1 with F0 rats, significant differences were detected for most of the indicators, with F1 rats always exhibiting more damage (p1 rats. Genotoxicity may be induced in rats after chronic oral exposure to a low dose of DU. (author)

  11. Effects of Sub-chronic Aluminum Exposure on Renal Structure in Rats

    Institute of Scientific and Technical Information of China (English)

    Li Yan-fei; Liu Jian-yu; Cao Zheng

    2015-01-01

    To investigate the effects of aluminum (Al) exposure on renal structure of rats, 60 Wistar rats were randomly divided into four treatment groups and were orally exposed to 0 (control group, GC), 64.18 (low-dose group, GL), 128.36 (middle-dose group, GM), and 256.72 (high-dose group, GH) mg• kg-1 BW AlCl3 in drinking water for 120 days. The body weight of different rats was recorded, the kidney pathologic structure and the ultrastructure were observed. The results showed that the body weight of different rats was markedly lower in Al-treated rats than those in GC (P<0.05;P<0.01). After masson staining, the collagen was deposited in the renal interstitium and aggravated with Al dose increases in Al-treated rats. Under electron microscope, the infolding of the plasma membrane was slight swollen, the mitochondrion was abundant with different sizes, the mitochondrion cristae was fused, the microvillus was swollen and fused in GH. Our findings indicated that sub-chronic Al exposure slowed the weight of rats and caused the kidney pathologic damage in rats.

  12. Chronic study on BHT in rats

    DEFF Research Database (Denmark)

    Würtzen, G.; Olsen, P.

    1986-01-01

    Groups of 40, 29, 39 and 44 F0 rats of each sex were fed a semi-synthetic diet containing butylated hydroxytoluene (BHT) in concentrations to provide intakes of 0, 25, 100 or 500 mg/kg body weight/day, respectively. The F0 rats were mated, and groups of 100, 80, 80 and 100 F1 rats of each sex were...... formed. After weaning, the highest dose of BHT was lowered to 250 mg/kg/day for the F1 rats. At weaning the BHT-treated F1 rats, especially the males, had lower body weights than the controls and the effect was dose related. The survival of the BHT-treated rats of both sexes was higher than that of the...

  13. Chronic exposure of juvenile rats to environmental noise impairs hippocampal cell proliferation in adulthood

    Directory of Open Access Journals (Sweden)

    Fernando Jáuregui-Huerta

    2011-01-01

    Full Text Available Increasing evidence indicates that chronic exposure to environmental noise may permanently affect the central nervous system. The aim of this study was to evaluate the long-term effects of early exposure to environmental noise on the hippocampal cell proliferation of the adult male rat. Early-weaned Wistar rats were exposed for 15 days to a rats′ audiogram-fitted adaptation to a noisy environment. Two months later, the rats were injected with the cellular proliferation marker 5΄bromodeoxiuridine (BrdU, and their brains were processed for immunohistochemical analysis. Coronal sections were immunolabeled with anti-BrdU antibodies to identify new-born cells in dentate gyrus (DG, cornu amonis areas CA1 and CA3. In addition, blood samples were obtained to evaluate corticosterone serum levels after noise exposure. All data are expressed as mean΁standard deviation. For mean comparisons between groups, we used the Student t test. We found an increase in corticosterone serum levels after environmental noise exposure. Interestingly, noise-exposed rats showed a long-term reduction of proliferating cells in the hippocampal formation, as compared to controls. These findings indicate that chronic environmental noise exposure at young ages produces persistent non-auditory impairment that modifies cell proliferation in the hippocampal formation.

  14. 孕前慢性应激对母鼠及其子代行为学和海马神经元再生的影响%Effects of maternal rats exposed to chronic unpredictable stress before pregnancy on the postpartum behavior and neurobiology of themselves and their progency

    Institute of Scientific and Technical Information of China (English)

    刘彬; 王克; 董继承; 郑占杰; 姜桂兰

    2013-01-01

    Objective To determine the effects of maternal rats exposed to chronic unpredictable stress before pregnancy on the behavior and neurobiology of the mother and their offspring.Methods Two-month Virgin female Sprague-Dawley(SD) rats were applied to study.Females were housed with sexually experienced males (ratio 3:1) for propagation after 21-day chronic unpredictable stress.The behaviors of rats and their two-month-offspring were tested.The two-month rats were injected intraperitoneally with BrdU,then the brains were removed and 20 μm frozen sections were used to detect the neurogenesis of hippocampus.Results 1.Open field test:after lactation,CUS + Pre group ((720.52 ± 238.99) cm),CUS group ((995.62 ± 191.77) cm),CON group ((464.95 ±210.11)cm) and CON + Pre group((740.76 ± 281.48)cm) had statistic difference in total distance(P < 0.05).The total distance((1281.10 ±247.89)cm) and border distance((1153.20 ±238.19)cm) in female two-monthprogeny were higher than these in male two-month-progeny ((1074.70 ± 263.35) cm,(957.28 ± 82.94) cm) in CUS + Pre group (P < 0.05).2.Sucrose consumption test:after lactation,the sucrose intake ((13.00 ± 3.46) g)and sucrose consumption percentage((87.00 ±9.01)%) in CUS + Pre group were higher than that in CUS group ((8.13 ± 3.36) g,(79.06 ± 6.45) %,P < 0.05).The sucrose intake ((12.43 ± 3.31) g) and sucrose consumption percentage((86.90 ± 5.80)%) in CON group were higher than that in CUS group ((8.13 ± 3.36) g,(79.06 ± 6.45) %,P < 0.05).The sucrose intake ((14.71 ± 4.39) g) and sucrose consumption percentage ((91.54 ± 1.89) %) in CON + Pre group were significantly higher than those in CUS group ((8.13 ± 3.36) g,(79.06 ± 6.45) %) (P < 0.01).3.Immunohistochemistry:there was no statistic difference on the new neuron in dentate gyrus of hippocampus in both female and male two-month-progeny of CUS group and CON group((1.18 ±0.37) cells,(1.24 ± 0.41) cells,(1.38 ± 0.47) cells,(1.41 ± 0.35) cells

  15. Sex-Dependent Changes in Striatal Dopamine Transport in Preadolescent Rats Exposed Prenatally and/or Postnatally to Methamphetamine.

    Science.gov (United States)

    Sirova, Jana; Kristofikova, Zdenka; Vrajova, Monika; Fujakova-Lipski, Michaela; Ripova, Daniela; Klaschka, Jan; Slamberova, Romana

    2016-08-01

    Methamphetamine (MA) is the most commonly used psychostimulant drug, the chronic abuse of which leads to neurodegenerative changes in the brain. The global use of MA is increasing, including in pregnant women. Since MA can cross both placental and haematoencephalic barriers and is also present in maternal milk, children of chronically abused mothers are exposed prenatally as well as postnatally. Women seem to be more vulnerable to some aspects of MA abuse than men. MA is thought to exert its effects among others via direct interactions with dopamine transporters (DATs) in the brain tissue. Sexual dimorphism of the DAT system could be a base of sex-dependent actions of MA observed in behavioural and neurochemical studies. Possible sex differences in the DATs of preadolescent offspring exposed to MA prenatally and/or postnatally have not yet been evaluated. We examined the striatal synaptosomal DATs (the activity and density of surface expressed DATs and total DAT expression) in preadolescent male and female Wistar rats (31-35-day old animals) exposed prenatally and/or postnatally to MA (daily 5 mg/kg, s.c. to mothers during pregnancy and lactation). To distinguish between specific and nonspecific effects of MA on DATs, we also evaluated the in vitro effects of lipophilic MA on the fluidity of striatal membranes isolated from preadolescent and young adult rats of both sexes. We observed similar changes in the DATs of preadolescent rats exposed prenatally or postnatally (MA-mediated drop in the reserve pool but no alterations in surface-expressed DATs). However, prenatal exposure evoked significant changes in males and postnatal exposure in females. A significant decrease in the activity of surface-expressed DATs was found only in postnatally exposed females sensitized to MA via prenatal exposure. MA applied in vitro increased the fluidity of striatal membranes of preadolescent female but not male rats. In summary, DATs of preadolescent males are more sensitive to

  16. Chronic study on BHT in rats

    DEFF Research Database (Denmark)

    Würtzen, G.; Olsen, P.

    1986-01-01

    Groups of 40, 29, 39 and 44 F0 rats of each sex were fed a semi-synthetic diet containing butylated hydroxytoluene (BHT) in concentrations to provide intakes of 0, 25, 100 or 500 mg/kg body weight/day, respectively. The F0 rats were mated, and groups of 100, 80, 80 and 100 F1 rats of each sex were...... formed. After weaning, the highest dose of BHT was lowered to 250 mg/kg/day for the F1 rats. At weaning the BHT-treated F1 rats, especially the males, had lower body weights than the controls and the effect was dose related. The survival of the BHT-treated rats of both sexes was higher than that of the...... controls. Dose-related increases in the numbers of hepatocellular adenomas and carcinomas were statistically significant in male F1 rats when all groups together were tested for heterogeneity or analysis for trend. The increases in hepatocellular adenomas and carcinomas in treated female F1 rats were only...

  17. Differential oxidative stress and DNA damage in rat brain regions and blood following chronic arsenic exposure.

    Science.gov (United States)

    Mishra, D; Flora, S J S

    2008-05-01

    Chronic arsenic poisoning caused by contaminated drinking water is a wide spread and worldwide problem particularly in India and Bangladesh. One of the possible mechanisms suggested for arsenic toxicity is the generation of reactive oxygen species (ROS). The present study was planned 1) to evaluate if chronic exposure to arsenic leads to oxidative stress in blood and brain - parts of male Wistar rats and 2) to evaluate which brain region of the exposed animals was more sensitive to oxidative injury. Male Wistar rats were exposed to arsenic (50A ppm sodium arsenite in drinking water) for 10A months. The brain was dissected into five major parts, pons medulla, corpus striatum, cortex, hippocampus, and cerebellum. A number of biochemical variables indicative of oxidative stress were studied in blood and different brain regions. Single-strand DNA damage using comet assay was also assessed in lymphocytes. We observed a significant increase in blood and brain ROS levels accompanied by the depletion of GSH/GSSG ratio and glucose-6-phosphate dehydrogenase (G6PD) activity in different brain regions of arsenic-exposed rats. Chronic arsenic exposure also caused significant single-strand DNA damage in lymphocytes as depicted by comet with a tail in arsenic-exposed cells compared with the control cells. On the basis of results, we concluded that the cortex region of the brain was more sensitive to oxidative injury compared with the other regions studied. The present study, thus, leads us to suggest that arsenic induces differential oxidative stress in brain regions with cortex followed by hippocampus and causes single-strand DNA damage in lymphocytes.

  18. Chronic contamination with 137Cesium affects Vitamin D3 metabolism in rats

    International Nuclear Information System (INIS)

    Twenty years after Chernobyl disaster, many people are still chronically exposed to low dose of 137Cs, mainly through the food consumption. A large variety of diseases have been described in highly exposed people with 137Cs, which include bone disorders. The aim of this work was to investigate the biological effects of a chronic exposure to 137Cs on Vitamin D3 metabolism, a hormone essential in bone homeostasis. Rats were exposed to 137Cs in their drinking water for 3 months at a dose of 6500 Bq/l (approximately 150 Bq/rat/day), a similar concentration ingested by the population living in contaminated territories in the former USSR countries. Cytochromes P450 enzymes involved in Vitamin D3 metabolism, related nuclear receptors and Vitamin D3 target genes were assessed by real time PCR in liver, kidney and brain. Vitamin D, PTH, calcium and phosphate levels were measured in plasma. An increase in the expression level of cyp2r1 (40%, p 137Cs-exposed rats. However a significant decrease of Vitamin D (1,25(OH)D3) plasma level (53%, p = 0.02) was observed. In brain, cyp2r1 mRNA level was decreased by 20% (p 137Cs contamination. In conclusion, this study showed for the first time that chronic exposure with post-accidental doses of 137Cs affects Vitamin D3 active form level and induces molecular modifications of CYPs enzymes involved its metabolism in liver and brain, without leading to mineral homeostasis disorders

  19. Alterations in the Masseter Muscle and Plasma IL-6 Level Following Experimentally Induced Occlusal Interference and Chronic Stress – A Study in Rats

    OpenAIRE

    Simonić-Kocijan, Sunčana; Uhač, Ivone; Tariba, Petra; Fugošić, Vesna; Kovačević Pavičić, Daniela; Lajnert, Vlatka; Braut, Vedrana

    2012-01-01

    This study was undertaken to examine the alteration of masseter and plasma interleukin-6 after inducing occlusal interference and chronic stress. Male Wistar rats were submitted to chronic stress procedure, exposed to occlusal interference, or exposed to both mentioned procedures. Whole blood and masseter tissue were collected to determine interleukin-6 level, measured by means of ELISA. Masseter pain was evaluated using the orofacial formalin test. Masseter interleukin- 6 level w...

  20. Chronic effects of mercuric chloride ingestion on rat adrenocortical function

    Energy Technology Data Exchange (ETDEWEB)

    Agrawal, R.; Chansouria, J.P.N. (Banaras Hindu Univ., Varanasi (India))

    1989-09-01

    Mercurial contamination of environment has increased. Mercury accumulates in various organs and adversely affects their functions. Some of the most prominent toxic effects of inorganic mercury compounds include neurotoxicity, hepatotoxicity and nephrotoxicity. Besides this, mercury has also been reported to affect various endocrine glands like pituitary, thyroid, gonadal and adrenal glands. There have been no reports on the toxic effects of chronic oral administration of varying doses of mercuric chloride on adrenocortical function in albino rats. The present work was undertaken to study the adrenocortical response to chronic oral administration of mercuric chloride of varying dose and duration in albino rats.

  1. Effect of diosmin on chronic nonbacterial prostatitis caused by pelvic congestion in rats

    Directory of Open Access Journals (Sweden)

    Gong-ting CUI

    2014-08-01

    Full Text Available Objective To explore the effect of diosmin on chronic nonbacterial prostatitis (CNP in rats and its possible mechanisms. Methods Thirty-two healthy adult male SD rats were randomly divided into 4 groups: Sham-operated group (SO group, chronic prostatitis model group (CPM group, chronic prostatitis model + prostat treatment group (CPM-P group, and chronic prostatitis model + diosmin treatment group (CPM-D group. Rats in SO group underwent laparotomy only to expose the prostate, and those in other groups received prostatic vein ligation to reproduce pelvic congestion. HE staining was used for the examination of the prostate 35 days after the operation. 80mg/(kg.d of diosmin was given to the rats in CPM-D group, and 60mg/(kg.d of diosmin to the rats in CPM-P group twice a day by gavage for 7 days. Same volume of 5% acacia gum was given to rats in SO and CPM groups. All of the rats were sacrificed 1h after the last administration, and the serum levels of interleukin-10 (IL-10, IL-8, IL-1β, malondialdehyde (MDA, nitric oxide (NO were determined by ELISA, and the pathological changes in the prostate tissue were observed after HE staining and compared between the groups. Results The serum levels of IL-1β, IL-8 and NO were significantly lower in CPM-D group and CPM-P group than in CPM group (P<0.05, the serum level of IL-10 was significantly higher in CPM-D group and CPM-P group than in CPM group (P<0.05, and the serum MDA level was similar between the 3 groups. HE staining showed that chronic inflammatory changes in rats' prostate were reduced more significantly in CPM-P group and CPM-D group than in CPM group. Conclusion The therapeutic effect of diosmin on pelvic-congestion-induced chronic prostatitis is similar to that of prostat tablets, and its mechanism may be related to the alleviation of local inflammatory response by reducing the IL-1β, IL-8 and NO levels and increasing the IL-10 content in serum. DOI: 10.11855/j.issn.0577-7402.2014.06.04

  2. α-硫辛酸和维生素C对慢性砷染毒大鼠氧化应激的保护作用%Effects of α-lipoic acid and vitamin C on oxidative stress in rat exposed to chronic arsenic toxicity

    Institute of Scientific and Technical Information of China (English)

    刘重斌; 冯彦红; 叶光华; 肖敏

    2010-01-01

    饮水砷毒性有重要作用.%Objective To explore arsenic-induced oxidative stress and the protective efficacy of α-lipoic acid and vitamin c.Methods 50 male SD rats were randomly divided into 5 groups.Ten rats(the control group)were exposed to deionized water for 6 weeks, and the others were alone exposed to sodium arsenite (50 mg/L water)for 6 weeks, at the same time, three group rats were administered intragastrically(I.g.)with α-lipoic acid 10 mg· kg-1· d-1 and vitamin C 25 mg· kg-1· d-1 either alone or in combination.At the end of experiment, blood was drawn from abdominal aorta, and then the blood, brain and liver of rats were used for biochemical assays, including blood glutathione(GSH), δ-aminolevulinic acid dehydratase(δ-ALAD), reactive oxygen species(ROS)and oxidized glutathione(GSSG)level.At the same time, the super oxide dismutase(SOD)activity, glutathione peroxidase(GSH-Px)activity, catalase(CAT)activity, ATPase activity of brain and liver were determined.The caspase activity of brain were also determined.Results There were a significant increase in ROS level(P<0.05), but a significant decrease in δ-ALAD activity(P<0.01)in the chronic arsenic toxicity model group compared with the control group.These alterations were marginally restored by co-administration of vitamin C and α-lipoic acid individually, while significant recovery was observed in the animals supplemented with both the antioxidants together with arsenite in rat(P<0.05).At the same time, there was a significant increase in the ROS and TBARS level of the brain and liver(P<0.05), and caspase activity of the brain(P<0.05), while there was a significant decrease in antioxidant enzymes and ATPase activity on arsenite exposure in rats(P<0.05).These alterations were also marginally restored by co-administration of vitamin C and α-lipoic acid individually, while significant recovery was observed in the animals supplemented with both the antioxidants together with arsenite

  3. Immune Alterations in Rats Exposed to Airborne Lunar Dust

    Science.gov (United States)

    Crucian, Brian; Quiriarte, Heather; Nelman, Mayra; Lam, Chiu-wing; James, John T.; Sams, Clarence

    2014-01-01

    The lunar surface is covered by a layer of fine, reactive dust. Very little is known regarding the toxicity of lunar dust on human physiology. This study assessed the toxicity of airborne lunar dust exposure in rats on pulmonary and systemic immune parameters.

  4. Psychophysical Evaluation of Achromatic and Chromatic Vision of Workers Chronically Exposed to Organic Solvents

    OpenAIRE

    Luiz Carlos de Lima Silveira; Dora Fix Ventura; Lauro José Barata de Lima; Cláudio Eduardo Correa Teixeira; Anderson Raiol Rodrigues; Eliza Maria da Costa Brito Lacerda; Monica Gomes Lima

    2012-01-01

    The purpose of this paper was to evaluate achromatic and chromatic vision of workers chronically exposed to organic solvents through psychophysical methods. Thirty-one gas station workers (31.5 ± 8.4 years old) were evaluated. Psychophysical tests were achromatic tests (Snellen chart, spatial and temporal contrast sensitivity, and visual perimetry) and chromatic tests (Ishihara's test, color discrimination ellipses, and Farnsworth-Munsell 100 hue test—FM100). Spatial contrast sensitivities of...

  5. Lung responses to secondary endotoxin challenge in rats exposed to pig barn air

    Directory of Open Access Journals (Sweden)

    Townsend Hugh GG

    2008-10-01

    Full Text Available Abstract Background Swine barn air contains endotoxin and many other noxious agents. Single or multiple exposures to pig barn air induces lung inflammation and loss of lung function. However, we do not know the effect of exposure to pig barn air on inflammatory response in the lungs following a secondary infection. Therefore, we tested a hypothesis that single or multiple exposures to barn air will result in exaggerated lung inflammation in response to a secondary insult with Escherichia coli LPS (E. coli LPS. Methods We exposed Sprague-Dawley rats to ambient (N = 12 or swine barn air (N = 24 for one or five days and then half (N = 6/group of these rats received intravenous E. coli LPS challenge, observed for six hours and then euthanized to collect lung tissues for histology, immunohistochemistry and ELISA to assess lung inflammation. Results Compared to controls, histological signs of lung inflammation were evident in barn exposed rat lungs. Rats exposed to barn air for one or five days and challenged with E. coli LPS showed increased recruitment of granulocytes compared to those exposed only to the barn. Control, one and five day barn exposed rats that were challenged with E. coli LPS showed higher levels of IL-1β in the lungs compared to respective groups not challenged with E. coli LPS. The levels of TNF-α in the lungs did not differ among any of the groups. Control rats without E. coli LPS challenge showed higher levels of TGF-β2 compared to controls challenged with E. coli LPS. Conclusion These results show that lungs of rats exposed to pig barn air retain the ability to respond to E. coli LPS challenge.

  6. Metabolic effects of chronic ozone exposure on rats

    Energy Technology Data Exchange (ETDEWEB)

    Hathway, J.A.; Terrill, R.E.

    1962-01-01

    Rats were exposed to 0.8 to 1.5 ppm O/sub 3/ for 6 hr/day, 4 days/wk for 19 weeks. Lower titratable acidity after 91 days exposure and higher urine pH after 98 days exposure were observed. No significant differences in urine creatine, creatinine, uric acid/creatinine, or amino acid/creatinine were observed. pH differences suggest respiratory alkalosis, possibly due to subjectively noticed hyperventilation in exposed group.

  7. Ethology assessment and detection of serum GPX-3 levels in rat model of depression induced by chronic unpredictable mild stress

    Directory of Open Access Journals (Sweden)

    Chang-qiang ZHU

    2013-09-01

    Full Text Available Objective To investigate the ethological changes and detect the serum level of glutathione peroxidase (GPX-3 in a rat model of primary and recurrent depression induced by chronic unpredictable mild stress (CUMS. Methods Rats were divided into four groups: group 1(normal feeding, group 2 (CUMS, group 3 (normal + saline + normal feeding and group 4 (CUMS + fluoxetine + CUMS. The behavior of rats in the four groups was assessed by sucrose preference test and open field test. GPX-3 concentration in serum was measured by ELISA. Results A four-week of CUMS was successful in inducing a significant decrease in sucrose preference and locomotor activity in rats in treatment groups (group 2 and 4 in contrast with that of control groups (group 1 and 3 (P<0.01. After 3 weeks of fluoxetine treatment, no obvious difference was found in rats between the group 4 and group 3 in the degree of sucrose preference and locomotor activity. Subsequently, after the treated rats were re-exposed to CUMS for 4 weeks, a significant difference was found again in sucrose preference test (P<0.01 and open field test in comparison with control group (P<0.05. GPX-3 levels in the rats exposed and re-exposed to CUMS were significantly higher than those in control groups (P<0.01. Conclusions CUMS may induce depression-like symptoms in rats, and fluoxetine can alleviate the symptoms induced by CUMS. The increase in GPX-3 concentration may reduce the level of oxidative stress in depression-like rats exposed and re-exposed to CUMS, accordingly it plays a protective role in these rats.

  8. Health status of grandchildren of subjects occupationally exposed to chronic radiation. Communication 4. Congenital developmental defects

    International Nuclear Information System (INIS)

    The purpose of this study was to analyze the incidence and structure of cogenital developmental defects in the grandchildren of subjects occupationally exposed to chronic external gamma-irradiation. For 830 children only grandfather was exposed, for 259 only grandmother, and for 468 grandfather and grandmother. The mean equivalent doses for gonads by the moment of conception of future parents of the cohort examined ranged from 17.3 to 145.3 sSv. The incidence and structure of congenital developmental defects in 1557 grandchildren of occupationally exposed subjects differed from that in controls. Multifactorial analysis failed to establish the effect of grandparents' and parents' exposure on the development of diseases in the progeny. Factors other than radiation proved to be significant. 13 refs.; 1 tab

  9. Micronucleated Erythrocytes in Newborn Rats Exposed to Raltegravir Placental Transfer

    Science.gov (United States)

    Torres-Mendoza, Blanca Miriam; Coronado-Medina, Damharis Elizabeth; Vázquez-Valls, Eduardo; Zamora-Perez, Ana Lourdes; Lemus-Varela, María de Lourdes

    2014-01-01

    The use of raltegravir in treating HIV/AIDS has been proposed due to its effectiveness in suppressing high loads of HIV RNA in pregnant women, thus preventing infection of the fetus. However, administration of raltegravir during pregnancy produces a compound which is transferred to high concentrations to the offspring. The objective of this study is to evaluate the transplacental genotoxic effect of raltegravir in newborn rats. We evaluated the number of micronucleated erythrocytes (MNE), micronucleated polychromatic erythrocytes (MNPCE), and polychromatic erythrocytes (PCE) in the peripheral blood samples of the offspring of Wistar rats treated 6 days before birth with oral administration of raltegravir. The animals were randomly assigned to five groups as follows: raltegravir at doses of 15, 30, or 60 mg/day, cyclophosphamide 10 mg/kg (positive control), or 0.5 ml of sterile water (negative control). In addition, the effect of these drugs on the weight and height of newborns was assessed. There were no differences in the number of MNE, MNPCE, and PCE, and a slight decrease in the weight and height was observed in the offspring of the rat mothers treated with raltegravir. Genotoxicity studies are required in pregnant women to determine the risk of using raltegravir to the fetuses. PMID:24977162

  10. Gene Expression Profiling in Lung Tissues from Rat Exposed to Lunar Dust Particles

    Science.gov (United States)

    Zhang, Ye; Lam, Chiu-Wing; Zalesak, Selina M.; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Scully, Robert R.; Williams, Kyle; Wu, Honglu; James, John T.

    2014-01-01

    The Moon's surface is covered by a layer of fine, reactive dust. Lunar dust contain about 1-2% of very fine dust (gene expression changes in lung tissues from rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m(exp 3) of lunar dust. Five rats per group were euthanized 1 day, and 3 months after the last inhalation exposure. The total RNAs were isolated from lung tissues after being lavaged. The Agilent Rat GE v3 microarray was used to profile global gene expression (44K). The genes with significant expression changes are identified and the gene expression data were further analyzed using various statistical tools.

  11. Chronic stress does not impair liver regeneration in rats

    DEFF Research Database (Denmark)

    Andersen, Kasper J; Knudsen, Anders Riegels; Wiborg, Ove;

    2015-01-01

    a 70 % partial hepatectomy (PHx). The animals were evaluated on postoperative day 2 or 4. Blood samples were collected to examine circulating markers of inflammation and liver cell damage. Additionally, liver tissues were sampled to evaluate liver weight and regeneration rate. RESULTS: None......BACKGROUND: Although wound healing is a simple regenerative process that is critical after surgery, it has been shown to be impaired under psychological stress. The liver has a unique capacity to regenerate through highly complex mechanisms. The aim of this study was to investigate the effects...... of chronic stress, which may induce a depression-like state, on the complex process of liver regeneration in rats. METHODS: Twenty rats were included in this study. The animals received either a standard housing protocol or were subjected to a Chronic Mild Stress (CMS) stress paradigm. All rats underwent...

  12. Water metabolism in rats subjected to chronic alcohol administration

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Pohl, C.; Bode, J.C.;

    2004-01-01

    AIM: While the diuretic action of acute ingestion of alcohol has been studied extensively, the effect of chronic alcohol consumption has received less attention. The aim of the present study was to investigate the effect of chronic alcohol consumption on the balance of water intake and excretion...... and certain renal functions in rats during a period of 12 months. ANIMALS AND STUDY DESIGN: Male Wistar rats received either alcohol (15% v/v; group A, n = 65) or tap water (group C, n = 35) as drinking fluid. Urine and faeces were collected from 6 rats of each group during 7 days, at monthly intervals......-protein/high-fat diet. The reduced urine excretion was not due to lower liquid consumption and the pattern of daily excretion of faeces was comparable with that observed for urine excretion. Both sodium and potassium excretion and the diuretic response to an acute water load were significantly reduced in group...

  13. Chronic gastritis rat model and role of inducing factors

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

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

    International Nuclear Information System (INIS)

    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 14C-arachidonic acid than rings from sham rats. Platelets from smoke-exposed rats synthesized more thromboxane (TXA2) from 14C-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

  15. Octreotide ameliorates gastric lesions in chronically mild stressed rats

    Institute of Scientific and Technical Information of China (English)

    Noha N Nassar; Mona F Schaalan; Hala F Zaki; Dalaal M Abdallah

    2011-01-01

    AIM: To evaluate the effect of chronic mild stress (CMS) on the emergence of gastric ulcers and possible modulation by octreotide, a synthetic somatostatin analogue. METHODS: Adult male Wistar rats were subjected to nine different unpredictable random stress procedures for 21 d, a multifactorial interactional animal model for CMS. Octreotide was administered daily for 21 d at two dose levels (50 and 90 μg/kg) before exposure to stress procedure. Macro-and microscopical assessments were made, in addition to quantification of plasma corticosterone and gastric mucosal inflammatory, oxidative stress, and apoptotic biomarkers. RESULTS: Exposure to CMS elevated plasma corticosterone (28.3 ± 0.6 μg/dL, P = 0.002), an event that was accompanied by gastric lesions (6.4 ± 0.16 mm,P = 0.01) and confirmed histopathologically. Moreover, the insult elevated gastric mucosal lipid peroxides (13 ± 0.5 nmol/g tissue, P = 0.001), tumor necrosis factor-α(3008.6 ± 78.18 pg/g tissue, P < 0.001), prostaglandin E2 (117.1 ± 4.31 pg/g tissue, P = 0.002), and caspase-3 activity (2.4 ± 0.14 OD/mg protein, P = 0.002). Conversely, CMS mitigated interleukin-10 (627.9 ± 12.82 pg/g tissue, P = 0.001). Furthermore, in animals exposed to CMS, octreotide restored plasma corticosterone (61% and 71% from CMS, P = 0.002) at both dose levels. These beneficial effects were associated with a remarkable suppression of gastric lesions (38% and 9% from CMS, P = 0.01) and reversal of derangements in gastric mucosa. CONCLUSION: The current investigation provides evidence that exposure to CMS induces gastric ulceration, which was alleviated by administration of octreotide possibly possessing antioxidant, anti-inflammatory, and anti-apoptotic actions.

  16. Chronic Voluntary Ethanol Consumption Induces Favorable Ceramide Profiles in Selectively Bred Alcohol-Preferring (P Rats.

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    Jessica Godfrey

    Full Text Available Heavy alcohol consumption has detrimental neurologic effects, inducing widespread neuronal loss in both fetuses and adults. One proposed mechanism of ethanol-induced cell loss with sufficient exposure is an elevation in concentrations of bioactive lipids that mediate apoptosis, including the membrane sphingolipid metabolites ceramide and sphingosine. While these naturally-occurring lipids serve as important modulators of normal neuronal development, elevated levels resulting from various extracellular insults have been implicated in pathological apoptosis of neurons and oligodendrocytes in several neuroinflammatory and neurodegenerative disorders. Prior work has shown that acute administration of ethanol to developing mice increases levels of ceramide in multiple brain regions, hypothesized to be a mediator of fetal alcohol-induced neuronal loss. Elevated ceramide levels have also been implicated in ethanol-mediated neurodegeneration in adult animals and humans. Here, we determined the effect of chronic voluntary ethanol consumption on lipid profiles in brain and peripheral tissues from adult alcohol-preferring (P rats to further examine alterations in lipid composition as a potential contributor to ethanol-induced cellular damage. P rats were exposed for 13 weeks to a 20% ethanol intermittent-access drinking paradigm (45 ethanol sessions total or were given access only to water (control. Following the final session, tissues were collected for subsequent chromatographic analysis of lipid content and enzymatic gene expression. Contrary to expectations, ethanol-exposed rats displayed substantial reductions in concentrations of ceramides in forebrain and heart relative to non-exposed controls, and modest but significant decreases in liver cholesterol. qRT-PCR analysis showed a reduction in the expression of sphingolipid delta(4-desaturase (Degs2, an enzyme involved in de novo ceramide synthesis. These findings indicate that ethanol intake levels

  17. Micronuclei rate and hypoxanthine phosphoribosyl transferase mutation in radon-exposed rats

    Institute of Scientific and Technical Information of China (English)

    Fengmei Cui; Saijun Fan; Mingjiang Hu; Jihua Nie; Hongmei Li; Jian Tong

    2008-01-01

    The genetic changes in rats with radon exposure were studied by the micronucleus technology and detection of hypoxanthine phosphoribosyl transferase (hprt) mutations.The rate of the micronuclei in peripheral blood lymphocytes and tracheal-bronchial epithelial cells in the radon-inhaled rats was higher than that of the controls (P < 0.05).A similar result was obtained from the hprt assay,which showed a higher mutation frequency in radon-exposed rats.Our results suggested that micronuclei rate and hprt deficiency could be used as biomarkers for the genetic changes with radon exposure.

  18. 慢性间歇低氧对大鼠肝脏的损伤及4-羟基-2,2,6,6-四甲基哌啶的干预作用%Hepatic injury in rats exposed to chronic intermittent hypoxia and the effect of tempol

    Institute of Scientific and Technical Information of China (English)

    姜秋芳; 陈宝元; 董丽霞; 林慧; 孔铖英; 张静; 郑立文

    2012-01-01

    Objective To investigate the mechanism of liver injury in rats exposed to chronic intermittent hypoxia (CIH) and to investigate the effect of tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl or 4-hydroxy-TEMPO).Methods A CIH animal model of rats was established to mimic the intermittent hypoxia/re-oxygenation(IH/ROX) of obstructive sleep apnea syndrome in humans.Thirty-two healthy male Wistar rats were randomly assigned to 4 groups:conventional intermittent hypoxia group( CIH group),intermittent hypoxia Tempol treatment group ( CIH + T group),intermittent hypoxia normal saline matched group( CIH + NS group),and normoxic control group( NC group),with 8 rats in each group.The frequency of every CIH group was 30 times/h,and the minimum oxygen concentration was 5%.After the experiment,sections of liver were stained with hematoxylin-eosin ( HE ) and the levels of nuclear factor-kappaB (NF-tcB),glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) in rat liver homogenate were measured.Results Liver histology revealed that the C1H group and the CIH + NS group showed hepatocellular swelling with rarefaction of the cytoplasm,hyperchromatosis and hepatocellular membrane disruption,but the liver histology of the CIH + T group and the NC group was normal.Compared with the NC group,the levels of NF-κB and MDA in the CIH group [ (12.4 ±2.0) ng/g,(101 +22) μ,mol/g]and the CIH + NS group [ ( 12.2 ± 1.9 ) ng/g,( 99 ± 18 ) μmol/g] were increased( all P < 0.05 ),but the activities of GSH-PX [ ( 88 ± 17 ) U/mg,(90 + 15 ) U/mg ] were decreased ( all P < 0.05 ).Compared with the CIH + NS group and the CIH group,the activity of GSH-PX in the CIH + T group [ ( 181 + 29 ) U/mg ]was increased(P <0.05),but the levels of NF-κB [ (7.8 ± 1.3) ng/g] and MDA [ (59 ± 10) μmol/g]were decreased(all P < 0.05 ).The levels of GSH-PX and MDA in the CIH + T group were not significantly different compared to the NC group ( P were 0.242,0.177 respectively),but the level of NF

  19. Effects of Chronic Exposure to Sodium Arsenate on Kidney of Rats

    Directory of Open Access Journals (Sweden)

    Namdar Yousofvand

    2015-09-01

    Full Text Available Background: In the present study, histopathological effects of chronic exposure to sodium arsenate in drinkable water were studied on a quantity of organs of rat. Methods: Rats were divided into two groups, group I; served as control group, were main-tained on deionized drinkable water for 2 months, and group II; the study group were given 60 g/ml of sodium arsenate in deionized drinkable water for 2 months. Blood and urine samples from two groups of animals were collected under anesthesia and the animals were sacrificed under deep anesthesia (a-chloralose, 100 mg/kg, I.P. Their kidney, liver, aorta, and heart were dissected out and cleaned of surrounding connective tissue. The organs were kept in formaldehyde (10% for histopathologic examination. Serum and urine samples from two groups were collected and analyzed for arsenic level. Total quantity of arsenic in serum and urine of animal was measured through graphic furnace atomic absorption spectrometry (GF-AAS. Results:Examination with light microscopy did not show any visible structural changes in the aorta, myocardium, and liver of chronic arsenic treated animals.However, a significant effect was observed in the kidneys of chronic arsenic treated rats showing distinct changes in proxi-mal tubular cells. There was high concentration of arsenic in serum and urine of arsenic ex-posed animals (group II significantly (P<0.001. Conclusion:Swollen tubular cells in histopathologic study of kidney may suggest toxic effects of arsenic in the body.

  20. Effects of glutamine pretreatment on learning and memory in heat-exposed rats

    Institute of Scientific and Technical Information of China (English)

    Shenghao Zhao; Lei Wang; Qin Wang; Siyi Wang; Chundi Deng; Xianfei Xie; Youe Yan; Hui Wang

    2008-01-01

    BACKGROUND: Glutamine (Gln) pretreatment can protect neural cells from injuries due to heat, ischemia, hypoxia, endotoxemia, and inflammatory factors.OBJECTIVE: To observe the effects of Gln pretreatment on learning and memory, survival time, and rectal temperature in heat-exposed rats.DESIGN, TIME AND SETTING: The present randomized grouping, neurobehavioral experiment was performed at the Laboratory of Department of Pharmacology, Basic School of Medicine, Wuhan University between March and September 2007.MATERIALS: Twenty-four healthy, Wistar rats were included in this study. SPX-160B biochemistry incubator (Shanghai Experimental Equipment Co., Ltd., China), probe electronic thermometer (11000 type, Maikepai Science and Technology Co., Ltd., China), Y-type maze box used in conjunction with MG-2 maze stimulator (Zhangjiagang Biomedical Instrument Factory, China), L-Gin (Batch No. 061218, 5 g/bottle, prepared into 10% aqueous solution, Amresco Company, USA) were used.METHODS: Twenty-four rats were randomly and evenly divided into 3 groups: heat-exposed, Gln low-lose, and Gln high-dose. Following learning and memory testing with the Y-maze, rats in the heat-exposed group were subjected to heat injury (40.5-41.5℃) in a biochemistry incubator. Rectal temperature was measured every 5 minutes. Thirty-five minutes after heat exposure, rats were removed and placed in the Y-type maze to test learning and memory again. Subsequently, the rats were returned to the same environment of thermal stimulation until they died. Rat survival time was recorded. Subsequent to learning and memory testing, rats in the Gln low-dose and high-dose groups received an i.p. injection of Gln (0.4 g/kg and 0.8 g/kg, respectively), and were exposed to heat injury. The remaining experimental procedures remained the same as for the heat-exposed group.MAIN OUTCOME MEASURES: Rat learning and memory, rectal temperature, and survival time in heat exposure environment.RESULTS: (1) In the Y

  1. Peripheral effect of NMDA receptor antagonists on adult rats exposed to neonatal colon pain

    Institute of Scientific and Technical Information of China (English)

    ChunLin; ElieD.Al-Chaer

    2004-01-01

    AIM: Previous work done by Al-Chaer' s lab has shown that colon irritation (CI) in neonates can lead to chronic visceral hypersensitivity in adult rats, with characteristics of visceral allodynia and hyperalgesia, associated with central neuronal sensitization in the absence of identifiable peripheral pathology (Al-Chaer et al. 2000) . The pathogenesis of

  2. The health status of grandchildren of subjects occupationally exposed to chronic radiation. Communication 2. Morphofunctional parameters

    International Nuclear Information System (INIS)

    The study was aimed at investigation of the parameters of physical development and specific features in the development of psychomotor habits and peripheral blood parameters in children aged 0 to 7 grandchildren of exposed individuals. A dynamic follow-up of physical and psychomotor development, as well as regular check-ups of peripheral blood were carried out in 877 grandchildren of test subjects occupationally exposed to chronic radiation before conception. Multifactorial analysis did not show a correlation between the deviations in the physical development of children in the studied cohort and exposure of their grandparents and/or parents. Factors other than radiation (poor health status of mother, gestosis) did influence the studied parameters. The mean levels of hemoglobin, red cells, platelets, and leukocytes in the test group were virtually the same as in controls and coincided with published data

  3. [Symptoms of atopy in persons exposed to chronic immunosuppression of polycyclic aromatic hydrocarbons].

    Science.gov (United States)

    Szczeklik, J; Kowalczyk, E; Gałuszka, Z

    1995-01-01

    The frequency of the atopy symptoms was estimated in 126 coke oven workers chronically exposed to polycyclic aromatic hydrocarbons (PAHs). The assessment was based on questionnaire, point skin tests with the allergens of dust, feathers, mould grass as well as on the measurements of total blood serum IgE concentration. The control group was consisted of 75 men, workers of cold rolling mill division where the environmental conditions were much better. It was observed that positive questionnaire data and positive skin tests were significantly less frequent in men exposed to PAHs. The men serum IgE values were not statistically different in both group workers although in coke oven workers the tendency to higher IgE values was observed. It is rather suggested that more useful method might be the measurement of specific serum IgE.

  4. Internal distribution of uranium and associated genotoxic damages in the chronically exposed bivalve Corbicula fluminea

    Energy Technology Data Exchange (ETDEWEB)

    Simon, Olivier, E-mail: olivier.simon@irsn.fr [Laboratoire de Radioecologie et Ecotoxicologie, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat, 186 BP3, 13115 Saint Paul-Lez-Durance Cedex (France); Floriani, Magali; Cavalie, Isabelle; Camilleri, Virginie; Adam, Christelle; Gilbin, Rodolphe; Garnier-Laplace, Jacqueline [Laboratoire de Radioecologie et Ecotoxicologie, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat, 186 BP3, 13115 Saint Paul-Lez-Durance Cedex (France)

    2011-08-15

    Uranium (U) internal distribution and involved effects in the bivalve Corbicula fluminea have been studied after direct chronic exposure (90 d, 10 {mu}g.L-1). U distribution was assessed at the subcellular level (Metal Rich Granules -MRG-, pellets and cytosol fractions) in two main organs of the bivalve (gills and visceral mass). Micro-localisation was investigated by TEM-EDX analysis in the gills epithelium. DNA damage in gill and hemolymph samples was measured by the Comet assay. The 90-d exposure period led to a significant increase of U concentration in gills over time (x5) and a large U quantity in subcellular granules in gills. Finally, a significant increase (x2) in DNA damage was noted in exposed gills and haemocytes. This study shows that the accumulation levels and consequently the potential toxicity cannot be successfully predicted only on the basis of concentration in water or in tissues and subcellular fractions after chronic exposure. - Highlights: > Relevant information concerning the chronic impact of uranium on biota is scarce. > We study its biological speciation to explain bioavailability, accumulation, toxicity. > 80% of U accumulated was measured in the pellet fraction (organelles + granules/MRG). > Chronic exposure to U induced genetic damage in gill and haemolymph cells of the bivalve.

  5. Comparison of three methods of exposing rats to cigarette smoke

    International Nuclear Information System (INIS)

    We compared smoke composition and biological effects resulting from exposures of rats for 5 wk to cigarette smoke by nose-only intermittent (NOI), nose-only continuous (NOC) and whole-body continuous (WBC) exposure methods. Exposure concentrations and times were adjusted to achieve the same daily concentration x time product for particulate matter. There were few differences in smoke composition or biological effects among exposure modes. WBC smoke was lower in particle-borne nicotine and higher in some organic vapors and carbon monoxide than smoke in nose-only modes. Body weight was depressed less by WBC than by NOI or NOC exposures. Plasma and urine nicotine levels were higher for WBC than for NOI or NOC, suggesting greater absorption from body surfaces or by grooming. Smoke exposures increased nasal epithelial proliferation, tracheal epithelial cell transformation, chromosomal aberrations in alveolar macrophages, and lung DNA adduct levels, and caused inflammatory changes in airway fluid and slight alterations of respiratory function, but there were no significant differences among exposure modes. The results indicate that WBC exposures should produce long-term effects similar to those of nose-only exposures, but might allow increased delivery of smoke to lungs while reducing stress, acute toxicity and the manpower requirements associated with performing these experiments. (author)

  6. Rat lung macrophage tumor cytotoxin production: impairment by chronic in vivo cigarette smoke exposure.

    Science.gov (United States)

    Flick, D A; Gonzalez-Rothi, R J; Harris, J O; Gifford, G E

    1985-11-01

    Macrophages in the presence of bacteria-derived lipopolysaccharide (LPS) stimuli produce a soluble cytotoxin which is toxic to tumor cells. In this study, we examined various parameters of cytotoxin production from pulmonary lavage cells obtained from Fisher 344 cesarean-derived rats. Cultures of macrophages were derived from pulmonary lavage cells and stimulated in vitro with LPS. Cytotoxin production was assayed in vitro using an L-929 cell target assay. Pulmonary lavage preparations contained a relatively pure population of macrophages, and adherence studies revealed that nonadherent lavage cells contributed negligible amounts of cytotoxin, indicating that macrophages were responsible for cytotoxin production. After LPS stimulation, cytotoxin production became maximal within 10 h and thereafter plateaued. Doses of LPS above 0.1 microgram/ml were optimal for production, and in the absence of LPS, no cytotoxin was detected. Because cigarette smoke is the major etiological factor in the development of lung cancers and because smoking is known to profoundly alter the function of alveolar macrophages in humans and experimental animals, subsequent experiments examined the role of chronic cigarette smoke exposure on tumoricidal activity of lung macrophages. Rats were exposed in vivo for 8 wk to either cigarette smoke or air (sham-treated controls). When lavage cells were cultured and stimulated with LPS (1 microgram/ml), 5- to 10-fold less cytotoxin was produced by lavage cells from rats exposed to cigarette smoke. Similarly, using a direct cytotoxicity assay, lung macrophages of smoke-exposed animals also revealed marked impairment in cytotoxicity against L-929 cell targets, and this was noted over a wide range of macrophage:tumor target cell ratios. Another product of macrophages, interferon, was also decreased in rats exposed in vivo to cigarette smoke when compared to sham-treated controls. These results suggest that cigarette smoke exposure may impair pulmonary

  7. Chronic intrathecal cannulation enhances nociceptive responses in rats

    Directory of Open Access Journals (Sweden)

    Almeida F.R.C.

    2000-01-01

    Full Text Available The influence of a chronically implanted spinal cannula on the nociceptive response induced by mechanical, chemical or thermal stimuli was evaluated. The hyperalgesia in response to mechanical stimulation induced by carrageenin or prostaglandin E2 (PGE2 was significantly increased in cannulated (Cn rats, compared with naive (Nv or sham-operated (Sh rats. Only Cn animals presented an enhanced nociceptive response in the first phase of the formalin test when low doses were used (0.3 and 1%. The withdrawal latency to thermal stimulation of a paw inflamed by carrageenin was significantly reduced in Cn rats but not in Nv or Sh rats. In contrast to Nv and Sh rats, injection in Cn animals of a standard non-steroid anti-inflammatory drug, indomethacin, either intraperitoneally or into the spinal cord via an implanted cannula or by direct puncture of the intrathecal space significantly blocked the intensity of the hyperalgesia induced by PGE2. Cannulated animals treated with indomethacin also showed a significant inhibition of second phase formalin-induced paw flinches. Histopathological analysis of the spinal cord showed an increased frequency of mononuclear inflammatory cells in the Cn groups. Thus, the presence of a chronically implanted cannula seems to cause nociceptive spinal sensitization to mechanical, chemical and thermal stimulation, which can be blocked by indomethacin, thus suggesting that it may result from the spinal release of prostaglandins due to an ongoing mild inflammation.

  8. Histopathological changes in Wistar albino rats exposed to aqueous extract of unripe Carica papaya

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    Taofeeq Oduola

    2010-05-01

    Full Text Available Background: Exposure of animals to xenobiotics may or may not trigger adverse response at cellular levels. Aqueous extract of unripe Carica papaya is consumed by sickle cell patients as antisickling agent in Western Nigeria. Aim: This study was undertaken to investigate the effects of Carica papaya on certain organs in Wister albino rats exposed to aqueous extract of unripe Carica papaya. Materials and Methods: Different doses of aqueous extract of unripe Carica papaya were administered orally daily for 42 days to six groups of rats. At the end of exposure, the animals were sacrificed and tissue sections were prepared from livers, kidneys, hearts and small intestines using standard techniques. Results: Histopathological results showed that no pathological changes were observed in tissue sections of experimental animals when compared with tissue sections of the same organs in control animals. Conclusion: No pathological changes were elicited in the organs of rats exposed to aqueous extract of unripe Carica papaya.

  9. Histopathological changes in Wistar albino rats exposed to aqueous extract of unripe Carica papaya

    Directory of Open Access Journals (Sweden)

    Taofeeq Oduola

    2010-01-01

    Full Text Available Background : Exposure of animals to xenobiotics may or may not trigger adverse response at cellular levels. Aqueous extract of unripe Carica papaya is consumed by sickle cell patients as antisickling agent in Western Nigeria. Aim : This study was undertaken to investigate the effects of Carica papaya on certain organs in Wister albino rats exposed to aqueous extract of unripe Carica papaya. Materials and Methods : Different doses of aqueous extract of unripe Carica papaya were administered orally daily for 42 days to six groups of rats. At the end of exposure, the animals were sacrificed and tissue sections were prepared from livers, kidneys, hearts and small intestines using standard techniques. Results : Histopathological results showed that no pathological changes were observed in tissue sections of experimental animals when compared with tissue sections of the same organs in control animals. Conclusion : No pathological changes were elicited in the organs of rats exposed to aqueous extract of unripe Carica papaya.

  10. Chronic subordinate colony housing (CSC as a model of chronic psychosocial stress in male rats.

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    Kewir D Nyuyki

    Full Text Available Chronic subordinate colony housing (CSC is an adequate and reliable mouse model of chronic psychosocial stress, resulting in reduced body weight gain, reduced thymus and increased adrenal weight, long-lasting anxiety-like behaviour, and spontaneous colitis. Furthermore, CSC mice show increased corticotrophin (ACTH responsiveness to acute heterotypic stressors, suggesting a general mechanism which allows a chronically-stressed organism to adequately respond to a novel threat. Therefore, the aim of the present study was to extend the CSC model to another rodent species, namely male Wistar rats, and to characterize relevant physiological, immunological, and behavioural consequences; placing particular emphasis on changes in hypothalamo-pituitary-adrenal (HPA axis responsiveness to an acute heterotypic stressor. In line with previous mouse data, exposure of Wistar rats to 19 days of CSC resulted in a decrease in body weight gain and absolute thymus mass, mild colonic barrier defects and intestinal immune activation. Moreover, no changes in stress-coping behaviour or social preference were seen; again in agreement with the mouse paradigm. Most importantly, CSC rats showed an increased plasma corticosterone response to an acute heterotypic stressor (open arm, 5 min despite displaying similar basal levels and similar basal and stressor-induced plasma ACTH levels. In contrast to CSC mice, anxiety-related behaviour and absolute, as well as relative adrenal weights remained unchanged in CSC rats. In summary, the CSC paradigm could be established as an adequate model of chronic psychosocial stress in male rats. Our data further support the initial hypothesis that adrenal hyper-responsiveness to ACTH during acute heterotypic stressors represents a general adaptation, which enables a chronically-stressed organism to adequately respond to novel challenges.

  11. Decreased Hippocampal 5-HT and DA Levels Following Sub-Chronic Exposure to Noise Stress: Impairment in both Spatial and Recognition Memory in Male Rats

    OpenAIRE

    Haider, Saida; Naqvi, Fizza; Batool, Zehra; Tabassum, Saiqa; Perveen, Tahira; Saleem, Sadia; Haleem, Darakhshan Jabeen

    2012-01-01

    Mankind is exposed to a number of stressors, and among them noise is one which can cause intense stress. High levels of background noise can severely impair one’s ability to concentrate. The present study was aimed to investigate the effect of sub-chronic noise stress on cognitive behavior and hippocampal monoamine levels in male rats. The study was performed on 12 male Wistar rats, divided into two groups; the control and noise-exposed. The rats in the test group were subjected to noise stre...

  12. DNA DAMAGE IN BUCCAL EPITHELIAL CELLS FROM INDIVIDUALS CHRONICALLY EXPOSED TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA, CHINA

    Science.gov (United States)

    The purpose of this pilot study was to assess DNA damage in buccal cells from individuals chronically exposed to arsenic via drinking water in Ba Men, Inner Mongolia. Buccal cells were collected from 19 Ba Men residents exposed to arsenic at 527.5 ? 23.7 g/L (mean ? SEM) and ...

  13. The Long Term Effects of Chronic Spinal Cord Injury on Sperm Parameters in Rats

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    MA Khalili

    2004-07-01

    Full Text Available Introduction: Spinal cord injury (SCI is a serious public health problem which seriously affects the victim, family, and even the society. Research studies have shown that 80% of SCI victims are men. In recent years, there have been extensive research works on the effect of SCI (acute and/or chronic on fertility potential of sperm and spermatogenesis in laboratory animals. SCI may disturb the spermatogenic cell lines in laboratory animals. The objective of this experimental study was to investigate the effect of chronic spinal cord injury (CSCI on sperm parameters in adult rats. Materials & Methods: Adult Wistar rats weighing between 225-275g were divided into 3groups of control (n=5, sham (n=10, and experimental CSCI (n=10. No surgery was done on control animals. Only laminectomy was done in the sham animals at T10. CSCI was developed in experimental rats using 10g weight dropped 5cm above the exposed T10 level. All animals were sacrificed 50 days post experiment to extract epididymal samples. Sperm parameters of count, motility, morphology, as well as number of round cells were evaluated with the aid of Makler chamber and Geimsa staining. Results: Progressive motility was significantly reduced in CSCI group (P<0.05. The percentage of normal morphology of spermatozoa was 99.0±1.0 in control rats which was significantly reduced to 74.90±37.64 in CSCI animals In addition, sperm counts in control and CSCI rats were 69.20±12.43 and 25.0±13.68, respectively (P<0.01. Round cell concentration was increased in CSCI group as compared to controls. Conclusion: The results suggest that reduction in parameters of progressive motility, morphology, as well as sperm count following CSCI in rats may disturb the fertility potential of spermatozoa.

  14. Effects of combined exposure of F344 rats to radiation and chronically inhaled cigarette smoke

    Energy Technology Data Exchange (ETDEWEB)

    Finch, G.L.; Nikula, K.J.; Barr, E.B. [and others

    1995-12-01

    Nuclear workers may be exposed to radiation in various forms, such as low-LET {gamma}-irradiation or {alpha}-irradiation from inhaled {sup 239}PuO{sub 2} particles. These workers may then have increased risk for lung cancer compared to the general population. Of additional concern is the possibility that interactions between radiation and other carcinogens may increase the risk of cancer induction, compared to the risks from either type of agent alone. An important and common lung carcinogen is cigarette smoke. The purpose of this project is to better determine the combined effects of chronically inhaled cigarette smoke and either inhaled {sup 239}PuO{sub 2} or external, thoracic X-irradiation on the induction of lung cancer in rats. Histologic and dosimetric evaluations of rats in the CS + {sup 239}PuO{sub 2} study continue, and the study of CS + X rays is beginning.

  15. Neuroprotective effect of estrogen after chronic spinal cord injury in ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: At present, there is still lack of effective drugs for chronic spinal cord injury, whereas it is found recently that estrogen has a neuroprotective effect on brain and spinal cord injuries.OBJECTIVE: To observe the effect of estrogen on the apoptosis of nerve cells after gradual chronic spinal cord injury in ovariectomized rats.DESIGN: A randomized controlled animal trial.SETTING: Institute of Orthopaedics, the Second Hospital of Lanzhou University.MATERIALS: Sixty-five female Wistar rats of common degree, weighing 220 - 250 g, were provided by the experimental animal center of Lanzhou University. The rats were randomly divided into sham-operated group (n =5), estrogen-treated group (n =30) and saline control group (n =30), and the latter two groups were observed at 1, 3, 7, 14, 28 and 60 days respectively, and 5 rats for each time point.METHODS: All the rats were treated with bilateral oophorectomy 2 weeks before the experiment. T10 vertebral lamina was revolved into using plastic screw. The spinal canal impingement was not induced initially. After that, the original incision was opened to expose the screw every 7 - 10 days.MAIN OUTCOME MEASURES: The apoptosis and Caspase-3 positive cells in the damaged spinal cord were detected using terminal deoxynucleotidal transferase-mediated dUTP-biotin nick end labeling (TUNEL) method and Caspase-3 immunohistochemical staining at 1, 3, 7, 14, 28 and 60 days after chronic spinal cord injury respectively.RESULTS: Totally 65 rats were used, and the deleted ones during the experiment were supplemented by others. Changes of Caspase-3 expression after spinal cord injury: In the sham-operated group, only a small amount of Caspase-3 proteins were observed in the rat spinal cord, mainly located in motor neurons of spinal cord anterior horn. In the estrogen-treated group and saline control group, positive cells expressed occasionally at 1 day postoperatively, began to increase obviously at 7 days after injury, strongly

  16. Chronic Alcohol Ingestion in Rats Alters Lung Metabolism, Promotes Lipid Accumulation, and Impairs Alveolar Macrophage Functions

    Science.gov (United States)

    Romero, Freddy; Shah, Dilip; Duong, Michelle; Stafstrom, William; Hoek, Jan B.; Kallen, Caleb B.; Lang, Charles H.

    2014-01-01

    Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. Although alcoholism has been shown to alter hepatic metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids (FAs). Furthermore, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triglycerides and free FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial type II cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and

  17. Chronic alcoholism-mediated metabolic disorders in albino rat testes

    Directory of Open Access Journals (Sweden)

    Shayakhmetova Ganna M.

    2014-09-01

    Full Text Available There is good evidence for impairment of spermatogenesis and reductions in sperm counts and testosterone levels in chronic alcoholics. The mechanisms for these effects have not yet been studied in detail. The consequences of chronic alcohol consumption on the structure and/or metabolism of testis cell macromolecules require to be intensively investigated. The present work reports the effects of chronic alcoholism on contents of free amino acids, levels of cytochrome P450 3A2 (CYP3A2 mRNA expression and DNA fragmentation, as well as on contents of different cholesterol fractions and protein thiol groups in rat testes. Wistar albino male rats were divided into two groups: I - control (intact animals, II - chronic alcoholism (15% ethanol self-administration during 150 days. Following 150 days of alcohol consumption, testicular free amino acid content was found to be significantly changed as compared with control. The most profound changes were registered for contents of lysine (-53% and methionine (+133%. The intensity of DNA fragmentation in alcohol-treated rat testes was considerably increased, on the contrary CYP3A2 mRNA expression in testis cells was inhibited, testicular contents of total and etherified cholesterol increased by 25% and 45% respectively, and protein SH-groups decreased by 13%. Multidirectional changes of the activities of testicular dehydrogenases were detected. We thus obtained complex assessment of chronic alcoholism effects in male gonads, affecting especially amino acid, protein, ATP and NADPH metabolism. Our results demonstrated profound changes in testes on the level of proteome and genome. We suggest that the revealed metabolic disorders can have negative implication on cellular regulation of spermatogenesis under long-term ethanol exposure.

  18. Disrupted NOS signaling in lymphatic endothelial cells exposed to chronically increased pulmonary lymph flow.

    Science.gov (United States)

    Datar, Sanjeev A; Gong, Wenhui; He, Youping; Johengen, Michael; Kameny, Rebecca J; Raff, Gary W; Maltepe, Emin; Oishi, Peter E; Fineman, Jeffrey R

    2016-07-01

    Associated abnormalities of the lymphatic circulation are well described in congenital heart disease. However, their mechanisms remain poorly elucidated. Using a clinically relevant ovine model of a congenital cardiac defect with chronically increased pulmonary blood flow (shunt), we previously demonstrated that exposure to chronically elevated pulmonary lymph flow is associated with: 1) decreased bioavailable nitric oxide (NO) in pulmonary lymph; and 2) attenuated endothelium-dependent relaxation of thoracic duct rings, suggesting disrupted lymphatic endothelial NO signaling in shunt lambs. To further elucidate the mechanisms responsible for this altered NO signaling, primary lymphatic endothelial cells (LECs) were isolated from the efferent lymphatic of the caudal mediastinal node in 4-wk-old control and shunt lambs. We found that shunt LECs (n = 3) had decreased bioavailable NO and decreased endothelial nitric oxide synthase (eNOS) mRNA and protein expression compared with control LECs (n = 3). eNOS activity was also low in shunt LECs, but, interestingly, inducible nitric oxide synthase (iNOS) expression and activity were increased in shunt LECs, as were total cellular nitration, including eNOS-specific nitration, and accumulation of reactive oxygen species (ROS). Pharmacological inhibition of iNOS reduced ROS in shunt LECs to levels measured in control LECs. These data support the conclusion that NOS signaling is disrupted in the lymphatic endothelium of lambs exposed to chronically increased pulmonary blood and lymph flow and may contribute to decreased pulmonary lymphatic bioavailable NO.

  19. Decreased neuron loss and memory dysfunction in pilocarpine-treated rats pre-exposed to hypoxia.

    Science.gov (United States)

    Do Val-da Silva, Raquel Araujo; Peixoto-Santos, José Eduardo; Scandiuzzi, Renata Caldo; Balista, Priscila Alves; Bassi, Mirian; Glass, Mogens Lesner; Romcy-Pereira, Rodrigo Neves; Galvis-Alonso, Orfa Yineth; Leite, João Pereira

    2016-09-22

    Preconditioning can induce a cascade of cellular events leading to neuroprotection against subsequent brain insults. In this study, we investigated the chronic effects of hypoxic preconditioning on spontaneous recurrent seizures (SRS), neuronal death, and spatial memory performance in rats subjected to pilocarpine (Pilo)-induced status epilepticus (SE). Rats underwent a short hypoxic episode (7% O2+93% N2; 30min on two consecutive days) preceding a 4-h SE (HSE group). Control groups were rats submitted to SE only (SE), rats subjected to hypoxia only (H) or normoxia-saline (C). Animals were monitored for the occurrence of SRS, and spatial memory performance was evaluated in the radial-arm maze. Hippocampal sections were analyzed for cell death and mossy fiber sprouting at 1 or 60days after SE. Compared to SE group, HSE had increased SE latency, reduced number of rats with SRS, reduced mossy fiber sprouting at 60days, and reduced cell death in the hilus and the CA3 region 1 and 60days after SE. Additionally, HSE rats had better spatial memory performance than SE rats. Our findings indicated that short hypoxic preconditioning preceding SE promotes long-lasting protective effects on neuron survival and spatial memory. PMID:27373771

  20. Effects of chronic stress on sleep in rats.

    Science.gov (United States)

    Kant, G J; Pastel, R H; Bauman, R A; Meininger, G R; Maughan, K R; Robinson, T N; Wright, W L; Covington, P S

    1995-02-01

    The present study was conducted to determine the effects of chronic stress on sleep using a rodent paradigm of around-the-clock signalled intermittent foot shock in which some rats can pull a chain to avoid/escape shock while another group of rats is yoked to the first group. We measured sleep using telemetry; four-channel EEG was collected 24 h/day in rats during 2 prestress days; days 1, 2, 3, 7, and 14 during chronic stress; and 3 poststress days. States of REM sleep, non-REM (NREM) sleep, and waking were scored for each 15-s period of the EEG recordings. During the prestress period, rats slept (REM plus NREM) 55% of available time during the light hours and 34% of the dark hours with the remainder represented by waking. On the first day of stress, total sleep and, especially REM sleep, decreased markedly. By the second day of stress, only REM sleep in the controllable stress group (but not the uncontrollable stress group) was still significantly decreased compared to prestress levels, and REM sleep returned to baseline levels by day 7 of stress. The recovery of sleep quantity was accomplished by increased sleep during the dark hours, resulting in a long-lasting disruption of normal circadian sleep patterning.

  1. Slimmer or fertile? Pharmacological mechanisms involved in reduced sperm quality and fertility in rats exposed to the anorexigen sibutramine.

    Directory of Open Access Journals (Sweden)

    Cibele S Borges

    Full Text Available Sperm acquire motility and fertility capacity during epididymal transit, under the control of androgens and sympathetic innervations. It is already known that the acceleration of epididymal sperm transit time can lead to lower sperm quality. In a previous work we showed that rats exposed to the anorexigen sibutramine, a non-selective serotonin-norepinephrine reuptake inhibitor, presented faster sperm transit time, lower epididymal sperm reserves and potentiation of the tension of epididymal duct to norepinephrine exposed acutely in vitro to sibutramine. In the present work we aimed to further investigate pharmacological mechanisms involved in these alterations and the impact on rat sperm quality. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/day or vehicle for 30 days. Sibutramine decreased final body, seminal vesicle, ventral prostate and epididymal weights, as well as sperm transit time in the epididymal cauda. On the contrary of the in vitro pharmacological assays, in which sibutramine was added directly to the bath containing strips of distal epididymal cauda, the ductal tension was not altered after in vivo sub-chronic exposure to sibutramine. However, there is pharmacological evidence that the endogenous epididymal norepinephrine reserves were reduced in these animals. It was also shown that the decrease in prostate weight can be related to increased tension developed of the gland, due to sibutramine sympathomimetic effects. In addition, our results showed reduced sperm quality after in utero artificial insemination, a more sensitive procedure to assess fertility in rodents. The epididymal norepinephrine depletion exerted by sibutramine, associated with decreases in sperm transit time, quantity and quality, leading to reduced fertility in this experimental model, reinforces the concerns about the possible impact on fertility of man taking sibutramine as well as other non-selective serotonin

  2. Evaluation of chronic chlorpyrifos-induced reproductive toxicity in male Wistar rat: protective effects of vitamin C

    OpenAIRE

    Mohammed M. Sulaiman; Mohammed Y. Fatihu; Joseph O. Ayo; Suleiman F. Ambali; Muftau Shittu; Lukuman S. Yaqub

    2013-01-01

    The aim of the present study was to evaluate the effect of vitamin C on reproductive toxicity, induced by chronic chlorpyrifos (CPF) exposure in male Wistar rats. Twenty adult male Wistar rats were divided into 4 groups of 5 animals in each group. Group I received soya oil (2 ml/kg); group II was given vitamin C only (100 mg/kg); group III was administered CPF only (10.6 mg/kg; ~1/8th LD50), while group IV was pretreated with vitamin C and then exposed to CPF, 30 min later. The regimens were ...

  3. Attenuation of the cortisol response to stress in female rainbow trout chronically exposed to dietary selenomethionine

    International Nuclear Information System (INIS)

    , abundances of transcripts of cytochrome P450 side-chain cleavage (p450scc) and cytochrome P450 11B1 (cyp11b1) were not significantly different between controls and Se-Met exposed trout. Exposure to Se-Met affected accumulation and tissue partitioning of glycogen and triglycerides in liver and muscle as concentrations of these energy reserves were greater in muscle, but not liver. Concentrations of glycogen and triglycerides in muscle, but not in liver, were lesser following the handling stressor suggesting that the muscle energy reserves are an important source of energy required for recovery from the handling stressor. The results of the study demonstrate that chronic exposure to dietary Se-Met elicits a stress response, but prevents a cortisol response to a secondary handling stressor, most likely due to cortisol inactivation. Moreover, exposure to Se-Met has effects on concentrations of energy reserves that are important for providing the energy necessary to cope with a secondary stressor.

  4. Attenuation of the cortisol response to stress in female rainbow trout chronically exposed to dietary selenomethionine

    Energy Technology Data Exchange (ETDEWEB)

    Wiseman, Steve, E-mail: steve.wiseman@usask.ca [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Thomas, Jith K.; McPhee, Landon; Hursky, Olesya; Raine, Jason C. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Pietrock, Michael [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Giesy, John P. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong (Hong Kong); School of Biological Sciences, University of Hong Kong, Hong Kong (Hong Kong); Department of Zoology, Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States); State Key Laboratory of Pollution Control and Resource Reuse and School of the Environment, Nanjing University, Nanjing (China); Hecker, Markus [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); School of Environment and Sustainability, University of Saskatchewan, Saskatoon, SK, S7N 5CB (Canada); Janz, David M. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada)

    2011-10-15

    , abundances of transcripts of cytochrome P450 side-chain cleavage (p450scc) and cytochrome P450 11B1 (cyp11b1) were not significantly different between controls and Se-Met exposed trout. Exposure to Se-Met affected accumulation and tissue partitioning of glycogen and triglycerides in liver and muscle as concentrations of these energy reserves were greater in muscle, but not liver. Concentrations of glycogen and triglycerides in muscle, but not in liver, were lesser following the handling stressor suggesting that the muscle energy reserves are an important source of energy required for recovery from the handling stressor. The results of the study demonstrate that chronic exposure to dietary Se-Met elicits a stress response, but prevents a cortisol response to a secondary handling stressor, most likely due to cortisol inactivation. Moreover, exposure to Se-Met has effects on concentrations of energy reserves that are important for providing the energy necessary to cope with a secondary stressor.

  5. Influence of perinatal trans fat on behavioral responses and brain oxidative status of adolescent rats acutely exposed to stress.

    Science.gov (United States)

    Pase, C S; Roversi, Kr; Trevizol, F; Roversi, K; Kuhn, F T; Schuster, A J; Vey, L T; Dias, V T; Barcelos, R C S; Piccolo, J; Emanuelli, T; Bürger, M E

    2013-09-01

    Because consumption of processed foods has increased in the last decades and so far its potential influence on emotionality and susceptibility to stress is unknown, we studied the influence of different fatty acids (FA) on behavioral and biochemical parameters after acute restrain stress (AS) exposure. Two sequential generations of female rats were supplemented with soybean oil (control group; C-SO), fish oil (FO) and hydrogenated vegetable fat (HVF) from pregnancy and during lactation. At 41days of age, half the animals of each supplemented group were exposed to AS and observed in open field and elevated plus maze task, followed by euthanasia for biochemical assessments. The HVF-supplemented group showed higher anxiety-like symptoms per se, while the C-SO and FO groups did not show these behaviors. Among groups exposed to AS, HVF showed locomotor restlessness in the open field, while both C-SO and HVF groups showed anxiety-like symptoms in the elevated plus maze, but this was not observed in the FO group. Biochemical evaluations showed higher lipoperoxidation levels and lower cell viability in cortex in the HVF group. In addition, HVF-treated rats showed reduced catalase activity in striatum and hippocampus, as well as increased generation of reactive species in striatum, while FO was associated with increased cell viability in the hippocampus. Among groups exposed to AS, HVF increased reactive species generation in the brain, decreased cell viability in the cortex and striatum, and decreased catalase activity in the striatum and hippocampus. Taken together, our findings show that the type of FA provided during development and growth over two generations is able to modify the brain oxidative status, which was particularly adversely affected by trans fat. In addition, the harmful influence of chronic consumption of trans fats as observed in this study can enhance emotionality and anxiety parameters resulting from stressful situations of everyday life, which can

  6. Quantification of DNA adducts formed in liver, lungs, and isolated lung cells of rats and mice exposed to (14)C-styrene by nose-only inhalation.

    Science.gov (United States)

    Boogaard, P J; de Kloe, K P; Wong, B A; Sumner, S C; Watson, W P; van Sittert, N J

    2000-10-01

    Bronchiolo-alveolar tumors were observed in mice exposed chronically to 160 ppm styrene, whereas no tumors were seen in rats up to concentrations of 1000 ppm. Clara cells, which are predominant in the bronchiolo-alveolar region in mouse lungs but less numerous in rat and human lung, contain various cytochrome P450s, which may oxidize styrene to the rodent carcinogen styrene-7,8-oxide (SO) and other reactive metabolites. Reactive metabolites may form specific DNA adducts and induce the tumors observed in mice. To determine DNA adducts in specific tissues and cell types, rats and mice were exposed to 160 ppm [ring-U-(14)C]styrene by nose-only inhalation for 6 h in a recirculating exposure system. Liver and lungs were isolated 0 and 42 h after exposure. Fractions enriched in Type II cells and Clara cells were isolated from rat and mouse lung, respectively. DNA adduct profiles differed quantitatively and qualitatively in liver, total lung, and enriched lung cell fractions. At 0 and 42 h after exposure, the two isomeric N:7-guanine adducts of SO (measured together, HPEG) were present in liver at 3.0 +/- 0.2 and 1.9 +/- 0.3 (rat) and 1.2 +/- 0.2 and 3.2 +/- 0.5 (mouse) per 10(8) bases. Several other, unidentified adducts were present at two to three times higher concentrations in mouse, but not in rat liver. In both rat and mouse lung, HPEG was the major adduct at approximately 1 per 10(8) bases at 0 h, and these levels halved at 42 h. In both rat Type II and non-Type II cells, HPEG was the major adduct and was about three times higher in Type II cells than in total lung. For mice, DNA adduct levels in Clara cells and non-Clara cells were similar to total lung. The hepatic covalent binding index (CBI) at 0 and 42 h was 0.19 +/- 0.06 and 0.14 +/- 0.03 (rat) and 0. 25 +/- 0.11 and 0.44 +/- 0.23 (mouse), respectively. The pulmonary CBIs, based on tissues combined for 0 and 42 h, were 0.17 +/- 0.04 (rat) and 0.24 +/- 0.04 (mouse). Compared with CBIs for other genotoxicants

  7. Effect of chronic alcohol ingestion on the progression of periodontitis induced in Fisher-344 rats

    Directory of Open Access Journals (Sweden)

    Éder Ricardo Biasoli

    2009-01-01

    Full Text Available Objective: Understand the effect of chronic alcohol on the progression of periodontitis induced in Fischer-344 rats.Methods: For the study, 22 Fischer-344 rats, two months old were used, divided into groups: alcohol (n=8, ligature (n=7 and control (n=7. On the first day, the animals in the alcohol group were exposed to ingestion of a water solution containing 20% alcohol (size/size, up to day 90. After thirty days from the beginning of the experiment, the animals in the alcohol group and the ligature group were submitted to the placement of a silk thread around the right maxillary second molar. Nothing was performed on the left side, serving as control. All the groups were submitted to euthanasia 60 days after ligature placement. To assess the destruction of periodontitis, a radiographic exam was used to measure the destruction of bone height. Results: The results of the study showed that on the side in which periodontitis was induced, the group that ingested alcohol suffered an increase in destruction, with statistical differences when compared with the ligature and control groups and increased bone destruction in the ligature group when compared to control. Conclusion: Within the limitations of the study, it was concluded that chronic alcohol consumption by Fischer-344 rats led to greater progression of induced periodontitis.

  8. Chronic Methamphetamine Effects on Brain Structure and Function in Rats

    Science.gov (United States)

    Thanos, Panayotis K.; Kim, Ronald; Delis, Foteini; Ananth, Mala; Chachati, George; Rocco, Mark J.; Masad, Ihssan; Muniz, Jose A.; Grant, Samuel C.; Gold, Mark S.; Cadet, Jean Lud; Volkow, Nora D.

    2016-01-01

    Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

  9. Chronic Methamphetamine Effects on Brain Structure and Function in Rats.

    Directory of Open Access Journals (Sweden)

    Panayotis K Thanos

    Full Text Available Methamphetamine (MA addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET studies have shown decreased brain glucose metabolism (BGluM in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls, or low dose (LD MA (4 mg/kg, or high dose (HD MA (8 mg/kg. Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG, and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

  10. Ultrastructural changes, increased oxidative stress, inflammation, and altered cardiac hypertrophic gene expressions in heart tissues of rats exposed to incense smoke.

    Science.gov (United States)

    Al-Attas, Omar S; Hussain, Tajamul; Ahmed, Mukhtar; Al-Daghri, Nasser; Mohammed, Arif A; De Rosas, Edgard; Gambhir, Dikshit; Sumague, Terrance S

    2015-07-01

    Incense smoke exposure has recently been linked to cardiovascular disease risk, heart rate variability, and endothelial dysfunction. To test the possible underlying mechanisms, oxidative stress, and inflammatory markers, gene expressions of cardiac hypertrophic and xenobiotic-metabolizing enzymes and ultrastructural changes were measured, respectively, using standard, ELISA-based, real-time PCR, and transmission electron microscope procedures in heart tissues of Wistar rats after chronically exposing to Arabian incense. Malondialdehyde, tumor necrosis alpha (TNF)-α, and IL-4 levels were significantly increased, while catalase and glutathione levels were significantly declined in incense smoke-exposed rats. Incense smoke exposure also resulted in a significant increase in atrial natriuretic peptide, brain natriuretic peptide, β-myosin heavy chain, CYP1A1 and CYP1A2 messenger RNAs (mRNAs). Rats exposed to incense smoke displayed marked ultrastructural changes in heart muscle with distinct cardiac hypertrophy, which correlated with the augmented hypertrophic gene expression as well as markers of cardiac damage including creatine kinase-myocardial bound (CK-MB) and lactate dehydrogenase (LDH). Increased oxidative stress, inflammation, altered cardiac hypertrophic gene expression, tissue damage, and architectural changes in the heart may collectively contribute to increased cardiovascular disease risk in individuals exposed to incense smoke. Increased gene expressions of CYP1A1 and CYP1A2 may be instrumental in the incense smoke-induced oxidative stress and inflammation. Thus, incense smoke can be considered as a potential environmental pollutant and its long-term exposure may negatively impact human health.

  11. [Effects of palmitic acid on activity of uncoupling proteins and proton leak in in vitro cerebral mitochondria from the rats exposed to simulated high altitude hypoxia].

    Science.gov (United States)

    Xu, Yu; Liu, Jun-Ze; Xia, Chen

    2008-02-25

    To reveal the roles of uncoupling proteins (UCPs) in disorder of mitochondrial oxidative phosphorylation induced by free fatty acid during hypoxic exposure, the effects of palmitic acid on activity of UCPs, proton leak and mitochondrial membrane potential in hypoxia-exposed rat brain mitochondria were observed in vitro. Adult Sprague-Dawley (SD) rats were set randomly into control, acute hypoxia and chronic hypoxia groups (n=8 in each group). The acute and chronic hypoxic rats were exposed to simulated 5000 m high altitude in a hypobaric chamber 23 h/d for 3 d and 30 d, respectively. The brain mitochondria were isolated by centrifugation. UCP content and activity were detected by [(3)H]-GTP binding method. The proton leak was measured by TPMP(+) electrode and oxygen electrode. The membrane potential of mitochondria was calculated by detecting the fluorescence from Rodamine 123. Hypoxic exposure resulted in an increase in UCP activity and content as well as proton leak, but a decrease in the membrane potential of rat brain mitochondria. Palmitic acid resulted in further increases in UCP activity and content as well as proton leak, and further decrease in membrane potential of brain mitochondria in vitro from hypoxia-exposed rats, but hypoxic exposure decreased the reactivity of cerebral mitochondria to palmitic acid, especially in the acute hypoxia group. There was a negative correlation between mitochondrial proton leak and K(d) value (representing derivative of UCP activity, PB(max) (representing the maximal content of UCPs in mitochondrial inner membrane, P<0.01, r = 0.856). Cerebral mitochondrial membrane potential was negatively correlated with proton leak (P<0.01, r = -0.880). It is suggested that hypoxia-induced proton leak enhancement and membrane potential decrease are correlated with the increased activity of UCPs. Hypoxia can also decrease the sensitivity of cerebral mitochondria to palmitic acid, which may be a self-protective mechanism in high altitude

  12. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Olivas-Calderón, Edgar, E-mail: edgar_olivascalderon@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico); Recio-Vega, Rogelio, E-mail: rrecio@yahoo.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gandolfi, A. Jay, E-mail: gandolfi@pharmacy.arizona.edu [Southwest Environmental Health Science Center, University of Arizona, Tucson, AZ (United States); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Lantz, R. Clark, E-mail: lantz@email.arizona.edu [Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ (United States); González-Cortes, Tania, E-mail: taniagc2201@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gonzalez-De Alba, Cesar, E-mail: cesargonzalezalba@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Froines, John R., E-mail: jfroines@ucla.edu [Center for Environmental and Occupational Health, School of Public Health, University of California at Los Angeles, Los Angeles, CA (United States); Espinosa-Fematt, Jorge A., E-mail: dr.jorge.espinosa@gmail.com [School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico)

    2015-09-01

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels

  13. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

    International Nuclear Information System (INIS)

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels

  14. Oral hydrogen water prevents chronic allograft nephropathy in rats.

    Science.gov (United States)

    Cardinal, Jon S; Zhan, Jianghua; Wang, Yinna; Sugimoto, Ryujiro; Tsung, Allan; McCurry, Kenneth R; Billiar, Timothy R; Nakao, Atsunori

    2010-01-01

    Reactive oxygen species (ROS) contribute to the development of interstitial fibrosis and tubular atrophy seen in chronic allograft nephropathy (CAN). As molecular hydrogen gas can act as a scavenger of ROS, we tested the effect of treatment with hydrogen water (HW) in a model of kidney transplantation, in which allografts from Lewis rats were orthotopically transplanted into Brown Norway recipients that had undergone bilateral nephrectomy. Molecular hydrogen was dissolved in water and recipients were given HW from day 0 until day 150. Rats that were treated with regular water (RW) gradually developed proteinuria and their creatinine clearance declined, ultimately leading to graft failure secondary to CAN. In contrast, treatment with HW improved allograft function, slowed the progression of CAN, reduced oxidant injury and inflammatory mediator production, and improved overall survival. Inflammatory signaling pathways, such as mitogen-activated protein kinases, were less activated in renal allografts from HW-treated rats as compared with RW-treated rats. Hence, oral HW is an effective antioxidant and antiinflammatory agent that prevented CAN, improved survival of rat renal allografts, and may be of therapeutic value in the setting of transplantation. PMID:19907413

  15. Influence of trans fat on skin damage in first-generation rats exposed to UV radiation.

    Science.gov (United States)

    Barcelos, Raquel Cristine S; Vey, Luciana T; Segat, Hecson Jesser; Benvegnú, Dalila M; Trevizol, Fabíola; Roversi, Karine; Roversi, Katiane; Dias, Verônica T; Dolci, Geisa S; Kuhn, Fábio T; Piccolo, Jaqueline; CristinaVeit, Juliana; Emanuelli, Tatiana; Bürger, Marilise E

    2015-01-01

    The influence of trans fatty acids (TFA) on lipid profile, oxidative damage and mitochondrial function in the skin of rats exposed to ultraviolet radiation (UVR) was assessed. The first-generation offspring of female Wistar rats supplemented from pregnancy with either soybean oil (C-SO, rich in n-6 FA; control group) or hydrogenated vegetable fat (HVF, rich in TFA) were continued with the same supplements until adulthood, when half of each group was exposed to UVR for 12 weeks. The HVF group showed higher TFA cutaneous incorporation, increased protein carbonyl (PC) levels, decreased functionality of mitochondrial enzymes and antioxidant defenses of the skin. After UVR, the HVF group showed increased skin thickness and reactive species (RS) generation, with decreased skin antioxidant defenses. RS generation was positively correlated with skin thickness, wrinkles and PC levels. Once incorporated to skin, TFA make it more susceptible to developing UVR-induced disorders.

  16. Effects of propoxur on male fertility in wistar rat exposed neonatally

    Directory of Open Access Journals (Sweden)

    Augustave Kenfack

    2014-08-01

    Full Text Available Background: Propoxur is a carbamate pesticide widely used in crop and foodstuff protection. They are known to cause a wide variety of symptoms in animals. Methods: Twenty four young male rats were exposed to 0.00, 1.73, 2.60 and 5.20 mg/kg body weight through oral intubation for 90 days. Results: The testis weight increased significantly (P 0.05 but the percentage of sperm motility decreased significantly (P 0.05 change was observed between the control and treated males for the litter size, viability rate and sex-ratio. Conclusions: Despite the impairment of seminal epithelia and sperm characteristics, male rats orally exposed to the studied doses of propoxur maintained their fertility at the 90th day of treatment. [Int J Reprod Contracept Obstet Gynecol 2014; 3(4.000: 898-902

  17. Antioxidant system correction in the persons with chronic gastroduodenitis exposed to radiation

    International Nuclear Information System (INIS)

    The authors report the results of investigation of lipids peroxide oxidation (LPO) and antioxidant system of leukocytes and blood serum in 103 patients with chronic gastroduodenitis. In 56 patients, the disease was diagnosed after exposure to radiation during 48 ± 4.5 days (total dose -19 ± 2.3 cGy). The control group included 48 patients with the same disease of similar age and sex which were not exposed to ionizing radiation. Unithiolum and vitamin E in generally accepted doses were used to control the state of the antioxidant system. Administration of the preparations produced a positive clinical effect which was confirmed by the data of biochemical studies (activization of antioxidant system under the background of LPO inhibition

  18. Effect of honey on the reproductive system of male rat offspring exposed to prenatal restraint stress.

    Science.gov (United States)

    Haron, M N; Mohamed, M

    2016-06-01

    Exposure to prenatal stress is associated with impaired reproductive function in male rat offspring. Honey is traditionally used by the Malays for enhancement of fertility. The aim of this study was to determine the effect of honey on reproductive system of male rat offspring exposed to prenatal restraint stress. Dams were divided into four groups (n = 10/group): control, honey, stress and honey + stress groups. Dams from honey and honey + stress groups received oral honey (1.2 g kg(-1) body weight) daily from day 1 of pregnancy, meanwhile dams from stress and honey + stress groups were subjected to restraint stress (three times per day) from day 11 of pregnancy until delivery. At 10 weeks old, each male rat offspring was mated with a regular oestrus cycle female. Male sexual behaviour and reproductive performance were evaluated. Then, male rats were euthanised for assessment on reproductive parameters. Honey supplementation during prenatal restraint stress significantly increased testis and epididymis weights as well as improved the percentages of abnormal spermatozoa and sperm motility in male rat offspring. In conclusion, this study might suggest that supplementation of honey during pregnancy seems to reduce the adverse effects of restraint stress on reproductive organs weight and sperm parameters in male rat offspring. PMID:26289766

  19. PHYTOTHERAPEUTIC EFFECT OF AVOCADOS AND SOYA AS DRUG ON HEART OF RATS EXPOSED TO GAMMA RADIATION

    International Nuclear Information System (INIS)

    This study was planed to determine the role of single oral dose of avocados and soya in irradiated rats exposed to gamma radiation. the experimental animals were randomly divided into four groups; 12 rats for each. Group 1: kept as control. Group 2: rats received piascledine for 14 consecutive days. Group 3: rats submitted to whole body gamma rays (4 Gy). Group 4: rats received the same piascledine 14 days post-exposure to 4 Gy gamma radiation. The animals were weighed then dissected after one and fourteen days post-administration and the cardiac tissue and plasma were stored at 12oC till used for biochemical analysis and kept in ice. The following parameters were determined: plasma total cholesterol, triacylglycerol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, LDH, phospholipids, ALT, CPK and TBARS. In cardiac tissue, determinations of total cholesterol, triacylglycerol, phospholipids and TBARS were conducted.It can be concluded that administration of avocados and soy as natural drug (piascledine) post-irradiation in rats is a favorable modificator against the impaired physiological processes in animal body due to gamma irradiation

  20. Metaplastic changes of nasal respiratory epithelium in rats exposed to hexamethylphosphoramide (HMPA) by inhalation.

    OpenAIRE

    K. P. Lee(University of Tokyo); Trochimowicz, H. J.

    1982-01-01

    Rats exposed by inhalation to hexamethylphosphoramide (HMPA) at concentrations of 50, 100, 400, and 4000 parts per billion (ppb) for 6-24 months revealed nasal tumors and squamous metaplasia with inflammation in the nasal epithelium, but no changes were observed at 10 ppb. The ciliated cells were most susceptible to HMPA, showing degenerative changes, with abnormal cilia and extensive deciliation. The desquamated nasal epithelium was repaired initially by undifferentiated mucus or microvillou...

  1. Renal, vascular and cardiac fibrosis in rats exposed to passive smoking and industrial dust fibre amosite

    Science.gov (United States)

    Boor, Peter; Casper, Sandra; Celec, Peter; Hurbánková, Marta; Beňo, Milan; Heidland, August; Amann, Kerstin; Šebeková, Katarína

    2009-01-01

    Passive smoking is an independent risk factor for cardiovascular diseases. Industrial fibrous dust, e.g. the asbestos group member, amosite, causes lung cancer and fibrosis. No data are available on renal involvement after inhalational exposure to these environmental pollutants or of their combination, or on cardiovascular and renal toxicity after exposure to amosite. Male Wistar rats were randomized into four groups (n= 6): control and amosite group received initially two intratracheal instillations of saline and amosite solution, respectively. Smoking group was subjected to standardized daily exposure to tobacco smoke for 2 hrs in a concentration resembling human passive smoking. Combined group was exposed to both amosite and cigarette smoke. All rats were killed after 6 months. Rats exposed to either amosite or passive smoking developed significant glomerulosclerosis and tubulointerstitial fibrosis. Combination of both exposures had additive effects. Histomorphological changes preceded the clinical manifestation of kidney damage. In both groups with single exposures, marked perivascular and interstitial cardiac fibrosis was detected. The additive effect in the heart was less pronounced than in the kidney, apparent particularly in changes of vascular structure. Advanced oxidation protein products, the plasma marker of the myeloperoxidase reaction in activated monocytes/macrophages, were increased in all exposed groups, whereas the inflammatory cytokines did not differ between the groups. In rats, passive smoking or amosite instillation leads to renal, vascular and cardiac fibrosis potentially mediated via increased myeloperoxidase reaction. Combination of both pollutants shows additive effects. Our data should be confirmed in subjects exposed to these environmental pollutants, in particular if combined. PMID:19292733

  2. PROTECTIVE EFFECT OF LORANTHUS LONGIFLORUS ON LEARNING AND MEMORY OF RATS EXPOSED TO ELECTROMAGNETIC RADIATION (EMR)

    OpenAIRE

    Hemant Nagar; Dilip Kumar Tiwari; Gaurav Dwivedi; Rishi Kant Tripathi; Pankaj Singh

    2013-01-01

    The interaction of mobile phone radio-frequency electromagnetic radiation (RF-EMR) with the brain is a serious concern of our society. In this study, we aimed to experiment on the antioxidative property of a parasitic plant Loranthus longiflorus (Loranthaceae) to protect central nervous system against oxidative damages of mobile phone electromagnetic radiation (EMR). Healthy male albino wistar rats were exposed to RF-EMR by giving 5 min calling/ 5min interval for 1 hour per day for two month,...

  3. Changes in serum thioredoxin among individuals chronically exposed to arsenic in drinking water.

    Science.gov (United States)

    Li, Yuanyuan; Gao, Yanhui; Zhao, Lijun; Wei, Yudan; Feng, Hongqi; Wang, Cheng; Wei, Wei; Ding, Yunpeng; Sun, Dianjun

    2012-02-15

    It is well known that oxidative damage plays a key role in the development of chronic arsenicosis. There is a complex set of mechanisms of redox cycling in vivo to protect cells from the damage. In this study, we examined the differences in the levels of serum thioredoxin1 (TRX1) among individuals exposed to different levels of arsenic in drinking water and detected early biomarkers of arsenic poisoning before the appearance of skin lesions. A total of 157 subjects from endemic regions of China were selected and divided into arsenicosis group with skin lesions (total intake of arsenic: 8.68-45.71mg-year) and non-arsenicosis group without skin lesions, which further divided into low (0.00-1.06mg-year), medium (1.37-3.55mg-year), and high (4.26-48.13mg-year) arsenic exposure groups. Concentrations of serum TRX1 were analyzed by an ELISA method. Levels of water arsenic and urinary speciated arsenics, including inorganic arsenic (iAs), monomethylated arsenic (MMA), and dimethylated arsenic (DMA), were determined by hydride generation atomic absorption spectrometry. Our results showed that the levels of serum TRX1 in arsenicosis patients were significantly higher than that of the subjects who were chronically exposed to arsenic, but without skin lesions. A positive correlation was seen between the levels of serum TRX1 and the total water arsenic intake or the levels of urinary arsenic species. The results of this study indicate that arsenic exposure could significantly change the levels of human serum TRX1, which can be detected before arsenic-specific dermatological symptoms occur. This study provides further evidence on revealing the mechanism of arsenic toxicity.

  4. Development of motor coordination and cerebellar structure in male and female rat neonates exposed to hypergravity

    Science.gov (United States)

    Nguon, K.; Ladd, B.; Baxter, M. G.; Sajdel-Sulkowska, E. M.

    2006-01-01

    We previously reported that the developing rat cerebellum is affected by exposure to hypergravity. In the present study, we explored the hypothesis that the changes in cerebellar structure in hypergravity-exposed rat neonates may affect their motor coordination. Furthermore, we hypothesized that the changes observed at 1.5G will be magnified at higher gravitational loading. To test this hypothesis, we compared motor behavior, cerebellar structure, and protein expression in rat neonates exposed to 1.5 1.75G on a 24-ft centrifuge daily for 22.5 h starting on gestational day (G) 10, through birth on G22/G23 and through postnatal day (P) 21. Exposure to hypergravity impacted the neurodevelopmental process as indicated by: (1) impaired righting response on P3, more than doubling the righting time at 1.75G, and (2) delayed onset of the startle response by one day, from P9 in controls to P10 in hypergravity-exposed pups. Hypergravity exposure resulted in impaired motor functions as evidenced by performance on a rotarod on P21; the duration of the stay on the rotarod recorded for 1.75G pups of both sexes was one tenth that of the stationary control (SC) pups. These changes in motor behavior were associated with cerebellar changes: (1) cerebellar mass on P6 was decreased by 7.5% in 1.5G-exposed male pups, 27.5% in 1.75G-exposed male pups, 17.5% in 1.5G-exposed female pups, and 22.5% in 1.75G female pups and (2) changes in the expression of glial and neuronal proteins. The results of this study suggest that perinatal exposure to hypergravity affects cerebellar development as evidenced by decreased cerebellar mass and altered cerebellar protein expression; cerebellar changes observed in hypergravity-exposed rat neonates are associated with impaired motor behavior. Furthermore, the response to hypergravity appears to be different in male and female neonates. If one accepts that the hypergravity paradigm is a useful animal model with which to predict those biological processes

  5. Changes in markers of oxidative stress and membrane properties in synaptosomes from rats exposed prenatally to toluene

    DEFF Research Database (Denmark)

    Edelfors, Sven; Hass, Ulla; Hougaard, Karin S.

    2002-01-01

    The present study was undertaken in order to investigate if toluene induced oxidative stress in brains from rats exposed prenatally to 1800 ppm toluene 6 hr/day at days 7-20 during the pregnancy. 35-42 days after birth the rats were killed and synaptosomal fractions were prepared for the...... experiments, Synaptosomes from rats exposed prenatally to toluene exhibited an increased level of oxidative stress when incubated with toluene in vitro compared to synaptosomes from unexposed offspring. Also the cell membrane was affected, as the calcium leakage was more increased from exposed synaptosomes...

  6. Sodium hydrosulfide relieves neuropathic pain in chronic constriction injured rats.

    Science.gov (United States)

    Lin, Jian-Qing; Luo, Hui-Qin; Lin, Cai-Zhu; Chen, Jin-Zhuan; Lin, Xian-Zhong

    2014-01-01

    Aberrant neuronal activity in injured peripheral nerves is believed to be an important factor in the development of neuropathic pain (NPP). Channel protein pCREB of that activity has been shown to mitigate the onset of associated molecular events in the nervous system, and sodium hydrosulfide (NaHS) could inhibit the expression of pCREB. However, whether NaHS could relieve the pain, it needs further experimental research. Furthermore, the clinical potential that NaHS was used to relieve pain was limited so it would be required. To address these issues, the rats of sciatic nerve chronic constriction injury (CCI) were given intraperitoneal injection of NaHS containing hydrogen sulfide (H2S). The experimental results showed that NaHS inhibited the reduction of paw withdrawal thermal latency (PWTL), mechanical withdrawal threshold (MWT), and the level of pCREB in CCI rats in a dose-dependent manner and they were greatly decreased in NaHSM group (P < 0.05). NaHS alleviates chronic neuropathic pain by inhibiting expression of pCREB in the spinal cord of Sprague-Dawley rats.

  7. Sodium Hydrosulfide Relieves Neuropathic Pain in Chronic Constriction Injured Rats

    Directory of Open Access Journals (Sweden)

    Jian-qing Lin

    2014-01-01

    Full Text Available Aberrant neuronal activity in injured peripheral nerves is believed to be an important factor in the development of neuropathic pain (NPP. Channel protein pCREB of that activity has been shown to mitigate the onset of associated molecular events in the nervous system, and sodium hydrosulfide (NaHS could inhibit the expression of pCREB. However, whether NaHS could relieve the pain, it needs further experimental research. Furthermore, the clinical potential that NaHS was used to relieve pain was limited so it would be required. To address these issues, the rats of sciatic nerve chronic constriction injury (CCI were given intraperitoneal injection of NaHS containing hydrogen sulfide (H2S. The experimental results showed that NaHS inhibited the reduction of paw withdrawal thermal latency (PWTL, mechanical withdrawal threshold (MWT, and the level of pCREB in CCI rats in a dose-dependent manner and they were greatly decreased in NaHSM group (P < 0.05. NaHS alleviates chronic neuropathic pain by inhibiting expression of pCREB in the spinal cord of Sprague-Dawley rats.

  8. Altered spontaneous contractions of the ileum by anesthetic agents in rats exposed to peritonitis

    Institute of Scientific and Technical Information of China (English)

    Cengiz Aydin; Ihsan Bagcivan; Sinan Gursoy; Ahmet Altun; Omer Topcu; Ayhan Koyuncu

    2009-01-01

    AIM: To investigate in vitro effects of propofol, midazolam and dexmedetomidine, which are commonly used anaesthesic or sedatives, on spontaneous contractions of the ileum both in normal rats and those exposed to hyperdynamic peritonitis. METHODS: Spontaneous contractions of isolated ileum muscle segments from sham operated rats and those exposed to peritonitis, were studied in vitro. The amplitude and the frequency of spontaneous contractions of ileum muscle segments were studied after adding dexmetetomidine, propofol, and midazolam to the organ bath in a cumulative manner. Spontaneous contractions in ileum smooth muscle segments were decreased significantly in the peritonitis group compared to the control group ( P<0.05). Dexmedetomidine significantly increased the amplitude and peritonitis groups. The frequency of spontaneous contractions were significantly decreased by propofol Dexmedetomidine and midazolam did not cause significant changes in the number of spontaneous contractions in both control and the peritonitis groups ( P>0.05). CONCLUSION: Propofol, midazolam and dexmedetomidine have various in vitro effects on spontaneous contractions of the rat ileum. While dexmedetomidine augments the spontaneous contraction of the rat ileum, propofol attenuates it. However, the effects of these compounds were parallel in both control and peritonitis groups.

  9. Chronic Ethanol Feeding to Rats Decreases Adiponectin Secretion by Subcutaneous Adipocytes

    OpenAIRE

    Chen, Xiaocong; Sebastian, Becky M.; Nagy, Laura E.

    2006-01-01

    Chronic ethanol feeding to mice and rats decreases serum adiponectin concentration and adiponectin treatment attenuates chronic ethanol-induced liver injury. While it is clear that lowered adiponectin has pathophysiological importance, the mechanisms by which chronic ethanol decreases adiponectin are not known. Here we have investigated the impact of chronic ethanol feeding on adiponectin expression and secretion by adipose tissue. Rats were fed a 36% Lieber-DeCarli ethanol-containing liquid ...

  10. Urinary Trivalent Methylated Arsenic Species in a Population Chronically Exposed to Inorganic Arsenic

    Science.gov (United States)

    Valenzuela, Olga L.; Borja-Aburto, Victor H.; Garcia-Vargas, Gonzalo G.; Cruz-Gonzalez, Martha B.; Garcia-Montalvo, Eliud A.; Calderon-Aranda, Emma S.; Del Razo, Luz M.

    2005-01-01

    Chronic exposure to inorganic arsenic (iAs) has been associated with increased risk of various forms of cancer and of noncancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAsIII) and dimethylarsinite (DMAsIII) may play a significant role in determining the extent and character of toxic and cancer-promoting effects of iAs exposure. In this study we examined the relationship between urinary profiles of MAsIII and DMAsIII and skin lesion markers of iAs toxicity in individuals exposed to iAs in drinking water. The study subjects were recruited among the residents of an endemic region of central Mexico. Drinking-water reservoirs in this region are heavily contaminated with iAs. Previous studies carried out in the local populations have found an increased incidence of pathologies, primarily skin lesions, that are characteristic of arseniasis. The goal of this study was to investigate the urinary profiles for the trivalent and pentavalent As metabolites in both high- and low-iAs–exposed subjects. Notably, methylated trivalent arsenicals were detected in 98% of analyzed urine samples. On average, the major metabolite, DMAsIII, represented 49% of total urinary As, followed by DMAsV (23.7%), iAsV (8.6%), iAsIII (8.5%), MAsIII (7.4%), and MAsV (2.8%). More important, the average MAsIII concentration was significantly higher in the urine of exposed individuals with skin lesions compared with those who drank iAs-contaminated water but had no skin lesions. These data suggest that urinary levels of MAsIII, the most toxic species among identified metabolites of iAs, may serve as an indicator to identify individuals with increased susceptibility to toxic and cancer-promoting effects of arseniasis. PMID:15743710

  11. Effect of bacoside A on membrane-bound ATPases in the brain of rats exposed to cigarette smoke.

    Science.gov (United States)

    Anbarasi, K; Vani, G; Balakrishna, K; Devi, C S Shyamala

    2005-01-01

    Membrane-bound enzymes play a vital role in neuronal function through maintenance of membrane potential and impulse propagation. We have evaluated the harmful effects of chronic cigarette smoking on membrane-bound ATPases and the protective effect of Bacoside A in rat brain. Adult male albino rats were exposed to cigarette smoke for a period of 12 weeks and simultaneously administered with Bacoside A (the active principle isolated from Bacopa monniera) at a dosage of 10 mg/kg b.w/day, p.o. The levels of lipid peroxides as marker for evaluating the extent of membrane damage, the activities of Na+/K+-ATPase, Ca2+-ATPase and Mg2+-ATPase, and associated cations sodium (Na+), potassium (K+), calcium (Ca2+), and magnesium (Mg2+) were investigated in the brain. Neuronal membrane damage was evident from the elevated levels of lipid peroxides and decreased activities of membrane-bound enzymes. Disturbances in the electrolyte balance with accumulation of Na+ and Ca2+ and depletion of K+ and Mg2+ were also observed. Administration of Bacoside A inhibited lipid peroxidation, improved the activities of ATPases, and maintained the ionic equilibrium. The results of our study indicate that Bacoside A protects the brain from cigarette smoking induced membrane damage.

  12. Biochemical and morphological changes in isolated rat liver mitochondria exposed to ultraviolet light

    International Nuclear Information System (INIS)

    The correlation between the ultrastructural change of mitochondria following ultraviolet exposure and the functional disorder of respiratory chain was discussed on the isolated mitochondria prepared from rat liver. The considerable swelling of mitochondria after exposure was recognized under an electron transmission microscope and a scanning electron microscope. The addition of ATP to the exposed mitochondria showed the reversion of ultrastructural changes caused by ultraviolet exposure. The exposed mitochondria showed the loss of ability to couple the phosphorylation with the respiration, the decrease of both respiratory control ratio and ADP/O ratio, the stimulation of state 4 oxygen consumption, the increase of ATPase activity and no effect of ADP to oxygen consumption. In the exposed mitochondria, there was a marked decrease in the component of cytochrome b, c + c1 and falvoprotein on the respiratory chain. Our results suggested that the effects of ultraviolet light on mitochondria may be mediated in part by the oxidation products of lipid constituents. (auth.)

  13. Changes in serum thioredoxin among individuals chronically exposed to arsenic in drinking water

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuanyuan; Gao, Yanhui; Zhao, Lijun [Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Key Lab of Etiology and Epidemiology, Education Bureau of Hei Long Jiang Province and Ministry of Health (23618104), Harbin 150081 (China); Wei, Yudan [Department of Community Medicine, Mercer University School of Medicine, Macon 31207, GA (United States); Feng, Hongqi; Wang, Cheng; Wei, Wei; Ding, Yunpeng [Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Key Lab of Etiology and Epidemiology, Education Bureau of Hei Long Jiang Province and Ministry of Health (23618104), Harbin 150081 (China); Sun, Dianjun, E-mail: hrbmusdj@163.com [Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Key Lab of Etiology and Epidemiology, Education Bureau of Hei Long Jiang Province and Ministry of Health (23618104), Harbin 150081 (China)

    2012-02-15

    It is well known that oxidative damage plays a key role in the development of chronic arsenicosis. There is a complex set of mechanisms of redox cycling in vivo to protect cells from the damage. In this study, we examined the differences in the levels of serum thioredoxin1 (TRX1) among individuals exposed to different levels of arsenic in drinking water and detected early biomarkers of arsenic poisoning before the appearance of skin lesions. A total of 157 subjects from endemic regions of China were selected and divided into arsenicosis group with skin lesions (total intake of arsenic: 8.68–45.71 mg-year) and non-arsenicosis group without skin lesions, which further divided into low (0.00–1.06 mg-year), medium (1.37–3.55 mg-year), and high (4.26–48.13 mg-year) arsenic exposure groups. Concentrations of serum TRX1 were analyzed by an ELISA method. Levels of water arsenic and urinary speciated arsenics, including inorganic arsenic (iAs), monomethylated arsenic (MMA), and dimethylated arsenic (DMA), were determined by hydride generation atomic absorption spectrometry. Our results showed that the levels of serum TRX1 in arsenicosis patients were significantly higher than that of the subjects who were chronically exposed to arsenic, but without skin lesions. A positive correlation was seen between the levels of serum TRX1 and the total water arsenic intake or the levels of urinary arsenic species. The results of this study indicate that arsenic exposure could significantly change the levels of human serum TRX1, which can be detected before arsenic-specific dermatological symptoms occur. This study provides further evidence on revealing the mechanism of arsenic toxicity. -- Highlights: ► Three regions are selected as the areas affected by endemic arsenicosis of China. ► We first examine changes in serum TRX1 among individuals exposed to arsenic. ► A positive correlation was seen between serum TRX1 and total water arsenic intake. ► The same relationship

  14. Chronic toxicity study of Hyptis suaveolens (L. Poit in rats

    Directory of Open Access Journals (Sweden)

    Bunjong Chaorai

    2005-09-01

    Full Text Available The effect of water extract of Hyptis suaveolens (H. suaveolens was evaluated for 6-month chronic toxicity in Wistar rats. Control group received distilled water orally 10 ml/kg/day. The extract was orally given to five treatment groups at the doses of 5, 50, 250, 500 and 500 mg/kg/day for 6 months. The last group was served as the recovery group. Changes in the body weights, actual and relative organ weights were not significantly demonstrated in all groups throughout the study. The results of hematological, biochemical parameters and histopathological lesions showed that the extract did not produce any significant doserelated changes. Therefore, it may be concluded that the extract of H. suaveolens at the given doses did not produce any significant toxic effect in rats during 6-month period of the treatment.

  15. Chronic administration of isocarbophos induces vascular cognitive impairment in rats.

    Science.gov (United States)

    Li, Peng; Yin, Ya-Ling; Zhu, Mo-Li; Pan, Guo-Pin; Zhao, Fan-Rong; Lu, Jun-Xiu; Liu, Zhan; Wang, Shuang-Xi; Hu, Chang-Ping

    2016-04-01

    Vascular dementia, being the most severe form of vascular cognitive impairment (VCI), is caused by cerebrovascular disease. Whether organophosphorus causes VCI remains unknown. Isocarbophos (0.5 mg/kg per 2 days) was intragastrically administrated to rats for 16 weeks. The structure and function of cerebral arteries were assayed. The learning and memory were evaluated by serial tests of step-down, step-through and morris water maze. Long-term administration of isocarbophos reduced the hippocampal acetylcholinesterase (AChE) activity and acetylcholine (ACh) content but did not alter the plasma AChE activity, and significantly damaged the functions of learning and memory. Moreover, isocarbophos remarkably induced endothelial dysfunction in the middle cerebral artery and the expressions of ICAM-1 and VCAM-1 in the posterior cerebral artery. Morphological analysis by light microscopy and electron microscopy indicated disruptions of the hippocampus and vascular wall in the cerebral arteries from isocarbophos-treated rats. Treatment of isocarbophos injured primary neuronal and astroglial cells isolated from rats. Correlation analysis demonstrated that there was a high correlation between vascular function of cerebral artery and hippocampal AChE activity or ACh content in rats. In conclusion, chronic administration of isocarbophos induces impairments of memory and learning, which is possibly related to cerebral vascular dysfunction. PMID:26818681

  16. Chronic Kidney Disease Impairs Bone Defect Healing in Rats.

    Science.gov (United States)

    Liu, Weiqing; Kang, Ning; Seriwatanachai, Dutmanee; Dong, Yuliang; Zhou, Liyan; Lin, Yunfeng; Ye, Ling; Liang, Xing; Yuan, Quan

    2016-03-09

    Chronic kidney disease (CKD) has been regarded as a risk for bone health. The aim of this study was to evaluate the effect of CKD on bone defect repair in rats. Uremia was induced by subtotal renal ablation, and serum levels of BUN and PTH were significantly elevated four weeks after the second renal surgery. Calvarial defects of 5-mm diameter were created and implanted with or without deproteinized bovine bone mineral (DBBM). Micro-CT and histological analyses consistently revealed a decreased newly regenerated bone volume for CKD rats after 4 and 8 weeks. In addition, 1.4-mm-diameter cortical bone defects were established in the distal end of femora and filled with gelatin sponge. CKD rats exhibited significantly lower values of regenerated bone and bone mineral density (BMD) within the cortical gap after 2 and 4 weeks. Moreover, histomorphometric analysis showed an increase in both osteoblast number (N.Ob/B.Pm) and osteoclast number (N.Oc/B.Pm) in CKD groups due to hyperparathyroidism. Notably, collagen maturation was delayed in CKD rats as verified by Masson's Trichrome staining. These data indicate that declined renal function negatively affects bone regeneration in both calvarial and femoral defects.

  17. Modulation of mammary gland development in prepubertal male rats exposed to genistein and methoxychlor.

    Science.gov (United States)

    You, Li; Sar, Madhabananda; Bartolucci, Erika J; McIntyre, Barry S; Sriperumbudur, Rajagopal

    2002-04-01

    The estrogenic isoflavone genistein is a common dietary component that has been shown to affect reproductive development in experimental animals at high doses. The objective of the present study was to examine interactions of genistein and the hormonally active pesticide methoxychlor on mammary gland development in juvenile rats. Timed-pregnant Sprague-Dawley rats were fed a soy- and alfalfa-free diet containing different combinations of genistein (300 and 800 ppm) and methoxychlor (800 ppm). Rats were fed these diets starting on gestation day (GD)1 and continuing through pregnancy and lactation until postnatal day (PND) 22, when the pups were killed. Inguinal mammary glands from both female and male pups were processed as whole-mount preparations for morphometric analysis. The total glandular area and the numbers of branch points, lateral buds, and terminal end buds in the male rats were found to be significantly greater in the groups exposed to methoxychlor than those exposed to genistein only. These effects were not observed in the female rats. In the male rats, methoxychlor had the most prominent effect on elongating the glandular ducts, while genistein enhanced the ductile branching. The 2 compounds in combination promoted the development of alveolar-lobular structure, an effect not observed with either compound alone. Immunostaining for proliferating cell nuclear antigen revealed a high percentage of immunopositive cells in the mammary epithelia of the males exposed to methoxychlor and genistein (800 ppm) compared to the controls. While no significant changes in serum levels of mammotrophic hormones were detected, increased immunostaining for insulin-like growth factor-1 receptor, estrogen receptor alpha, and progesterone receptor in the genistein + methoxychlor group suggested that local factors involved in regulating mammary growth may have played a role in propagating the endocrine effects of these two compounds. These results indicated that the mammary

  18. Lung angiotensin converting enzyme activity in chronically hypoxic rats.

    OpenAIRE

    Kay, J M; Keane, P. M.; Suyama, K L; Gauthier, D.

    1985-01-01

    A study was carried out to test the hypothesis that the reduced lung angiotensin converting enzyme (ACE) activity which occurs in chronic hypoxia is related to the development of pulmonary hypertension rather than to hypoxia per se. Right ventricular mean systolic pressure (Prvs, mm Hg) and ACE activity (nmol/mg protein/min) in lung tissue homogenates were measured in seven groups of four rats placed in a hypobaric chamber (380 mm Hg; 51 kPa) for two to 24 days. Identical measurements were ma...

  19. Protective Effects of Hydroalcoholic Extract of Nasturtium officinale on Rat Blood Cells Exposed to Arsenic

    Directory of Open Access Journals (Sweden)

    Felor Zargari

    2015-06-01

    Full Text Available Background: Arsenic is one of the most toxic metalloids. Anemia and leukopenia are common results of poisoning with arsenic, which may happen due to a direct hemolytic or cytotoxic effect on blood cells. The aim of this study was to examine the effects of hydroalcoholic extract of Nasturtium officinale on blood cells and antioxidant enzymes in rats exposed to sodium (metaarsenite. Methods: 32 Male Sprague Dawley rats were randomly divided into four groups; Group I (normal healthy rats, Group II (treated with 5.5mg/kg of body weight of NaAsO2, Group III (treated with 500mg/kg of body weight of hydro-alcoholic extract of N. officinale, and Group IV (treated with group II and III supplementations. Blood samples were collected and red blood cell, white blood cell, hematocrit, hemoglobin, platelet, total protein and albumin levels and total antioxidant capacity were measured. Data was analyzed with Mann-Whitney U test. Results: WBC, RBC and Hct were decreased in the rats exposed to NaAsO2 (p<0.05. A significant increase was seen in RBC and Hct after treatment with the plant extract (p<0.05. There was no significant decrease in serum albumin and total protein in the groups exposed to NaAsO2 compared to the group I, but NaAsO2 decreased the total antioxidant capacity, significantly. Conclusion: The Nasturtium officinale extract have protective effect on arsenic-induced damage of blood cells.

  20. Memantine prevents cardiomyocytes nuclear size reduction in the left ventricle of rats exposed to cold stress

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    Adriano Meneghini

    2009-01-01

    Full Text Available OBJECTIVES: Memantine is an N-methyl-d-aspartate (NMDA glutamate receptor antagonist used to treat Alzheimer's disease. Previous studies have suggested that receptor blockers act as neuroprotective agents; however, no study has specifically investigated the impact that these drugs have on the heart. We sought to evaluate the effects of memantine on nuclear size reduction in cardiac cells exposed to cold stress. METHOD: We used male EPM-Wistar rats (n=40 divided into 4 groups: 1 Matched control (CON; 2 Memantine-treated rats (MEM; 3 Rats undergoing induced hypothermia (IH and 4 Rats undergoing induced hypothermia that were also treated with memantine (IHM. Animals in the MEM and IHM groups were treated by oral gavage administration of 20 mg/kg/day memantine over an eight-day period. Animals in the IH and IHM groups were submitted to 4 hours of hypothermia in a controlled environment with a temperature of - 8ºC on the last day of the study. RESULTS: The MEM group had the largest cardiomyocyte nuclear size (151 ± 3.5 μm³ vs. CON: 142 ± 2.3 μm³; p<0.05, while the IH group had the smallest mean value of nuclear size. The nuclear size of the IHM group was preserved (125 ± 2.9 μm³ compared to the IH group (108 ± 1.7 μm³; p<0.05. CONCLUSION: Memantine prevented the nuclear size reduction of cardiomyocytes in rats exposed to cold stress.

  1. Some biochemical changes in male rats exposed to the pesticide actellic

    International Nuclear Information System (INIS)

    The present study has been carried out to evaluate the toxicity of acute and chronic treatments of the commercial pesticide actelli (5%) on some vital biochemical processes in male rats. Rats were treated with 1 g commercial actellic/kh body weight as one single acute oral dose or as daily portions mixed with food for 28 days. In the acute treatment, acetylcholinesterase (ACHE) activity was estimated in both serum and brain 24 hours after application. The enzyme recorded 71%, of its activity in serum and 75% in brain, while in the chronic treatment, the enzyme activity dropped to 58.6%, 60.2%, 61.4% and 68.0% in serum and 56.5%, 56.6%, 58.4% and 58.8% in brain as recorded after 7 14, 21 and 28 days, respectively. In the chronic treatment, the data obtained weekly for 28 days showed highly significant decreases in T3, T4, testosterone and cholesterol while highly significant increases were observed in both creatinine and urea.Triglycerides and organ/ body weight ratios showed insignificant changes. According to the data, the pesticide actellic should be used, only if necessary, under restricted precautions, in order to minimize environmental pollution and health hazards

  2. Yohimbine reinstates extinguished 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) seeking in rats with prior exposure to chronic yohimbine.

    Science.gov (United States)

    Ball, Kevin T; Jarsocrak, Hanna; Hyacinthe, Johanna; Lambert, Justina; Lockowitz, James; Schrock, Jordan

    2015-11-01

    Although exposure to acute stress has been shown to reinstate extinguished responding for a wide variety of drugs, no studies have investigated stress-induced reinstatement in animals with a history of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) self-administration. Thus, rats were trained to press a lever for MDMA (0.50 mg/kg/infusion) in daily sessions, and lever pressing was subsequently extinguished in the absence of MDMA and conditioned cues (light and tone). We then tested the ability of acute yohimbine (2.0 mg/kg), a pharmacological stressor, to reinstate lever-pressing under extinction conditions. Additionally, to model chronic stress, some rats were injected daily with yohimbine (5.0 mg/kg × 10 days) prior to reinstatement tests. To assess dopaminergic involvement, chronic yohimbine injections were combined with injections of SCH-23390 (0.0 or 10.0 μg/kg), a dopamine D1-like receptor antagonist. In a separate experiment, rats with a history of food self-administration were treated and tested in the same way. Results showed that acute yohimbine injections reinstated extinguished MDMA and food seeking, but only in rats with a history of chronic yohimbine exposure. Co-administration of SCH-23390 with chronic yohimbine injections prevented the potentiation of subsequent food seeking, but not MDMA seeking. These results suggest that abstinent MDMA users who also are exposed to chronic stress may be at increased risk for future relapse, and also that the effects of chronic stress on relapse may be mediated by different mechanisms depending on one's drug use history.

  3. Plasma renin is increased in young rats exposed to lead in utero and during nursing

    Energy Technology Data Exchange (ETDEWEB)

    Victery, W.; Vander, A.J.; Schoeps, P.; Germain, C.

    1983-01-01

    Rats were exposed continuously to Pb in utero and after birth by giving their mothers, during pregnancy and lactation, drinking water containing 0, 5, 25, 100, or 500 ppm Pb (as Pb acetate); they were sacrificed at 1 month of age, at which time their mean blood Pb concentrations were, respectively, approximately 3, 9, 19, 30, and 70 ..mu..g/dl. All Pb-exposed groups sacrificed by decapitation had elevated mean plasma renin activities (PRA), relative to controls. Pentobarbital-anesthesia and laparotomy markedly increased PRA in the 0, 100, and 500 ppm groups, but the increase was significantly less in the 100 ppm group. Renal renin concentration was normal in the 5 and 25 ppm groups, but was significantly increased in the 100 and 500 ppm groups. The ratio of plasma angiotensin II to PRA was normal in the 100 ppm group but significantly reduced in the 500 ppm group. We conclude that exposure of rats to those generally present in human populations stimulates basal renin secretion in 1-month-old rats, but partially inhibits the response to renin-releasing stimuli. The highest dose reduces plasma angiotensin II at any given PRA. These results, taken with previous publications, emphasize that the effects of lead on plasma renin even within a single species are greatly affected by the timing of the exposure.

  4. Inhibition of HMGB1 Translocation by Green Tea Extract in Rats Exposed to Environmental Tobacco Smoke

    Directory of Open Access Journals (Sweden)

    Sirintip Chaichalotornkul

    2012-01-01

    Full Text Available Environmental tobacco smoke (ETS exposure is linked to carcinogenic, oxidative and inflammatory cellular reactions. Green tea polyphenol reportedly plays a role in the prevention of inflammation-related diseases. To evaluate the effects of green tea extract (GTE on cellular location of High Mobility Group Box-1 (HMGB1 protein, we studied the lung tissue in rats exposed to cigarette smoke (CS. Rats were divided into three groups; CS, CSG, and C, which were groups of CS-treated only, CS-treated with GTE dietary supplement, and the control, respectively. Our findings by immunocytochemistry showed that abundant HMGB1 translocated from the nucleus to the cytoplasm in the lung tissues of rats that were exposed to CS, whereas HMGB1 was localized to the nuclei of CSG and C group. For in vitro studies, cotinine stimulated the secretion of HMGB1 in a dose and time dependent manner and the HMGB1 level was suppressed by GTE in murine macrophage cell lines. Our results could suggest that GTE supplementation which could suppress HMGB1 may offer a beneficial effect against diseases.

  5. Morphology of respiratory tract lesions in rats exposed to radon progeny

    Energy Technology Data Exchange (ETDEWEB)

    Dagle, G.E.; Cross, F.T.; Gies, R.A. [Pacific Northwest Lab., Richland, WA (United States)

    1992-12-31

    We will discuss the morphologic features of lesions in the respiratory tract of rats exposed to radon and radon progeny. Groups of male Wister rats were exposed to from 10 to 1000 working levels (WL) of radon progeny in the presence of less than 1 to about 15 mg m{sup {minus}3} uranium ore dust. Cumulative exposures ranged from 20 to approximately 10,000 working level months (WLM). Higher exposure levels produced radiation pneumonitis characterized by interstitial fibrosis, associated with alveolar epithelial cell hyperplasia and accumulations of alveolar macrophages containing phagocytosed uranium ore dust. Nodular fibrosis and alveolar proteinosis were correlated with deposits of uranium ore dust. Vesicular emphysema also occurred at higher exposure levels. Pulmonary adenomatosis appeared to be a preneoplastic lesion; it was composed of nodular proliferation of bronchioloalveolar epithelium without disruption of the general architecture of the parenchyma. At exposure levels where rats lived longer than 1 y, lung tumors and a few tumors of the nasal cavity developed. The principal lung tumors were pulmonary adenomas, bronchioloalveolar carcinomas, papillary adenocarcinomas, epidermoid carcinomas, and adenosquamous carcinomas. Occasionally, malignant mesotheliomas and sarcomas were also present. The malignant lung tumors were characterized by invasion and occasionally metastasized to regional lymph nodes. Lower exposure rates produced more tumors, generally of different histologic types, and more fatal tumors than higher exposure rates. The similarity to relationships of human radon progeny exposure as far as incidence and types of lung tumors establish the validity of this animal model for studying radon carcinogenesis in humans.

  6. Morphology of respiratory tract lesions in rats exposed to radon progeny

    International Nuclear Information System (INIS)

    We will discuss the morphologic features of lesions in the respiratory tract of rats exposed to radon and radon progeny. Groups of male Wister rats were exposed to from 10 to 1000 working levels (WL) of radon progeny in the presence of less than 1 to about 15 mg m-3 uranium ore dust. Cumulative exposures ranged from 20 to approximately 10,000 working level months (WLM). Higher exposure levels produced radiation pneumonitis characterized by interstitial fibrosis, associated with alveolar epithelial cell hyperplasia and accumulations of alveolar macrophages containing phagocytosed uranium ore dust. Nodular fibrosis and alveolar proteinosis were correlated with deposits of uranium ore dust. Vesicular emphysema also occurred at higher exposure levels. Pulmonary adenomatosis appeared to be a preneoplastic lesion; it was composed of nodular proliferation of bronchioloalveolar epithelium without disruption of the general architecture of the parenchyma. At exposure levels where rats lived longer than 1 y, lung tumors and a few tumors of the nasal cavity developed. The principal lung tumors were pulmonary adenomas, bronchioloalveolar carcinomas, papillary adenocarcinomas, epidermoid carcinomas, and adenosquamous carcinomas. Occasionally, malignant mesotheliomas and sarcomas were also present. The malignant lung tumors were characterized by invasion and occasionally metastasized to regional lymph nodes. Lower exposure rates produced more tumors, generally of different histologic types, and more fatal tumors than higher exposure rates. The similarity to relationships of human radon progeny exposure as far as incidence and types of lung tumors establish the validity of this animal model for studying radon carcinogenesis in humans

  7. Chronic toxicity and oncogenicity of decamethylcyclopentasiloxane in the Fischer 344 Rat.

    Science.gov (United States)

    Jean, Paul A; Plotzke, Kathleen P; Scialli, Anthony R

    2016-02-01

    Decamethylcyclopentasiloxane (D5) is a cyclic polydimethylsiloxane used in the synthesis of silicon-based materials and as a component in consumer products. Male and female Fischer 344 rats were exposed to D5 vapor (0, 10, 40, 160 ppm; whole-body inhalation) for 6 h/d, 5 d/wk, for up to 104 weeks. Microscopic examination of tissues revealed test article effects at 160 ppm in the upper respiratory tract (hyaline inclusions in males and females at 6, 12, and 24 months) and an increased incidence of uterine endometrial adenocarcinoma at 24-months. The hyaline inclusions were considered a non-adverse tissue response for lack of any other respiratory tract non-neoplastic or neoplastic changes. Uterine endometrial adenocarcinoma was not anticipated. Toxicity testing (mutagenicity/genotoxicity, acute, sub-acute and sub-chronic descriptive toxicity) performed prior to the conduct of the chronic bioassay provided no indication that the uterus was a potential target organ. The target organ and tumor type specificity (adenocarcinoma is a common spontaneous tumor in the aged Fischer 344 rat) suggests the effect is associated with estrous cycle alteration. A robust assessment of potential mode(s) of action responsible for the uterine tumors and relevance to humans is addressed in a companion manuscript (Klaunig et al., 2015). PMID:26184430

  8. Disruption of erythrocyte antioxidant defense system, hematological parameters, induction of pro-inflammatory cytokines and DNA damage in liver of co-exposed rats to aluminium and acrylamide.

    Science.gov (United States)

    Ghorbel, Imen; Maktouf, Sameh; Kallel, Choumous; Ellouze Chaabouni, Semia; Boudawara, Tahia; Zeghal, Najiba

    2015-07-01

    The individual toxic effects of aluminium and acrylamide are well known but there are no data on their combined effects. The present study was undertaken to determine (i) hematological parameters during individual and combined chronic exposure to aluminium and acrylamide (ii) correlation of oxidative stress in erythrocytes with pro-inflammatory cytokines expression, DNA damage and histopathological changes in the liver. Rats were exposed to aluminium (50 mg/kg body weight) in drinking water and acrylamide (20 mg/kg body weight) by gavage, either individually or in combination for 3 weeks. Exposure rats to AlCl3 or/and ACR provoked an increase in MDA, AOPP, H2O2 and a decrease in GSH and NPSH levels in erythrocytes. Activities of catalase, glutathione peroxidase and superoxide dismutase were decreased in all treated rats. Our results showed that all treatments induced an increase in WBC, erythrocyte osmotic fragility and a decrease in RBC, Hb and Ht. While MCV, MCH, MCHC remained unchanged. Hepatic pro-inflammatory cytokines expression including tumor necrosis factor-α, interleukin-6, interleukin-1β was increased suggesting leucocytes infiltration in the liver. A random DNA degradation was observed on agarose gel only in the liver of co-exposed rats to AlCl3 and ACR treatment. Interestingly, co-exposure to these toxicants exhibited synergism based on physical and biochemical variables in erythrocytes, pro-inflammatory cytokines and DNA damage in liver.

  9. Expression profiling reveals novel hypoxic biomarkers in peripheral blood of adult mice exposed to chronic hypoxia.

    Directory of Open Access Journals (Sweden)

    Matias Mosqueira

    Full Text Available Hypoxia induces a myriad of changes including an increase in hematocrit due to erythropoietin (EPO mediated erythropoiesis. While hypoxia is of importance physiologically and clinically, lacunae exist in our knowledge of the systemic and temporal changes in gene expression occurring in blood during the exposure and recovery from hypoxia. To identify these changes expression profiling was conducted on blood obtained from cohorts of C57Bl-10 wild type mice that were maintained at normoxia (NX, exposed for two weeks to normobaric chronic hypoxia (CH or two weeks of CH followed by two weeks of normoxic recovery (REC. Using stringent bioinformatic cut-offs (0% FDR, 2 fold change cut-off, 230 genes were identified and separated into four distinct temporal categories. Class I contained 1 transcript up-regulated in both CH and REC; Class II contained 202 transcripts up-regulated in CH but down-regulated after REC; Class III contained 9 transcripts down-regulated both in CH and REC; Class IV contained 18 transcripts down-regulated after CH exposure but up-regulated after REC. Profiling was independently validated and extended by analyzing expression levels of selected genes as novel biomarkers from our profile (e.g. spectrin alpha-1, ubiquitin domain family-1 and pyrroline-5-carboxylate reductase-1 by performing qPCR at 7 different time points during CH and REC. Our identification and characterization of these genes define transcriptome level changes occurring during chronic hypoxia and normoxic recovery as well as novel blood biomarkers that may be useful in monitoring a variety of physiological and pathological conditions associated with hypoxia.

  10. Concentration and distribution of 210Po in rats exposed to radon

    International Nuclear Information System (INIS)

    Objective: To study the concentration and distribution of 210Po in rats exposed to radon and its daughters. Methods: Fifteen male wistar rats were randomly divided into three groups, including one control group and two radon exposed groups with the cumulative doses of 100 WLM (low dose) and 200 WLM (high dose), respectively. Tissue samples containing 210Po were spontaneously deposited onto silvery discs with the diameter of 20 mm by means of wet ashing and electrodeposition. The concentration of 210Po in tissues were measured by α spectroscopy, and tissue burden were calculated. Results: The concentrations of 210Po were significantly different among the three dose groups in femur, liver, sex gland and hair (P210Po were different between the exposed groups and the control group in lung and soleus muscle (P210Po in lung, spleen and hair were higher than that in liver, bone and sex gland, the lowest was in intestine. The tissue burdens of liver, bone and sex gland were significantly different from those in other organs or tissues. Conclusions: 210Po was mainly distributed in lung, liver, spleen, femur and sex gland. The concentrations of 210Po in organs or tissues and the tissue burdens were correspondingly increased with the exposure dose of radon and its daughters. The results of this experiment provide a dosimetric basis for further studies on the carcinogenic effect of radon and its daughters. (authors)

  11. Intersex occurrence in rainbow trout (Oncorhynchus mykiss male fry chronically exposed to ethynylestradiol.

    Directory of Open Access Journals (Sweden)

    Sophie Depiereux

    Full Text Available This study aimed to investigate the male-to-female morphological and physiological transdifferentiation process in rainbow trout (Oncorhynchus mykiss exposed to exogenous estrogens. The first objective was to elucidate whether trout develop intersex gonads under exposure to low levels of estrogen. To this end, the gonads of an all-male population of fry exposed chronically (from 60 to 136 days post fertilization--dpf to several doses (from environmentally relevant 0.01 µg/L to supra-environmental levels: 0.1, 1 and 10 µg/L of the potent synthetic estrogen ethynylestradiol (EE2 were examined histologically. The morphological evaluations were underpinned by the analysis of gonad steroid (testosterone, estradiol and 11-ketotestosterone levels and of brain and gonad gene expression, including estrogen-responsive genes and genes involved in sex differentiation in (gonads: cyp19a1a, ER isoforms, vtg, dmrt1, sox9a2; sdY; cyp11b; brain: cyp19a1b, ER isoforms. Intersex gonads were observed from the first concentration used (0.01 µg EE2/L and sexual inversion could be detected from 0.1 µg EE2/L. This was accompanied by a linear decrease in 11-KT levels, whereas no effect on E2 and T levels was observed. Q-PCR results from the gonads showed downregulation of testicular markers (dmrt1, sox9a2; sdY; cyp11b with increasing EE2 exposure concentrations, and upregulation of the female vtg gene. No evidence was found for a direct involvement of aromatase in the sex conversion process. The results from this study provide evidence that gonads of male trout respond to estrogen exposure by intersex formation and, with increasing concentration, by morphological and physiological conversion to phenotypic ovaries. However, supra-environmental estrogen concentrations are needed to induce these changes.

  12. Alteration of cytokine profiles in mice exposed to chronic low-dose ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Suk Chul [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Lee, Kyung-Mi [Global Research Lab, BAERI Institute, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Kang, Yu Mi [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Kim, Kwanghee [Global Research Lab, BAERI Institute, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Kim, Cha Soon; Yang, Kwang Hee; Jin, Young-Woo [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Kim, Chong Soon [Department of Nuclear Medicine, Haeundae Paik Hospital, Inje University, Busan 612-030 (Korea, Republic of); Kim, Hee Sun, E-mail: hskimdvm@khnp.co.kr [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of)

    2010-07-09

    While a high-dose of ionizing radiation is generally harmful and causes damage to living organisms, a low-dose of radiation has been shown to be beneficial in a variety of animal models. To understand the basis for the effect of low-dose radiation in vivo, we examined the cellular and immunological changes evoked in mice exposed to low-dose radiation at very low (0.7 mGy/h) and low (3.95 mGy/h) dose rate for the total dose of 0.2 and 2 Gy, respectively. Mice exposed to low-dose radiation, either at very low- or low-dose rate, demonstrated normal range of body weight and complete blood counts. Likewise, the number and percentage of peripheral lymphocyte populations, CD4{sup +} T, CD8{sup +} T, B, or NK cells, stayed unchanged following irradiation. Nonetheless, the sera from these mice exhibited elevated levels of IL-3, IL-4, leptin, MCP-1, MCP-5, MIP-1{alpha}, thrombopoietin, and VEGF along with slight reduction of IL-12p70, IL-13, IL-17, and IFN-{gamma}. This pattern of cytokine release suggests the stimulation of innate immunity facilitating myeloid differentiation and activation while suppressing pro-inflammatory responses and promoting differentiation of naive T cells into T-helper 2, not T-helper 1, types. Collectively, our data highlight the subtle changes of cytokine milieu by chronic low-dose {gamma}-radiation, which may be associated with the functional benefits observed in various experimental models.

  13. Intersex occurrence in rainbow trout (Oncorhynchus mykiss) male fry chronically exposed to ethynylestradiol.

    Science.gov (United States)

    Depiereux, Sophie; Liagre, Mélanie; Danis, Lorraine; De Meulder, Bertrand; Depiereux, Eric; Segner, Helmut; Kestemont, Patrick

    2014-01-01

    This study aimed to investigate the male-to-female morphological and physiological transdifferentiation process in rainbow trout (Oncorhynchus mykiss) exposed to exogenous estrogens. The first objective was to elucidate whether trout develop intersex gonads under exposure to low levels of estrogen. To this end, the gonads of an all-male population of fry exposed chronically (from 60 to 136 days post fertilization--dpf) to several doses (from environmentally relevant 0.01 µg/L to supra-environmental levels: 0.1, 1 and 10 µg/L) of the potent synthetic estrogen ethynylestradiol (EE2) were examined histologically. The morphological evaluations were underpinned by the analysis of gonad steroid (testosterone, estradiol and 11-ketotestosterone) levels and of brain and gonad gene expression, including estrogen-responsive genes and genes involved in sex differentiation in (gonads: cyp19a1a, ER isoforms, vtg, dmrt1, sox9a2; sdY; cyp11b; brain: cyp19a1b, ER isoforms). Intersex gonads were observed from the first concentration used (0.01 µg EE2/L) and sexual inversion could be detected from 0.1 µg EE2/L. This was accompanied by a linear decrease in 11-KT levels, whereas no effect on E2 and T levels was observed. Q-PCR results from the gonads showed downregulation of testicular markers (dmrt1, sox9a2; sdY; cyp11b) with increasing EE2 exposure concentrations, and upregulation of the female vtg gene. No evidence was found for a direct involvement of aromatase in the sex conversion process. The results from this study provide evidence that gonads of male trout respond to estrogen exposure by intersex formation and, with increasing concentration, by morphological and physiological conversion to phenotypic ovaries. However, supra-environmental estrogen concentrations are needed to induce these changes. PMID:25033040

  14. Alteration of cytokine profiles in mice exposed to chronic low-dose ionizing radiation

    International Nuclear Information System (INIS)

    While a high-dose of ionizing radiation is generally harmful and causes damage to living organisms, a low-dose of radiation has been shown to be beneficial in a variety of animal models. To understand the basis for the effect of low-dose radiation in vivo, we examined the cellular and immunological changes evoked in mice exposed to low-dose radiation at very low (0.7 mGy/h) and low (3.95 mGy/h) dose rate for the total dose of 0.2 and 2 Gy, respectively. Mice exposed to low-dose radiation, either at very low- or low-dose rate, demonstrated normal range of body weight and complete blood counts. Likewise, the number and percentage of peripheral lymphocyte populations, CD4+ T, CD8+ T, B, or NK cells, stayed unchanged following irradiation. Nonetheless, the sera from these mice exhibited elevated levels of IL-3, IL-4, leptin, MCP-1, MCP-5, MIP-1α, thrombopoietin, and VEGF along with slight reduction of IL-12p70, IL-13, IL-17, and IFN-γ. This pattern of cytokine release suggests the stimulation of innate immunity facilitating myeloid differentiation and activation while suppressing pro-inflammatory responses and promoting differentiation of naive T cells into T-helper 2, not T-helper 1, types. Collectively, our data highlight the subtle changes of cytokine milieu by chronic low-dose γ-radiation, which may be associated with the functional benefits observed in various experimental models.

  15. Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2

    International Nuclear Information System (INIS)

    Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.

  16. Chronic Cigarette Smoking Impairs Erectile Function through Increased Oxidative Stress and Apoptosis, Decreased nNOS, Endothelial and Smooth Muscle Contents in a Rat Model.

    Directory of Open Access Journals (Sweden)

    Yun-Ching Huang

    Full Text Available Cigarette use is an independent risk factor for the development of erectile dysfunction (ED. While the association between chronic smoking and ED is well established, the fundamental mechanism(s of cigarette-related ED are incompletely understood, partly due to no reliable animal model of smoking-induced ED. The present study was designed to validate an in vivo rat model of chronic cigarette-induced ED. Forty 12-week old male Sprague-Dawley rats were divided into 4 groups. Ten rats served as control group and were exposed only to room air. The remaining 30 rats were passively exposed to cigarette smoke (CS for 4 weeks (n = 10, 12 weeks (n = 10, and 24 weeks (n = 10. At the 24-week time point all rats were assessed with intracavernous pressure (ICP during cavernous nerve electrostimulation. Blood and urine were collected to measure serum testosterone and oxidative stress, respectively. Corporal tissue was assessed by Western blot for neuronal nitric oxide synthase (nNOS. Penile tissues were subjected to immunohistochemistry for endothelial, smooth muscle, and apoptotic content. Mean arterial pressure (MAP was significantly higher in 24-week cigarette exposed animals compared to the control animals. Mean ICP/MAP ratio and cavernosal smooth muscle/endothelial contents were significantly lower in the 12- and 24-week rats compared to control animals. Oxidative stress was significantly higher in the 24-week cigarette exposed group compared to control animals. Mean nNOS expression was significantly lower, and apoptotic index significantly higher, in CS-exposed animals compared to control animals. These findings indicate that the rat model exposure to CS increases apoptosis and oxidative stress and decreases nNOS, endothelial and smooth muscle contents, and ICP in a dose dependent fashion. The rat model is a useful tool for further study of the molecular and cellular mechanisms of CS-related ED.

  17. Influence of imipramine on the duration of immobility in chronic forced-swim-stressed rats.

    Science.gov (United States)

    Kitamura, Yoshihisa; Araki, Hiroaki; Nagatani, Tadashi; Takao, Katsuyuki; Shibata, Kazuhiko; Gomita, Yutaka

    2004-12-01

    We studied the influence of imipramine on the duration of immobility in chronic forced-swim-stressed rats. Both single and chronic administration of imipramine potently shortened immobility in naive rats during forced-swim testing. However, chronic, 14-day forced-swim stress testing blocked the immobility-decreasing effect induced by a single administration of imipramine. When imipramine was administered for 14 days concurrently with forced-swim stress testing, immobility was shortened significantly. From the viewpoint of imipramine's effect, these findings suggest that chronic forced-swim stress testing in rats may be an effective animal model for depression.

  18. Influence of imipramine on the duration of immobility in chronic forced-swim-stressed rats.

    Directory of Open Access Journals (Sweden)

    Kitamura,Yoshihisa

    2004-12-01

    Full Text Available

    We studied the influence of imipramine on the duration of immobility in chronic forced-swim-stressed rats. Both single and chronic administration of imipramine potently shortened immobility in naive rats during forced-swim testing. However, chronic, 14-day forced-swim stress testing blocked the immobility-decreasing effect induced by a single administration of imipramine. When imipramine was administered for 14 days concurrently with forced-swim stress testing, immobility was shortened significantly. From the viewpoint of imipramine's effect, these findings suggest that chronic forced-swim stress testing in rats may be an effective animal model for depression.

  19. Enhanced oxidative stress and endothelial dysfunction in streptozotocin-diabetic rats exposed to fine particles.

    Science.gov (United States)

    Lei, Yu-Chen; Hwang, Jing-Shiang; Chan, Chang-Chuan; Lee, Chung-Te; Cheng, Tsun-Jen

    2005-11-01

    The association between ambient particulate matter (PM) and cardiovascular diseases has been demonstrated in epidemiological studies. Recent studies suggest that diabetic patients are at greater risk for PM-associated cardiovascular events. Although diabetes and PM exposure individually have been reported to be associated with increased oxidative stress, inflammation, and endothelial dysfunction, it is not clear whether PM may induce synergistic interaction effects on these parameters in diabetics. Strepotozotocin-induced diabetic (n=4) and healthy (n=4) rats were intratracheally administered with PM2.5 collected from a busy traffic area in a dose of 200 microg suspended in 0.5 mL phosphate-buffered saline (PBS). The same number of rats was exposed to PBS as controls. Cell and differential counts and protein and lactate dehydrogenase activity were determined in bronchoalveolar lavage. Markers of 8-hydroxydeoxy-guanosine (8-OHdG), endothelin-1 (ET-1), and [nitrate+nitrite], an indicator of nitric oxide (NO) production, in addition to C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in peripheral blood were also determined. Our results showed that diabetic rats were associated with increased 8-OHdG, IL-6, and ET-1 decreased [nitrate+nitrite]. In nondiabetic rats PM exposure was also associated with increased 8-OHdG, IL-6, TNF-alpha, and CRP but decreased [nitrate+nitrite]. Interestingly, increases of 8-OHdG and ET-1 after PM exposure were more prominent in diabetic rats than in nondiabetic rats. The general linear model further indicated that there were interactions between diabetes and PM on 8-OHdG (P<0.01) and ET-1 (P=0.08). We suggest that PM exposure may enhance the risk of cardiovascular diseases through interaction between PM and diabetes on excess reactive oxygen species generation and endothelial dysfunction. These findings provide further support for previous epidemiological studies. PMID:16307975

  20. Biochemical, Metabolic, and Behavioral Characteristics of Immature Chronic Hyperphenylalanemic Rats.

    Science.gov (United States)

    Dienel, Gerald A; Cruz, Nancy F

    2016-02-01

    Phenylketonuria and hyperphenylalanemia are inborn errors in metabolism of phenylalanine arising from defects in steps to convert phenylalanine to tyrosine. Phe accumulation causes severe mental retardation that can be prevented by timely identification of affected individuals and their placement on a Phe-restricted diet. In spite of many studies in patients and animal models, the basis for acquisition of mental retardation during the critical period of brain development is not adequately understood. All animal models for human disease have advantages and limitations, and characteristics common to different models are most likely to correspond to the disorder. This study established similar levels of Phe exposure in developing rats between 3 and 16 days of age using three models to produce chronic hyperphenylalanemia, and identified changes in brain amino acid levels common to all models that persist for ~16 h of each day. In a representative model, local rates of glucose utilization (CMRglc) were determined at 25-27 days of age, and only selective changes that appeared to depend on Phe exposure were observed. CMRglc was reduced in frontal cortex and thalamus and increased in hippocampus and globus pallidus. Behavioral testing to evaluate neuromuscular competence revealed poor performance in chronically-hyperphenylalanemic rats that persisted for at least 3 weeks after cessation of Phe injections and did not occur with mild or acute hyperphenylalanemia. Thus, the abnormal amino acid environment, including hyperglycinemia, in developing rat brain is associated with selective regional changes in glucose utilization and behavioral abnormalities that are not readily reversed after they are acquired. PMID:26224289

  1. Comparison of rats and dogs exposed to 239PuO2

    International Nuclear Information System (INIS)

    Rats and dogs inhaled aerosols of 239PuO2 at comparable ages relative to their lifespan. Both received a single exposure. The estimated lung doses at death in dogs were between 1100 and 11,000 rad. From two inhalation experiments, rats receiving doses in this range were chosen from the high-level exposed animals for comparison. Based on this data base, several comparisons were investigated. Metabolism of the material was compared for all animals and for animals which developed lung tumors. The differences in histopathology and tumor incidence in the lung were also reviewed. Although there were several differences between species, there were also many similarities. On-going research in dogs should produce data which will allow clarification of these relationships

  2. Chronic kidney disease aggravates arteriovenous fistula damage in rats.

    Science.gov (United States)

    Langer, Stephan; Kokozidou, Maria; Heiss, Christian; Kranz, Jennifer; Kessler, Tina; Paulus, Niklas; Krüger, Thilo; Jacobs, Michael J; Lente, Christina; Koeppel, Thomas A

    2010-12-01

    Neointimal hyperplasia (NIH) and impaired dilatation are important contributors to arteriovenous fistula (AVF) failure. It is unclear whether chronic kidney disease (CKD) itself causes adverse remodeling in arterialized veins. Here we determined if CKD specifically triggers adverse effects on vascular remodeling and assessed whether these changes affect the function of AVFs. For this purpose, we used rats on a normal diet or on an adenine-rich diet to induce CKD and created a fistula between the right femoral artery and vein. Fistula maturation was followed noninvasively by high-resolution ultrasound (US), and groups of rats were killed on 42 and 84 days after surgery for histological and immunohistochemical analyses of the AVFs and contralateral femoral vessels. In vivo US and ex vivo morphometric analyses confirmed a significant increase in NIH in the AVFs of both groups with CKD compared to those receiving a normal diet. Furthermore, we found using histological evaluation of the fistula veins in the rats with CKD that the media shrank and their calcification increased significantly. Afferent artery dilatation was significantly impaired in CKD and the downstream fistula vein had delayed dilation after surgery. These changes were accompanied by significantly increased peak systolic velocity at the site of the anastomosis, implying stenosis. Thus, CKD triggers adverse effects on vascular remodeling in AVFs, all of which contribute to anatomical and/or functional stenosis.

  3. Global Gene Expression Profiling in Lung Tissues of Rat Exposed to Lunar Dust Particles

    Science.gov (United States)

    Yeshitla, Samrawit A.; Lam, Chiu-Wing; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Wu, Honglu; James, John T.; Meyers, Valerie E.; Zhang, Ye

    2014-01-01

    The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1-2% respirable very fine dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues of rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m3 of lunar dust. Animals were euthanized at 1 day and 13 weeks after the last inhalation exposure. After being lavaged, lung tissue from each animal was collected and total RNA was isolated. Four samples of each dose group were analyzed using Agilent Rat GE v3 microarray to profile global gene expression of 44K transcripts. After background subtraction, normalization, and log transformation, t tests were used to compare the mean expression levels of each exposed group to the control group. Correction for multiple testing was made using the method of Benjamini, Krieger, and Yekuteli (1) to control the false discovery rate. Genes with significant changes of at least 1.75 fold were identified as genes of interest. Both low and high doses of lunar dust caused dramatic, dose-dependent global gene expression changes in the lung tissues. However, the responses of lung tissue to low dose lunar dust are distinguished from those of high doses, especially those associated with 61mg/m3 dust exposure. The data were further integrated into the Ingenuity system to analyze the gene ontology (GO), pathway distribution and putative upstream regulators and gene targets. Multiple pathways, functions, and upstream regulators have been identified in response to lunar dust induced damage in the lung tissue.

  4. Summary of high field diffusion MRI and microscopy data demonstrate microstructural aberration in chronic mild stress rat brain.

    Science.gov (United States)

    Khan, Ahmad Raza; Chuhutin, Andrey; Wiborg, Ove; Kroenke, Christopher D; Nyengaard, Jens R; Hansen, Brian; Jespersen, Sune Nørhøj

    2016-09-01

    This data article describes a large, high resolution diffusion MRI data set from fixed rat brain acquired at high field strength. The rat brain samples consist of 21 adult rat brain hemispheres from animals exposed to chronic mild stress (anhedonic and resilient) and controls. Histology from amygdala of the same brain hemispheres is also included with three different stains: DiI and Hoechst stained microscopic images (confocal microscopy) and ALDH1L1 antibody based immunohistochemistry. These stains may be used to evaluate neurite density (DiI), nuclear density (Hoechst) and astrocytic density (ALDH1L1). This combination of high field diffusion data and high resolution images from microscopy enables comparison of microstructural parameters derived from diffusion MRI to histological microstructure. The data provided here is used in the article (Jespersen, 2016) [1]. PMID:27508246

  5. Morbidity rate of nervous system among medical personnel occupationally exposed to chronic low dose irradiation

    International Nuclear Information System (INIS)

    The morbidity rate of the nervous system among 1190 subjects, medical personnel, working with sources and environment of ionizing radiation was studied by the personal analysis of the diseases, written down in the personal out-patient department cards as well as of a control group of 870 medical workers of various other specialities. The morbidity rate of the nervous system among the medical personnel, exposed to chronic occupational radiation effect, was established not to be higher than that of the other medical workers - 38.0 and 40.3% respectively. Neuroses and peripheral nervous diseases have the greatest relative share in the structure of morbidity rate of the nervous system in both groups examined, with no statistical significance in the differences of the indices. The significantly higher incidence of autonome dystonias, established among the personnel from the X-ray departments and consulting rooms could be discussed in connection with the great relative share of the subjects from that group with a length of service over 15 years and had received the possible maximum cumulative equivalent doses. 3 tabs., 21 refs

  6. Nutritional traits of bean ( Phaseolus vulgaris ) seeds from plants chronically exposed to ozone pollution.

    Science.gov (United States)

    Iriti, Marcello; Di Maro, Antimo; Bernasconi, Silvana; Burlini, Nedda; Simonetti, Paolo; Picchi, Valentina; Panigada, Cinzia; Gerosa, Giacomo; Parente, Augusto; Faoro, Franco

    2009-01-14

    The effect of chronic exposure to ozone pollution on nutritional traits of bean ( Phaseolus vulgaris L. cv. Borlotto Nano Lingua di Fuoco) seeds from plants grown in filtered and nonfiltered open-top chambers (OTCs) has been investigated. Results showed that, among seed macronutrients, ozone significantly raised total lipids, crude proteins, and dietary fiber and slightly decreased total free amino acid content, although with a significant reduction of asparagine, lysine, valine, methionine, and glycine, compensated by a conspicuous augmentation of ornithine and tryptophan. Phytosterol analysis showed a marked increase of beta-sitosterol, stigmasterol, and campesterol in seeds collected from nonfiltered OTCs. With regard to secondary metabolites, ozone exposure induced a slight increase of total polyphenol content, although causing a significant reduction of some flavonols (aglycone kaempferol and its 3-glucoside derivative) and hydroxycinnamates (caffeic, p-coumaric, and sinapic acids). Total anthocyanins decreased significantly, too. Nevertheless, ozone-exposed seeds showed higher antioxidant activity, with higher Trolox equivalent antioxidant capacity (TEAC) values than those measured in seeds collected from filtered air.

  7. Regional alterations of brain biogenic amines in young rats following chronic lead exposure

    Energy Technology Data Exchange (ETDEWEB)

    Dubas, T.C.; Stevenson, A.; Singhal, R.L.; Hrdina, P.D.

    1978-02-01

    An examination was made of neurochemical changes that occur in discrete brain regions of rats that have been chronically exposed to low levels of lead from birth, in order to provide further information on the involvement of brain biogenic amines in lead-induced neurotoxicity. Results indicate a relationship between exposure to lead and alterations in the brain levels of various putative neurotransmitters. However, changes in the functional activity of the neurotransmitter may not be adequately reflected in the change of its steady-state levels or may occur even in the absence of any changes in the actual concentrations. Lead may influence central neurotransmitter function by affecting one or several of the processes involved in the synthesis, release and/or disposition of biogenic amines.

  8. Ex vivo exposure of bone marrow from chronic kidney disease donor rats to pravastatin limits renal damage in recipient rats with chronic kidney disease

    NARCIS (Netherlands)

    Koppen, A. van; Papazova, D.A.; Oosterhuis, N.R.; Gremmels, H.; Giles, R.H.; Fledderus, J.O.; Joles, J.A.; Verhaar, M.C.

    2015-01-01

    Introduction: Healthy bone marrow cell (BMC) infusion improves renal function and limits renal injury in a model of chronic kidney disease (CKD) in rats. However, BMCs derived from rats with CKD fail to retain beneficial effects, demonstrating limited therapeutic efficacy. Statins have been reported

  9. Alterations in DRH and DRL performance in rats developmentally exposed to an environmental PCB mixture.

    Science.gov (United States)

    Sable, Helen J K; Powers, Brian E; Wang, Victor C; Widholm, John J; Schantz, Susan L

    2006-01-01

    Schedule-controlled responding was examined in offspring of rats exposed to a PCB mixture formulated to mimic the PCB congener profile in fish from the Fox River in Green Bay, WI. Female rats were administered 0, 1, 3, or 6 mg/kg/day of the PCB mixture beginning four weeks prior to breeding until weaning on postnatal day 21. When offspring were approximately 235 days old, they were tested on three different schedules of a differential reinforcement of high rate (DRH) operant task (DRH 2:1, DRH 4:2, and DRH 8:4). DRH testing was followed by testing on the differential reinforcement of low rate (DRL) operant task in which rats had to inhibit responding until 15 s had elapsed (DRL 15) from the previous response in order to obtain a food reinforcer. After completion of DRL 15 testing, 3 days of extinction testing were conducted (DRL EXT) during which no reinforcers were delivered. Developmental exposure to the higher PCB doses resulted in shorter inter-response times (IRTs) and shorter response durations during DRH 8:4, which translated into a greater percentage of reinforced trials. For DRL 15, no significant exposure-related effects were observed on the number of responses or reinforcers earned, or the number or proportion of responses with long or short inter-response times during acquisition or steady state performance. However, during DRL EXT, rats developmentally exposed to the highest PCB dose responded more than controls, produced significantly more short IRT responses, and had a significantly lower proportion of long IRT responses. Overall, exposure to this PCB mixture resulted in increased responding which was suggestive of a deficit in inhibitory control. PMID:16930942

  10. Dose and temporal effects on gene expression profiles of urothelial cells from rats exposed to diuron

    International Nuclear Information System (INIS)

    Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide that at high dietary levels (2500 ppm) induces rat urinary bladder hyperplasia after 20 weeks of exposure and neoplasia after 2 years. The effects on the urothelium after short-term exposure have not been described. The present 7-day study evaluated the dose-dependency of urothelial alterations in the urinary bladder using light microscopy, scanning electron microscopy, and genome-wide transcriptional profiling. Male Wistar rats were fed 0, 125, 500, 2500 ppm diuron for 7 days. The urinary bladder and isolated urothelial cells of these animals were processed for microscopic examination and gene expression profiling, respectively. No significant treatment-related morphologic effects were observed. The number of differentially expressed genes (DEGs) in the exposed groups increased with diuron levels. Diuron-altered genes involved in cell-to-cell interactions and tissue organization were identified in all treatment groups. After 7 days of diuron exposure, transcriptional responses were observed in the urothelium in the absence of clear morphologic changes. These morphological findings are different from those observed in a previous study in which 20 weeks of diuron exposure was associated with simple hyperplasia secondary to the persistent cytotoxicity and necrosis associated with continuous cellular regeneration. Comparison of the gene expression profiles of rats exposed to the 2500 ppm carcinogenic diuron dose for 7 days versus 20 weeks revealed few similarities between these two time points at the gene or pathway level. Taken together, these data provide insight into the dose- and temporal-dependent morphological and transcriptional changes associated with diuron exposure that may lead to the development of tumors in the rat urinary bladder

  11. Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats

    OpenAIRE

    Morel, Gustavo R.; Sosa, Yolanda E.; Bellini, Maria J.; Carri, Nestor G.; Rodriguez, Silvia S.; Bohn, Martha C.; Goya, Rodolfo G.

    2010-01-01

    Progressive dysfunction of hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons during normal aging is associated in the female rat with chronic hyperprolactinemia. We assessed the effectiveness of glial cell line-derived neurotrophic factor (GDNF) gene therapy to restore TIDA neuron function in senile female rats and reverse their chronic hyperprolactinemia. Young (2.5 months) and senile (29 months) rats received a bilateral intrahypothalamic injection (1010 pfu) of either an adenovir...

  12. Gene Expression Profiling of Lung Tissue of Rats Exposed to Lunar Dust Particles

    Science.gov (United States)

    Zhang, Ye; Feiveson, Alan H.; Lam, Chiu-Wing; Kidane, Yared H.; Ploutz-Snyder Robert; Yeshitla, Samrawit; Zalesak, Selina M.; Scully, Robert R.; Wu, Honglu; James, John T.

    2014-01-01

    The purpose of the study is to analyze the dynamics of global gene expression changes in the lung tissue of rats exposed to lunar dust particles. Multiple pathways and transcription factors were identified using the Ingenuity Pathway Analysis tool, showing the potential networks of these signaling regulations involved in lunar dust-induced prolonged proflammatory response and toxicity. The data presented in this study, for the first time, explores the molecular mechanisms of lunar dust induced toxicity. This work contributes not only to the risk assessment for future space exploration, but also to the understanding of the dust-induced toxicity to humans on earth.

  13. Oxidative DNA damage in male wistar rats exposed to di-n-butyl phthalate

    DEFF Research Database (Denmark)

    Wellejus, A.; Dalgaard, Majken; Loft, S.

    2002-01-01

    Dialkyl phthalate esters are used in the plastic industry and widely distributed in the environment, Previously, it has been shown that di-n-butyl phthalate (DBP) produces testicular atrophy and liver enlargement in rodents, and the mechanisms behind this could involve reactive oxygen species (ROS...... in the formation of testicular atrophy in phthalate-exposed rats, no apparent sign of oxidative DNA damage was found after phthalate exposure perinatally or during the preadult stage, With respect to phthalate-induced oxidative DNA damage in the liver, it appears that the developmental stage during exposure...

  14. Effect of kombucha on some trace element levels in different organs of electromagnetic field exposed rats

    OpenAIRE

    Ola A. Gharib

    2014-01-01

    Mobile phones have increased exponentially all over the world. The present study was performed to evaluate the effect of kombucha (KT) on some trace element levels of brain, spleen and intestine in male albino rats exposed to a 950 MHz electromagnetic field (EMF). Four experimental groups labelled as controls, EMF group, KT group and KT + EMF group were formed with six randomly chosen animals in each group. After EMF exposure for eight weeks and the animals were sacrificed by decapitation. Br...

  15. Chronic mild stressors and diet affect gene expression differently in male and female rats.

    Science.gov (United States)

    Liang, Shuwen; Byers, Donna M; Irwin, Louis N

    2007-01-01

    While depression is reportedly more prevalent in women than men, a neurobiological basis for this difference has not been documented. Chronic mild stress (CMS) is a widely recognized animal model, which uses mild and unpredictable environmental stressors to induce depression. Studies of chronic stress, mainly in males, have reported an increase in the relative intake of "comfort food" as a means of counteracting the effects of stress. This study was designed to test the hypothesis that genes for certain neurotrophic factors, stress markers, and appetite regulators would be expressed differentially in male and female rats exposed to chronic, mild stressors with access to a preferred diet. Gene expression for neuropeptide Y was upregulated in females purely in response to stressors, whereas that for the epidermal growth factor receptor (EGFR) and arginine vasopressin (AVP) in males and fatty acid synthase (FASN) in females responded primarily to diet. Genes for brain-derived neurotrophic factor (BDNF), AVP, and the cocaine-amphetamine regulator of transcription (CART) in males, and leptin in females, showed a significant response to the interaction between stressors and diet. Every affected gene showed a different pattern of expression in males and females. This study confirms the intimate relationship between dietary intake and response to stress at the molecular level, and emphasizes the sex- and gene-specific nature of those interactions. Therefore, it supports a neurobiological basis for differences in the affective state response to stress in males and females. PMID:17917078

  16. Combined action of cadmium(II) and lead(II) and chronic γ-radiation on radiosensitivity of rat bone marrow cells

    International Nuclear Information System (INIS)

    Heavy metals are the most widespread and harmful contaminants of environment. Cadmium and lead compounds have a particularly high genotoxic action. In addition, long-term, low-dose chronic irradiation occurs most frequently in nature. Thus, the goal of the present work was to study the effect of salts of heavy metals, lead and cadmium, on the cytogenetic damage in bone marrow cells of rats exposed to chronic and acute gamma irradiation, as well as on the magnitude of the adaptive response induced by chronic irradiation. Adult male rats were exposed to chronic gamma irradiation at low dose rate from 137Cs in a gamma-chamber (dose rate of 0.0013 Gy/h). Cumulative doses of chronic irradiation were 3, 9, 21 and 40 cGy at 1, 3, 7 and 14 days of exposition, respectively. Solutions of heavy metals Pb(CH3COO)2 . 3H2O and CdCl2 . 2.5H2O (50 mg/l) were given per os throughout the period of chronic irradiation. Rats subjected to chronic irradiation with an appropriate dose were immediately subjected to single acute dose 4 or 6 Gy (dose rate 47 cGy/min). Chromosome preparations of bone marrow cells were carried out by standard procedures. Percent of cells with aberrations and all types of chromosome aberrations were recorded. Five animals were used in each experiment. From each animal 100-200 cells were scored. The results of this study indicate that the administration of heavy metal salts to the diet of rats 1) enhances the cytogenetic damage in unirradiated animals; 2) increases the genotoxic effect of chronic and acute irradiation; 3) slightly decreases the value of the adaptive response induced by chronic irradiation. (author)

  17. Influence of imipramine on the duration of immobility in chronic forced-swim-stressed rats.

    OpenAIRE

    Kitamura, Yoshihisa; Araki,Hiroaki; Nagatani,Tadashi; Takao,Katsuyuki; Shibata, Kazuhiko; Gomita,Yutaka

    2004-01-01

    We studied the influence of imipramine on the duration of immobility in chronic forced-swim-stressed rats. Both single and chronic administration of imipramine potently shortened immobility in naive rats during forced-swim testing. However, chronic, 14-day forced-swim stress testing blocked the immobility-decreasing effect induced by a single administration of imipramine. When imipramine was administered for 14 days concurrently with forced-swim stress testing, immobility was shorten...

  18. Anti-inflammatory and antioxidant effects of umbelliferone in chronic alcohol-fed rats

    OpenAIRE

    Sim, Mi-Ok; Lee, Hae-In; Ham, Ju Ri; Seo, Kwon-Il; Kim, Myung-Joo; Lee, Mi-Kyung

    2015-01-01

    BACKGROUND/OBJECTIVES Inflammation is associated with various types of acute and chronic alcohol liver diseases. In this study, we examined whether umbelliferone (7-hydroxycoumarin, UF) ameliorates chronic alcohol-induced liver damage by modulating inflammatory response and the antioxidant system. METHODS Rats were fed a Liber-Decarli liquid diet containing 5% alcohol with or without UF (0.05 g/L) for 8 weeks, while normal rats received an isocaloric carbohydrate liquid diet. RESULTS Chronic ...

  19. Effects of treadmill exercise-intensity on short-term memory in the rats born of the lipopolysaccharide-exposed maternal rats

    OpenAIRE

    Kim, Kijeong; Sung, Yun-Hee; Seo, Jin-Hee; Lee, Sang-Won; Lim, Baek-Vin; Lee, Choong-Yeol; Chung, Yong-Rak

    2015-01-01

    Maternal infection is an important factor causing neonatal brain injury and later developmental disability. In the present study, we investigated the effects of treadmill exercise intensity on short-term memory, hippocampal neurogenesis, and expression of brain-derived neurotrophic factor (BDNF), and tyrosine kinase receptor B (TrkB) in the rats born of lipopolysaccharide (LPS)-exposed maternal rats. The rats were divided into six groups: control group, mild-intensity exercise group, moderate...

  20. Chronic lithium treatment increased intracellular S100ß levels in rat primary neuronal culture.

    Directory of Open Access Journals (Sweden)

    Masoumeh Emamghoreishi

    2015-02-01

    Full Text Available S100ß a neurotrophic factor mainly released by astrocytes, has been implicated in the pathogenesis of bipolar disorder. Thus, lithium may exert its neuroprotective effects to some extent through S100ß. Furthermore, the possible effects of lithium on astrocytes as well as on interactions between neurons and astrocytes as a part of its mechanisms of actions are unknown. This study was undertaken to determine the effect of lithium on S100β in neurons, astrocytes and a mixture of neurons and astrocytes. Rat primary astrocyte, neuronal and mixed neuro-astroglia cultures were prepared from cortices of 18-day's embryos. Cell cultures were exposed to lithium (1mM or vehicle for 1day (acute or 7 days (chronic. RT-PCR and ELISA determined S100β mRNA and intra- and extracellular protein levels. Chronic lithium treatment significantly increased intracellular S100β in neuronal and neuro-astroglia cultures in comparison to control cultures (P<0.05. Acute and chronic lithium treatments exerted no significant effects on intracellular S100β protein levels in astrocytes, and extracellular S100β protein levels in three studied cultures as compared to control cultures. Acute and chronic lithium treatments did not significantly alter S100β mRNA levels in three studied cultures, compared to control cultures. Chronic lithium treatment increased intracellular S100ß protein levels in a cell-type specific manner which may favor its neuroprotective action. The findings of this study suggest that lithium may exert its neuroprotective action, at least partly, by increasing neuronal S100ß level, with no effect on astrocytes or interaction between neurons and astrocytes.

  1. Chronic toxicity study of cyclohexanone in rats and mice.

    Science.gov (United States)

    Lijinsky, W; Kovatch, R M

    1986-10-01

    A 2-year chronic toxicity assay of cyclohexanone (CAS: 108-94-1) was conducted in F344 rats and (C57BL/6 X C3H)F1 mice by administering a solution of cyclohexanone in drinking water. Two concentrations were given to rats, 6,500 and 3,300 ppm (wt/vol). Male mice received 13,000 and 6,500 ppm, while female mice were given three concentrations, 25,000, 13,000, and 6,500 ppm. Each treatment group consisted of 50 or 52 male and 50 or 52 female rats or mice, except 47 male mice treated with the highest dose and 41 female mice treated with the highest dose, and there was a group of untreated controls of each species. Survival and weight gain were similar to those of controls at the lowest cyclohexanone dose in both sexes of both species, but weight gain was depressed at all of the higher doses. Survival was good (greater than 80% at 90 wk) in all groups except in female mice at the 2 highest doses; at 25,000 ppm of cyclohexanone, only 50% of mice lived beyond 1 year. Most of the neoplasms in the treated groups did not differ significantly in number from those in the controls. Male rats receiving 3,300 ppm cyclohexanone had a 13% incidence of adrenal cortex adenomas (7 animals) compared with an incidence of 2% in controls; the incidence of this neoplasm did not increase in the male rats receiving 6,500 ppm or in the female rats given either dose. The mice had a statistically significant increase in incidence of lymphomas-leukemias among the females given 6,500 ppm, but not among the groups given higher doses of cyclohexanone. Male mice given 6,500 ppm cyclohexanone showed an increased incidence of hepatocellular adenomas and carcinomas, 50% versus 32.5% in controls, but the incidence of these neoplasms was only 37% in the male mice given 13,000 ppm cyclohexanone. The incidence of lymphomas in male mice and of hepatocellular neoplasms in female mice given cyclohexanone did not differ from that in the controls. The evidence for carcinogenic activity of cyclohexanone is

  2. Chronic ethanol exposure decreases CB1 receptor function at GABAergic synapses in the rat central amygdala.

    Science.gov (United States)

    Varodayan, Florence P; Soni, Neeraj; Bajo, Michal; Luu, George; Madamba, Samuel G; Schweitzer, Paul; Parsons, Loren H; Roberto, Marisa

    2016-07-01

    The endogenous cannabinoids (eCBs) influence the acute response to ethanol and the development of tolerance, dependence and relapse. Chronic alcohol exposure alters eCB levels and Type 1 cannabinoid receptor (CB1 ) expression and function in brain regions associated with addiction. CB1 inhibits GABA release, and GABAergic dysregulation in the central nucleus of the amygdala (CeA) is critical in the transition to alcohol dependence. We investigated possible disruptions in CB1 signaling of rat CeA GABAergic transmission following intermittent ethanol exposure. In the CeA of alcohol-naive rats, CB1 agonist WIN 55,212-2 (WIN) decreased the frequency of spontaneous and miniature GABAA receptor-mediated inhibitory postsynaptic currents (s/mIPSCs). This effect was prevented by CB1 antagonism, but not Type 2 cannabinoid receptor (CB2 ) antagonism. After 2-3 weeks of intermittent ethanol exposure, these WIN inhibitory effects were attenuated, suggesting ethanol-induced impairments in CB1 function. The CB1 antagonist AM251 revealed a tonic eCB/CB1 control of GABAergic transmission in the alcohol-naive CeA that was occluded by calcium chelation in the postsynaptic cell. Chronic ethanol exposure abolished this tonic CB1 influence on mIPSC, but not sIPSC, frequency. Finally, acute ethanol increased CeA GABA release in both naive and ethanol-exposed rats. Although CB1 activation prevented this effect, the AM251- and ethanol-induced GABA release were additive, ruling out a direct participation of CB1 signaling in the ethanol effect. Collectively, these observations demonstrate an important CB1 influence on CeA GABAergic transmission and indicate that the CeA is particularly sensitive to alcohol-induced disruptions of CB1 signaling.

  3. Endothelial dysfunction in normal and prediabetic rats with metabolic syndrome exposed by oral gavage to carbon black nanoparticles

    DEFF Research Database (Denmark)

    Folkmann, Janne Kjærsgaard; Vesterdal, Lise Kristine; Sheykhzade, Majid;

    2012-01-01

    Exposure to nanosized particles may increase the risk of cardiovascular diseases by endothelial dysfunction, particularly in susceptible subjects with metabolic syndrome. We investigated vasomotor dysfunction in aorta from obese and lean Zucker rats after oral exposure to nanosized carbon black (CB......-induced vasorelaxation and phenylephrine-induced vasocontraction was not affected in rats exposed to CB. The endothelial dysfunction was not observed in rats sacrificed 13 weeks after the last CB exposure. There was unaltered expression of Chrm3, Nos3, Nos2, Ccl2, and Hmox1 in aorta tissue of CB-exposed rats. In...... conclusion, repeated oral exposure to CB was associated with endothelial dysfunction in rats, further aggravating the effect of metabolic syndrome....

  4. Chronic inhalation studies of two types of stone wool fibers in rats.

    Science.gov (United States)

    Kamstrup, O; Ellehauge, A; Chevalier, J; Davis, J M; McConnell, E E; Thévenaz, P

    2001-07-01

    A summary is given of the pathology results after long-term inhalation in rats of insulation wool representing the new biosoluble types. The pathology results are compared with previously conducted long-term inhalation study with MMVF21 (traditional stone wool). The biosoluble fiber MMVF34/HT (HT) is characterized by a relatively high content of aluminum and a relatively low content of silica compared to the older MMVF21. HT has a high in vitro dissolution rate at pH 4.5, and a relatively low dissolution rate at pH 7.5. Male Fischer 344 rats were exposed at one exposure level of 30 mg/m(3) by nose-only inhalation of a well-characterized fiber test atmosphere. The fibers had been size selected to be largely rat respirable. The negative control group was exposed to filtered air. The exposure duration was 6 h/day, 5 days/wk for 104 wk, with a subsequent nonexposure period lasting until approximately 20% survival in the air control group. Interim sacrifices were performed at wk 13, 26, 52, 78, and 104 to monitor the progression of pulmonary change and fiber numbers. Effectively the main protocol for the previously conducted chronic study with MMVF21 was the same, except that there were three concentration levels (3, 16, and 30 mg/m(3)). In addition to the endpoints measured in the previous study, slides from both studies were evaluated for collagen deposition using a quantitative morphometric method. The results of the comparative study clearly showed a marked difference in the pulmonary pathogenicity of the MMVF21 and HT in terms of their fibrogenic potential. MMVF21 caused pulmonary fibrosis, but the HT fiber did not. The incidence of tumors for both the HT and the MMVF21 fiber was comparable to the control groups. PMID:11452357

  5. Ultrastructural and tissue restructuring of the rat atrial myocardium under the influence of acute and chronic prenatal hypoxia

    Directory of Open Access Journals (Sweden)

    Shevchenko K. M.

    2015-09-01

    Full Text Available Background. There are relatively few researches that focused on the study of the influence of hypoxia on atrial myocardium. However the results of previous researches are contradictory and fragmentary, that leades to the further study of this item. Objective. Purpose of the work was to determine the tissue, cellular and ultrastructural changes of the rat atrial myocardium during the stages of cardiogenesis under the conditions of acute and chronic prenatal hypoxia. Methods. Embryo hearts were investigated on 14th, 16th and 18th day of prenatal ontogenesis, newborn rat hearts and the hearts of rats on the 3rd, 14th and 30th day of postnatal ontogenesis. Animals were subdivided into three groups: first experimental group animals were exposed to acute prenatal hypoxia, second experimental group animals were exposed to chronic prenatal hypoxia and control group animals. Hypoxia modeling was conducted on pregnant females by injection of 1% sodium nitrite intraperitonealy in doses that lead to moderate hypoxia. During the work complex of histological, immunohistochemical and morphometric methods was used. Results and conclusion. Effect of acute hypoxia leads to stimulation of proliferative activity of fibroblasts and endothelial cells on the right atrium, which causes to increasing of the relative volume of connective tissue and blood vessels of microvasculature of myocardium. Relative volume of connective tissue of the atrial myocardium exceeds significantly the control level of newborn rats. Ultrastructural changes of the atrial cardiomyocytes in 3 days after the influence of acute prenatal hypoxia reveals on violation of mitochondrial structure, significant inhibition of myofibrils accumulation. Until the birth of most of morphometric parameters renewal and reach control levels, however changes of the degree of myofibrils orientation on the left atrium proves stability of hypoxic damages. Chronic prenatal hypoxia causes a significant increase of

  6. Effect of Retinoic Acid on Lung Injury in Hyperoxia-Exposed Newborn Rats

    Institute of Scientific and Technical Information of China (English)

    常立文; 容志惠; 张谦慎; 钱莉玲

    2003-01-01

    To investigate whether treatment with retinoic acid (RA) could improve level of lung alveolarization and influence lung collagen in newborn rats exposed to hyperoxia, newborn SpragueDawley rats aged 2 days were randomly assigned to 8 groups: (1) air, (2) O2, (3) air+NS, (4)O2 +NS, (5) air+dex, (6) O2+dex, (7) air+RA and (8) O2+RA. Group 2, 4 6 and 8 were kept in chambers containing 85 % oxygen, the values were checked 3 times a day. The other 4 groups were exposed to room air. Level of alveolarization and lung collagen were analyzed at age of 14 or 21 days through radial alveolar counts, alveolar airspace measurements, type Ⅰ , Ⅲ collagen immunohistochemical methods (SP method) and image processing system. Transforming growth factor-β receptors and procollagen mRNA accumulation were examined at age of 14 days through immunohistochemical methods and in situ hybridization. Our results showed that radial alveolar counts were increased and distal airspace was enlarged in group 8. Type I collagen was markedly increased, and transforming growth factor-β receptors and procollagen mRNA were decreased by retinoic acid in bronchial epithelial cells, alveolar epithelial cells and alveolar intersitium. It is concluded that retinoic acid can partially reverse lung development arrest during exposure to hyperoxia by increasing lung collagen.

  7. Cytomorphometric changes in hippocampal CA1 neurons exposed to simulated microgravity using rats as model

    Directory of Open Access Journals (Sweden)

    Amit eRanjan

    2014-05-01

    Full Text Available Microgravity and sleep loss lead to cognitive and learning deficits. These behavioral alterations are likely to be associated with cytomorphological changes and loss of neurons. To understand the phenomenon, we exposed rats (225-275g to 14 days simulated microgravity (SMg and compared its effects on CA1 hippocampal neuronal plasticity, with that of normal cage control rats. We observed that the mean area, perimeter, synaptic cleft and length of active zone of CA1 hippocampal neurons significantly decreased while dendritic arborization and number of spines significantly increased in SMg group as compared with controls. The mean thickness of the post synaptic density and total dendritic length remained unaltered. The changes may be a compensatory effect induced by exposure to microgravity; however, the effects may be transient or permanent, which need further study. These findings may be useful for designing effective prevention for those, including the astronauts, exposed to microgravity. Further, subject to confirmation we propose that SMg exposure might be useful for recovery of stroke patients.

  8. Evaluation of reproductive function of female rats exposed to radiofrequency fields (27. 12 MHz) near a shortwave diathermy device

    Energy Technology Data Exchange (ETDEWEB)

    Brown-Woodman, P.D.; Hadley, J.A.; Richardson, L.; Bright, D.; Porter, D.

    1989-04-01

    In recent years, there has been increased concern regarding effects of operator exposure to the electromagnetic (EM) field associated with shortwave diathermy devices. The present study was designed to investigate the effects, on rats, of repeated exposure to such an EM field. Following repeated exposure for 5 wk, a reduction in fertility occurred as indicated by a reduced number of matings in exposed rats compared to sham-irradiated rats and a reduction in the number of rats that conceived after mating. The data suggest that female operators could experience reduced fertility, if they remained close to the console for prolonged periods. This has particular significant for the physiotherapy profession.

  9. Antidepressant-like effects and possible mechanisms of amantadine on cognitive and synaptic deficits in a rat model of chronic stress.

    Science.gov (United States)

    Yu, Mei; Zhang, Yuan; Chen, Xiaoyu; Zhang, Tao

    2016-01-01

    The aim of this study was to examine whether amantadine (AMA), as a low-affinity noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, is able to improve cognitive deficits caused by chronic stress in rats. Male Wistar rats were divided into four groups: control, control + AMA, stress and stress + AMA groups. The chronic stress model combined chronic unpredictable stress (CUS) with isolated feeding. Animals were exposed to CUS continued for 21 days. AMA (25 mg/kg) was administrated p.o. for 20 days from the 4th day of CUS to the 23rd. Weight and sucrose consumption were measured during model establishing period. Spatial memory was evaluated using the Morris water maze (MWM) test. Following MWM testing, both long-term potentiation (LTP) and depotentiation were recorded in the hippocampal CA1 region. NR2B and postsynaptic density protein 95 (PSD-95) proteins were measured by Western-blot analysis. AMA increased weight and sucrose consumption of stressed rats. Spatial memory and reversal learning in stressed rats were impaired relative to controls, whereas AMA significantly attenuated cognitive impairment. AMA also mitigated the chronic stress-induced impairment of hippocampal synaptic plasticity, in which both the LTP and depotentiation were significantly inhibited in stressed rats. Moreover, AMA enhanced the expression of hippocampal NR2B and PSD-95 in stressed rats. The data suggest that AMA may be an effective therapeutic agent for depression-like symptoms and associated cognitive disturbances.

  10. Antidepressant-like effects and possible mechanisms of amantadine on cognitive and synaptic deficits in a rat model of chronic stress.

    Science.gov (United States)

    Yu, Mei; Zhang, Yuan; Chen, Xiaoyu; Zhang, Tao

    2016-01-01

    The aim of this study was to examine whether amantadine (AMA), as a low-affinity noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, is able to improve cognitive deficits caused by chronic stress in rats. Male Wistar rats were divided into four groups: control, control + AMA, stress and stress + AMA groups. The chronic stress model combined chronic unpredictable stress (CUS) with isolated feeding. Animals were exposed to CUS continued for 21 days. AMA (25 mg/kg) was administrated p.o. for 20 days from the 4th day of CUS to the 23rd. Weight and sucrose consumption were measured during model establishing period. Spatial memory was evaluated using the Morris water maze (MWM) test. Following MWM testing, both long-term potentiation (LTP) and depotentiation were recorded in the hippocampal CA1 region. NR2B and postsynaptic density protein 95 (PSD-95) proteins were measured by Western-blot analysis. AMA increased weight and sucrose consumption of stressed rats. Spatial memory and reversal learning in stressed rats were impaired relative to controls, whereas AMA significantly attenuated cognitive impairment. AMA also mitigated the chronic stress-induced impairment of hippocampal synaptic plasticity, in which both the LTP and depotentiation were significantly inhibited in stressed rats. Moreover, AMA enhanced the expression of hippocampal NR2B and PSD-95 in stressed rats. The data suggest that AMA may be an effective therapeutic agent for depression-like symptoms and associated cognitive disturbances. PMID:26466744

  11. Responsiveness of cerebral and hepatic cytochrome P450s in rat offspring prenatally exposed to lindane

    International Nuclear Information System (INIS)

    ABSTRACT: Prenatal exposure to low doses of lindane has been shown to affect the ontogeny of xenobiotic metabolizing cytochrome P450s (CYPs), involved in the metabolism and neurobehavioral toxicity of lindane. Attempts were made in the present study to investigate the responsiveness of CYPs in offspring prenatally exposed to lindane (0.25 mg/kg b. wt.; 1/350th of LD50; p. o. to mother) when challenged with 3-methylcholanthrene (MC) or phenobarbital (PB), inducers of CYP1A and 2B families or a sub-convulsant dose of lindane (30 mg/kg b. wt., p. o.) later in life. Prenatal exposure to lindane was found to produce an increase in the mRNA and protein expression of CYP1A1, 1A2, 2B1, 2B2 isoforms in brain and liver of the offspring at postnatal day 50. The increased expression of the CYPs in the offspring suggests the sensitivity of the CYPs during postnatal development, possibly, to low levels of lindane, which may partition into mother's milk. A higher increase in expression of CYP1A and 2B isoenzymes and their catalytic activity was observed in animals pretreated prenatally with lindane and challenged with MC (30 mg/kg, i. p. x 5 days) or PB (80 mg/kg, i. p. x 5 days) when young at age (approx. 7 weeks) compared to animals exposed to MC or PB alone. Further, challenge of the control and prenatally exposed offspring with a single sub-convulsant dose of lindane resulted in an earlier onset and increased incidence of convulsions in the offspring prenatally exposed to lindane have demonstrated sensitivity of the CYPs in the prenatally exposed offspring. Our data assume significance as the subtle changes in the expression profiles of hepatic and cerebral CYPs in rat offspring during postnatal development could modify the adult response to a later exposure to xenobiotics

  12. Concentration and depuration of some radionuclides present in a chronically exposed population of mussels (Mytilus edulis)

    Energy Technology Data Exchange (ETDEWEB)

    Clifton, R.J.; Stevens, H.E.; Hamilton, E.I.

    1983-03-01

    Factors are described which affect the concentration (p Ci g/sup -1/ dry wt) and loss of /sup 241/ Am, /sup 239 +240/Pu, /sup 238/Pu, /sup 144/Ce, /sup 137/Cs, /sup 134/Cs, /sup 106/Ru, /sup 95/Zr and /sup 95/Nb in an exposed population of mussels Mytilus edulis L. from Ravenglass on the Esk estuary, Cumbria, UK which receives radioeffluents from the British Nuclear Fuels Ltd. (BNFL) plant at Sellafield, some 10 km to the north. Tidal position and mussel body size have a negligible influence on the concentration of /sup 241/Am, /sup 137/Cs and /sup 106/Ru in the total soft tissue, but variation in soft tissue weight throughout the year has a considerable influence on the apparent concentration and depuration times of these radionuclides. Apart from the clearance (tsub(1/2) biol, 1 to 3 h) of sediment-associated activity from the digestive tract, the depuration rate profiles follow a single component clearance curve with a biological half-life in excess of 200 d for /sup 241/ Am, /sup 239 +240/Pu, /sup 238/Pu and /sup 144/Ce, and of 40 d for /sup 137/Cs. The clearance of /sup 106/Ru is more complex and consists of a 3 component depuration profile with biological half-lives of 6 h, 12 d and 260 d. The depuration profiles presented in this work are for chronically ingested isotopes under natural conditions; acute exposure will most likely result in different profiles, especially those derived from laboratory spiking experiments. Isotope ratio data support the hypothesis that the main route of entry into the mussel for the majority of the radionuclides studied is from the water.

  13. Effects of High-Butterfat Diet on Embryo Implantation in Female Rats Exposed to Bisphenol A.

    Science.gov (United States)

    Martinez, Alan M; Cheong, Ana; Ying, Jun; Xue, Jingchuan; Kannan, Kurunthachalam; Leung, Yuet-Kin; Thomas, Michael A; Ho, Shuk-Mei

    2015-12-01

    Bisphenol A (BPA) is an endocrine disruptor associated with poor pregnancy outcomes in human and rodents. The effects of butterfat diets on embryo implantation and whether it modifies BPA's actions are currently unknown. We aimed to determine the effects of butterfat diet on embryo implantation success in female rats exposed to an environmentally relevant dose of BPA. Female Sprague-Dawley rats were exposed to dietary butterfat (10% or 39% kcal/kg body weight [BW]) in the presence or absence of BPA (250 μg/kg BW) or ethinylestradiol (0.1 μg/kg BW) shortly before and during pregnancy to assess embryo implantation potentials by preimplantation development and transport, in vitro blastulation, outgrowth, and implantation. On gestational day (GD) 4.5, rats treated with BPA alone had higher serum total BPA level (2.3-3.7 ng/ml). They had more late-stage preimplantation embryos, whereas those receiving high butterfat (HBF) diet had the most advanced-stage embryos; dams cotreated with HBF and BPA had the most number of advanced embryos. BPA markedly delayed embryo transport to the uterus, but neither amount of butterfat had modifying effects. An in vitro implantation assay showed HBF doubled the outgrowth area, with BPA having no effect. In vivo, BPA reduced the number of implanted embryos on GD8, and cotreatment with HBF eliminated this adverse effect. HBF diet overall resulted in more and larger GD8 embryos. This study reveals the implantation disruptive effects of maternal exposure to an environmentally relevant dose of BPA and identifies HBF diet as a modifier of BPA in promoting early embryonic health.

  14. Protective effects of emodin and astragalus polysaccharides on chronic hepatic injury in rats

    Institute of Scientific and Technical Information of China (English)

    DANG Shuang-suo; ZHANG Xin; JIA Xiao-li; CHENG Ya-nan; SONG Ping; LIU En-qi; HE Qian; LI Zong-fang

    2008-01-01

    Background Chinese medicine plays an important role in hepatoprotective treatment. This study was conducted to investigate the protective effects of emodin and astragalus polysaccharides (APS) in a rat model of chronic hepatic injury.Methods Chronic hepatic injury was induced by hypodermic injection of an olive oil solution containing 40% carbon tetrachloride (CCI4) twice a week, in addition to a diet of 79.5% maizena, 20% fat, 0.5% cholesterol, and 10% alcohol in the drinking water ad libitum for 12 weeks. Meanwhile, the rats were exposed to different concentrations of emodin (40 mg·kg-1·d-1), APS (200 mg·kg-1·d-1), combination drug (emodin 40 mg.kg-1·d-1 combined with APS 200 mg.kg-1·d-1) and colchicine (0.1 mg·kg-1·d-1) in parallel by oral gavage (once a day for 12 weeks). At the end of 12 weeks, blood serum and liver tissue were taken. Serum was collected to determine the levels of total bilirubin (TBIL), alanine transaminase (ALT),aspartate transaminose (AST), and albumin (ALB). Liver and spleen indexes were assayed, followed by the measurements of the liver associated enzyme superoxide dismutase (SOD) and malondialdehyde (MDA). Histopathological changes were studied using optical microscopy.Results Splenohepatomegalia was alleviated and serum levels of TBIL and ALT were reduced in the groups treated with emodin and APS when compared to the control group. In addition, the ALB level in the APS and combination groups was higher. Similarly, the SOD activity of liver homogenates was significantly higher in the groups treated with emodin and APS, while administration of the herbal derivatives prevented the elevation in MDA levels. Histological analysis showed that the APS and combination groups significantly ameliorated the hepatic injury.Conclusions Co-administration of emodin and APS demonstrated a synergistic action in reducing ALT and restoring ALB in the serum from a rat model of chronic hepatic injury. Emodin and APS may ameliorate the CCI4-induced

  15. Expression and function of Oat1 and Oat3 in rat kidney exposed to mercuric chloride

    Energy Technology Data Exchange (ETDEWEB)

    Di Giusto, Gisela; Torres, Adriana M. [Universidad Nacional de Rosario, CONICET, Area Farmacologia, Facultad de Ciencias Bioquimicas y Farmaceuticas, Rosario (Argentina); Anzai, Naohiko; Endou, Hitoshi [Kyorin University School of Medicine, Department of Pharmacology and Toxicology, Tokyo (Japan); Ruiz, Maria L. [Universidad Nacional de Rosario, CONICET, Instituto de Fisiologia Experimental, Facultad de Ciencias Bioquimicas y Farmaceuticas, Rosario (Argentina)

    2009-10-15

    This study was designed to evaluate the expression and function of the organic anion transporters, Oat1 and Oat3, in rats exposed to a nephrotoxic dose of HgCl{sub 2}. Oat1 protein expression increased in renal homogenates and decreased in renal basolateral membranes from HgCl{sub 2} rats, while Oat3 protein abundance decreased in both kidney homogenates and basolateral membranes. The lower protein levels of Oat1 and Oat3 in basolateral membranes explain the lower uptake capacity for p-aminohippurate (in vitro assays) and the diminution of the systemic clearance of this organic anion (in vivo studies) observed in treated rats. Since both transporters mediate mercury access to the renal cells, their down-regulation in basolateral membranes might be a defensive mechanism developed by the cell to protect itself against mercury injury. The pharmacological modulation of the expression and/or the function of Oat1 and Oat3 might be an effective therapeutic strategy for reducing the nephrotoxicity of mercury. (orig.)

  16. Steroidogenesis-related gene expression in the rat ovary exposed to melatonin supplementation

    Directory of Open Access Journals (Sweden)

    Gisele Negro Lima

    2015-02-01

    Full Text Available OBJECTIVE: To analyze steroidogenesis-related gene expression in the rat ovary exposed to melatonin supplementation. METHODS: Thirty-two virgin adult female rats were randomized to two groups as follows: the control group GI received vehicle and the experimental group GII received melatonin supplementation (10 µg/night per animal for 60 consecutive days. After the treatment, animals were anesthetized and the collected ovaries were immediately placed in liquid nitrogen for complementary deoxyribonucleic acid microarray analyses. A GeneChip¯ Kit Rat Genome 230 2.0 Affymetrix Array was used for gene analysis and the experiment was repeated three times for each group. The results were normalized with the GeneChip¯ Operating Software program and confirmed through analysis with the secondary deoxyribonucleic acid-Chip Analyzer (dChip software. The data were confirmed by real-time reverse transcription polymerase chain reaction analysis. Genes related to ovarian function were further confirmed by immunohistochemistry. RESULTS: We found the upregulation of the type 9 adenylate cyclase and inhibin beta B genes and the downregulation of the cyclic adenosine monophosphate response element modulator and cytochrome P450 family 17a1 genes in the ovarian tissue of GII compared to those of the control group. CONCLUSION: Our data suggest that melatonin supplementation decreases gene expression of cyclic adenosine monophosphate, which changes ovarian steroidogenesis.

  17. Lead exposure increases oxidative stress in the gastric mucosa of HCI/ethanol-exposed rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the role of reactive oxygen species in the ulcer-aggravating effect of lead in albino rats.METHODS: Albino Wistar rats were randomly divided into three groups and treated orally with 100 mg/L (low dose) or 5000 mg/L (high dose) of lead acetate for 15 wk. A third group received saline and served as control.At the end of wk 15, colorimetric assays were applied to determine the concentrations of total protein and nitrite, the activities of the oxidative enzymes catalase and superoxide dismutase, and lipid peroxidation in homogenized gastric mucosal samples.RESULTS: Exposure of rats to lead significantly increased the gastric mucosal damage caused by acidified ethanol. Although the basal gastric acid secretory rate was not significantly altered, the maximal response of the stomach to histamine was significantly higher in the lead-exposed animals than in the unexposed control group. Exposure to low and high levels of lead significantly increased gastric lipid peroxidation to 183.2% ± 12.7% and 226.1% ± 6.8% of control values respectively (P < 0.0). On the other hand, lead exposure significantly decreased catalase and superoxide dismutase (SOD) activities and the amount of nitrite in gastric mucosal samples.CONCLUSION: Lead increases the formation of gastric ulcers by interfering with the oxidative metabolism in the stomach.

  18. Neurobehavioral, reflexological and physical development of Wistar rat offspring exposed to ayahuasca during pregnancy and lactation

    Directory of Open Access Journals (Sweden)

    Carolina Dizioli Rodrigues de Oliveira

    2011-12-01

    Full Text Available Ayahuasca is a hallucinogenic beverage prepared by the decoction of plants native to the Amazon Basin region. The beverage has been used throughout the world by members of some syncretic religious movements. Despite the recent legalization of ayahuasca in Brazil for religious purposes, there is little pre-clinical and clinical information attesting to its safety, particularly in relation to the use during pregnancy. The aim of the current work was to determine the effects of perinatal exposure to ayahuasca (from the 6th day of pregnancy to the 10th day of lactation on physical, reflexology and neurobehavioral parameters of the Wistar rat offspring. The offspring showed no statistically significant changes in the physical and reflexology parameters evaluated. However, in adult rats, perinatally exposed to ayahuasca, an increase in frequency of entries in open arms in elevated plus-maze test, a decrease in total time of interaction in social interaction test, a decrease in time of latency for the animal to start swimming and a decrease of the minimum convulsant dose induced by pentylenetetrazol were observed. In conclusion, our results showed that the use of ayahuasca by mothers during pregnancy and lactation reduced the general anxiety and social motivation of the rat offspring. Besides, it promoted a higher sensitivity for initiation and spread of seizure activity.

  19. A combined chronic toxicity/carcinogenicity study of sucralose in Sprague-Dawley rats.

    Science.gov (United States)

    Mann, S W; Yuschak, M M; Amyes, S J; Aughton, P; Finn, J P

    2000-01-01

    The chronic toxicity and potential carcinogenicity of sucralose was evaluated by exposing Sprague-Dawley rats to dietary concentrations of this low-calorie sweetener both in utero and for up to 104 weeks following parturition. The rats assigned to the toxicity phase of this investigation were administered diets containing either 0% (control), 0.3% (3000 ppm), 1.0% (10,000 ppm) or 3.0% (30,000 ppm) sucralose. Each treatment group comprised 30 male and 30 female rats, of which 15 males and 15 females were sacrificed after 52 weeks of treatment. The surviving rats were killed following 78 weeks of sucralose administration. In the carcinogenicity phase of this investigation, groups of 50 male and 50 female rats were administered dietary sucralose at concentrations of 0% (control 1), 0% (control 2), 0.3%, 1.0% or 3.0% for 104 weeks. Evaluation of the data obtained from the two phases of this study showed that sucralose was not carcinogenic. Sucralose did not adversely affect the survival or clinical condition of the rats, and there were no toxicologically significant findings. Group mean body weight gain and food consumption were significantly decreased in a dose-dependent manner in sucralose-treated rats throughout the treatment period as compared to the controls. The primary effect of sucralose on food consumption, and secondarily on body weight gain, was established in later studies to be due to the fact that diets containing high concentrations of sucralose are unpalatable to rats. These subsequent studies established that the reduction of body weight gain seen in previous rat studies using sucralose in the diet at concentrations of 1% and below resulted from reduced food intake as a direct consequence of the unpalatable nature of sucralose. Similarly, at concentrations of 3% in the diet, it was shown that approximately 95% of the effect on body weight gain could be attributed to the reduction in food intake due to the reduced palatability of the diet, the remainder

  20. Effects of treadmill exercise-intensity on short-term memory in the rats born of the lipopolysaccharide-exposed maternal rats.

    Science.gov (United States)

    Kim, Kijeong; Sung, Yun-Hee; Seo, Jin-Hee; Lee, Sang-Won; Lim, Baek-Vin; Lee, Choong-Yeol; Chung, Yong-Rak

    2015-12-01

    Maternal infection is an important factor causing neonatal brain injury and later developmental disability. In the present study, we investigated the effects of treadmill exercise intensity on short-term memory, hippocampal neurogenesis, and expression of brain-derived neurotrophic factor (BDNF), and tyrosine kinase receptor B (TrkB) in the rats born of lipopolysaccharide (LPS)-exposed maternal rats. The rats were divided into six groups: control group, mild-intensity exercise group, moderate-intensity exercise group, maternal LPS-exposed group, maternal LPS-exposed and mild-intensity exercise group, maternal LPS-exposed and moderate-intensity exercise group. The rats in the exercise groups were forced to run on a treadmill for 30 min 5 times a week for 4 weeks. The exercise load consisted of running at the speed of 8 m/min for the mild-intensity exercise groups and 14 m/min for moderate-intensity exercise groups. The latency in the step-down avoidance task was deter-mined for the short-term memory. Immunohistochemistry for 5-bro-mo-2'-deoxyuridine was performed to determine hippocampal cell proliferation and neurogenesis. Western blot analysis was performed for the detection of BDNF and TrkB expression. In the present study, tread-mill exercise improved short-term memory deteriorated by maternal LPS exposure. Treadmill exercise increased cell proliferation and neurogenesis in the hippocampal dentate gyrus of the rats born of the LPS-exposed maternal rats. Treadmill exercise increased BDNF and TrkB expression in the hippocampus of the rats born of the LPS-exposed maternal rats. These effects of treadmill exercise were similarly appeared at both mild-intensity and moderate-intensity. PMID:26730379

  1. Mechanical properties and reactivity of vessels in isolated perfused lungs of chronically hypoxic rats.

    Science.gov (United States)

    Emery, C J; Bee, D; Barer, G R

    1981-11-01

    1. Chronically hypoxic rats kept in 10% (v/v) O2 for 3--6 weeks, were compared with littermate control rats. Pulmonary vascular resistance, measured from the slope of the pressure-flow relationship in isolated lungs perfused with blood of normal packed cell volume was higher in chronically hypoxic than control rats even during normoxia. 2. Chronically hypoxic rats weighed less than control rats but their pulmonary vascular volume, measured with labelled albumin was similar to control rats. This, together with evidence that the number of precapillary vessels is not reduced, does not suggest a large reduction in the vascular bed in chronic hypoxia. 3. A greater vasodilator action of isoprenaline and adenosine in chronically hypoxic than control lungs suggested a higher normoxic vascular tone. This higher tone was not the sole cause of increased resistance in chronically hypoxic lungs, since maximal vasodilatation did not reduce resistance to control levels. The chief cause was probably encroachment of new muscle on the vascular lumen of small vessels. 4. Pulmonary arterial compliance was reduced in chronically hypoxic lungs. 5. Reactivity of vessels to ventilation hypoxia, over a wide range of oxygen tension, to angiotensin II (ANG II) and to adenosine 5'-triphosphate (ATP) was significantly greater in chronically hypoxic than control lungs, but thresholds to these stimuli were not reduced. PMID:7285503

  2. Structural characterization of rat ventricular tissue exposed to the smoke of two types of waterpipe

    Directory of Open Access Journals (Sweden)

    Wajdy Al-Awaida

    2015-10-01

    Full Text Available Objective(s:this study focused on the effect of waterpipe smoke exposure toxicity on the structure of albino rat’s ventricular tissue and their recovery. Materials and Methods: Albino rats were divided into three groups: control, flavored, and unflavored. The control group was exposed to normal air while the flavored and unflavored groups were exposed to waterpipe smoke for a period of 90 days. Each group was followed by a period of 90 days of fresh air exposure. Following each period, the ventricular tissue was removed for biochemical and histopathological studies. Results:The ventricular tissues of waterpipe exposed rats showed some degree of separation between cardiac muscle fibers, infiltration of lymphocytes, and congestion of blood vessel. Also, thin cross sections of ventricular cells revealed pleomorphic mitochondria with partially disrupted cristae, partial disruption of the myofibrils, and deposited toxic materials. The unflavored waterpipe has more deleterious effects on heart ventricular tissues than the flavored one. Waterpipe smoke didn't induce apoptosis in the ventricular tissue. We also found very high levels of plasma thiocyanate after exposure to smoke in the flavored and unflavored groups, while the control group showed no increase. After the recovery period, those tissues showed partial recovery. Conclusion: Waterpipe smoke induces structural changes in the heart ventricle tissues, causing a negative impact on the capacity of the cardiac muscle for pumping blood and may lead to heart attack due to accumulation of free radicals and tissue inflammation. Cessation of smoking is important in returning most of these changes to their normal structure.

  3. Masked rat: an x-ray-induced mutant with chronic blepharitis, alopecia, and pasteurellosis

    International Nuclear Information System (INIS)

    An autosomal recessive mutation had been previously x-ray-induced in the rat and named the masked rat (genotype mk/mk). This study describes the mutant's appearance, histology, and microflora. The rat's eyelids were swollen, often to the point of closure, and its face was partially covered by a brownish crust, giving the mutant a mask-like appearance. The chronic blepharitis was also accompanied by alopecia that appeared as bare patches across the mutant's back. Pasteurella pneumotropica was found in eyelids and on skin from all masked rats. The normal rat demonstrated a resistance to Pasteurella pneumotropica infection, or, conversely, the masked rat appeared to be genetically predisposed to pasteurellosis

  4. Impaired response inhibition in the rat 5 choice continuous performance task during protracted abstinence from chronic alcohol consumption.

    Directory of Open Access Journals (Sweden)

    Cristina Irimia

    Full Text Available Impaired cognitive processing is a hallmark of addiction. In particular, deficits in inhibitory control can propel continued drug use despite adverse consequences. Clinical evidence shows that detoxified alcoholics exhibit poor inhibitory control in the Continuous Performance Task (CPT and related tests of motor impulsivity. Animal models may provide important insight into the neural mechanisms underlying this consequence of chronic alcohol exposure though pre-clinical investigations of behavioral inhibition during alcohol abstinence are sparse. The present study employed the rat 5 Choice-Continuous Performance Task (5C-CPT, a novel pre-clinical variant of the CPT, to evaluate attentional capacity and impulse control over the course of protracted abstinence from chronic intermittent alcohol consumption. In tests conducted with familiar 5C-CPT conditions EtOH-exposed rats exhibited impaired attentional capacity during the first hours of abstinence and impaired behavioral restraint (increased false alarms during the first 5d of abstinence that dissipated thereafter. Subsequent tests employing visual distractors that increase the cognitive load of the task revealed significant increases in impulsive action (premature responses at 3 and 5 weeks of abstinence, and the emergence of impaired behavioral restraint (increased false alarms at 7 weeks of abstinence. Collectively, these findings demonstrate the emergence of increased impulsive action in alcohol-dependent rats during protracted alcohol abstinence and suggest the 5C-CPT with visual distractors may provide a viable behavioral platform for characterizing the neurobiological substrates underlying impaired behavioral inhibition resulting from chronic intermittent alcohol exposure.

  5. ERK signaling mediates enhanced angiotensin Ⅱ-induced rat aortic constriction following chronic intermittent hypoxia

    Institute of Scientific and Technical Information of China (English)

    GUO Xue-ling; DENG Yan; SHANG Jin; LIU Kui; XU Yong-jian; LIU Hui-guo

    2013-01-01

    Background Obstructive sleep apnea (OSA) has been recognized as an independent risk factor for systemic hypertension.The study investigated the functional consequences of chronic intermittent hypoxia (CIH) on aortic constriction induced by angiotensin Ⅱ (Ang Ⅱ) and the possible signaling involving ERK1/2 and contractile proteins such as myosin light chain kinase (MLCK),myosin phosphatase targeting subunit (MYPT1) and myosin light chain (MLC).Methods Male Wistar rats were randomly divided into CIH group and normoxia group and exposed to either CIH procedure or air-air cycles.Phosphorylation of ERK1/2,MYPT1 and MLC was assessed by Western blotting following constrictor studies in the presence or absence of PD98059 (10 μmol/L).Results CIH-exposure resulted in more body weight gain and elevated blood pressure,which could be attenuated by pretreatment with PD98059.Endothelium-removed aortic rings from CIH rats exhibited higher constrictor sensitivity to Ang Ⅱ (Emax:(138.56±5.78)% versus (98.45±5.31)% of KCI; pD2:7.98±0.14 versus 8.14±0.05,respectively).CIH procedure exerted complex effects on ERK expressions (total ERK1/2 decreased whereas the ratio of phosphorylated to total ERK1/2increased).CIH aortas had higher MLCK mRNA and basal phosphorylation of MYPT1 and MLC.In parallel to greater increases in phosphorylation of ERK1/2,MYPT1 and MLC,Ang Ⅱ-induced aortic constriction was significantly enhanced in CIH rats,which was largely reversed by PD98059.However vascular constriction of normoxia rats remained unchanged despite similar but smaller changing tendency of proteins phosphorylation.Conclusion These data suggest that CIH exposure results in aortic hyperresponsiveness to Ang Ⅱ,presumably owing to more activated ERK1/2 signaling pathway.

  6. The Effects of Chronic Ingestion of Mercuric Chloride on Fertility and Testosterone Levels in Male Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    John C. Heath

    2012-01-01

    Full Text Available Although male infertility is well researched, the effects of inorganic mercury on male reproduction and fertility are less well known. Studies pertaining to mercury and male fertility identified reduced concentration of testosterone in the serum of male workers, a toxic influence on fertility of organic mercury compounds within concentrations at the workplace, and increased days to pregnancy. We evaluated the effect of chronic mercuric chloride (HgCl2 exposure in male rats on reproductive endpoints. Thirty-day old male Sprague Dawley rats (n=31 were exposed to 0.0, 1.0, or 2.0 mg/kg/day of HgCl2 via gavage. After 60 days exposure, they were housed with nonexposed females for 21 days. A survivor analysis revealed the exposed animals took longer to impregnate the females and had a lower rate of impregnation. Further statistical analysis revealed a lower correlation between testicular testosterone levels and days to impregnate, and also lower sperm counts in the epididymis head and body of the exposed males. The results indicate that HgCl2 exposure had significant adverse effects on male rat reproduction endpoints including fertility at a dose that was not clinically toxic.

  7. Effect of pregabalin on apoptotic regulatory genes in hippocampus of rats with chronic temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    ZHANG Yi-dan

    2012-04-01

    Full Text Available Objective To observe the effect of pregabalin on the expression of Bcl-2 and Bax in hippocampus of chronic epileptic rats induced by pilocarpine, to explore the anti-epileptic pharmacology mechanism of pregabalin, and its anti-apoptotic effect on hippocampal neurons of rats. Methods The model of chronic temporal lobe epileptic rats induced by lithium-pilocarpine was established, then the rats in pregabalin treatment group received intraperitoneal injection of pregabalin (40 mg/kg once daily for three weeks. The expression of Bcl-2 and Bax in hippocampus of all rats was detected by immunohistochemical technique and Western blotting. Results Compared with normal saline group rats, the expression of Bcl-2 and Bax in hippocampus of rats with chronic temporal lobe epilepsy was significantly increased (P = 0.000, for all. Pregabalin can down-regulate the expression of Bax and up-regulate the expression of Bcl-2 in hippocampus of rats compared to model group rats (P = 0.000, for all. Conclusion Pregabalin may have the effects of inhibiting cell apoptosis and protecting neurons through lowing Bax level and increasing Bcl-2 level in hippocampus of chronic temporal lobe epileptic rats.

  8. Antioxidant Role of Pomegranates on Liver and Brain Tissues of Rats Exposed to an Organophosphorus Insecticide

    International Nuclear Information System (INIS)

    Toxicities of organophosphorus insecticides cause oxidative damage on many organs such as the liver and brain due to generation of reactive oxygen species. Pomegranate is among the richest fruit in poly - phenols. The aim of this study was to compare between the antioxidant strength of pomegranate juice (PJ) and pomegranate molasses (PM) and their effects on alanine transferase (ALT), aspartate aminotransferase (AST), Alkaline phosphatase (ALP) and total protein (TP) in liver and levels of malondialdehyde (MAD), reduced glutathione (GSH) and nitric oxide (NO) in rat liver and brain tissues exposed to 1/10 LD 50 diazinon (DI). Six groups each of 6 male albino rats were used comprising control, DI, PJ, PM, PJ + DI and PM + DI for 15 days. The activities of ALT, AST, and TP concentration in liver have been increased due to treatment of rats with DI. These increases restored to normalcy when rats were supplemented with PJ or PM with DI. The results demonstrate that treatment with DI induced significant increase in MDA and NO concentrations and significant decrease in GSH levels of liver and brain tissues. The administration of PJ or PM along with DI significant decrease in MDA and NO levels and significant increase in GSH level compared to DI-group. The present study suggest that PJ or PM has a potential protective effect as it can elevate antioxidant defense system, lessens induced oxidative dam - ages and protect the brain and liver tissue against DI-induced toxicity. In addition, comaring PJ with PM it was noticed that PJ had higher antioxidant activity as evidenced by increased GSH content and decreased NO level in the liver by greater extend than PM.

  9. Changes in the antioxidant defence and in selenium concentration in tissues of vanadium exposed rats.

    Science.gov (United States)

    Sanchez-Gonzalez, Cristina; Bermudez-Peña, Carmen; Trenzado, Cristina E; Goenaga-Infante, Heidi; Montes-Bayon, María; Sanz-Medel, Alfredo; Llopis, Juan

    2012-08-01

    Vanadium is an element whose role as a micronutrient for humans is not yet completely established, but which has been shown to possess hypoglycaemic properties in diabetes. In an earlier study, we showed that in STZ-diabetic rats, exposure to 1 mg V per day has no effect on glycaemia or on antioxidant status. When the exposure was raised to 3 mg V per day there was a hypoglycaemic effect, together with reduced Se in the tissues, which reduced antioxidant defences. The aim of the present study was to examine whether exposure to 1 mg V per day modifies Se nutritional status and/or antioxidant defences in healthy rats. Two groups of rats were examined: control and vanadium-treated. Vanadium, as bis(maltolato)oxovanadium(iv), was supplied in the drinking water. The experiment had a duration of five weeks. Selenium was measured in excreta, serum, skeletal muscle, kidneys, liver, heart, femur and adipose tissue. Number of red (RBC) and white (WBC) blood cells and haemoglobin (Hb) were determined in samples of whole blood. Glutathione peroxidase (GPx), glutathione transferase (GST), catalase (CAT) and NAD(P)H:quinine-oxidoreductase1 (NQO1) activity, and malondialdehyde (MDA) in the liver were evaluated. Treatment significantly reduced food intake, produced an anaemic state, and decreased Se absorption and Se content in serum, kidneys and the liver. GPx, GST and NQO1 activity were decreased in the liver, while MDA levels rose. We conclude that healthy rats are more sensitive than diabetic ones to the effects of V. This should be taken into account for populations that are particularly exposed to V for environmental reasons, and/or that consume V as a nutritional supplement.

  10. Features of changes of higher nervous performance indicators on stress influence in preliminary gamma-radiation-exposed of rats

    International Nuclear Information System (INIS)

    Studies of active avoidance behavioral reactions (shuttle box) changes under exposure of stress (foot-shock) in the rats preliminary exposed to single total ?-radiation at doses of 0.5 and 1.0 Gy gave the following results. Reactions of conditioned behavior indices to stress are individual, but in general they are characterized by significant direct effect of activation, which could be followed by depression during time period after stress application. Effects of stress in the rats previously exposed at the dose of 1.0 Gy exceed those in the animals both directly after stress application and during the time periods without stress. Interaction between factors of ionizing radiation and stress were found for the tested indices at the dose of 1.0 Gy. Rats exposed at the dose of 0.5 Gy increase of direct response to stressing was not found, but it was evident in delayed responses

  11. Telomere Length in Aged Mayak PA Nuclear Workers Chronically Exposed to Internal Alpha and External Gamma Radiation.

    Science.gov (United States)

    Scherthan, Harry; Sotnik, Natalia; Peper, Michel; Schrock, Gerrit; Azizova, Tamara; Abend, Michael

    2016-06-01

    Telomeres consist of GC-rich DNA repeats and the "shelterin" protein complex that together protect chromosome ends from fusion and degradation. Telomeres shorten with age due to incomplete end replication and upon exposure to environmental and intrinsic stressors. Exposure to ionizing radiation is known to modulate telomere length. However, the response of telomere length in humans chronically exposed to radiation is poorly understood. Here, we studied relative telomere length (RTL) by IQ-FISH to leukocyte nuclei in a group of 100 workers from the plutonium production facility at the Mayak Production Association (PA) who were chronically exposed to alpha-emitting ((239)Pu) radiation and/or gamma (photon) radiation, and 51 local residents serving as controls, with a similar mean age of about 80 years. We applied generalized linear statistical models adjusted for age at biosampling and the second exposure type on a linear scale and observed an age-dependent telomere length reduction. In those individuals with the lowest exposure, a significant reduction of about 20% RTL was observed, both for external gamma radiation (≤1 Gy) and internal alpha radiation (≤0.05-0.1 Gy to the red bone marrow). In highly exposed individuals (>0.1 Gy alpha, 1-1.5 Gy gamma), the RTL was similar to control. Stratification by gender revealed a significant (∼30%) telomere reduction in low-dose-exposed males, which was absent in females. While the gender differences in RTL may reflect different working conditions, lifestyle and/or telomere biology, absence of a dose response in the highly exposed individuals may reflect selection against cells with short telomeres or induction of telomere-protective effects. Our observations suggest that chronic systemic exposure to radiation leads to variable dose-dependent effects on telomere length. PMID:27340887

  12. Telomere Length in Aged Mayak PA Nuclear Workers Chronically Exposed to Internal Alpha and External Gamma Radiation.

    Science.gov (United States)

    Scherthan, Harry; Sotnik, Natalia; Peper, Michel; Schrock, Gerrit; Azizova, Tamara; Abend, Michael

    2016-06-01

    Telomeres consist of GC-rich DNA repeats and the "shelterin" protein complex that together protect chromosome ends from fusion and degradation. Telomeres shorten with age due to incomplete end replication and upon exposure to environmental and intrinsic stressors. Exposure to ionizing radiation is known to modulate telomere length. However, the response of telomere length in humans chronically exposed to radiation is poorly understood. Here, we studied relative telomere length (RTL) by IQ-FISH to leukocyte nuclei in a group of 100 workers from the plutonium production facility at the Mayak Production Association (PA) who were chronically exposed to alpha-emitting ((239)Pu) radiation and/or gamma (photon) radiation, and 51 local residents serving as controls, with a similar mean age of about 80 years. We applied generalized linear statistical models adjusted for age at biosampling and the second exposure type on a linear scale and observed an age-dependent telomere length reduction. In those individuals with the lowest exposure, a significant reduction of about 20% RTL was observed, both for external gamma radiation (≤1 Gy) and internal alpha radiation (≤0.05-0.1 Gy to the red bone marrow). In highly exposed individuals (>0.1 Gy alpha, 1-1.5 Gy gamma), the RTL was similar to control. Stratification by gender revealed a significant (∼30%) telomere reduction in low-dose-exposed males, which was absent in females. While the gender differences in RTL may reflect different working conditions, lifestyle and/or telomere biology, absence of a dose response in the highly exposed individuals may reflect selection against cells with short telomeres or induction of telomere-protective effects. Our observations suggest that chronic systemic exposure to radiation leads to variable dose-dependent effects on telomere length.

  13. Chronic ethanol consumption depresses hypothalamic-pituitary-adrenal function in aged rats

    Energy Technology Data Exchange (ETDEWEB)

    Nolan, C.J.; Bestervelt, L.L.; Mousigian, C.A.; Maimansomsuk, P.; Yong Cai; Piper, W.N. (Univ of Michigan, Ann Arbor (United States))

    1991-01-01

    In separate experiments, nine (n=20) and fifteen (n=12) month old rats were treated with either 6% ethanol or 12% sucrose in the drinking water to examine the effect of chronic ethanol consumption on the hypothalamic-pituitary-adrenal axis of aged rats. Blood was collected and plasma concentrations of adrenocorticotropin (ACTH) and corticosterone were determined by radioimmunoassay. Adrenal glands were cleaned, quartered and used to test in vitro responsiveness to ACTH. Anterior pituitary glands from all 15 month old rats and one half of the nine month old rats were collected, frozen and extracted for measurement of tissue ACTH concentration. The remaining anterior pituitary glands from the nine month old rats were challenged with corticotropin releasing hormone (CRH) to test in vitro responsiveness. In nine month old rats, chronic ethanol consumption decreased plasma ACTH and corticosterone. Pituitary ACTH concentrations were unchanged in treated nine month old rats, but the amount of pituitary ACTH released in response to CRH was decreased in rats consuming ethanol. In vitro responsiveness of the adrenal gland to ACTH in nine month old rats consuming ethanol was unchanged. Plasma ACTH and corticosterone concentrations were also decreased in 15 month old rats chronically consuming ethanol. No differences were noted in responsiveness of the adrenal gland or in the amount of pituitary ACTH due to ethanol consumptions in 15 month old rats.

  14. Bioactive compounds from Paecilomyces tenuipes regulating the function of the hypothalamo-hypophyseal system axis in chronic unpredictable stress rats

    Institute of Scientific and Technical Information of China (English)

    YIN Yan-yan; MING Liang; ZHENG Li-fang; KAN Hong-wei; LI Chun-ru; LI Wei-ping

    2007-01-01

    Background A bioactive compound from Paecilomyces tenuipes (BGPT) has an inhibitory effect on monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) in vitro and in vivo, which indicates BCPT may be a potential antidepressant. In this study we aimed to study the antidepressant effects of BCPT in the chronic unpredictable stress(CUS) model in rats and explore underlying mechanisms in the hypothalamic-pituitary-adrenal (HPA) axis.Methods The antidepressant effects of BCPT were studied in the chronic unpredictable stress model in rats. Animals were housed isolated, except the control group. Rats were exposed daily to different random stressors from day 1 to 21.Awarding response was detected by calculating the 24-hour consumption of sucrose water. Cortisol (CORT) and adrenocorticotropic hormone (ATCH) contents in serum and arginine vasopressin (AVP) contents in the pituitary body were detected by radio immunoassays. Total RNA of hippocampus or hypothalamus was extracted and subjected to reverse transcription-polymerase chain reaction (RT-PCR) for the measurement of corticotrophin releasing hormone(CRH) mRNA or mineralocorticoid receptor (MR) mRNA and glucocorticoid receptor (GR) mRNA levels. Statistical analyses were performed using one way analysis of variance (ANOVA) followed by Student-Newman-Keuls (SNK) test.Results Chronic unpredictable stress resulted in reduction of sensitivity to reward and abnormality in the HPA axis in the animal model. BCPT improved the reward reaction as measured by increasing sucrose consumption, remarkably reduced serum CORT and ACTH levels and the AVP content in the pituitary body in the CUS-treated rats, decreased the expression of CRH mRNA, enhanced the expression of hippocampus MR mRNA, GR mRNA and decreased the ratio of MR/GR.Conclusions BCPT has potentially antidepressant-like activity and normalized the HPA axis hyperactivity in a CUS model of depression in rats. This may be an important mechanism of its antidepressant effect.

  15. Effects of pentoxifylline on Wnt/β-catenin signaling in mice chronically exposed to cigarette smoke

    Institute of Scientific and Technical Information of China (English)

    WANG Zheng; ZHANG Jin-nong; HU Xiao-fei; CHEN Xue-lin; WANG Xiao-rong; ZHAO Ting-ting; PENG Mei-jun; ZOU Ping

    2010-01-01

    Background Previous discovery that long-term administration of pentoxifylline (PTX) to mice chronically exposed to smoke led to the development of pulmonary fibrosis rather than emphysema initiated our curiosity on whether the Wnt/β-catenin pathway, a set of signaling proteins essential to organ development and lung morphogenesis in particular were activated in the pathogenesis of pulmonary fibrosis.Methods Male BALB/c mice were randomized into four study groups: Group Sm, smoke exposure and taken regular forage; Group PTX, no smoke but taken PTX-rich forage; Group Sm+PTX, smoke exposure and taken PTX-rich forage;Group control: shamed smoke exposure and taken regular forage. Animals were sacrificed at day 120. Morphometry of the lung sections and the expressions of TGF-β, hydroxyproline, β-catenin, cyclin D1, T cell factor 1 (Tcf-1) and lymphoid enhancer factor 1 (Lef-1) mRNA, etc, in the lung homogenate or in situ were qualitatively or quantitatively analyzed.Results As expected, smoke exposure along with PTX administration for 120 days, lungs of the mice progressed to be a fibrosis-like phenotype, with elevated fibrosis score (3.9±1.1 vs. 1.7±-0.6 in Group Sm, P <0.05). TGF-β (pg/g)(1452.4±465.7 vs. 818.9±202.8 in Group Sm, P <0.05) and hydroxyproline (mg/g) (5.6±0.6, vs. 2.4±0.1 in Group Sm, P<0.05) were also consistently increased. The upregulation of β-catenin measured either by counting the cell with positive staining in microscopic field (17.4±7.9 vs. 9.9±2.9 in Group Sm, P <0.05) or by estimation of the proportion of blue-stained area by Masson's trichrome (11.8±5.6 vs. 4.7±2.4 in Group Sm) in Group SM+PTX was much more noticeable as than those in Group Sm. The expression of β-catenin measured by positive cell counts was correlated to TGF-β1 concentration in lung tissue (r=0.758, P <0.001). PTX per se caused neither fibrosis nor emphysema though expression of β-catenin and downstream gene cyclin D1 may also be altered by this

  16. Effect of administration of vitamins C and E on fertilization capacity of rats exposed to noise stress

    Directory of Open Access Journals (Sweden)

    Ghasem Saki

    2013-01-01

    Full Text Available The aims of this study were to evaluate the effects of administration of Vitamins C and E on fertilization capacity in rats exposed to noise stress. 40 adult male rats were randomly divided into 5 equal groups. Group 1 as controls who were not exposed to noise and groups 2-5 exposed to noise with 90-120 dB intensity and 300-350 Hz frequency from 7 pm to 7 am everyday for 50 days. Group 2 exposed to noise and did not receive Vitamins. Group 3 received vitamin C, Group 4 received Vitamin E. Group 5 received Vitamins C and E concomitantly. After 50 days, serum Follicle-stimulating hormone (FSH, Luteinizing hormone (LH and testosterone were calculated. Then each rat was left with three female rats for mating. Pregnant females were sacrificed on the 19 th day of pregnancy and evaluated for the presence and number of viable, dead and absorbed fetuses. The level of FSH, LH and testosterone significantly decreased in rats exposed to noise (P < 0.05. By administration of Vitamins in groups 3-5 we observed that the level of hormones significantly increased in compared to group 2 (P < 0.05. The fertilization capacity of male rats in groups 3-5 significantly increased in compared to group 2 (P < 0.05. There was significant difference between groups 1 and 2 in case of fertilization capacity (P = 0.001. The data in this study strongly suggests a negative role for noise stress on level of FSH, LH and testosterone level and also fertilization capacity of male rats. To complement the information it is suggested that this research be done on human samples.

  17. The Efficacy of Syzygium aromaticum Essential Oil in Cognitive Disorders against Manganese Chronic Exposure in Rats during Development

    Directory of Open Access Journals (Sweden)

    Djallal Eddine Houari ADLI

    2014-06-01

    Full Text Available The essential oil of Syzygium aromaticum has been widely used in traditional medicine to treat a variety of diseases, including some neurological disorders. This study aims at testing, in vivo, the possible anxiolytic and antidepressant effects, of the Syzygium aromaticum essential oil against chronic manganese chloride (4.79 mg/l intoxication during the gestation and lactation period, in Wistar rat pups. Wistar rat pups were exposed to manganese via their dams’ drinking water from postnatal day (PND 1 to (PND 21. After their weaning, the rats exposed to manganese received injections of essential oil of Syzygium aromaticum (0.1 ml/kg for 18 days. The level of anxiety, depression and locomotor activity were studied. Locomotor activity (open field test, anxiety (elevated plus maze tests, and depression (forced swimming test were evaluated. The results of the present study indicate that Manganese exposure induces, on the one hand, impairments of body (p<0.001 and of brain weight (p<0.05. On the other hand, it increases level of anxiety (p<0.05, depression (p<0.001 and locomotor hyporactivity (p<0.001, when compared to control rats. Administration of essential oil of Syzygium aromaticum leads to a reduction in the level of anxiety (p<0.05, of depression (p<0.001 and corrects locomotor hyporactivity (p<0.05 in rats exposed to manganese beforehand. These results suggest that essential oil of Syzygium aromaticum can employ as a natural, protective agent against neuro-toxicity induced by manganese chloride during the gestation and lactation periods.

  18. Evaluation of the serum catalase and myeloperoxidase activities in chronic arsenic-exposed individuals and concomitant cytogenetic damage

    International Nuclear Information System (INIS)

    Chronic arsenic exposure through contaminated drinking water is a major environmental health issue. Chronic arsenic exposure is known to exert its toxic effects by a variety of mechanisms, of which generation of reactive oxygen species (ROS) is one of the most important. A high level of ROS, in turn, leads to DNA damage that might ultimately culminate in cancer. In order to keep the level of ROS in balance, an array of enzymes is present, of which catalase (CAT) and myeloperoxidase (MPO) are important members. Hence, in this study, we determined the activities of these two enzymes in the sera and chromosomal aberrations (CA) in peripheral blood lymphocytes in individuals exposed and unexposed to arsenic in drinking water. Arsenic in drinking water and in urine was used as a measure of exposure. Our results show that individuals chronically exposed to arsenic have significantly higher CAT and MPO activities and higher incidence of CA. We found moderate positive correlations between CAT and MPO activities, induction of CA and arsenic in urine and water. These results indicate that chronic arsenic exposure causes higher CAT and MPO activities in serum that correlates with induction of genetic damage. We conclude that the serum levels of these enzymes might be used as biomarkers of early arsenic exposure induced disease much before the classical dermatological symptoms of arsenicosis begin to appear.

  19. Effects of Supplementation of Turmeric Extract on Balance Antioxidant-Prooxidant Spleen and Heart Tissues in Rats Exposed to Lead

    OpenAIRE

    Sadegh Saberi; Parvin Farzanegi1; Shima Ranjbar; Ahmad Gholizade; Jalil Jafari; Hadis Saberi; Amin Talebolhagh-Kakhki

    2013-01-01

    Background: One of today's environmental crisis that industrial technology it produces. Lead is one of the most important environmental contaminants that prolonged contact with the production of free radicals. Study results show that air pollution is increases mortality due to cardiovascular disease. Materials and Methods: To study the effects of consumption turmeric extracts on prooxidant- antioxidant balance of rats' spleen and heart tissues exposed to lead acetate. Thirty-six male rats ran...

  20. Chronic Lunar Dust Exposure on Rat Cornea: Evaluation by Gene Expression Profiling

    Science.gov (United States)

    Theriot, C. A.; Glass, A.; Lam, C-W.; James, J.; Zanello, S. B.

    2014-01-01

    Lunar dust is capable of entering habitats and vehicle compartments by sticking to spacesuits or other objects that are transferred into the spacecraft from the lunar surface and has been reported to cause irritation upon exposure. During the Apollo missions, crewmembers reported irritation specifically to the skin and eyes after contamination of the lunar and service modules. It has since been hypothesized that ocular irritation and abrasion might occur as a result of such exposure, impairing crew vision. Recent work has shown that both ultrafine and unground lunar dust exhibited minimal irritancy of the ocular surface (i.e., cornea); however, the assessment of the severity of ocular damage resulting from contact of lunar dust particles to the cornea has focused only on macroscopic signs of mechanical irritancy and cytotoxicity. Given the chemical reactive properties of lunar dust, exposure of the cornea may contribute to detrimental effects at the molecular level including but not limited to oxidative damage. Additionally, low level chronic exposures may confound any results obtained in previous acute studies. We report here preliminary results from a tissue sharing effort using 10-week-old Fischer 344 male rats chronically exposed to filtered air or jet milled lunar dust collected during Apollo 14 using a Jaeger-NYU nose-only chamber for a total of 120 hours (6 hours daily, 5 days a week) over a 4-week period. RNA was isolated from corneas collected from rats at 1 day and 7 days after being exposed to concentrations of 0, 20, and 60 mg/m3 of lunar dust. Microarray analysis was performed using the Affymetrix GeneChip Rat Genome 230 2.0 Array with Affymetrix Expression Console and Transcriptome Analysis Console used for normalization and secondary analysis. An Ingenuity iReport"TM" was then generated for canonical pathway identification. The number of differentially expressed genes identified increases with dose compared to controls suggesting a more severe

  1. Pulmonary sensitivity to ozone exposure in sedentary versus chronically trained, female rats

    Data.gov (United States)

    U.S. Environmental Protection Agency — Pulmonary effects to ozone with rats that have chronically exercised or have been continuously sedentary. Also includes body composition of both groups throughout...

  2. Altered anxiety-related and abnormal social behaviors in rats exposed to early life seizures

    Directory of Open Access Journals (Sweden)

    Adelisandra S. S. Castelhano

    2013-05-01

    Full Text Available Neonatal seizures are the most common manifestation of neurological dysfunction in the neonate. The prognosis of neonatal seizures is highly variable, and the controversy remains whether the severity, duration or frequency of seizures may contribute to brain damage independently of its etiology. Animal data indicates that seizures during development are associated with a high probability of long-term adverse effects such as learning and memory impairment, behavioral changes and even epilepsy, which is strongly age dependent, as well as the severity, duration and frequency of seizures. In preliminary studies, we demonstrated that adolescent male rats exposed to one-single neonatal status epilepticus (SE episode showed social behavior impairment, and we proposed the model as relevant for studies of developmental disorders. Based on these facts, the goal of this study was to verify the existence of a persistent deficit and if the anxiety-related behavior could be associated with that impairment. To do so, male Wistar rats at 9 days postnatal were submitted to a single episode of status epilepticus (SE by pilocarpine injection (380 mg/kg, i.p. and control animals received saline (0.9 %, 0,1mL/10 g. It was possible to demonstrate that in adulthood, animals exposed to neonatal SE displayed low preference for social novelty, anxiety-related behavior and increased stereotyped behavior in anxiogenic environment with no locomotor activity changes. On the balance, these data suggests that neonatal status epilepticus in rodents leads to altered anxiety-related and abnormal social behaviors.

  3. How various drugs affect anxiety-related behavior in male and female rats prenatally exposed to methamphetamine.

    Science.gov (United States)

    Macúchová, E; Ševčíková, M; Hrebíčková, I; Nohejlová, K; Šlamberová, R

    2016-06-01

    Different forms of anxiety-related behavior have been reported after a single drug use of many abused substances, however, less is known about how males and females are affected differently from exposure to various drugs. Furthermore, chronic prenatal methamphetamine (MA) exposure was shown to predispose the animal to an increased sensitivity to drugs administrated in adulthood. Using the Elevated plus-maze test (EPM), the first aim of the present study was to examine how male and female rats are affected by acute drug treatment with subcutaneously (s.c.) administrated (a) MA (1mg/kg); (b) drugs with a similar mechanism of action to MA: amphetamine (AMP, 1mg/kg), cocaine (COC, 5mg/kg), 3,4-methylenedioxymethamphetamine (MDMA, 5mg/kg); and (c) drugs with different mechanisms of action: morphine (MOR, 5mg/kg), and Δ 9-tetrahydrocannabinol (THC, 2mg/kg). The second aim was to determine if prenatally MA-exposed (5mg/kg) animals show an increased sensitivity to adult drug treatment. The parameters analyzed were divided into two categories: anxiety-related behavior and anxiety-unrelated/exploratory behavior. Our results showed in female rats a decreased percentage of the time spent in the closed arms (CA) after MA, and an increased percentage of the time spent in the open arms (OA) after MA, AMP, and COC treatment, indicating an anxiolytic-like effect. In females, MDMA and THC treatment increased the percentage of the time spent in the CA. An increased percentage of the time spent in the CA was also seen after MOR treatment in females as well as in males, indicating an anxiogenic-like effect. As far as the interaction between prenatal MA exposure and adult drug treatment is concerned, there was no effect found. In conclusion, it seems that: (a) in some cases female rats are more vulnerable to acute drug treatment, in terms of either anxiogenic- or anxiolytic-like effects; (b) prenatal MA exposure does not sensitize animals to the anxiety-related effects of any of the

  4. Health implications of chronic hepatosplenomegaly in Kenyan school-aged children chronically exposed to malarial infections and Schistosoma mansoni

    DEFF Research Database (Denmark)

    Wilson, Shona; Vennervald, Birgitte J; Kadzo, Hilda;

    2010-01-01

    Hepatosplenomegaly among school-aged children in sub-Saharan Africa is highly prevalent. Two of the more common aetiological agents of hepatosplenomegaly, namely chronic exposure to malaria and Schistosoma mansoni infection, can result in similar clinical presentation, with the liver and spleen b...

  5. Temporal Development of Gut Microbiota in Triclocarban Exposed Pregnant and Neonatal Rats

    Science.gov (United States)

    Kennedy, Rebekah C.; Fling, Russell R.; Robeson, Michael S.; Saxton, Arnold M.; Donnell, Robert L.; Darcy, John L.; Bemis, David A.; Liu, Jiang; Zhao, Ling; Chen, Jiangang

    2016-01-01

    Alteration of gut microbial colonization process may influence susceptibility of the newborn/infant to infectious and chronic disease. Infectious disease risk leads to widespread use of non-prescription antimicrobials in household products such as Triclocarban (TCC), an antimicrobial compound in personal care products. TCC concentrates in and is transferred through the milk to suckling offspring. TCC exposure during gestation and lactation significantly reduced phylogenetic diversity (PD) among exposed dams and neonates. Among dams using weighted UniFrac distances, TCC induced significant dysbiosis of gut microbiota by gestational day (GD) 18, a trend that continued after delivery. Similarly, an overall restructuring of gut microbiota occurred in neonates. By postnatal day (PND) 12, communities separated based on exposure status and became significantly different at PND 16. The ability of TCC to drive microbial dysbiosis warrants future investigation to evaluate the safety of non-prescription antimicrobial use, including TCC, during critical exposure windows. PMID:27646684

  6. [Effects of carbocisteine on airway inflammation and related events in SO2-exposed rats].

    Science.gov (United States)

    Ishibashi, Y; Okamura, T; Masumoto, Y; Tachiiri, T; Momo, K

    2001-01-01

    Airway inflammation leads to secretion of abnormal mucous glycoprotein and ciliary injury. To investigate the possible usefulness of carbocisteine against airway inflammation and events related to it, we conducted a study in SO2-exposed rats of the effects of carbocisteine and ambroxol, as an active control drug, on components of mucous glycoprotein (fucose, sialic acid and protein) in bronchoalveolar lavage fluid (BALF); on infiltration and activation of inflammatory cells in BALF; on tracheal and bronchial-ciliary lesions; and on cAMP levels in tracheal and alveolar tissues. Carbocisteine inhibited or improved all SO2-induced changes tested, and dosages of 125 and 250 mg/kg b.i.d. reduced fucose, sialic acid and protein contents, inflammatory cells (as markers of inflammation), free radicals, and elastase activity in BALF, and suppressed the development of ciliary lesions of the tracheal and bronchial mucosa, while ambroxol (10 mg/kg b.i.d.) showed no such effects. In addition, carbocisteine improved cAMP levels in the tracheal and alveolar tissues. These results indicate that carbocisteine is able to prevent the development of inflammation-related respiratory disease in this rat model, and that this remission of airway inflammation may be associated with carbocisteine-induced normalization of cAMP levels in tracheal and alveolar tissues as well as with its mucoregulant and anti-inflammatory effects. In conclusion, carbocisteine has a unique mucoregulant action and inhibits SO2-induced airway inflammation in a manner different from that of ambroxol.

  7. PROTECTIVE EFFECT OF LORANTHUS LONGIFLORUS ON LEARNING AND MEMORY OF RATS EXPOSED TO ELECTROMAGNETIC RADIATION (EMR

    Directory of Open Access Journals (Sweden)

    Hemant Nagar

    2013-06-01

    Full Text Available The interaction of mobile phone radio-frequency electromagnetic radiation (RF-EMR with the brain is a serious concern of our society. In this study, we aimed to experiment on the antioxidative property of a parasitic plant Loranthus longiflorus (Loranthaceae to protect central nervous system against oxidative damages of mobile phone electromagnetic radiation (EMR. Healthy male albino wistar rats were exposed to RF-EMR by giving 5 min calling/ 5min interval for 1 hour per day for two month, Keeping a GSM (0.9 GHz/1.8 GHz mobile phone in Silent mode (no ring tone in the cage. After 15, 30, 45, 60 days exposure, three randomly picked animals from both groups were tested with using Morris water maze. Antioxidant compounds and their Neuroprotective action of Loranthus longiflorus bark sample collected from Ficus religiosa host trees were assessed. Rats which have been feed with Ethyl acetate Extract of Loranthus longiflorus (EAL bark (700mg/kg body weight, p.o.

  8. Impact on behavioral changes due to chronic use of sertraline in Wistar albino rats

    OpenAIRE

    Shatavisa Mukherjee; Sukanta Sen; Arunava Biswas; Tapan Kumar Barman; Santanu Kumar Tripathi

    2015-01-01

    Aim: Despite having better tolerability and a wide range of clinical applications over other antidepressants, selective serotonin reuptake inhibitors (SSRIs) are also known to be associated with serious adverse effects like suicidal ideation on chronic use. The present study had explored the impact of the chronic use of sertraline, an SSRI, on the behavioral changes in Wistar albino rats. Materials and Methods: The study was conducted on 30 Wistar albino rats of either sex; divided into f...

  9. Gene Expression Profile of the Hippocampus of Rats Subjected to Chronic Immobilization Stress

    OpenAIRE

    Li, Xiao-Hong; Chen, Jia-Xu; Yue, Guang-Xin; Liu, Yue-Yun; Zhao, Xin; Guo, Xiao-Ling; Liu, Qun; Jiang, You-Ming; Bai, Ming-Hua

    2013-01-01

    Objective This study systematically investigated the effect of chronic stress on the hippocampus and its damage mechanism at the whole genome level. Methods The rat whole genome expression chips (Illumina) were used to detect gene expression differences in the hippocampus of rats subjected to chronic immobilization stress (daily immobilization stress for 3 h, for 7 or 21 days). The hippocampus gene expression profile was studied through gene ontology and signal pathway analyses using bioinfor...

  10. Nitric oxide synthase and nitric oxide alterations in chronically stressed rats: a model for nitric oxide in major depressive disorder.

    Science.gov (United States)

    Gao, Shang-Feng; Lu, Yun-Rong; Shi, Li-Gen; Wu, Xue-Yan; Sun, Bo; Fu, Xin-Yan; Luo, Jian-Hong; Bao, Ai-Min

    2014-09-01

    Nitric oxide (NO) and NO synthase-1 (NOS1) are involved in the stress response and in depression. We compared NOS-NO alterations in rats exposed to chronic unpredictable stress (CUS) with alterations in major depressive disorder (MDD) in humans. In the hypothalamus of male CUS rats we determined NOS activity, and in the paraventricular nucleus (PVN) we determined NOS1-immunoreactive (ir) cell densities and co-localization of NOS1 with stress-related neuropeptides corticotropin-releasing hormone (CRH), vasopressin (AVP) or oxytocin (OXT). We measured plasma NO levels and cortisol in male medicine-naïve MDD patients and plasma NO and corticosterone (CORT) in CUS rats. In the CUS rat total NOS activity in the hypothalamus (P=0.018) and NOS1-ir cell density in the PVN were both significantly decreased (P=0.018), while NOS1 staining was mainly expressed in OXT-ir neurons in this nucleus. Interestingly, plasma NO levels were significantly increased both in male CUS rats (P=0.001) and in male MDD patients (Pdepression.

  11. Is it stress? The role of stress related systems in chronic food restriction-induced augmentation of heroin seeking in the rat

    Directory of Open Access Journals (Sweden)

    Firas eSedki

    2013-06-01

    Full Text Available Drug addiction is a chronic disease characterized by recurring episodes of abstinence and relapse. The precise mechanisms underlying this pattern are yet to be elucidated, but stress is thought to be a major factor in relapse. Recently, we reported that rats under withdrawal and exposed to a mild chronic stressor, prolonged food restriction, show increased heroin seeking compared to sated controls. Previous studies demonstrated a critical role for corticotropin-releasing factor (CRF and corticosterone, hormones involved in the stress response, in acute food deprivation-induced reinstatement of extinguished drug seeking. However, the role of CRF and corticosterone in chronic food restriction-induced augmentation of drug seeking remains unknown. Here, male Long-Evans rats were trained to self-administer heroin for 10 days in operant conditioning chambers. Rats were then removed from the training chambers, and subjected to 14 days of unrestricted (sated rats or a mildly restricted (FDR rats access to food, which maintained their body weight at 90% of their baseline weight. On day 14, different groups of rats were administered a selective CRF1 receptor antagonist (R121919; 0.0, 20.0 mg/kg; s.c., a non-selective CRF receptor antagonist (α-helical CRF; 0.0, 10.0, 25.0 μg/μl; i.c.v. or a glucocorticoid receptor antagonist (RU486; 0.0, 30.0 mg/kg; i.p., and underwent a 1 h drug seeking test under extinction conditions. An additional group of rats was tested following adrenalectomy. All FDR rats showed a statistically significant increase in heroin seeking compared to the sated rats. No statistically significant effects for treatment with α-helical CRF, R121919, RU486 or adrenalectomy were observed. These findings suggest that stress may not be a critical factor in the augmentation of heroin seeking in food-restricted rats.

  12. Salivary Alterations in Rats with Experimental Chronic Kidney Disease

    Science.gov (United States)

    Romero, Ana Carolina; Bergamaschi, Cassia Toledo; de Souza, Douglas Nesadal; Nogueira, Fernando Neves

    2016-01-01

    Objective This study aimed to analyze changes in saliva composition and salivary secretion process of rats with chronic kidney disease induced by 5/6 nephrectomy to set the foundation for salivary studies related to CKD. Methods CKD was induced in Wistar rats via 5/6 nephrectomy. Blood and saliva samples were collected from Control, Sham and CKD groups at 8 and 12 weeks after the surgery. Salivation was stimulated via intraperitoneal injections of pilocarpine (1.0 mg/Kg body weight) or isoproterenol (5.0 mg/Kg body weight). Saliva was collected and immediately stored at -80°C until analysis. The salivary flow rate, total protein, amylase and peroxidase activities, and urea concentrations were measured. The blood urea nitrogen (BUN) and serum creatinine concentrations were also evaluated. Results Increases in BUN and serum creatinine concentrations were observed in the CKD groups. Amylase activity was significantly reduced in response to both stimuli in the CKD groups at 8 weeks and increased in the CKD groups at 12 weeks in response to isoproterenol stimulus. The peroxidase activities of the CKD groups were significantly reduced in response to isoproterenol stimulation and were increased at 12 weeks in response to pilocarpine stimulation. Salivary urea was significantly increased in the CKD groups at 8 weeks in response to the isoproterenol stimuli and at 12 weeks in response to both salivary agonists. Conclusions The pattern of alterations observed in this experimental model is similar to those observed in patients and clearly demonstrates the viability of 5/6 nephrectomy as an experimental model in future studies to understand the alterations in salivary compositions and in salivary glands that are elicited by CKD. PMID:26859883

  13. Development of circadian rhythms in rat pups exposed to microgravity during gestation.

    Science.gov (United States)

    Hoban-Higgins, T M; Murakami, D M; Tang, I H; Fuller, P M; Fuller, C A

    1999-10-01

    Ten pregnant Sprague Dawley rat dams were exposed to spaceflight aboard the Space Shuttle (STS-70) for gestational days 11-20 (G 11-20; FLT group). Control dams were maintained in either a flight-like (FDS group) or vivarium cage environment (VIV group) on earth. All dams had ad lib access to food and water and were exposed to a light-dark cycle consisting of 12 hours of light (approximately 30 lux) followed by 12 hours of darkness. The dams were closely monitored from G 22 until parturition. All pups were cross-fostered at birth; each foster dam had a litter of 10 pups. Pups remained with their foster dam until post natal day 21 (PN 21). Pup body mass was measured twice weekly. At PN 14 FLT pups had a smaller body mass than did the VIV pups (p < 0.01). Circadian rhythms of body temperature and activity of pups from two FLT dams (n = 8), two FDS dams (n = 9) and two VIV dams (n = 7) were studied starting from age PN 21. All pups had circadian rhythms of temperature and activity at this age. There were no significant differences in rhythms between groups that could be attributed to microgravity exposure. These results indicate that exposure to the microgravity environment of spaceflight during this embryonic development period does not affect the development of the circadian rhythms of body temperature and activity. PMID:11543088

  14. Effects of sub-chronic exposure to SO{sub 2} on lipid and carbohydrate metabolism in rats

    Energy Technology Data Exchange (ETDEWEB)

    Lovati, M.R. [Institute of Pharmacological Sciences, Milan (Italy); Manzoni, C. [Institute of Pharmacological Sciences, Milan (Italy); Daldossi, M. [Institute of Pharmacological Sciences, Milan (Italy); Spolti, S. [Institute of Pharmacological Sciences, Milan (Italy); Sirtori, C.R. [Institute of Pharmacological Sciences, Milan (Italy)

    1996-01-01

    Sulfur dioxide (SO{sub 2}) is a ubiquitous air pollutant, present in low concentrations in the urban air, and in higher concentrations in the working environment. While toxicological reports on SO{sub 2} have extensively dealt with the pulmonary system, essentially no data are available on the effects of chronic exposure to this pollutant on intermediary metabolism, although some biochemical changes in lipid metabolism have been detected. The present investigation was aimed at evaluating the effects of sub-chronic exposure to SO{sub 2} on concentrations of serum lipids/lipoproteins and on glucose metabolism, in animal models of hypercholesterolemia and diabetes. A specially designed controlinert atmosphere chamber was used, where male Sprague-Dawley rats fed on either standard or cholesterol enriched (HC) diets, as well as streptozotocin diabetics, were exposed to SO{sub 2} at 5 and 10 ppm, 24 h per day for 14 days. In rats, both on a standard diet and on a HC regimen, SO{sub 2} exposure determined a significant dose-dependent increase in plasma triglycerides, up to +363% in the 10 ppm HC exposed animals. This same gas concentration significantly reduced HDL cholesterol levels. In contrast, exposure of diabetic animals to 10 ppm SO{sub 2} resulted in a fall (-41%) of plasma and liver triglycerides and in a concomitant increase (+62%) of plasma HDL cholesterol. This discrepancy could apparently be related to diverging effects of SO{sub 2} exposure on plasma insulin levels in the different animal groups. Kinetic analyses of triglyceride synthesis carried out in rats on a standard diet revealed, in exposed animals, a significant reduction in the secretory rate, in spite of the concomitant hypertriglyceridemia. These findings suggest that SO{sub 2} exposure can markedly modify major lipid and glycemic indices, also indicating a differential response in normo/hyperlipidemic versus diabetic animals. (orig.)

  15. Physiological investigations on the effect of olive and rosemary leaves extracts in male rats exposed to thioacetamide.

    Science.gov (United States)

    Al-Attar, Atef M; Shawush, Nessreen A

    2014-11-01

    Physiologically, it is known that thioacetamide (TAA) toxicity is generally associated with hepatic fibrosis induction, complicated metabolic disorders and health problems. The capability of extracts of olive and rosemary leaves to attenuate the severe physiological disturbances induced by thioacetamide (TAA) intoxication in male rats has been evaluated. Healthy male Wistar rats were used in the present study and were divided randomly into eight groups. Rats of the first group were served as normal control. Rats of the second group were administrated with TAA. Rats of the third, fourth and fifth groups were exposed to TAA plus olive leaves extract, TAA plus rosemary leaves extract and TAA plus olive and rosemary leaves extracts respectively. The sixth, seventh and eighth groups were supplemented with olive leaves extract, rosemary leaves extract, and olive and rosemary leaves extracts respectively. After 12 weeks of experimental treatments, the levels of serum glucose, total protein, albumin and high density lipoprotein cholesterol were significantly decreased, while the levels of triglycerides, cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, creatine kinase and lactate dehydrogenase were statistically increased in rats exposed to TAA. Administration of the studied extracts inhibited the hematobiochemical parameters and improved the physiological disturbances induced by TAA intoxication. Additionally, most improvements were noted in rats administrated with rosemary leaves extract followed by olive and rosemary leaves extracts and olive leaves extract. These results suggested that the effect of these extracts might be due to their antioxidant activities against TAA toxicity. PMID:25313283

  16. Proteomic analysis of hippocampal proteins of F344 rats exposed to 1-bromopropane

    International Nuclear Information System (INIS)

    1-Bromopropane (1-BP) is a compound used as an alternative to ozone-depleting solvents and is neurotoxic both in experimental animals and human. However, the molecular mechanisms of the neurotoxic effects of 1-BP are not well known. To identify the molecular mechanisms of 1-BP-induced neurotoxicity, we analyzed quantitatively changes in protein expression in the hippocampus of rats exposed to 1-BP. Male F344 rats were exposed to 1-BP at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks by inhalation. Two-dimensional difference in gel electrophoresis (2D-DIGE) combined with matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) were conducted to detect and identify protein modification. Changes in selected proteins were further confirmed by western blot. 2D-DIGE identified 26 proteins with consistently altered model (increase or decrease after both 1- and 4-week 1-BP exposures) and significant changes in their levels (p < 0.05; fold change ≥ ± 1.2) at least at one exposure level or more compared with the corresponding controls. Of these proteins, 19 were identified by MALDI-TOF-TOF/MS. Linear regression analysis of 1-BP exposure level identified 8 differentially expressed proteins altered in a dose-dependent manner both in 1- and 4-week exposure experiments. The identified proteins could be categorized into diverse functional classes such as nucleocytoplasmic transport, immunity and defense, energy metabolism, ubiquitination-proteasome pathway, neurotransmitter and purine metabolism. Overall, the results suggest that 1-BP-induced hippocampal damage involves oxidative stress, loss of ATP production, neurotransmitter dysfunction and inhibition of ubiquitination-proteasome system. -- Highlights: ► 1-BP modified hippocampal proteome in rat and 19 altered proteins were identified. ► Expression of Ran, TPI, HSP60, PSMA1, ECH1, TPI, B-CK and DJ-1 was changed by 1-BP. ► 1-BP exposure might change biological processes such as

  17. Study of pathological and anti-hyperlipidemic offects of ginger Zingiber officinalae in rats exposed to oxidative stress

    Directory of Open Access Journals (Sweden)

    A. M. A. Al-Saidya

    2010-01-01

    Full Text Available This study was conducted to investigate the role of Ginger as antihyperlipidemic agent and its histopathological effects inrats exposed to oxidative stress. Results of rats treated with hydrogen peroxide (H2O2 1% in drinking water, showed highlysignificant increase in the level of low density lipoprotein cholesterol (LDL-C, very low density lipoprotein cholesterol(VLDL-C and atherogenic index, which are indicators for the occurrence of serum hyperlipidemia. Rats treated with H2O2then with Ginger at 2 mg/kg in diet, revealed significant decrease in the level of LDL-C, VLDL-C and atherogenic index.Histopathological study illustrate no changes in rats treated with Ginger in heart and liver tissues, while rats treated with H2O2then with Ginger, showed amelioration in histological picture of heart and liver tissues compared with rats treated with H2O2.In conclusion, The Ginger considered as a good antihyperlipidemic agent.

  18. Reduced Bone and Body Mass in Young Male Rats Exposed to Lead

    Directory of Open Access Journals (Sweden)

    Fellipe Augusto Tocchini de Figueiredo

    2014-01-01

    Full Text Available The aim of this study was to see whether there would be differences in whole blood versus tibia lead concentrations over time in growing rats prenatally. Lead was given in the drinking water at 30 mg/L from the time the dams were pregnant until offspring was 28- or 60-day-old. Concentrations of lead were measured in whole blood and in tibia after 28 (28D and 60 days (60D in control (C and in lead-exposed animals (Pb. Lead measurements were made by GF-AAS. There was no significant difference (P>0.05 in the concentration of whole blood lead between Pb-28D (8.0±1.1 μg/dL and Pb-60D (7.2±0.89 μg/dL, while both significantly varied (P<0.01 from controls (0.2 μg/dL. Bone lead concentrations significantly varied between the Pb-28D (8.02±1.12 μg/g and the Pb-60D (43.3±13.26 μg/g lead-exposed groups (P<0.01, while those exposed groups were also significantly higher (P<0.0001 than the 28D and 60D control groups (Pb < 1 μg/g. The Pb-60D group showed a 25% decrease in tibia mass as compared to the respective control. The five times higher amount of lead found in the bone of older animals (Pb-60D versus Pb-28D, which reinforces the importance of using bone lead as an exposure biomarker.

  19. Prolactin and its receptors in the chronic mild stress rat model of depression.

    Science.gov (United States)

    Faron-Górecka, A; Kuśmider, M; Kolasa, M; Zurawek, D; Gruca, P; Papp, M; Szafran, K; Solich, J; Pabian, P; Romańska, I; Antkiewicz-Michaluk, L; Dziedzicka-Wasylewska, M

    2014-03-25

    Prolactin (PRL) exhibits many physiological functions with wide effects on the central nervous system including stress responses. Our study aimed to investigate the effect of chronic unpredictable mild stress (CMS) - which is a good animal model of depression - on PRL receptor (PRLR) expression in the rat brain. Rats were exposed to CMS for two weeks and subsequently to CMS in combination with imipramine (IMI) treatment for five consecutive weeks. Behavioral deficit measured in anhedonic animals is a reduced intake of sucrose solution. Two weeks of CMS procedure allowed the selection of animals reactive to stress and displaying anhedonia, and the group which is considered as stress-non-reactive as far as behavioral measures are concerned. In this group the elevated level of PRL in plasma was observed, decrease in dopamine release in the hypothalamus, increase in [(125)I]PRL binding to PRLR in the choroid plexus, increase of mRNA encoding the long form of PRLR in the arcuate nucleus and the decrease of mRNA encoding its short form, and decrease in the mRNA encoding dopamine D2 receptor. All these alterations indicate these parameters as involved in the phenomenon of stress-resilience. The prolongation of the CMS procedure for additional five weeks shows the form of habituation to the stressful conditions. The most interesting result, however, was the up-regulation of PRLR in the choroid plexus of rats subjected to full CMS procedure combined with treatment with IMI, which may speak in favor of the role of this receptor in the mechanisms of antidepressant action.

  20. Effect of methanol extract of Basella alba L. (Basellaceae) on the fecundity and testosterone level in male rats exposed to flutamide in utero.

    Science.gov (United States)

    Nantia, E A; Manfo, P F T; Beboy, N E; Travert, C; Carreau, S; Monsees, T K; Moundipa, P F

    2012-02-01

    We evaluated the effect of the methanol extract of Basella alba (MEBa) on testosterone level and fecundity/fertility in male rats exposed in utero to flutamide - an androgen receptor antagonist. For this purpose, 1.5- and 2.5 -month-old male rats exposed in utero to flutamide were treated with the MEBa (1 mg kg(-1) ) for 2 and 1 month respectively. Five days before the end of treatment, rats were housed with females to assess their fecundity/fertility. Thereafter, rats were sacrificed and blood collected for the quantification of testosterone. Flutamide-exposed male rats showed a decrease in their ano-genital distance (AGD, P < 0.05) and were infertile. In normal (methylcellulose-exposed) animals, MEBa provoked an increase in testosterone level in 1.5- (P < 0.008) and 2.5 -month-old rats (P < 0.01) concomitantly with the improvement in their fecundity by 25%. In flutamide-exposed male rats, MEBa increased testosterone level in 1.5 -month-old rats (P < 0.001) without any effect on their fecundity; while in 2.5- month-old rats, MEBa did not affect the testosterone level but improved fecundity (by 25%) and fertility (P < 0.001). This study demonstrated the positive effect of MEBa to enhance fecundity/fertility in normal male rats and in rats exposed to the antiandrogen flutamide during their foetal life. PMID:21592171

  1. Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats

    DEFF Research Database (Denmark)

    Graebe, Martin; Brond, Lone; Christensen, Sten;

    2004-01-01

    The present study investigated sodium balance and renal tubular function in cirrhotic rats with chronic blockade of the nitric oxide (NO) system. Rats were treated with the nonselective NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) starting on the day of common bile duct ligatio...

  2. Phosphodiesterase 4 inhibitor rolipram prevents depression- and anxiety-like behaviors in rats exposed to chronic restraint stress%磷酸二酯酶4抑制剂咯利普兰逆转慢性束缚应激诱导的大鼠抑郁和焦虑样行为

    Institute of Scientific and Technical Information of China (English)

    张俊芳; 张忠敏; 赵鑫; 刘爱明; 郭洁洁; 沈璐艳; 王钦文; 王闯

    2012-01-01

    诱导了大鼠海马内PDE4D表达的上调,PKA、p-CREB及p-Ser9-GSK3β的下调.Rolipram显著逆转了上述效应,且H89显著阻断了Rolipram的药物效应.结论:Rolipram抗抑郁及抗焦虑作用不仅通过CREB/BDNF信号通路,而且还有GSK3 抑制性丝氨酸残基磷酸化信号通路的参与,且CREB介导的信号转导通路对GSK3 抑制性丝氨酸残基磷酸化信号通路发挥重要调节作用.%AIM: To discuss the impact of phosphodiesterase 4 (PDE4) inhibitor rolipram on chronic restraint stress - induced depression - and anxiety - like behaviors in rats. METHODS: (1) Forty SD rats were randomly divided into 4 weight -matched groups: unstressed animals injected with vehicle of lithium chloride (LiCl) and rolipram, restraint - stressed animals injected daily with vehicle prior to stress, restraint stress plus 100 mg/kg LiCl group and restraint stress plus 1 mg/kg rolipram group. The open field test was conducted 24 h before the first stress and drug administration, and then the rats received drugs daily 1 h prior to restraint stress (6 h/d) for 25 d. Daily body weight recording, forced swim-ming test, elevated plus - maze and open field test were conducted to determine the changes of depression - and anxiety -like behaviors. The expression of phosphorylated cAMP response element - binding protein (p - CREB) , brain - derived Reurotrophic factor ( BDNF) , p - Ser21 - glycogen synthase kinase ( GSK) 3α, p - Ser9 - GSK3β, p - Tyr279 - GSK3α, p -Tyr216 - GSK3β, total GSK3α and total GSK3β was measured by Western blotting. (2) Thirty SD rats were randomly divided into 6 groups and the cannula was surgically placed above the CA1 region in the hippocampus. Seven days after the surgery, the restraint stress was conducted for 21 d after microinjection of protein kinase A (PKA) antagonist H89 and in-traperitoneal injection of LiCl and rolipram everyday. The expression of PDE4D, PKA, p - CREB and p - Ser9 - GSK3β was measured by Western blotting. RESULTS: ( 1) No

  3. Baroreflex impairment precedes hypertension during chronic cerebroventricular infusion of hypertonic sodium chloride in rats.

    OpenAIRE

    Buñag, R D; Miyajima, E

    1984-01-01

    Osmotic minipumps were implanted chronically for continuous 11-d infusion of hypertonic sodium chloride (NaCl) into the third cerebral ventricle (ICV) of awake rats to determine whether baroreflex sensitivity would be altered. Systolic and mean pressures, recorded from aortic catheters on day 11 while the rats were anesthetized with alpha-chloralose, were significantly higher in rats infused with artificial cerebrospinal fluid (CSF) containing hypertonic NaCl than in controls similarly infuse...

  4. EXPOSURE PARAMETERS NECESSARY FOR DELAYED PUBERTY AND MAMMARY GLAND DEVELOPMENT IN LONG-EVANS RATS EXPOSED IN UTERO TO ATRAZINE

    Science.gov (United States)

    Exposure Parameters Necessary For Delayed Puberty And Mammary Gland Development In Long-Evans Rats Exposed In Utero To AtrazineJennifer L. Rayner1, 2, Carmen Wood2, and Suzanne E. Fenton21 Department of Environmental Sciences and Engineering, School of Public Heal...

  5. Different Effects of Testosterone on Acute and Chronic Pain in Gonadectomized Male Rats

    Directory of Open Access Journals (Sweden)

    A Zarifkar

    2008-01-01

    Full Text Available ABSTRACT: Introduction & Objective: Nociception and behavioral responses to noxious stimuli are different in males and females. It seems that these differences are due to the effects of sex hormones on the pain mechanisms. The aim of the current study was to evaluate the effect of testosterone administration on nociception by formalin test in gonadectomized rats. Material & Methods: In this study 32 male wistar rats were divided into four groups (n=8 the control rats without receiving any drug or surgical operation, the sham – operated animals with surgical stress, the gonadectomized rats receiving 0.5 ml vehicle (olive oil i.p., and the gonadectomized rats receiving testosterone enantate (6 mg/100 gr body weight in 0.5 ml vehicle i.p.. On the sixth day after gonadectomy operation, formalin test was done in all rats. Pain scores in formalin test were statistically analyzed by SPSS and ANOVA. Results: The results showed that testosterone caused an increase in pain score in acute phase of formalin test in gonadectomized rats compared with sham-operated group (p<0.001. However, pain score in chronic phase was significantly reduced in testosterone received rats (p<0.001. Conclusion: It can be concluded that testosterone increases nociception in acute phase of formalin test in gonadectomized rats. On the other hand, testosterone relieved pain during chronic phase. Anti-nociceptive effects of testosterone in chronic phase may be through central nervous system by interacting with endogenous pain modulatory systems

  6. Effects of an acute and a sub-chronic 900 MHz GSM exposure on brain activity and behaviors of rats

    Energy Technology Data Exchange (ETDEWEB)

    Elsa Brillaud; Aleksandra Piotrowski; Anthony Lecomte; Franck Robidel; Rene de Seze [Toxicology Unit, INERIS, Verneuil en Halatte (France)

    2006-07-01

    Radio frequencies are suspected to produce health effects. Concerning the mobile phone technology, according to position during use (close to the head), possible effects of radio frequencies on the central nervous system have to be evaluated. Previous works showed contradictory results, possibly due to experimental design diversity. In the framework of R.A.M.P. 2001 project, we evaluated possible effect of a 900 MHz GSM exposure on the central nervous system of rat at a structural, a functional and a behavioral level after acute or sub-chronic exposures. Rats were exposed using a loop antenna system to different S.A.R. levels and durations, according to results of the French C.O.M.O.B.I.O. 2001 project. A functional effect was found (modification of the cerebral activity and increase of the glia surface) after an acute exposure, even at a low level of brain averaged S.A.R. (1.5 W/kg). No cumulative effect was observed after a sub-chronic exposure (same amplitude of the effect). No structural or behavioral consequence was noted. We do not conclude on the neurotoxicity of the 900 MHz GSM exposure on the rat brain. Our results do not indicate any health risk. (authors)

  7. Effect of chronic exposure to cadmium on serum lipid, lipoprotein and oxidative stress indices in male rats

    Directory of Open Access Journals (Sweden)

    Samarghandian Saeed

    2015-09-01

    Full Text Available Cadmium (Cd is an environmental toxic metal implicated in lipid abnormalities. The present study was designed to elucidate the possible association between chronic exposure to Cd concentration and alterations in plasma lipid, lipoprotein, and oxidative stress indices in rats. Sixteen male rats were assigned to 2 groups of 8 rats each (test and control. The Cd-exposed group obtained drinking water containing cadmium chloride (CdCl2 in the concentration of 2.0 mg Cd/L in drinking water for 3 months. At the end of the experimental period, blood samples were obtained to determine the changes of serum triglycerides (TG, total cholesterol (TC, high-density lipoprotein cholesterol (HDL-C, low-density lipoprotein cholesterol (LDL-C, reduced glutathione (GSH, malondialdehyde (MDA and also serum Cd contents. The results of the present study indicated that Cd administration significantly increased the serum levels of TG, TC, LDL-C, MDA and Cd with reduction in the HDL-C and GSH levels. In conclusion, evidence is presented that chronic exposure to low Cd concentration can adversely affect the lipid and lipoprotein profile via lipid peroxidation.

  8. Chronic phase shifts of the photoperiod throughout pregnancy programs glucose intolerance and insulin resistance in the rat.

    Directory of Open Access Journals (Sweden)

    Tamara J Varcoe

    Full Text Available Shift work during pregnancy is associated with an increased risk for preterm birth and low birth weight. However, the impact upon the long term health of the children is currently unknown. In this study, we used an animal model to determine the consequences of maternal shift work exposure on the health of the adult offspring. Pregnant rats were exposed to chronic phase shifts (CPS in their photoperiod every 3-4 days throughout gestation and the first week after birth. Adult offspring were assessed for a range of metabolic, endocrine, circadian and neurobehavioural parameters. At 3 months of age, male pups exposed to the CPS schedule in utero had increased adiposity (+29% and hyperleptinaemia (+99% at 0700h. By 12 months of age, both male and female rats displayed hyperleptinaemia (+26% and +41% respectively and hyperinsulinaemia (+110% and +83% respectively. 12 month old female CPS rats displayed poor glucose tolerance (+18% and increased insulin secretion (+29% in response to an intraperitoneal glucose tolerance test. In CPS males the glucose response was unaltered, but the insulin response was reduced by 35%. The glucose response to an insulin tolerance test was decreased by 21% in CPS females but unaltered in males. Disruption of circadian rhythmicity during gestation resulted in gender dependent metabolic consequences for the adult offspring. These results highlight the need for a thorough analysis of shift work exposure in utero on the health of the adult offspring in humans.

  9. Effect of Chronic Administration of Melatonin on Ethanol Drinking in Rat Models of Chronic Voluntary Ethanol Consumption

    Directory of Open Access Journals (Sweden)

    Zahoor Ahmad Rather

    2016-06-01

    Full Text Available Objective: This study is planned to examine the possible beneficial effect of chronic administration of melatonin on ethanol drinking in rat models chronic voluntary ethanol consumption. Methods: Intermittent access 10% ethanol two-bottle-choice drinking paradigm was employed in 4 groups of rats where the rats had access to ethanol on alternate days in a week and a free access to water on all day. The ethanol and water intake was recorded on each ethanol day. All rats received drug treatment (Distilled water, naltrexone, melatonin 50 mg/kg and melatonin 100 mg/kg for 6 days continuously once they attain stable ethanol drinking pattern. The ethanol consumption on the last drinking session before the drug administration was noted as pretreatment baseline ethanol drinking value. The ethanol consumption on the first drinking session after the last dose of drug administration was noted as the post treatment value. Results: There was no change in the amount of ethanol consumption by rats in groups receiving distilled water and melatonin 50 mg/kg body weight. There was significant reduction in the ethanol consumption in rats receiving melatonin 100 mg/kg body weight and naltrexone. Comparison among different groups showed statistically significant difference between melatonin 100 mg/kg and distilled water as well as between naltrexone and distilled water.

  10. Novel non-thermal atrial fibrillation treatment with photosensitization reaction: possibility of permanent electrical blockade in rat chronic model

    Science.gov (United States)

    Matsuo, Hiroki; Ito, Arisa; Miyoshi, Shunichiro; Soejima, Kyoko; Ogawa, Satoshi; Arai, Tsunenori

    2009-06-01

    We demonstrated a possibility of electrical conduction block by ex vivo and in vivo experiments using rat models to establish a non-thermal treatment for atrial fibrillation by photosensitization reaction (PR). One hour after the injection of 2 mg/kg Talaporfin sodium to Wistar rat, the right ventricle (1.4 mmT) was extracted. Paced with a stimulation electrode, this tissue was placed in a tissue bath and immersed in irrigated Tyrode's solution of 37°C with 8 μg/ml Talaporfin sodium and the gas mixture bubbling of 95% CO2 and 5% O2. The propagated electrical signal was measured by two bipolar electrodes. Exciting light of 670 nm in wavelength was irradiated to the tissue between the bipolar electrodes by the power density of 1 W/cm2. After this irradiation, propagation signal blockade was obtained and continued up to three hours. Rat atrioventricular (AV) node was employed as a target region for chronic model. The heart of Wistar rat was surgically exposed. External four-lead electrocardiogram of this rat was measured. Thirty minutes after the injection of 10 mg/kg Talaporfin sodium to the rat, exciting light of 663 nm in wavelength was irradiated to the AV node by the power density of 500 mW/cm2 for ten minutes. Acute AV block was obtained during the irradiation. Two weeks after this procedure, complete AV block was confirmed. The rat was sacrificed to obtain the tissue specimen. We found that the AV node was replaced by scarring tissue under the microscopic observation of the specimen. We verified possibility of permanent electrical conduction block using PR.

  11. MRP1 expression in bronchoalveolar lavage cells in subjects with lung cancer who were chronically exposed to arsenic.

    Science.gov (United States)

    Recio-Vega, Rogelio; Dena-Cazares, Jose Angel; Ramirez-de la Peña, Jorge Luis; Jacobo-Ávila, Antonio; Portales-Castanedo, Arnulfo; Gallegos-Arreola, Martha Patricia; Ocampo-Gomez, Guadalupe; Michel-Ramirez, Gladis

    2015-12-01

    Alteration of multidrug resistance-associated protein-1 (MRP1) expression has been associated with certain lung diseases, and this protein may be pivotal in protecting the lungs against endogenous or exogenous toxic compounds. The aim of this study was to evaluate and compare the expression of MRP1 in bronchoalveolar cells from subjects with and without lung cancer who had been chronically exposed to arsenic through drinking water. MRP1 expression was assessed in bronchoalveolar cells in a total of 102 participants. MRP1 expression was significantly decreased in those with arsenic urinary levels >50 μg/L when compared with the controls. In conclusion, chronic arsenic exposure negatively correlates with the expression of MRP1 in BAL cells in patients with lung cancer.

  12. RELAXANT EFFECTS OF VASOACTIVE INTESTINAL PEPTIDE ON PULMONARY ARTERY IN CHRONICALLY HYPOXIC RATS

    Institute of Scientific and Technical Information of China (English)

    陈玉玲; 罗慰慈; 蔡英年

    1996-01-01

    The object of this study is to investigate the effect of VIP on pulmonary artery of chronically hypoxic rats. It was shown that chronic hypoxla depressed significantly pulmnonary artery relaxation induced by VIP as compared with those of control (Prats was endotbelium-independent, and was not prevented by indomethaein or nordihydroguaiaretie acid, but was abolished completely by methylene blue. These results suggest that the lower relaxation of pulmonary artery in rats might not be due to the endothelial injury caused by chronic hypoxxia, and chronic hypoxiamay inhibit directly the soluble guanylate cyclase in vascular smooth muscle cells invioved in synthesis of cGMP and thus reduced the sensitivity and reactivity of pulmonary artery to VIP.

  13. Early ovarian follicular development in prepubertal Wistar rats acutely exposed to androgens.

    Science.gov (United States)

    Paixão, L; Velez, L M; Santos, B R; Tusset, C; Lecke, S B; Motta, A B; Spritzer, P M

    2016-08-01

    Androgens may directly modulate early ovarian follicular development in preantral stages and androgen excess before puberty may disrupt this physiological process. Therefore, the aim of this study was to investigate the dynamics of follicular morphology and circulating androgen and estradiol levels in prepubertal Wistar rats acutely exposed to androgens. Prepubertal female Wistar rats were distributed into three groups: control, equine chorionic gonadotropin (eCG) intervention and eCG plus dehydroepiandrosterone (DHEA) intervention (eCG+DHEA). Serum DHEA, testosterone and estradiol levels were determined, and ovarian morphology and morphometry were assessed. The eCG+DHEA group presented increased serum estradiol and testosterone levels as compared with the control group (P<0.01), and higher serum DHEA concentration v. the eCG-only and control groups (P<0.01). In addition, the eCG+DHEA group had a higher number of, and larger-sized, primary and secondary follicles as compared with the control group (P<0.05). The eCG group presented intermediate values for number and size of primary and secondary follicles, without significant differences as compared with the other two groups. The number of antral follicles was higher in the eCG+DHEA and eCG groups v. controls (P<0.05). The number of primordial, atretic and cystic follicles were similar in all groups. In conclusion, the present experimental model using an acute eCG+DHEA intervention was useful to investigate events involved in initial follicular development under hyperandrogenic conditions, and could provide a reliable tool to study defective follicular development with possible deleterious reproductive consequences later in life. PMID:27256620

  14. Weakness in the mechanical properties of the femurs of growing female rats exposed to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Brzoska, Malgorzata M.; Moniuszko-Jakoniuk, Janina [Medical University of Bialystok, Department of Toxicology, Bialystok (Poland); Majewska, Katarzyna [University of Warmia and Mazury (Poland). Faculty of Food Science

    2005-09-01

    The study assessed the effect of cadmium (Cd) intoxication on the risk of deformities and fractures of the growing bones of female rats, in order to model human exposure to this metal. For this purpose, bone mineral density and mechanical properties of the proximal and distal ends and diaphysis of the femur were investigated in female Wistar rats exposed to 1, 5 and 50 mg Cd/l in drinking water for 3, 6, 9 and 12 months after the onset of weaning. Daily Cd doses received from drinking water during the treatment period were in the following ranges: 0.059-0.219, 0.236-1.005 and 2.247-9.649 mg/kg body weight at 1, 5 and 50 mg Cd/l, respectively. Biomechanical properties of the femoral proximal and distal ends were evaluated in a compression test, and those of the femoral diaphysis in a cutting test, with loading perpendicular to the longitudinal axis of the bone in all tests. The mineralization and mechanical properties of the bone tissue at various locations on the femur were affected by exposure to Cd in a dose- and duration-dependent manner. Exposure to 1 mg Cd/l (corresponding to low human exposure) during skeletal development weakened the fracture strength of the femoral neck and the trabecular bone at the level of the distal end of the femur and affected the elastic properties of the cortical bone at the femoral diaphysis. At higher levels of Cd exposure, adverse effects were generally observed after a shorter exposure period than for 1 mg Cd/l, and were more advanced. The cadmium-induced weakening of the biomechanical properties of bone at particular sites on the femur correlated with the decreased bone mineralization. The results indicate that even a low exposure to Cd may affect the mineralization and biomechanical properties of growing bone, thus enhancing the risk of fracture. (orig.)

  15. Weakness in the mechanical properties of the femur of growing female rats exposed to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Brzoska, Malgorzata M.; Moniuszko-Jakoniuk, Janina [Medical University of Bialystok, Department of Toxicology, Bialystok (Poland); Majewska, Katarzyna [University of Warmia and Mazury, Olsztyn (Poland). Faculty of Food Science

    2005-05-01

    This study was aimed at assessing the effect of cadmium (Cd) intoxication on the risk of deformities and fractures of the growing bone on a female rat model of human exposure to this metal. For this purpose, bone mineral density (BMD) and mechanical properties of the proximal and distal ends and diaphysis of the femur were investigated in female Wistar rats exposed to 1, 5, and 50 mg Cd L{sup -1} in drinking water for 3, 6, 9, and 12 months since weaning. Daily Cd doses received from the drinking water during the treatment period were in the ranges 0.059-0.219, 0.236-1.005, and 2.247-9.649 mg kg{sup -1} body weight at 1, 5, and 50 mg Cd L{sup -1}, respectively. Biomechanical properties of the femoral proximal and distal ends were evaluated in a compression test and those of the femoral diaphysis in a cutting test with loading perpendicular to the bone longitudinal axis in all tests. Cd dose- and exposure duration-dependently affected the mineralization and mechanical properties of the bone tissue at various locations of the femur. Exposure to 1 mg Cd L{sup -1} (corresponding to low human exposure) during skeletal development weakened the fracture strength of the femoral neck and of the trabecular bone at the level of the distal end of the femur and affected the elastic properties of the cortical bone at the femoral diaphysis. At the higher levels of Cd treatment, the adverse action generally occurred after shorter exposure than at 1 mg Cd L{sup -1} and was more seriously advanced. The Cd-induced weakening in the bone biomechanical properties at particular sites of the femur correlated with the decreased bone mineralization. The results indicate that even low exposure to Cd may affect the mineralization and biomechanical properties of growing bone, thus increasing the risk of fractures. (orig.)

  16. A brain proteome profile in rats exposed to methylmercury or thimerosal (ethylmercury).

    Science.gov (United States)

    de Oliveira Souza, Vanessa Cristina; de Marco, Kátia Cristina; Laure, Hélen Julie; Rosa, José Cesar; Barbosa, Fernando

    2016-01-01

    Exposure to organomercurials has been associated with harmful effects on the central nervous system (CNS). However, the mechanisms underlying organomercurial-mediated neurotoxic effects need to be elucidated. Exposure to toxic elements may promote cellular modifications such as alterations in protein synthesis in an attempt to protect tissues and organs from damage. In this context, the use of a "proteomic profile" is an important tool to identify potential early biomarkers or targets indicative of neurotoxicity. The aim of this study was to investigate potential modifications in rat cerebral cell proteome following exposure to methylmercury (MeHg) or ethylmercury (EtHg). For MeHg exposure, animals were administered by gavage daily 140 µg/kg/d of Hg (as MeHg) for 60 d and sacrificed 24 h after the last treatment. For EtHg exposure, 800 µg/kg/d of Hg (as EtHg) was given intramuscularly (im) in a single dose and rats were sacrificed after 4 h. Control groups received saline either by gavage or im. After extraction of proteins from whole brain samples and separation by two-dimensional electrophoresis (2-DE), 26 differentially expressed proteins were identified from exposed animals by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF/TOF). Both MeHg and EtHg exposure induced an overexpression of calbindin, a protein that acts as a neuroprotective agent by (1) adjusting the concentration of Ca(2+) within cells and preventing neurodegenerative diseases and (2) decreasing expression of glutamine synthetase, a crucial protein involved in regulation of glutamate concentration in synaptic cleft. In contrast, expression of superoxide dismutase (SOD), a protein involved in antioxidant defense, was elevated in brain of MeHg-exposed animals. Taken together, our data provide new valuable information on the possible molecular mechanisms associated with MeHg- and EtHg-mediated toxicity in cerebral tissue. These observed protein alterations may be considered as

  17. Comparison of transfer and effects of Cd on rats exposed in a short experimental snail-rat food chain or to CdCl2 dosed food.

    Science.gov (United States)

    Hispard, F; de Vaufleury, A; Cosson, R P; Devaux, S; Scheifler, R; Coeurdassier, M; Gimbert, F; Martin, H; Richert, L; Berthelot, A; Badot, P-M

    2008-04-01

    Transfer and toxic effects of two cadmium (Cd) forms, inorganic (CdCl2 dosed rat food) or organic (contaminated snail-based rat food) were studied in Wistar rat. Cd concentrations in rat food were 0 and 2.5 microg Cd g(-1) for both inorganic and organic forms and a high concentration of 100 microg Cd g(-1) was also tested for the inorganic form. Rats were exposed for four weeks to contaminated food. Both forms of Cd were bioavailable to rats, with a percentage of transfer from food to rats of around 1% for all contaminated groups. Cd concentrations in rat tissues increased with increasing Cd concentrations in the food. Rats fed with organic form of Cd accumulated significantly more Cd in the main organ for Cd toxicity, the kidney, than those eating the inorganic form. Survival was not affected for any rat group but a decrease in growth and food consumption was observed for the inorganic form. As a defence system against Cd toxicity, rats increased their metallothionein (MT) synthesis at the highest Cd concentration in the target organs (kidney, liver and small intestine) and even did the same at low Cd concentrations (2.5 microg Cd g(-1)) in the kidney. At this low Cd concentration, MT induction was lower in the small intestine of rats ingesting organic Cd than those ingesting inorganic Cd. Bioavailability of organic and inorganic forms of Cd was similar, but subsequent Cd distribution within organs was different. This quantification of the trophic transfer of both inorganic and organic forms of a toxicant is a basis for a better assessment of the fate and effects of chemicals in food webs.

  18. Development of the Circadian Timing System in Rat Pups Exposed to Microgravity during Gestation

    Science.gov (United States)

    Fuller, Charles A.

    2000-01-01

    Ten pregnant Sprague Dawley rat dams were exposed to spaceflight aboard the Space Shuttle (STS-70) for gestational days 11-20 (G 11-20; FILT group). Control dams were maintained in either a flight-like (FIDS group) or vivarium cage environment (VIV group) on earth. All dams had ad lib access to food and water and were exposed to a light-dark cycle consisting of 12 hours of light (- 30 lux) followed by 12 hours of darkness. The dams were closely monitored from G 22 until parturition. All pups were cross-fostered at birth; each foster dam had a litter of 10 pups. Pups remained with their foster dam until post-natal day 21 (PN 21). Pup body mass was measured twice weekly. At PN14 FILT pups had a smaller body mass than did the VIV pups (p < 0.01). Circadian rhythms of body temperature and activity of pups from two FILT dams (n = 8), two FIDS dams (n = 9) and two VIV dams (n = 7) were studied starting from age PN 21. All pups had circadian rhythms of temperature and activity at this age. There were no significant differences in rhythms between groups that could be attributed to microgravity exposure. We also examined the development of neural structures involved in circadian rhythmicity: the retina, the intergeniculate leaflet (IGL) and the circadian pacemaker, the suprachiasmatic nucleus (SCN). There were small differences between the flight and control groups at very early stages of development (G 20 and PN3) which indicated that the development of both the SCN and the IGL. These results indicate that exposure to the microgravity environment of spaceflight during this embryonic development period does not affect the development of the circadian rhythms of body temperature and activity, but may affect the early development of the neural structures involved in circadian timing.

  19. Memory, learning, and participation of the cholinergic system in young rats exposed to environmental enrichment.

    Science.gov (United States)

    Lima, Aline P A S; Silva, Kelly; Padovan, Cláudia Maria; Almeida, Sebastião Sousa; Fukuda, Marisa Tomoe Hebihara

    2014-02-01

    The present study demonstrates the consequences of animal exposure to an enriched environment compared to animals living in a standard environment regarding learning and space memory. Male albino Wistar rats were exposed to an enriched environment for 4 weeks after the lactation period and tested in the Morris water maze in the distal and proximal clue version and in the arena. In the former test, the animals were tested at 50 days of age with 12 daily trials on two consecutive days. At the end of each session, scopolamine at the dose of 0.6 mg/kg/ml or saline solution was injected intraperitoneally. Twenty-eight days after the first phase, a new test consisting of a single trial was held (retest). An independent group of animals receiving no drug was subjected to the arena test and to the proximal clue version of the Morris maze. In the distal clue version the results did not show differences between groups in the first phase of the experiment. After 28 days (retest), the animals reared in a standard environment and treated with scopolamine exhibited a significant increase in latency compared to the group receiving the same drug and stimulated and to the group receiving saline. The arena data demonstrated a significant increase in exploratory activity in the group of animals reared in an enriched environment. The proximal clue version of the Morris maze did not show differences between groups. The results of the present study indicate that animals exposed to environmental enrichment react less to the amnesic effects of scopolamine and show an increase in exploratory activity.

  20. Reduced number of alpha- and beta-adrenergic receptors in the myocardium of rats exposed to tobacco smoke

    Energy Technology Data Exchange (ETDEWEB)

    Larue, D.; Kato, G.

    1981-04-09

    The concentration of alpha- and beta-adrenergic receptors--as measured by specific (/sup 3/H)WB-4101 and (-)-(/sup 3/H)dihydroalprenolol binding--was diminished by 60% below control values in the hearts of rats exposed to tobacco smoke. These changes in receptor numbers took place almost immediately after tobacco smoke exposure and were rapidly reversible after termination of the exposure. The dissociation constant, KD, for (/sup 3/H)WB-4101 was identical in exposed (KD . 0.34 +/- 0.09 nM) and control (KD . 0.35 +/- 0.07 nM) hearts but was significantly different in the case of (-)-(3H)dihydroalprenolol binding (exposed, KD . 2.83 +/- 0.30 mM vs. control KD . 5.22 +/- 0.61 nM). For beta-receptor binding there was no significant difference between exposed and control animals in the Ki values for (-)-epinephrine, (-)-norepinephrine, (-)-alprenolol, (+/-)-propranolol or timolol. (-)-Isoproterenol, however, was found to bind with lower affinity in exposed compared with control hearts. For alpha-receptor binding there was no significant difference between control and 'smoked' animals in the Ki values for (-)-epinephrine, (-0)-norepinephrine or phentolamine. The decrease in alpha- and beta-adrenergic receptor concentration may be related to the phenomenon of receptor desensitization resulting from a release of catecholamines in rats exposed to tobacco smoke.

  1. Chronic high fat feeding increases anxiety-like behaviour and reduces transcript abundance of glucocorticoid signalling genes in the hippocampus of female rats.

    Science.gov (United States)

    Sivanathan, Shathveekan; Thavartnam, Kabriya; Arif, Shahneen; Elegino, Trisha; McGowan, Patrick O

    2015-06-01

    The consumption of diets high in saturated fats and obesity have been associated with impaired physical and mental health. Previous studies indicate that chronic high fat diet consumption leads to systemic inflammation in humans and non-human animal models. Studies in non-human animals suggest that altered physiological responses to stress are also a consequence of high fat diet consumption. Glucocorticoid signalling mechanisms may link immune and stress-related pathways in the brain, and were shown to be significantly altered in the brains of female rat offspring of mothers exposed to chronic high fat diet during pregnancy and lactation. For adult females, the consequence of chronic high fat diet consumption on these signalling pathways and their relationship to stress-related behaviour is not known. In this study, we examined the effects of chronic consumption of a high fat diet compared to a low fat control diet among adult female Long Evans rats. We found significant differences in weight gain, caloric intake, anxiety-related behaviours, and glucocorticoid-related gene expression over a 10-week exposure period. As expected, rats in the high fat diet group gained the most weight and consumed the greatest number of calories. Rats in the high fat diet group showed significantly greater levels of anxiety-related behaviour in the Light Dark and Open Field tasks compared to rats in the low fat diet group. Rats consuming high fat diet also exhibited reduced transcript abundance in the hippocampus of stress-related mineralocorticoid receptor and glucocorticoid receptor genes, as well as nuclear factor kappa beta gene expression, implicated in inflammatory processes. Together, these data indicate that chronic high fat diet consumption may increase anxiety-like behaviour at least in part via alterations in glucocorticoid signalling mechanisms in limbic brain regions.

  2. Chronic and acute risk assessment of human exposed to novaluron-bifenthrin mixture in cabbage.

    Science.gov (United States)

    Shi, Kaiwei; Li, Li; Li, Wei; Yuan, Longfei; Liu, Fengmao

    2016-09-01

    Based on the dissipation and residual level in cabbage determined by gas chromatography coupled with an electron capture detector (GC-ECD), chronic and acute risk assessments of the novaluron and bifenthrin were investigated. At different spiked levels, mean recoveries were between 81 and 108 % with relative standard deviations (RSDs) from 1.1 to 6.8 %. The limit of quantification (LOQ) was 0.01 mg kg(-1), and good linearity with correlation coefficient (>0.9997) were obtained. The half-lives of novaluron and bifenthrin in cabbage were in the range of 3.2~10 days. Based on the consumption data in China, the risk quotients (RQs) of novaluron and bifenthrin were all below 100 %. The chronic and acute risk of novaluron in cabbage was relatively low, while bifenthrin exerts higher acute risk to humans than chronic risk. The obtained results indicated that the use of novaluron-bifenthrin mixture does not seem to pose any chronic or acute risk to humans even if cabbages are consumed at high application dosages and short preharvest interval (PHI). PMID:27550439

  3. Mood and Memory Function in Ovariectomised Rats Exposed to Social Instability Stress

    OpenAIRE

    Badriya Al-Rahbi; Rahimah Zakaria; Zahiruddin Othman; Asma’ Hassan; Sangu Muthuraju; Wan Mohd Zahiruddin Wan Mohammad

    2013-01-01

    This study aims to compare the effects of social instability stress on memory and anxiety- and depressive-like behaviour between sham-operated controls and ovariectomised (OVX) rats. Forty adult female Sprague-Dawley rats (8 weeks old) were randomly divided into four groups, (n = 10 per group). These were non-stressed sham-operated control rats, stressed sham-operated control rats, non-stressed OVX rats, and stressed OVX rats. The rats were subjected to social instability stress procedure for...

  4. Reductions in circulating endocannabinoid 2-arachidonoylglycerol levels in healthy human subjects exposed to chronic stressors.

    Science.gov (United States)

    Yi, Buqing; Nichiporuk, Igor; Nicolas, Michel; Schneider, Stefan; Feuerecker, Matthias; Vassilieva, Galina; Thieme, Detlef; Schelling, Gustav; Choukèr, Alexander

    2016-06-01

    Increasing evidence indicates that chronic stress, such as social isolation, plays an important role in the development of a variety of psychiatric and somatic disorders. Meanwhile, chronic stress imposed by prolonged isolation and confinement in the spacecraft is also one of the major concerns for the health of future interplanetary space travelers. Preclinical studies suggest that the peripheral endocannabinoid (eCB) system is involved in the regulation of the stress response and eCB signaling is implicated in the pathogenesis of stress-related diseases. However, there are only few human studies addressing this topic, of which most focusing on patients who have already developed a certain type of disorder. It remains unknown whether chronic stress may affect eCB signaling in healthy humans. A 520-d isolation and confinement study simulating a flight to Mars provided an extraordinary chance to study the effects of prolonged stress in healthy humans. During the study period, the participants lived in confinement and could not meet their families, friends, or strangers for more than 500 days. We examined the impact of chronic exposure to isolation and confinement through monitoring their psychological state, brain cortical activity, sympathetic adrenal-medullary system response and eCB signaling response. We observed reduced positive emotion ratings, decreased brain cortical activities and high levels of catecholamine release, indicating that prolonged exposure to isolation and confinement stressors may bring about changes both psychologically and physiologically. Importantly, for eCB signaling response, blood concentrations of eCB 2-arachidonoylglycerol (2-AG), but not anandamide (AEA), were significantly reduced (p<0.001), suggesting that dysregulation of 2-AG signaling might be specifically implicated in the response to chronic stressors.

  5. Reductions in circulating endocannabinoid 2-arachidonoylglycerol levels in healthy human subjects exposed to chronic stressors.

    Science.gov (United States)

    Yi, Buqing; Nichiporuk, Igor; Nicolas, Michel; Schneider, Stefan; Feuerecker, Matthias; Vassilieva, Galina; Thieme, Detlef; Schelling, Gustav; Choukèr, Alexander

    2016-06-01

    Increasing evidence indicates that chronic stress, such as social isolation, plays an important role in the development of a variety of psychiatric and somatic disorders. Meanwhile, chronic stress imposed by prolonged isolation and confinement in the spacecraft is also one of the major concerns for the health of future interplanetary space travelers. Preclinical studies suggest that the peripheral endocannabinoid (eCB) system is involved in the regulation of the stress response and eCB signaling is implicated in the pathogenesis of stress-related diseases. However, there are only few human studies addressing this topic, of which most focusing on patients who have already developed a certain type of disorder. It remains unknown whether chronic stress may affect eCB signaling in healthy humans. A 520-d isolation and confinement study simulating a flight to Mars provided an extraordinary chance to study the effects of prolonged stress in healthy humans. During the study period, the participants lived in confinement and could not meet their families, friends, or strangers for more than 500 days. We examined the impact of chronic exposure to isolation and confinement through monitoring their psychological state, brain cortical activity, sympathetic adrenal-medullary system response and eCB signaling response. We observed reduced positive emotion ratings, decreased brain cortical activities and high levels of catecholamine release, indicating that prolonged exposure to isolation and confinement stressors may bring about changes both psychologically and physiologically. Importantly, for eCB signaling response, blood concentrations of eCB 2-arachidonoylglycerol (2-AG), but not anandamide (AEA), were significantly reduced (p<0.001), suggesting that dysregulation of 2-AG signaling might be specifically implicated in the response to chronic stressors. PMID:26780604

  6. Targeting anandamide metabolism rescues core and associated autistic-like symptoms in rats prenatally exposed to valproic acid

    Science.gov (United States)

    Servadio, M; Melancia, F; Manduca, A; di Masi, A; Schiavi, S; Cartocci, V; Pallottini, V; Campolongo, P; Ascenzi, P; Trezza, V

    2016-01-01

    Autism spectrum disorders (ASD) are characterized by altered sociability, compromised communication and stereotyped/repetitive behaviors, for which no specific treatments are currently available. Prenatal exposure to valproic acid (VPA) is a known, although still underestimated, environmental risk factor for ASD. Altered endocannabinoid activity has been observed in autistic patients, and endocannabinoids are known to modulate behavioral traits that are typically affected in ASD. On this basis, we tested the hypothesis that changes in the endocannabinoid tone contribute to the altered phenotype induced by prenatal VPA exposure in rats, with focus on behavioral features that resemble the core and associated symptoms of ASD. In the course of development, VPA-exposed rats showed early deficits in social communication and discrimination, compromised sociability and social play behavior, stereotypies and increased anxiety, thus providing preclinical proof of the long-lasting deleterious effects induced by prenatal VPA exposure. At the neurochemical level, VPA-exposed rats displayed altered phosphorylation of CB1 cannabinoid receptors in different brain areas, associated with changes in anandamide metabolism from infancy to adulthood. Interestingly, enhancing anandamide signaling through inhibition of its degradation rescued the behavioral deficits displayed by VPA-exposed rats at infancy, adolescence and adulthood. This study therefore shows that abnormalities in anandamide activity may underlie the deleterious impact of environmental risk factors on ASD-relevant behaviors and that the endocannabinoid system may represent a therapeutic target for the core and associated symptoms displayed by autistic patients. PMID:27676443

  7. The Effect of Citrus aurantium on Uterus Apoptosis and Serum Antioxidants in Rats Exposed to Electromagnetic Fields

    Directory of Open Access Journals (Sweden)

    Mansouri Elham

    2014-10-01

    Full Text Available Objective: In the industrial world, almost everyone is unavoidably exposed to ambient electromagnetic field (EMF generated from various technical and household appliances. Thus, the aim of this study was to evaluate the diminishing effects of Citrus aurantium on uterus cell injury induced by EMF. Materials and Methods: In order to examine this, 40 female Wistar rats were selected and kept for 1 week in quarantine, and then, subdivided into two groups of 20 rats and were exposed to 40 Hz of EMF (non-ionizing radiation, 0.1 tesla for 6 weeks. Group 1 received 3 cc/rat Citrus aurantium juice, and group 2 only received 3 cc Citrus aurantium. The control group only received 3 cc water using gavage method. The materials were processed and apoptosis was observed under a light microscope using TUNEL method. Results: In the experimental rats, apoptotic cells showed significant increase in the EMF groups. However, in the exposed group that received Citrus aurantium, apoptotic cells and serum malondialdehyde (MDA were decreased and superoxide dismutase (SOD was increased (P < 0.05. Conclusion: This study showed that EMF could induce cell injury on uterus tissue, and 3 cc Citrus aurantium juice has antioxidative effects on uterus tissue by reduction of apoptosis.

  8. Effect of kombucha on some trace element levels in different organs of electromagnetic field exposed rats

    Directory of Open Access Journals (Sweden)

    Ola A. Gharib

    2014-01-01

    Full Text Available Mobile phones have increased exponentially all over the world. The present study was performed to evaluate the effect of kombucha (KT on some trace element levels of brain, spleen and intestine in male albino rats exposed to a 950 MHz electromagnetic field (EMF. Four experimental groups labelled as controls, EMF group, KT group and KT + EMF group were formed with six randomly chosen animals in each group. After EMF exposure for eight weeks and the animals were sacrificed by decapitation. Brain, spleen and intestine samples were collected for trace element analysis. The group of animals subjected to electromagnetic waves caused significant increases in iron copper levels and copper/zinc ratio accompanied with a decrease of zinc level in all studied organs. Combined treatment of kombucha with EMF resulted in a successful attenuation of these adverse effects of EMF. From present findings we can state that kombucha as a supplement has an ameliorative signs against the effects of electromagnetic radiation.

  9. Transfer of tritium to prenatal and neonatal rats from their mothers exposed to tritiated compounds

    International Nuclear Information System (INIS)

    The transfer of tritium through the placenta or milk was investigated to estimate the radiation dose to the fetus and newborn. Female rats at gestational stages or after delivery were exposed to tritium in the form of water, thymidine and lysine by a single oral administration and radioactivity in tissues including conceptuses (placenta, fetal membrane and fetus) and in the newborn was determined at various times after administration. In all cases of the investigated triated compounds, there was no significant difference between the tritium concentration in the fetus and that in the maternal tissues, suggesting that the placenta has no effect in preventing or accelerating the placental transfer of tritium. The time course of tritium concentration and tritium content in the fetus and newborn were, however, dependent on the chemical form of tritium and on the prenatal or neonatal stages at the time of ingestion. In general, the tritium concentration and tritium content after the ingestion of 3H-lysine were higher than that after the ingestion of tritiated water or 3H-thymidine. The result of dose estimation showed that 3H-lysine gave higher prenatal and neonatal doses than tritiated water or 3H-thymidine by a factor of 1.5 to 6.0. (author)

  10. Delayed extinction and stronger drug-primed reinstatement of methamphetamine seeking in rats prenatally exposed to morphine.

    Science.gov (United States)

    Shen, Ying-Ling; Chen, Shao-Tsu; Chan, Tzu-Yi; Hung, Tsai-Wei; Tao, Pao-Luh; Liao, Ruey-Ming; Chan, Ming-Huan; Chen, Hwei-Hsien

    2016-02-01

    Prenatal morphine (PM) affects the development of brain reward system and cognitive function. The present study aimed to determine whether PM exposure increases the vulnerability to MA addiction. Pregnant Sprague-Dawley rats were administered saline or morphine during embryonic days 3-20. The acquisition, extinction and reinstatement of methamphetamine (MA) conditioned place preference (CPP) and intravenous self-administration (SA) paradigms were assessed in the male adult offspring. There was no difference in the acquisition and expression of MA CPP between saline- and PM-exposed rats, whereas PM-exposed rats exhibited slower extinction and greater MA priming-induced reinstatement of drug-seeking behavior than controls. Similarly, MA SA under progressive ratio and fixed ratio schedules was not affected by PM exposure, but PM-exposed rats required more extinction sessions to reach the extinction criteria and displayed more severe MA priming-, but not cue-induced, reinstatement. Such alterations in extinction and reinstatement were not present when PM-exposed rats were tested in an equivalent paradigm assessing operant responding for food pellets. Our results demonstrate that PM exposure did not affect the association memory formation during acquisition of MA CPP or SA, but impaired extinction learning and increased MA-primed reinstatement in both tasks. These findings suggest that the offspring of women using morphine or heroin during pregnancy might predict persistent MA seeking during extinction and enhanced propensity to MA relapse although they might not be more susceptible to the reinforcing effect of MA during initiation of drug use. PMID:26743042

  11. Altered feeding patterns in rats exposed to a palatable cafeteria diet: increased snacking and its implications for development of obesity.

    Directory of Open Access Journals (Sweden)

    Sarah I Martire

    Full Text Available BACKGROUND: Rats prefer energy-rich foods over chow and eat them to excess. The pattern of eating elicited by this diet is unknown. We used the behavioral satiety sequence to classify an eating bout as a meal or snack and compared the eating patterns of rats fed an energy rich cafeteria diet or chow. METHODS: Eight week old male Sprague Dawley rats were exposed to lab chow or an energy-rich cafeteria diet (plus chow for 16 weeks. After 5, 10 and 15 weeks, home-cage overnight feeding behavior was recorded. Eating followed by grooming then resting or sleeping was classified as a meal; whereas eating not followed by the full sequence was classified as a snack. Numbers of meals and snacks, their duration, and waiting times between feeding bouts were compared between the two conditions. RESULTS: Cafeteria-fed rats ate more protein, fat and carbohydrate, consistently ingesting double the energy of chow-fed rats, and were significantly heavier by week 4. Cafeteria-fed rats tended to take multiple snacks between meals and ate fewer meals than chow-fed rats. They also ate more snacks at 5 weeks, were less effective at compensating for snacking by reducing meals, and the number of snacks in the majority of the cafeteria-fed rats was positively related to terminal body weights. CONCLUSIONS: Exposure to a palatable diet had long-term effects on feeding patterns. Rats became overweight because they initially ate more frequently and ultimately ate more of foods with higher energy density. The early increased snacking in young cafeteria-fed rats may represent the establishment of eating habits that promote weight gain.

  12. Effect of chronic 60-Hz electric field exposure on mammary tumorigenesis in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, L.E.; Leung, F.C.; Rommereim, D.N.; Buschbom, R.L.; Wilson, B.W.; Stevens, R.G.

    1989-07-01

    Female rats were administered a single dosage of 7 or 10 mg of DMBA intragastrically between 50 and 55 days of age and palpated weekly for mammary tumors in two experiments. Rats were either exposed to a 40 kV/m 60-Hz electric field or sham-exposed in utero through 18 or 23 weeks of age. There was no difference between electric field exposed and sham-exposed in incidence of first tumor. When the results of the two experiments were combined, the electric field exposed groups had significantly more tumors per tumor-bearing animal than the sham-groups. These results may have implications for the role of electric power use in the etiology and promotion of breast cancer. 21 refs., 1 fig., 1 tab.

  13. Parallel assessment of male reproductive function in workers and wild rats exposed to pesticides in banana plantations in Guadeloupe

    Directory of Open Access Journals (Sweden)

    Huc-Terki Farida

    2008-07-01

    Full Text Available Abstract Background There is increasing evidence that reproductive abnormalities are increasing in frequency in both human population and among wild fauna. This increase is probably related to exposure to toxic contaminants in the environment. The use of sentinel species to raise alarms relating to human reproductive health has been strongly recommended. However, no simultaneous studies at the same site have been carried out in recent decades to evaluate the utility of wild animals for monitoring human reproductive disorders. We carried out a joint study in Guadeloupe assessing the reproductive function of workers exposed to pesticides in banana plantations and of male wild rats living in these plantations. Methods A cross-sectional study was performed to assess semen quality and reproductive hormones in banana workers and in men working in non-agricultural sectors. These reproductive parameters were also assessed in wild rats captured in the plantations and were compared with those in rats from areas not directly polluted by humans. Results No significant difference in sperm characteristics and/or hormones was found between workers exposed and not exposed to pesticide. By contrast, rats captured in the banana plantations had lower testosterone levels and gonadosomatic indices than control rats. Conclusion Wild rats seem to be more sensitive than humans to the effects of pesticide exposure on reproductive health. We conclude that the concept of sentinel species must be carefully validated as the actual nature of exposure may varies between human and wild species as well as the vulnerable time period of exposure and various ecological factors.

  14. Palm vitamin E reduces catecholamines, xanthine oxidase activity and gastric lesions in rats exposed to water-immersion restraint stress

    Directory of Open Access Journals (Sweden)

    Mohd Fahami Nur Azlina

    2012-05-01

    Full Text Available Abstract Background This study examined the effects of Palm vitamin E (PVE and α-tocopherol (α-TF supplementations on adrenalin, noradrenalin, xanthine oxidase plus dehydrogenase (XO + XD activities and gastric lesions in rats exposed to water-immersion restraint stress (WIRS. Methods Sixty male Sprague–Dawley rats (200-250 g were randomly divided into three equal sized groups. The control group was given a normal diet, while the treated groups received the same diet with oral supplementation of PVE or α-TF at 60 mg/kg body weight. After the treatment period of 28 days, each group was further subdivided into two groups with 10 rats without exposing them to stress and the other 10 rats were subjected to WIRS for 3.5 hours. Blood samples were taken to measure the adrenalin and noradrenalin levels. The rats were then sacrificed following which the stomach was excised and opened along the greater curvature and examined for lesions and XO + XD activities. Results The rats exposed to WIRS had lesions in their stomach mucosa. Our findings showed that dietary supplementations of PVE and α-TF were able to reduce gastric lesions significantly in comparison to the stressed control group. WIRS increased plasma adrenalin and noradrenalin significantly. PVE and α-TF treatments reduced these parameters significantly compared to the stressed control. Conclusions Supplementations with either PVE or α-TF reduce the formation of gastric lesions. Their protective effect was related to their abilities to inhibit stress induced elevation of adrenalin and noradrenalin levels as well as through reduction in xanthine oxidase and dehydrogenase activities.

  15. Effect of Amygdalin on the Proliferation of Hyperoxia-exposed Type Ⅱ Alveolar Epithelial Cells Isolated from Premature Rat

    Institute of Scientific and Technical Information of China (English)

    祝华平; 常立文; 李文斌; 刘汉楚

    2004-01-01

    Summary: The pathogenesis of hyperoxia lung injury and the mechanism of amygdalin on type 2 alveolar epithelial cells (AEC2) isolated from premature rat lungs in vitro were investigated. AEC2 were obtained by primary culture from 20-days fetal rat lung and hyperoxia-exposed cell model was established. Cell proliferating viability was examined by MTT assay after treatment of amygdalin at various concentrations. DNA content and the proliferating cell nuclear antigen (PCNA) protein expression of AEC2 were measured by using flow cytometry and immunocytochemistry respectively after 24 h of hyperoxia exposure or amygdalin treatment. The results showed that hyperoxia inhibited the proliferation and decreased PCNA protein expression in AEC2 of premature rat in vitro. Amygdalin at the concentration range of 50-200 μmol/L stimulated the proliferation of AEC2 in a dose-dependent manner, however, 400 μmol/L amygdalin inhibited the proliferation of AEC2. Amygdalin at the concentration of 200 μmol/L played its best role in facilitating proliferation of AEC2s in vitro and could partially ameliorated the changes of proliferation in hyperoxia exposed AEC2 of premature rat. It has been suggested that hyperoxia inhibited the proliferation of AEC2s of premature rat, which may contribute to hyperoxia lung injury. Amygdalin may play partial protective role in hyperoxia-induced lung injury.

  16. Baclofen reversed thermal place preference in rats with chronic constriction injury.

    Science.gov (United States)

    Salte, K; Lea, G; Franek, M; Vaculin, S

    2016-06-20

    Chronic constriction injury to the sciatic nerve was used as an animal model of neuropathic pain. Instead of frequently used reflex-based tests we used an operant thermal place preference test to evaluate signs of neuropathic pain and the effect of baclofen administration in rats with neuropathy. Chronic constriction injury was induced by four loose ligations of the sciatic nerve. Thermal place preference (45 °C vs. 22 °C and 45 °C vs. 11 °C) was measured after the ligation and after the administration of baclofen in sham and experimental rats. Rats with the chronic constriction injury spent significantly less time on the colder plate compared to sham operated animals at the combination 45 °C vs. 11 °C. After administration of baclofen (10 mg/kg s.c.), the aversion to the colder plate in rats with chronic constriction injury disappeared. At the combination 45 °C vs. 22 °C, no difference in time spent on colder and/or warmer plate was found between sham and experimental animals. These findings show the importance of cold allodynia evaluation in rats with chronic constriction injury and the effectiveness of baclofen in this neuropathic pain model. PMID:26447518

  17. The effect of chronic calcium treatment on thyroid C cells in ovariectomized rats.

    Science.gov (United States)

    Filipović, B; Jurjević, B Sosić; Stojanoski, M Manojlović; Nestorović, N; Milosević, V; Sekulić, M

    2005-05-27

    The purpose of this study was to investigate the influence of chronic calcium treatment on the structure and function of thyroid C cells in ovariectomzed adult female rats. Eighteen 3-month-old, female Wistar rats were divided into three groups. The first group was used as the sham-operated control, and the other two were surgically ovariectomized (Ovx). One month after gonadectomy, one group of Ovx rats was injected with 28.55 mg Ca-glucoheptonate (Ca)/kg b.w., while the other two groups were chronically treated with vehicle alone (Ovx and sham control). Two months after surgery, the animals were killed. In the thyroid C cells, calcitonin (CT) was localized with the peroxidase-antiperoxidase method. Stereology was used to evaluate morphometric changes in the volume of C cells, their nuclei and relative volume density. The number of C cells per unit area was calculated. Serum CT content was determined by radioimmunoassay. After chronic Ca treatment C cells were numerous with darker cytoplasm than in C cells of sham-operated control animals, but more degranulated than the corresponding cells of Ovx rats. Their volume was significantly decreased by 14% (p Calcium treatment of Ovx rats led to a 32% increase of serum CT concentration in relation to untreated Ovx animals. These results suggest that chronic Ca treatment of Ovx female rats positively affected CT release from thyroid C cells, without any significant changes in morphometric parameters.

  18. Adaptive response in frogs chronically exposed to low doses of ionizing radiation in the environment

    International Nuclear Information System (INIS)

    Using the micronucleus assay, decreased levels of DNA damage were found after high dose ionizing radiation exposure of liver cells taken from frogs inhabiting a natural environment with above-background levels of ionizing radiation, compared to cells taken from frogs inhabiting background areas. The data obtained from a small number of animals suggest that stress present in the above-background environment could induce an adaptive response to ionizing radiation. This study did not reveal harmful effects of exposure to low levels of radioactivity. On the contrary, stress present in the above-background area may serve to enhance cellular defense mechanisms. - Highlights: → Frogs were collected from background and higher tritium level habitats. → The micronucleus assay was conducted on liver cells obtained from the frogs. → No detrimental effects were noted in frogs exposed to elevated tritium. → Adaptive responses were observed in frogs exposed to elevated tritium.

  19. Adaptive response in frogs chronically exposed to low doses of ionizing radiation in the environment

    Energy Technology Data Exchange (ETDEWEB)

    Audette-Stuart, M., E-mail: stuartm@aecl.ca [Environmental Technologies Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, Ontario, K0J 1P0 (Canada); Kim, S.B.; McMullin, D.; Festarini, A.; Yankovich, T.L.; Carr, J.; Mulpuru, S. [Environmental Technologies Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, Ontario, K0J 1P0 (Canada)

    2011-06-15

    Using the micronucleus assay, decreased levels of DNA damage were found after high dose ionizing radiation exposure of liver cells taken from frogs inhabiting a natural environment with above-background levels of ionizing radiation, compared to cells taken from frogs inhabiting background areas. The data obtained from a small number of animals suggest that stress present in the above-background environment could induce an adaptive response to ionizing radiation. This study did not reveal harmful effects of exposure to low levels of radioactivity. On the contrary, stress present in the above-background area may serve to enhance cellular defense mechanisms. - Highlights: > Frogs were collected from background and higher tritium level habitats. > The micronucleus assay was conducted on liver cells obtained from the frogs. > No detrimental effects were noted in frogs exposed to elevated tritium. > Adaptive responses were observed in frogs exposed to elevated tritium.

  20. Silicosis in Workers Exposed to Artificial Quartz Conglomerates: Does It Differ From Chronic Simple Silicosis?

    Science.gov (United States)

    Paolucci, Valentina; Romeo, Riccardo; Sisinni, Antonietta Gerardina; Bartoli, Dusca; Mazzei, Maria Antonietta; Sartorelli, Pietro

    2015-12-01

    Recently, a number of reports have been published on silicosis in workers exposed to artificial quartz conglomerates containing high levels of crystalline silica particles (70-90%) used in the construction of kitchen and bathroom surfaces. Three cases of silicosis in workers exposed to artificial quartz conglomerates are reported. The diagnosis was derived from both the International Labour Office and the International Classification of HRCT for Occupational and Environmental Respiratory Diseases (ICOERD) classifications and cytological analysis of bronchoalveolar lavage fluid. In 2 cases, levels of respirable silica greatly in excess of recommended standards were measured in the workplace, and cytological analysis of bronchoalveolar lavage fluid highlighted a prevalence of lymphocytes, meeting criteria for the diagnosis of accelerated silicosis. The prevention of pneumoconiosis caused by the use of innovative materials, such as artificial conglomerates with high crystalline silica content must be addressed. PMID:26410340

  1. Effects of chronic ethanol administration on hepatic glycoprotein secretion in the rat

    International Nuclear Information System (INIS)

    The effects of chronic ethanol feeding on protein and glycoprotein synthesis and secretion were studied in rat liver slices. Liver slices from rats fed ethanol for 4-5 wk showed a decreased ability to incorporate [14C]glucosamine into medium trichloracetic acid-precipitable proteins when compared to the pair-fed controls; however, the labeling of hepatocellular glycoproteins was unaffected by chronic ethanol treatment. Immunoprecipitation of radiolabeled secretory (serum) glycoproteins with antiserum against rat serum proteins showed a similar marked inhibition in the appearance of glucosamine-labeled proteins in the medium of slices from ethanol-fed rats. Minimal effects, however, were noted in the labeling of intracellular secretory glycoproteins. Protein synthesis, as determined by measuring [14C]leucine incorporation into medium and liver proteins, was decreased in liver slices from ethanol-fed rats as compared to the pair-fed controls. This was the case for both total proteins as well as immunoprecipitable secretory proteins, although the labeling of secretory proteins retained in the liver slices was reduced to a lesser extent than total radiolabeled hepatic proteins. When the terminal sugar, [14C]fucose, was employed as a precursor in order to more closely focus on the final steps of hepatic glycoprotein secretion, liver slices obtained from chronic ethanol-fed rats exhibited impaired secretion of fucose-labeled proteins into the medium. When ethanol (5 or 10 mM) was added to the incubation medium containing liver slices from the ethanol-fed rats, the alterations in protein and glycoprotein synthesis and secretion caused by the chronic ethanol treatment were further potentiated. The results of this study indicate that liver slices prepared from chronic ethanol-fed rats exhibit both impaired synthesis and secretion of proteins and glycoproteins, and these defects are further potentiated by acute ethanol administration

  2. Zonal corticosteroid hormone biosynthesis in the adrenal cortex in rats exposed to emotional stress combined with salt loading

    International Nuclear Information System (INIS)

    The authors study the pattern of biosynthesis of corticosteroid hormones in the zona glomerulosa and the combined zona fasciculata + zona reticularis of the adrenals, which are responsible for the mineralocorticoid and glucocorticoid function of the glands, during simultaneous exposure of animals to salt loading and emotional stress. Experiments were carried out on rats. The adrenals were divided into parts and samples were incubated in vitro with the addition of 3H-progesterone to each sample. The specific activity of the 3H-labeled corticosteroids decreased significantly in rats with a normal salt intake exposed to emotional stress

  3. Effects of chronic multiple stress on learning and memory and the expression of Fyn, BDNF, TrkB in the hippocampus of rats

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-heng; LIU Neng-bao; ZHANG Min-hai; ZHOU Yan-ling; LIAO Jia-wan; LIU Xiang-qian; CHEN Hong-wei

    2007-01-01

    Background The effect of chronic stress on cognitive functions has been one of the hot topics in neuroscience. But there has been much controversy over its mechanism. The aim of this study was to investigate the effects of chronic multiple stress on spatial learning and memory as well as the expression of Fyn, BDNF and TrkB in the hippocampus of rats.Methods Adult rats were randomly divided into control and chronic multiple stressed groups. Rats in the multiple stressed group were irregularly and alternatively exposed to situations of vertical revolution, sleep expropriation and restraint lasting for 6 weeks, 6 hours per day with night illumination for 6 weeks. Before and after the period of chronic multiple stresses, the performance of spatial learning and memory of all rats was measured using the Morris Water Maze (MWM). The expression of Fyn, BDNF and TrkB proteins in the hippocampus was assayed by Western blotting and immunohistochemical methods. The levels of Fyn and TrkB mRNAs in the hippocampus of rats were detected by RT-PCR technique.Results The escape latency in the control group and the stressed group were 15.63 and 8.27 seconds respectively.The performance of spatial learning and memory of rats was increased in chronic multiple stressed group (P<0.05). The levels of Fyn, BDNF and TrkB proteins in the stressed group were higher than those of the control group (P<0.05). The results of immunoreactivity showed that Fyn was present in the CA3 region of the hippocampus and BDNF positive particles were distributed in the nuclei of CA1 and CA3 pyramidal cells as well as DG granular cells. Quantitative analysis indicated that level of Fyn mRNA was also upregulated in the hippocampus of the stressed group (P<0.05).Conclusions Chronic multiple stress can enhance spatial learning and memory function of rats. The expression of Fyn,BDNF and TrkB proteins and the level of Fyn mRNA are increased in the stessed rat hippocampus. These suggest that Fyn and BDNF

  4. Chronic intermittent hypoxia alters ventilatory and metabolic responses to acute hypoxia in rats.

    Science.gov (United States)

    Morgan, Barbara J; Adrian, Russell; Wang, Zun-Yi; Bates, Melissa L; Dopp, John M

    2016-05-15

    We determined the effects of chronic exposure to intermittent hypoxia (CIH) on chemoreflex control of ventilation in conscious animals. Adult male Sprague-Dawley rats were exposed to CIH [nadir oxygen saturation (SpO2), 75%; 15 events/h; 10 h/day] or normoxia (NORM) for 21 days. We assessed the following responses to acute, graded hypoxia before and after exposures: ventilation (V̇e, via barometric plethysmography), V̇o2 and V̇co2 (analysis of expired air), heart rate (HR), and SpO2 (pulse oximetry via neck collar). We quantified hypoxia-induced chemoreceptor sensitivity by calculating the stimulus-response relationship between SpO2 and the ventilatory equivalent for V̇co2 (linear regression). An additional aim was to determine whether CIH causes proliferation of carotid body glomus cells (using bromodeoxyuridine). CIH exposure increased the slope of the V̇e/V̇co2/SpO2 relationship and caused hyperventilation in normoxia. Bromodeoxyuridine staining was comparable in CIH and NORM. Thus our CIH paradigm augmented hypoxic chemosensitivity without causing glomus cell proliferation. PMID:26917692

  5. Gastric dilatation syndrome associated with chronic nephropathy, hypergastrinemia, and gastritis in mice exposed to high levels of environmental antigens.

    Science.gov (United States)

    García, A; Erdman, S; Sheppard, B J; Murphy, J C; Fox, J G

    2001-06-01

    Gastric dilatation (GD) has been observed in Tac:(SW)fBR surveillance mice, with mean age of 10 months, that are exposed to high levels of environmental antigens during routine exposure to dirty bedding. The aim of the study reported here was to determine whether GD was associated with other systemic conditions affecting mice. Three groups of nine animals including-surveillance mice not exposed to dirty bedding (control), surveillance mice with out GD (NGD), and surveillance mice with GD (group GD)-had mean stomach weight with ingesta of 0.5 +/- 0.02 g, 1.09 +/- 0.07 g (P < 0.0001), and 2.54 +/- 0.4 g (P < 0.0001), respectively. Mean serum creatinine concentration was significantly higher in GD (1.6 +/- 0.25 mg/dl), compared with NGD (0.17 +/- 0.22 mg/dl, P < 0.0001) and control (0.2 +/- 0.16 mg/ dl, P < 0.0001) mice. In addition, lesions consistent with severe chronic nephropathy and mild gastritis were common in GD, compared with NGD and control mice. Finally, serum amidated gastrin concentration was significantly high in GD (179.37 +/- 53.86 pM, P < 0.03) and NGD (264.89 +/- 115.89 pM, P < 0.009), compared with control (60.77 +/- 8.39 pM) mice. Gastric dilatation syndrome is associated with chronic nephropathy, hypergastrinemia, and gastritis in surveillance mice exposed to high levels of environmental antigens. PMID:11924783

  6. Proteomic analysis of down-regulated proteins in colonic mucosa of chronic slow transit constipation rats

    Institute of Scientific and Technical Information of China (English)

    Wang Xingwei; Liu Haifeng; Xu Mei; Chen Gang; He Juntang; Wang Guoan; Teng Xiaochun; Fang Dianchun

    2009-01-01

    Objective: To investigate the alternations of proteins in the colonic mucosa of chronic slow transit constipation (STC) rats with a 2-DE-based proteomic method and analyze the function of these down-regulated proteins so as to provide theoretical basis for the pathogenesis of intestinal mucosa of chronic STC rats. Methods: STC model was established by feeding rats with 8 mg/(kg·d) diphenoxylate for 120 d. An experimental model of chronic STC rat was used for separation of proteomics from colonic mucosa using two-dimensional electrophoresis (2-DE). Proteins altered in expressional level were identified by Image Master 2DElite, mass spectrometry, and bibliometrics were applied to identify the differential protein expression and their clinical significance and function were analyzed. Results: Obvious differential protein expression was observed in the pathogenesis of STC, including mast cell protease (Al), non-specific dipeptidase (A2) and chondrosome succinate dehydrogenase precursor (A3). The expressions of Al, A2 and A3 were down-regulated in the gel graph of STC rats. Conclusion: The down-regulation of chondrosome succinate dehydrogenase, mast cell protease as well as non-specific dipeptidase in rat colon suggests the functional impairment of the oxidoreduction of mitochondrion is very important in the genesis and development of STC. The immunological reaction of STC rats is weakened, and the function of digesting and absorbing protein may be damaged to some extent.

  7. Chronic Toxicity of a Novel Recombinant Human Granulocyte Colony-stimulating Factor in Rats

    Institute of Scientific and Technical Information of China (English)

    Fei Xia; Qing-yu Zhang; Yong-ping Jiang

    2011-01-01

    Objective To assess the severity and reversibility of the chronic toxicity of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and the dose-effect relationship. Methods A total of 100 Sprague-Dawley rats (equal numbers of male and female) were randomly divided into five groups (20 rats in each group): four groups were treated with rhG-CSFa at 500, 100,10, 1 μg/kg, respectively, and one group was treated with vehicle only to serve as the control. The rats were received subcutaneous injections of rhG-CSFa or vehicle daily for 13 weeks. During the course of the chronic toxicity study, the physical status, body weight, and food consumption were monitored. Half of the rats in each group (n= 10) were sacrificed after the last rhG-CSFa administration, and the other half were sacrificed at five weeks after the last rhG-CSFa administration. Urinalyses, blood biochemistry, hematological analysis, histopathological examination, and immunological tests were performed for each of the rats. Results The hematological analyses revealed that the mean white blood cells count, neutrophils count, and neutrophils percentage were increased in male rats at the dose of 10 μg/kg or higher, and these were related with the biological activity of rhG-CSFa. Some small abnormalities were observed in the spleen of a few rats when used highest dose (500 μg/kg, a dosage of 200 folds higher than the normal clinical dosage), but these abnormalities were recovered within S-week recovery period. No other rhG-CSFa-related abnormalities were observed in this chronic toxicity study.Conclusion No significant toxicity and immunogenicity are observed with rhG-CSFa administration to rats in the chronic toxicity studies.

  8. A STUDY OF FISCHER 344 RATS EXPOSED TO SILICA DUST FOR SIX MONTHS AT CONCENTRATIONS OF 0, 2, 10 OR 20 MG / M3.

    Energy Technology Data Exchange (ETDEWEB)

    KUTZMAN,R.S.

    1984-02-01

    The major objective of this study was to relate the results of a series of functional tests to the compositional and structural alterations in the rat lung induced by subchronic exposure to silica dust. Fischer-344 rats were exposed for 6 hours/day, 5 days/week for 6 months to either 0, 2, 10, or 20 mg SiO{sub 2}/m{sup 3}. The general appearance of the exposed rats was not different from that of the controls. Interestingly, female rats exposed to silica dust, at all tested concentrations, gained more weight than the controls. The lung weight and the lung-to-body weight ratio was greater in the male rats exposed to the highest concentration of silica dust.

  9. Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia in rats

    DEFF Research Database (Denmark)

    Johansen, H K; Hougen, H P; Cryz, S J;

    1995-01-01

    In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF) we studied whether the inflammatory response could be altered by vaccination. Rats were immunized with either a depolymerized alginate toxin A conjugate (D-ALG toxin A), purified alginate, an O......-polysaccharide toxin A conjugate, or sterile saline. After challenge none of the rats immunized with D-ALG toxin A died, in contrast to the other two vaccine groups combined (p = 0.03). A significant reduction in the severity of the macroscopic lung inflammation was seen in rats immunized with D-ALG toxin A, compared...... with the other three groups (p = 0.009). The histopathologic response in the control rats was dominated by numerous polymorphonuclear leukocytes (PMN) surrounding the alginate beads. In contrast, the histopathologic response in rats immunized with D-ALG toxin A changed within the first week after challenge from...

  10. Transcriptomic responses in mouse brain exposed to chronic excess of the neurotransmitter glutamate

    Directory of Open Access Journals (Sweden)

    Pal Ranu

    2010-06-01

    Full Text Available Abstract Background Increases during aging in extracellular levels of glutamate (Glu, the major excitatory neurotransmitter in the brain, may be linked to chronic neurodegenerative diseases. Little is known about the molecular responses of neurons to chronic, moderate increases in Glu levels. Genome-wide gene expression in brain hippocampus was examined in a unique transgenic (Tg mouse model that exhibits moderate Glu hyperactivity throughout the lifespan, the neuronal Glutamate dehydrogenase (Glud1 mouse, and littermate 9 month-old wild type mice. Results Integrated bioinformatic analyses on transcriptomic data were used to identify bio-functions, pathways and gene networks underlying neuronal responses to increased Glu synaptic release. Bio-functions and pathways up-regulated in Tg mice were those associated with oxidative stress, cell injury, inflammation, nervous system development, neuronal growth, and synaptic transmission. Increased gene expression in these functions and pathways indicated apparent compensatory responses offering protection against stress, promoting growth of neuronal processes (neurites and re-establishment of synapses. The transcription of a key gene in the neurite growth network, the kinase Ptk2b, was significantly up-regulated in Tg mice as was the activated (phosphorylated form of the protein. In addition to genes related to neurite growth and synaptic development, those associated with neuronal vesicle trafficking in the Huntington's disease signalling pathway, were also up-regulated. Conclusions This is the first study attempting to define neuronal gene expression patterns in response to chronic, endogenous Glu hyperactivity at brain synapses. The patterns observed were characterized by a combination of responses to stress and stimulation of nerve growth, intracellular transport and recovery.

  11. Chromosome aberrations in human lymphocytes, chronically exposed to different doses of gamma radiation in vitro

    International Nuclear Information System (INIS)

    Man's blood, not stimulated with phytohemagglutinin has been subjected to a chronic gamma irradiation from the 226Ra(99 mg) source at the temperature of 37 deg C. The obtained metaphase plates have been used to carry out the quantitative analysis of separate types of structural chromosomal aberrations. Quantitative results on aberrant cells have been statistically processed. It is established, that the increase of dose rate lends to the increase in the share of those dicentrics, that appeared as a result of one-trail process, while that output of two-trail dicentrics remains constant

  12. Chronic ethanol exposure increases voluntary home cage intake in adult male, but not female, Long-Evans rats.

    Science.gov (United States)

    Morales, Melissa; McGinnis, Molly M; McCool, Brian A

    2015-12-01

    The current experiment examined the effects of 10 days of chronic intermittent ethanol (CIE) exposure on anxiety-like behavior and home cage ethanol intake using a 20% intermittent access (M, W, F) paradigm in male and female Long-Evans rats. Withdrawal from alcohol dependence contributes to relapse in humans and increases in anxiety-like behavior and voluntary ethanol consumption in preclinical models. Our laboratory has shown that 10 days of CIE exposure produces both behavioral and neurophysiological alterations associated with withdrawal in male rats; however, we have yet to examine the effects of this exposure regime on ethanol intake in females. During baseline, females consumed more ethanol than males but, unlike males, did not show escalations in intake. Rats were then exposed to CIE and were again given intermittent access to 20% ethanol. CIE males increased their intake compared to baseline, whereas air-exposed males did not. Ethanol intake in females was unaffected by CIE exposure. Notably, both sexes expressed significantly elevated withdrawal-associated anxiety-like behavior in the plus maze. Finally, rats were injected with the cannabinoid CB1 receptor antagonist, SR141716A (0, 1, 3, 10mg/kg, i.p.) which reduced ethanol intake in both sexes. However, females appear to be more sensitive to lower doses of this CB1 receptor antagonist. Our results show that females consume more ethanol than males; however, they did not escalate their intake using the intermittent access paradigm. Unlike males, CIE exposure had no effect on drinking in females. It is possible that females may be less sensitive than males to ethanol-induced increases in drinking after a short CIE exposure. Lastly, our results demonstrate that males and females may have different pharmacological sensitivities to CB1 receptor blockade on ethanol intake, at least under the current conditions.

  13. Chronic Mild Prenatal Stress Exacerbates the Allergen-Induced Airway Inflammation in Rats

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    Paulo J. Nogueira

    1999-01-01

    Full Text Available The effects of chronic mild prenatal stress on leukocyte infiltration into the airways was investigated in rat offspring. The chronic prenatal stress consisted of transitory and variable changes in the rat's living conditions. Offspring at adult age were actively sensitized (day 0 and intratracheally challenged (day 14 with ovalbumin. Bronchoalveolar lavage was performed in the offspring at 48 h after intratracheal challenge with ovalbumin. A significant increase in total leukocyte infiltration was observed in the nonstressed offspring group and this was associated with a marked recruitment of eosinophils without a significant effect on the influx of neutrophils and mononuclear cells. In the prenatal stressed offspring, the counts of both total leukocyte and eosinophils, as well as mononuclear cells, was increased by 50% compared to the non-stressed offspring. We provide here the first experimental evidence that chronic mild unpredictable prenatal stress produces a marked increase in the allergen-induced airway inflammation in the rat offspring.

  14. Dosimetry by means of DNA and hemoglobin adducts in propylene oxide-exposed rats

    International Nuclear Information System (INIS)

    The main purpose of the study was to establish the relation between exposure dose of propylene oxide (PO) and dose in various tissues of male F344 rats exposed to the compound by inhalation. The animals were exposed to 0, 5, 25, 50, 300, or 500 ppm PO in the air for 3 days (6 h/day) or 4 weeks (6 h/day, 5 days/week). Blood, nasal respiratory epithelium, lung, and liver were collected. 2-Hydroxypropylvaline (HPVal) in hemoglobin was quantified using the N-alkyl Edman method and gas chromatography/tandem mass spectrometry. 7-(2-Hydroxypropyl)guanine (7-HPG) in DNA was quantified using 32P postlabeling. The levels of 7-HPG in DNA of nasal respiratory epithelium and lung increased linearly with concentration as measured both after 3 days and 4 weeks of exposure. Similarly, 7-HPG in liver DNA and HPVal in hemoglobin showed a linear increase with PO concentration in the 3-day exposure group, whereas a deviation from linearity was observed above 300 ppm in the 4-week exposure group. The new results confirm previous observations of a dose difference between tissues with the highest dose present in the nasal respiratory epithelium. The measured adduct levels were used for calculation of adduct increments and corresponding tissue doses per unit of external exposure dose. For this purpose, the buildup of adducts was modeled considering the different kinetics of formation and elimination of adducts with DNA and hemoglobin, respectively, and also considering the increasing body weight of the animals. The half-life of 7-HPG in vivo, as well as tissue doses, could be solved from DNA adduct data at the 3rd and 26th days. Within the range of concentrations where the dose-response curves for adduct formation are linear, the relationship between exposure dose and resulting tissue doses could be based equally well on adduct data from the short-term exposure as on adduct data from the prolonged exposure

  15. 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.

  16. The context specificity of anxiety responses induced by chronic psychosocial stress in rats: a shift from anxiety to social phobia?

    Science.gov (United States)

    Barsy, Boglárka; Leveleki, Csilla; Zelena, Dóra; Haller, József

    2010-05-01

    The aim of the present study was to evaluate whether the anxiety-increasing effects of chronic psychosocial stress generalize to non-social (i.e. heterotypic) stressful situations. To investigate this issue, we repeatedly exposed rats to predictable or unpredictable psychosocial stress for 5 or 12 days and examined their anxiety in two markedly different contexts: the elevated plus maze and social interaction tests. Psychosocial stress and the social interaction test were administered under highly similar conditions, i.e. the two situations were homotypic. Psychosocial stress did not affect anxiety in the elevated plus-maze under any condition, but markedly increased anxiety in the social interaction test. In contrast, repeated restraint-a non-social stressor heterotypic to both the elevated plus maze and social interaction tests-increased plus-maze anxiety, demonstrating that anxiety in this test was sensitive to repeated restraint, and the effects were manifested in heterotypic situations. Thus, the anxiety-related effects of chronic psychosocial stress-unlike those of the chronic non-social stressor-were context-dependent. This is reminiscent of phobic anxiety, which manifests in specific situations only. In addition, behavior in the social interaction test showed changes that went beyond simple anxiogenesis. Socially stressed rats spent nearly 40% of total time in aggressive interactions. Based on recent data showing that social phobics are prone to violence under social pressure, and also based on the situation-dependent effects of the social stressor, we suggest that chronic psychosocial stress leads to a behavioral profile akin to social phobia.

  17. Chronic ethanol intake-induced changes in open-field behavior and calcium/calmodulin-dependent protein kinase Ⅳ expression in nucleus accumbens of rats: naloxone reversal

    Institute of Scientific and Technical Information of China (English)

    Jing LI; Wei-liang BIAN; Gui-qin XIE; Sheng-zhong CUI; Mei-ling WU; Yue-hua LI; Ling-li QUE; Xiao-ru YUAN

    2008-01-01

    Aim: To investigate the effects of chronic ethanol intake on the locomotor activity and the levels of calcium/calmodulin-dependent protein kinase Ⅳ (CaM kinase Ⅳ) in the nucleus accumbens (NAc) of rats. Simultaneously, the effects of non-selective opioid antagonist (naloxone) on the CaM kinase Ⅳ expression in the NAc and ethanol consumption of rats were also observed. Methods: Ethanol was administered in drinking water at the concentrations of 6% (v/v), for 28 d. The locomotor activity of rats was investigated in the open-field apparatus. CaM kinase Ⅳ levels in the NAc were analyzed using Western blotting. Results: Rats consuming ethanol solution exhibited a significant decrease of ambulation activity, accompanied by a reduced frequency of explorative rearing in an open-field task on d 7 and d 14 of chronic ethanol ingestion, whereas presumed adaptation to the neurological effects of ethanol was observed on d 28. Chronic ethanol intake elicited a significant decrease of the CaM kinase Ⅳ expression in the nuclei, but not in the cytoplasm of the NAc on d 28. Naloxone treatment significantly attenu-ated ethanol intake of rats and antagonized the decrease of CaM kinase Ⅳ in the nuclei of NAc neurons. The cytosolic CaM kinase Ⅳ protein levels of the NAc also increased in rats exposed to ethanol plus naloxone. Conclusion: Chronic ethanol intake-induced changes in explorative behavior is mediated at least partly by changes in CaM kinase Ⅳ signaling in the nuclei of the NAc, and naloxone attenuates ethanol consumption through antagonizing the downregulation of CaM kinase Ⅳ in the NAc.

  18. Acute heroin intoxication in a baby chronically exposed to cocaine and heroin: a case report

    Directory of Open Access Journals (Sweden)

    Pichini Simona

    2011-07-01

    Full Text Available Abstract Introduction Acute intoxication with drugs of abuse in children is often only the tip of the iceberg, actually hiding chronic exposure. Analysis using non-conventional matrices such as hair can provide long-term information about exposure to recreational drugs. Case presentation We report the case of a one-month-old Caucasian boy admitted to our pediatric emergency unit with respiratory distress and neurological abnormalities. A routine urine test was positive for opiates, suggesting an acute opiate ingestion. No other drugs of misuse, such as cocaine, cannabis, amphetamines or derivatives, were detected in the baby's urine. Subsequently, hair samples from the baby and the parents were collected to evaluate the possibility of chronic exposure to drug misuse by segmental analysis. Opiates and cocaine metabolites were detected in hair samples from the baby boy and his parents. Conclusions In light of these and previous results, we recommend hair analysis in babies and children from risky environments to detect exposure to heroin and other drug misuse, which could provide the basis for specific social and health interventions.

  19. Chromosome studies in human subjects chronically exposed to arsenic in drinking water

    Energy Technology Data Exchange (ETDEWEB)

    Vig, B.K.; Figueroa, M.L.; Cornforth, M.N.; Jenkins, S.H.

    1984-01-01

    A two-year study was carried out on human subjects of various ages and backgrounds who had been drinking water containing more than 0.05 mg/liter (0.05 ppm) arsenic for a period of at least five years. The main aim was to correlate the frequency of chromosome aberrations and sister chromatid exchanges in the lymphocytes with the amount of arsenic in the water. In addition, the incidence of skin cancer, fetal wastage, and genetic or developmental abnormalities were explored. Several other variables--eg, coffee, wine, and cigarette consumption; sex; residence (rural vs urban); and exposure to chemicals, smelters, or pesticides--were also taken into consideration. The data on chromosome aberrations (104 exposed and 86 control individuals) and on sister chromatid exchanges (98 exposed and 83 control individuals) did not show that arsenic at concentrations (greater than 0.05 mg/liter) has any effect on these parameters. Similarly, no other health effects of arsenic at these concentrations were found.

  20. Study on serum metabonomics of rats exposed to low-dose ionizing radiation, carbon monoxide, benzene and noise

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    Qing-rong WANG

    2015-07-01

    Full Text Available Objective To investigate the combined effects of low-dose ionizing radiation, carbon monoxide, benzene and noise on serum metabolites and the mechanism of injury induced by these complex environmental factors in rats. Methods  Sixteen adult SD rats were randomly divided into control group and exposed group (8 each. The exposed group received the combined effect every day for 7 days. At the end of experiment, sera were collected from the abdominal aorta of rats. The metabolic fingerprint of serum was obtained by 1H nuclear magnetic resonance (1H NMR spectroscopy and determined with pattern recognition techniques of principal component analysis (PCA and orthogonal signal correction-partial least squares (OSC-PLS. The similarities and differences in metabolic profiles between two groups were visualized by SIMCA-P software. Results The rat serum 1H NMR spectra revealed different metabolic spectra between the control group and exposed group. The OSC-PLS plots of the serum samples presented respectively marked clustering between the two groups. Compared with the control group, the contents of lipid, high density lipoprotein, glycine/glucose, N-acetyl glycoprotein 1, N-acetyl glycoprotein 2, phosphatidyl choline and unsaturated fatty acid increased, while those of lactic acid, threonine/lipid, alanine, creatine, glycerylphosphorylcholine/ trimethylamine oxide, low density lipoprotein/high density lipoprotein, low density lipoprotein, very low density lipoprotein/ low density lipoprotein, very low density lipoprotein and saturated fatty acid decreased. Conclusions Combination of low-dose ionizing radiation, carbon monoxide, benzene and noise could induce changes of serum metabolites in rats, involving in immune function, renal function and energy metabolism. The NMR-based-metabonomics method has potential of application in research on combined biological effects of the complex environmental factors. DOI: 10.11855/j.issn.0577-7402.2015.07.09

  1. The effects of honey and vitamin E administration on apoptosis in testes of rat exposed to noise stress

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    Masoud Hemadi

    2013-01-01

    Full Text Available Aims: A variety of stress factors are known to inhibit male reproductive functions. So this study was conducted in order to investigate the effects of honey and vitamin E on the germinative and somatic cells of testes of rats exposed to noise stress. Materials and Methods: Mature male wistar rats (n0 = 24 were randomly grouped as follows: Group 1 (honey + noise stress, 2 (vitamin E + noise stress, 3 (noise stress, and 4 as the control group. In groups 1, 2, and 3, rats were exposed to noise stress. In groups 1 and 2, rats also were given honey and vitamin E, respectively, orally for 50 days. After that, the germinative and somatic cells of testes parenchyma were isolated by digesting the whole testes by a standard method. Next, viability, apoptosis, and necrosis of the cells were evaluated by TUNEL kit and flow cytometry. Results: The rates of apoptosis and necrosis of the testicular cells were increased (P = 0.003 and P = 0.001, respectively, but viability of these cells decreased in testes of rats exposed to noise stress (P = 0.003. However, administration of honey and vitamin E were significantly helpful in keeping the cells of testis parenchyma alive, which suffers from noise pollution (P < 0.05 and P < 0.05, respectively. Conclusions: Noise stress has negative influences on the cells of testicular tissue by increasing apoptotic and necrotic cells. However, the associated enhancement in healthy cells suggests that honey and vitamin E have positive influences on the testis parenchyma.

  2. FOS EXPRESSION IN LUMBARSACRAL SPINAL CORD AND MEDULLA OBLONGATA INDUCED BY CHRONIC COLONIC INFLAMMATION IN RATS

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To investigate Fos expression in rat lumbarsacral spinal cord and medulla oblongata induced by chronic colonic inflammation. Methods Thirty-three male Sprague-Dawley rats were randomly divided into two groups: experimental group: colonic inflammation was induced in seventeen rats by intraluminal administration of trinitrobenzenesulfonic acid (TNBS); control group: saline was administered intraluminally in sixteen rats; After 3, 7, 14 and 28 days of administration, lumbarsacral spinal cord and medulla oblongata were removed and processed for Fos immunohistochemistry. Results Fos-immunoreactive (Fos-IR) neurons induced by TNBS administration were primarily distributed in deep laminae (laminae Ⅲ-Ⅳ,Ⅴ-Ⅵ) in the spinal dorsal horn and in medullary visceral zone (MVZ) in the medulla oblongata. The number of Fos-IR cells in the spinal cord and MVZ in rats after 7 and 14 days of TNBS administration were significantly higher than that in the control rats (P<0.05). After 28 days of TNBS instillation, the number of Fos-IR neurons in MVZ decreased and became comparable to the control group. However, the number of Fos cells in the spinal cord in some rats were still significantly increased compared with the control rats (P<0.05). Conclusion Fos-IR neurons after colonic inflammation recovery may play an important role in the development of visceral hypersensitivity. Medulla oblongata was a less important structure than the spinal cord in inducing visceral hypersensitivity after chronic colonic inflammation.

  3. Inhalation toxicity of multiwall carbon nanotubes in rats exposed for 3 months.

    Science.gov (United States)

    Ma-Hock, Lan; Treumann, Silke; Strauss, Volker; Brill, Sandra; Luizi, Frederic; Mertler, Michael; Wiench, Karin; Gamer, Armin O; van Ravenzwaay, Bennard; Landsiedel, Robert

    2009-12-01

    Carbon nanotubes (CNT) are of great commercial interest. Theoretically, during processing and handling of CNT and in abrasion processes on composites containing CNT, inhalable CNT particles might be set free. For hazard assessment, we performed a 90-day inhalation toxicity study with a multiwall CNT (MWCNT) material (Nanocyl NC 7000) according to Organisation for Economic Co-operation and Development test guideline 413. Wistar rats were head-nose exposed for 6 h/day, 5 days/week, 13 weeks, total 65 exposures, to MWCNT concentrations of 0 (control), 0.1, 0.5, or 2.5 mg/m(3). Highly respirable dust aerosols were produced with a proprietary brush generator which neither damaged the tube structure nor increased reactive oxygen species on the surface. Inhalation exposure to MWCNT produced no systemic toxicity. However, increased lung weights, pronounced multifocal granulomatous inflammation, diffuse histiocytic and neutrophilic inflammation, and intra-alveolar lipoproteinosis were observed in lung and lung-associated lymph nodes at 0.5 and 2.5 mg/m(3). These effects were accompanied by slight blood neutrophilia at 2.5 mg/m(3). Incidence and severity of the effects were concentration related. At 0.1 mg/m(3), there was still minimal granulomatous inflammation in the lung and in lung-associated lymph nodes; a no observed effect concentration was therefore not established in this study. The test substance has low dust-forming potential, as demonstrated by dustiness measurements, but nonetheless strict industrial hygiene measures must be taken during handling and processing. Toxicity and dustiness data such as these can be used to compare different MWCNT materials and to select the material with the lowest risk potential for a given application. PMID:19584127

  4. Cannabinoid modulation of chronic mild stress-induced selective enhancement of trace fear conditioning in adolescent rats.

    Science.gov (United States)

    Reich, Christian G; Iskander, Anthony N; Weiss, Michael S

    2013-10-01

    History of stress is considered a major risk factor for the development of major depression and posttraumatic stress disorder (PTSD). Elucidating the neurobiological mechanisms of Pavlovian fear conditioning may provide insight into the etiology of PTSD. In the current study, adolescent male Sprague-Dawley rats were exposed to 3 weeks of a chronic-mild-unpredictable stress (CMS) protocol. Immediately following the CMS, the animals were subjected to hippocampal-dependent (trace and contextual) and hippocampal-independent (delay) fear conditioning. CMS exposure enhanced trace freezing behavior compared to non-stress controls. This effect was not observed in contextual or delay conditioned animals. Given that the endocannabinoid system is negatively affected by CMS procedures, separate groups of stressed rats were administered the CB1 receptor agonist, ACEA (0.1 mg/kg), prior to trace fear conditioning or a memory-recall test. Regardless of administration time, ACEA significantly reduced freezing behavior in stressed animals. Furthermore, when administered during the first memory recall test, ACEA enhanced long-term extinction in both stress and non-stress groups. The results demonstrate that chronic unpredictable stress selectively enhances hippocampal-dependent episodic fear memories. Pathologies of the episodic memory and fear response may increase the susceptibility of developing PTSD. Reduction in fear responses via exogenous activation of the CB1 receptor suggests that a deficiency in the endocannabinoid system contributes to this pathology.

  5. Salt-induced changes in cardiac phosphoproteome in a rat model of chronic renal failure.

    Directory of Open Access Journals (Sweden)

    Zhengxiu Su

    Full Text Available Heart damage is widely present in patients with chronic kidney disease. Salt diet is the most important environmental factor affecting development of chronic renal failure and cardiovascular diseases. The proteins involved in chronic kidney disease -induced heart damage, especially their posttranslational modifications, remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy (chronic renal failure model or sham operation were treated for 2 weeks with a normal-(0.4% NaCl, or high-salt (4% NaCl diet. We employed TiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for phosphoproteomic profiling of left ventricular free walls in these animals. A total of 1724 unique phosphopeptides representing 2551 non-redundant phosphorylation sites corresponding to 763 phosphoproteins were identified. During normal salt feeding, 89 (54% phosphopeptides upregulated and 76 (46% phosphopeptides downregulated in chronic renal failure rats relative to sham rats. In chronic renal failure rats, high salt intake induced upregulation of 84 (49% phosphopeptides and downregulation of 88 (51% phosphopeptides. Database searches revealed that most of the identified phospholproteins were important signaling molecules such as protein kinases, receptors and phosphatases. These phospholproteins were involved in energy metabolism, cell communication, cell differentiation, cell death and other biological processes. The Search Tool for the Retrieval of Interacting Genes analysis revealed functional links among 15 significantly regulated phosphoproteins in chronic renal failure rats compared to sham group, and 23 altered phosphoproteins induced by high salt intake. The altered phosphorylation levels of two proteins involved in heart damage, lamin A and phospholamban were validated. Expression of the downstream genes of these two proteins, desmin and SERCA2a, were also analyzed.

  6. Hypertension and Cardiovascular Remodelling in Rats Exposed to Continuous Light: Protection by ACE-Inhibition and Melatonin

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    Fedor Simko

    2014-01-01

    Full Text Available Exposure of rats to continuous light attenuates melatonin production and results in hypertension development. This study investigated whether hypertension induced by continuous light (24 hours/day exposure induces heart and aorta remodelling and if these alterations are prevented by melatonin or angiotensin converting enzyme inhibitor captopril. Four groups of 3-month-old male Wistar rats (10 per group were treated as follows for six weeks: untreated controls, exposed to continuous light, light-exposed, and treated with either captopril (100 mg/kg/day or melatonin (10 mg/kg/day. Exposure to continuous light led to hypertension, left ventricular (LV hypertrophy and fibrosis, and enhancement of the oxidative load in the LV and aorta. Increase in systolic blood pressure by continuous light exposure was prevented completely by captopril and partially by melatonin. Both captopril and melatonin reduced the wall thickness and cross-sectional area of the aorta and reduced the level of oxidative stress. However, only captopril reduced LV hypertrophy development and only melatonin reduced LV hydroxyproline concentration in insoluble and total collagen in rats exposed to continuous light. In conclusion, captopril prevented LV hypertrophy development in the continuous light-induced hypertension model, while only melatonin significantly reduced fibrosis. This antifibrotic action of melatonin may be protective in hypertensive heart disease.

  7. Intercellular adhesion molecule-1 expression in the hippocampal CA1 region of hyperlipidemic rats with chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Yingying Cheng; Ying Zhang; Hongmei Song; Jiachun Feng

    2012-01-01

    Chronic cerebral ischemia is a pathological process in many cerebrovascular diseases and it is induced by long-term hyperlipidemia, hypertension and diabetes mellitus. After being fed a high-fat diet for 4 weeks, rats were subjected to permanent occlusion of bilateral common carotid arteries to establish rat models of chronic cerebral ischemia with hyperlipidemia. Intercellular adhesion molecule-1 expression in rat hippocampal CA1 region was determined to better understand the mechanism underlying the effects of hyperlipidemia on chronic cerebral ischemia. Water maze test results showed that the cognitive function of rats with hyperlipidemia or chronic cerebral ischemia, particularly in rats with hyperlipidemia combined with chronic cerebral ischemia, gradually decreased between 1 and 4 months after occlusion of the bilateral common carotid arteries. This correlated with pathological changes in the hippocampal CA1 region as detected by hematoxylin-eosin staining. Immunohistochemical staining showed that intercellular adhesion molecule-1 expression in the hippocampal CA1 region was noticeably increased in rats with hyperlipidemia or chronic cerebral ischemia, in particular in rats with hyperlipidemia combined with chronic cerebral ischemia. These findings suggest that hyperlipidemia aggravates chronic cerebral ischemia-induced neurological damage and cognitive impairment in the rat hippocampal CA1 region, which may be mediated, at least in part, by up-regulated expression of intercellular adhesion molecule-1.

  8. Chronic toxicity and carcinogenicity study of erythritol in rats

    NARCIS (Netherlands)

    Lina, B.A.R.; Bos-Kuijpers, M.H.M.; Til, H.P.; Bär, A.

    1996-01-01

    The potential toxicity and carcinogenicity of erythritol, a low-calorie sugar substitute, were examined in Wistar Crl:(WI) WU BR rats. Groups of 50 rats of each sex consumed diets with 0, 2, 5, or 10% erythritol, or 10% mannitol, for a period of 104-107 weeks. To each of these main groups, two satel

  9. L-citrulline supplementation reverses the impaired airway relaxation in neonatal rats exposed to hyperoxia

    Directory of Open Access Journals (Sweden)

    Sopi Ramadan B

    2012-08-01

    Full Text Available Abstract Background Hyperoxia is shown to impair airway relaxation via limiting L-arginine bioavailability to nitric oxide synthase (NOS and reducing NO production as a consequence. L-arginine can also be synthesized by L-citrulline recycling. The role of L-citrulline supplementation was investigated in the reversing of hyperoxia-induced impaired relaxation of rat tracheal smooth muscle (TSM. Methods Electrical field stimulation (EFS, 2–20 V-induced relaxation was measured under in vitro conditions in preconstricted tracheal preparations obtained from 12 day old rat pups exposed to room air or hyperoxia (>95% oxygen for 7 days supplemented with L-citrulline or saline (in vitro or in vivo. The role of the L-citrulline/L-arginine cycle under basal conditions was studied by incubation of preparations in the presence of argininosuccinate synthase (ASS inhibitor [α-methyl-D, L-aspartate, 1 mM] or argininosuccinate lyase inhibitor (ASL succinate (1 mM and/or NOS inhibitor [Nω-nitro-L-arginine methyl ester; 100 μM] with respect to the presence or absence of L-citrulline (2 mM. Results Hyperoxia impaired the EFS-induced relaxation of TSM as compared to room air control (p ; 0.5 ± 0.1% at 2 V to 50.6 ± 5.7% at 20 V in hyperoxic group: 0.7 ± 0.2 at 2 V to 80.0 ± 5.6% at 20 V in room air group. Inhibition of ASS or ASL, and L-citrulline supplementation did not affect relaxation responses under basal conditions. However, inhibition of NOS significantly reduced relaxation responses (p in vivo and in vitro also reversed the hyperoxia-impaired relaxation. The differences were significant (p ; 0.8 ± 0.3% at 2 V to 47.1 ± 4.1% at 20 V without L-citrulline; 0.9 ± 0.3% at 2 V to 68.2 ± 4.8% at 20 V with L-citrulline. Inhibition of ASS or ASL prevented this effect of L-citrulline. Conclusion The results indicate the presence of an L-citrulline/L-arginine cycle in the airways of rat pups

  10. Ovariectomy-induced chronic abdominal hypernociception in rats: Relation with brain oxidative stress

    OpenAIRE

    Bárbara B. Garrido-Suárez; Gabino Garrido-Garrido; Marian Castro Labrada; Addis Bellma Menéndez; Roberto Menéndez Soto del Valle; René Delgado-Hernández

    2015-01-01

    Context: Ovarian hormone deficiency observed in menopausal women increases the production of reactive oxygen species, which could be implicated in central sensitization subjacent in chronic functional pain syndromes. Aims: To examine the hyperalgesic state induced by ovariectomy in adult rats and its relation to some oxidative stress outcomes. Methods: The female Wistar rats were divided into normal, sham ovariectomized (OVX) and OVX groups, which were tested for mechanical and therma...

  11. Distinct histologic patterns of acute, prolonged, and chronic rejection in vascularized rat pancreas allografts.

    OpenAIRE

    Steiniger, B; Klempnauer, J

    1986-01-01

    In a model of pancreas whole organ transplantation in streptozotocin diabetic rats distinct histologic patterns of acute, prolonged and chronic rejection were defined by light microscopy. Allotransplantation between major histocompatibility complex (MHC) congenic and recombinant rat strains allowed an immunogenetic analysis of the effect of defined histocompatibility antigens on graft morphology. The impact of surgical techniques with preserved and suppressed exocrine secretion on graft histo...

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

    Science.gov (United States)

    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 water or ethanol) drinking from 2 to 5 g/kg/day; control rats without ethanol (only water). After 120 days of treatment, rats displaying estrus were euthanized. Uterine epithelial cells of the UCh rats showed dilated cisterns of the rough endoplasmic reticulum, presence of lipid droplets, altered nuclear chromatin, and disrupted mitochondria. The UCh rats exhibited intense atrophied epithelial cells with smaller areas and perimeters of cytoplasm and nuclei. The endometrium of UChA rats showed higher levels of caspase-3 while Xiap and Bcl2 varied from moderate to weak. Both UChA and UChB rats exhibited a stronger immunoreaction to Ki-67 and IGFR-1 on epithelial and stromal cells. 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. PMID:27139238

  13. Chronic Stress Induces Structural Alterations in Splenic Lymphoid Tissue That Are Associated with Changes in Corticosterone Levels in Wistar-Kyoto Rats

    Directory of Open Access Journals (Sweden)

    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.

  14. Expression of fibroblast growth factor-2 and fibroblast growth factor receptor-1 protein in the hippocampus in rats exhibiting chronic stress-induced depression

    Institute of Scientific and Technical Information of China (English)

    Gonglin Hou; Mingming Tang

    2011-01-01

    There is evidence that the expression of members of the fibroblast growth factor (FGF) protein family is altered in post-mortem brains of humans suffering from major depressive disorder. The present study examined whether the expression of fibroblast growth factor-2 (FGF2) and fibroblast growth factor receptor-1 (FGFR1) protein is altered following chronic stress in an animal model. Rats were exposed to 35 days of chronic unpredictable mild stress, and then tested using open-field and sucrose consumption tests. Compared with the control group, rats in the chronic stress group exhibited obvious depressive-like behaviors, including anhedonia, anxiety and decreased mobility. The results of western blot analysis and immunohistochemical analysis revealed a downregulation of the expression of FGF2 and FGFR1 in the hippocampus of rats, particularly in the CA1, CA3 and dentate gyrus. This decreased expression is in accord with the results of post-mortem studies in humans with major depressive disorder. These findings suggest that FGF2 and FGFR1 proteins participate in the pathophysiology of depressive-like behavior, and may play an important role in the mechanism of chronic stress-induced depression.

  15. Effects of chloramphenicol preconditioning on oxidative respiratory function of cerebral mitochondria in rats exposed to acute hypoxia

    Institute of Scientific and Technical Information of China (English)

    陈丽峰; 柳君泽; 党永明; 宋熔

    2004-01-01

    Objective: To investigate the roles of chloramphenicol (CAP) preconditioning in the oxidative respiratory function of cerebral mitochondria in rats exposed to acute hypoxia during acute hypoxia by observing the changes of mitochondrial oxidative respiratory function and cytochrome C oxidase (COX) activity. Methods: Adult male Wistar rats were randomly divided into 4 groups: control (C), medication (M), hypoxia (H), and medication plus hypoxia (MH). Rats in groups M and MH were administered by peritoneal injection of CAP (50 mg/kg) every 12 h for 7 d before decapitation, but those in groups H and MH were exposed to a hypobaric chamber simulating 5 000 m high altitude for 24 h. The rat cerebral cortex was removed and mitochondria were isolated by centrifugation. Mitochondrial respiratory function and COX activity were measured by Clark oxygen electrode. Results: Compared with Group C, Group H showed significantly elevated state 4respiration (ST4), decreased state 3 respiration (ST3), and respiratory control rate (RCR) in mitochondrial respiration during acute hypoxic exposure. ST3 in Group MH was significantly lower than that in Group C, but was not significantly different from that in Groups H and M, while ST4 in Group MH was significantly lower than that in groups C and H. RCR in Group MH was higher than that in Group H, but lower than that in Group C. COX activity in Group H was significantly lower than that in Group C. In Group MH, COX activity increased and was higher than that in Group H, but was still lower than that in Group C. Conclusion: Acute hypoxic exposure could lead to mitochondrial respiratory dysfunction, suggesting that CAP preconditioning might be beneficial to the recovery of rat respiratory finction. The change of COX activity is consistent with that of mitochondrial respiratory function during acute hypoxic exposure and CAP-administration, indicating that COX plays an important role in oxidative phosphorylation function of mitochondria from

  16. Effect of Electro—acupuncture on Rat Joint Pathomorphology of Chronic Adjuvant Arthritis Model

    Institute of Scientific and Technical Information of China (English)

    ZHANGYou-mei; HULing; 等

    2003-01-01

    Objective:To study the effect of electro-acupuncture(EA) on pathomorphological changes of joints in rat model of chronic adjuvant arthritis.Methods:The rat chronic adjuvant arthritis model was established by subcutaneous injection of 0.1 ml of complete Freunds adjuvant to the left hind sole.Forty Wistar rats were randomly divided into the model group,the low frequency(2Hz) EA group,the high frequency EA(100Hz)group and the body acupuncture group.After being modeled except the model group,the other three groups were treated with EA or body acupuncture in Yanglingquan points(bilater-al)for 3weeks,the left ankle joints and metatarsal joints of rats were taken for pathological examination by fixing with 10% formalin and embedding in paraffin,sectioning and staining with HE.Results:Obvious inflammatory cell infiltration,loosened synovial tissue,damage of articular cartilage and proliferation of synovial cells and granulation tissue were observed in the sections of joints in model rats.These pathologi-cal changes were significantly improved after treatment,and the effect in the high frequency EA group were significantly superior to that in the low frequency EA and body acupuncture group.Conclusion:High frequency EA could significantly improve the pathomorphological changes of joints in chronic adjuvant ar-thritis rat models.

  17. Effect of Electro-acupuncture on Rat Joint Patho-morphology of Chronic Adjuvant Arthritis Model

    Institute of Scientific and Technical Information of China (English)

    张幼美; 胡玲; 唐纯志; 曹伟

    2003-01-01

    Objective:To study the effect of electro-acupuncture (EA) on pathomorphological changes of joints in rat model of chronic adjuvant arthritis. Methods: The rat chronic adjuvant arthritis model was established by subcutaneous injection of 0.1 ml of complete Freund's adjuvant to the left hind sole. Forty Wistar rats were randomly divided into the model group, the low frequency (2 Hz) EA group, the high frequency EA (100 Hz) group and the body acupuncture group. After being modeled except the model group, the other three groups were treated with EA or body acupuncture in Yanglingquan points (bilateral) for 3 weeks, the left ankle joints and metatarsal joints of rats were taken for pathological examination by fixing with 10% formalin and embedding in paraffin, sectioning and staining with HE. Results: Obvious inflammatory cell infiltration, loosened synovial tissue, damage of articular cartilage and proliferation of synovial cells and granulation tissue were observed in the sections of joints in model rats. These pathological changes were significantly improved after treatment, and the effect in the high frequency EA group were significantly superior to that in the low frequency EA and body acupuncture group. Conclusion: High frequency EA could significantly improve the pathomorphological changes of joints in chronic adjuvant arthritis rat models.

  18. Female cotton rats (Sigmodon hispidus) develop chronic anemia with renal inflammation and cystic changes.

    Science.gov (United States)

    Ichii, Osamu; Nakamura, Teppei; Irie, Takao; Kouguchi, Hirokazu; Nakamura, Daisuke; Nakamura, Saori; Sato, Shinobu; Yokoyama, Keisuke; Horino, Taro; Sunden, Yuji; Elewa, Yaser Hosny Ali; Kon, Yasuhiro

    2016-09-01

    The cotton rat (Sigmodon hispidus) is a laboratory rodent that has been used for studies on human infectious diseases. In the present study, we observed that female cotton rats, not the male cotton rats, developed chronic anemia characterized by reduced red blood cell, hemoglobin, and hematocrit levels from 5 to 9 months of age without any changes in the mean corpuscular hemoglobin and volume levels. In peripheral blood, the reticulocyte count did not increase in response to anemia in female cotton rats, and no extramedullary hematopoiesis was observed in the liver or spleen. Further, the serum levels of urea nitrogen and creatinine increased from 5 to 9 months of age in female cotton rats compared to male cotton rats, and these increases became more prominent from 10 months of age onward, indicating chronic kidney disease. Histopathologically, female cotton rats manifested tubulointerstitial lesions characterized by the infiltration of mononuclear cells, including plasma cells and CD3(+) T-cells, as well as the dilation of calbindin-D28k(+) distal tubules from 5 to 9 months of age. The severity of these lesions progressed from 10 months of age onward, and renal fibrotic features and numerous tubular cysts appeared without any obvious glomerular lesions. A significant decrease in the erythropoietin protein levels was observed in the kidney of aged female cotton rats, and significant correlations were detected between anemia and tubulointerstitial damage. These results suggest that aged female cotton rats chronically develop renal anemia, and this rodent may serve as a novel model to elucidate its pathogenesis. PMID:27099161

  19. Oxidative stress is reduced in Wistar rats exposed to smoke from tobacco and treated with specific broad-band pulse electromagnetic fields

    Directory of Open Access Journals (Sweden)

    Bajić V.

    2009-01-01

    Full Text Available There have been a number of attempts to reduce the oxidative radical burden of tobacco. A recently patented technology, pulse electromagnetic technology, has been shown to induce differential action of treated tobacco products versus untreated products on the production of reactive oxygen species (ROS in vivo. In a 90-day respiratory toxicity study, Wistar rats were exposed to cigarette smoke from processed and unprocessed tobacco and biomarkers of oxidative stress were compared with pathohistological analysis of rat lungs. Superoxide dismutase (SOD activity was decreased in a dose-dependent manner to 81% in rats exposed to smoke from normal cigarettes compared to rats exposed to treated smoke or the control group. These results correspond to pathohistological analysis of rat lungs, in which those rats exposed to untreated smoke developed initial signs of emphysema, while rats exposed to treated smoke showed no pathology, as in the control group. The promise of inducing an improved health status in humans exposed to smoke from treated cigarettes merits further investigation.

  20. Effect of chronic ethanol consumption in female rats subjected to experimental sepsis

    International Nuclear Information System (INIS)

    The objective of this research was to evaluate the interference of ethanol consumption by female rats with cytokines involved in the sepsis process and its correlation with mortality, the main outcome of sepsis. Female Wistar rats in estrus phase were evaluated in three experiments. Experiment 1 (n=40) was performed to determine survival rates. Experiment 2 (n=69) was designed for biochemical analysis, measurement of cytokine and estrogen levels before and after sepsis, and experiment 3 (n=10) was performed to evaluate bacterial growth by colony counts of peritoneal fluid. In all experiments, treated animals were exposed to a 10% ethanol/water solution (v/v) as the single drinking source, while untreated animals were given tap water. After 4 weeks, sepsis was induced in the rats by ip injection of feces. In experiment 1, mortality in ethanol-exposed animals was delayed compared with those that drank water (48 h; P=0.0001). Experiment 2 showed increased tumor necrosis factor alpha (TNF-α) and decreased interleukin-6 (IL-6) and macrophage migration inhibitory factor in septic animals exposed to ethanol compared to septic animals not exposed. Sepsis also increased TNF-α and IL-6 levels in both ethanol- and water-exposed groups. Biochemical analysis showed higher creatinine, alanine aminotransferase and aspartate aminotransferase and decreased glucose levels in septic animals that were exposed to ethanol. In experiment 3, septic animals exposed to ethanol showed decreased numbers of colony-forming units than septic animals exposed to water. These results suggest that ethanol consumption delays the mortality of female rats in estrus phase after sepsis induction. Female characteristics, most probably sex hormones, may be involved in cytokine expression

  1. Effect of chronic ethanol consumption in female rats subjected to experimental sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Castro, C.L. [Programa de Pós-Graduação em Patologia, Universidade Federal Fluminense, Niterói, RJ (Brazil); Aguiar-Nemer, A.S. [Departamento de Nutrição, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora, MG (Brazil); Castro-Faria-Neto, H.C. [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ (Brazil); Barros, F.R. [Programa de Pós-Graduação em Patologia, Universidade Federal Fluminense, Niterói, RJ (Brazil); Rocha, E.M.S. [Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói, RJ (Brazil); Silva-Fonseca, V.A. [Departamento de Fisiologia e Farmacologia, Universidade Federal Fluminense, Niterói, RJ (Brazil)

    2013-12-10

    The objective of this research was to evaluate the interference of ethanol consumption by female rats with cytokines involved in the sepsis process and its correlation with mortality, the main outcome of sepsis. Female Wistar rats in estrus phase were evaluated in three experiments. Experiment 1 (n=40) was performed to determine survival rates. Experiment 2 (n=69) was designed for biochemical analysis, measurement of cytokine and estrogen levels before and after sepsis, and experiment 3 (n=10) was performed to evaluate bacterial growth by colony counts of peritoneal fluid. In all experiments, treated animals were exposed to a 10% ethanol/water solution (v/v) as the single drinking source, while untreated animals were given tap water. After 4 weeks, sepsis was induced in the rats by ip injection of feces. In experiment 1, mortality in ethanol-exposed animals was delayed compared with those that drank water (48 h; P=0.0001). Experiment 2 showed increased tumor necrosis factor alpha (TNF-α) and decreased interleukin-6 (IL-6) and macrophage migration inhibitory factor in septic animals exposed to ethanol compared to septic animals not exposed. Sepsis also increased TNF-α and IL-6 levels in both ethanol- and water-exposed groups. Biochemical analysis showed higher creatinine, alanine aminotransferase and aspartate aminotransferase and decreased glucose levels in septic animals that were exposed to ethanol. In experiment 3, septic animals exposed to ethanol showed decreased numbers of colony-forming units than septic animals exposed to water. These results suggest that ethanol consumption delays the mortality of female rats in estrus phase after sepsis induction. Female characteristics, most probably sex hormones, may be involved in cytokine expression.

  2. Effect of chronic ethanol consumption in female rats subjected to experimental sepsis

    Directory of Open Access Journals (Sweden)

    C.L. Castro

    2013-12-01

    Full Text Available The objective of this research was to evaluate the interference of ethanol consumption by female rats with cytokines involved in the sepsis process and its correlation with mortality, the main outcome of sepsis. Female Wistar rats in estrus phase were evaluated in three experiments. Experiment 1 (n=40 was performed to determine survival rates. Experiment 2 (n=69 was designed for biochemical analysis, measurement of cytokine and estrogen levels before and after sepsis, and experiment 3 (n=10 was performed to evaluate bacterial growth by colony counts of peritoneal fluid. In all experiments, treated animals were exposed to a 10% ethanol/water solution (v/v as the single drinking source, while untreated animals were given tap water. After 4 weeks, sepsis was induced in the rats by ip injection of feces. In experiment 1, mortality in ethanol-exposed animals was delayed compared with those that drank water (48 h; P=0.0001. Experiment 2 showed increased tumor necrosis factor alpha (TNF-α and decreased interleukin-6 (IL-6 and macrophage migration inhibitory factor in septic animals exposed to ethanol compared to septic animals not exposed. Sepsis also increased TNF-α and IL-6 levels in both ethanol- and water-exposed groups. Biochemical analysis showed higher creatinine, alanine aminotransferase and aspartate aminotransferase and decreased glucose levels in septic animals that were exposed to ethanol. In experiment 3, septic animals exposed to ethanol showed decreased numbers of colony-forming units than septic animals exposed to water. These results suggest that ethanol consumption delays the mortality of female rats in estrus phase after sepsis induction. Female characteristics, most probably sex hormones, may be involved in cytokine expression.

  3. Evaluation of chronic chlorpyrifos-induced reproductive toxicity in male Wistar rat: protective effects of vitamin C

    Directory of Open Access Journals (Sweden)

    Mohammed M. Sulaiman

    2013-02-01

    Full Text Available The aim of the present study was to evaluate the effect of vitamin C on reproductive toxicity, induced by chronic chlorpyrifos (CPF exposure in male Wistar rats. Twenty adult male Wistar rats were divided into 4 groups of 5 animals in each group. Group I received soya oil (2 ml/kg; group II was given vitamin C only (100 mg/kg; group III was administered CPF only (10.6 mg/kg; ~1/8th LD50, while group IV was pretreated with vitamin C and then exposed to CPF, 30 min later. The regimens were administered by gavage once daily for 15 weeks. At the end of the treatment period, the animals were sacrificed by jugular venesection after light chloroform anesthesia, and sera obtained from the blood samples were analyzed for follicle-stimulating hormone (FSH, luteinizing hormone (LH and testosterone concentrations. Pituitary gland and the testicular tissues of each rat were quickly dissected, removed and assayed for the levels of glycogen and acetylcholinesterase (AChE activity. The right caudal epididymis was evaluated for spermatozoa concentrations. The results showed that decrease in concentrations of spermatozoa, luteinizing and follicle-stimulating hormones, testosterone, testicular glycogen, and inhibition of pituitary gland and testicular AChE activities caused by CPF were ameliorated by vitamin C. [J Exp Integr Med 2013; 3(1: 23-30

  4. Phosphorylation of PTEN increase in pathological right ventricular hypertrophy in rats with chronic hypoxia induced pulmonary hypertension

    Institute of Scientific and Technical Information of China (English)

    Nie Xin; Shi Yiwei; Yu Wenyan; Xu Jianying; Hu Xiaoyun; Du Yongcheng

    2014-01-01

    Background Phosphatase and tensin homologue on chromosome ten (PTEN) acts as a convergent nodal signalling point for cardiomyocyte hypertrophy,growth and survival.However,the role of PTEN in cardiac conditions such as right ventricular hypertrophy caused by chronic hypoxic pulmonary,hypertension remains unclear.This study preliminarily discussed the role of PTEN in the cardiac response to increased pulmonary vascular resistance using the hypoxia-induced PH rats.Methods Male Sprague Dawley rats were exposed to 10% oxygen for 1,3,7,14 or 21 days to induce hypertension and right ventricular hypertrophy.Right ventricular systolic pressure was measured via catheterization.Hypertrophy index was calculated as the ratio of right ventricular mass to left ventricle plus septum mass.Tissue morphology and fibrosis were measured using hematoxylin,eosin and picrosirius red staining.The expression and phosphorylation levels of PTEN in ventricles were determined by real time PCR and Western blotting.Results Hypoxic exposure of rats resulted in pathological hypertrophy,interstitial fibrosis and remodelling of the right ventricle.The phosphorylation of PTEN increased significantly in the hypertrophic right ventricle compared to the normoxic control group.There were no changes in protein expression in either ventricle.Conclusion Hypoxia induced pulmonary hypertension developed pathological right ventricular hypertrophy and remodelling probablv related to an increased phosohorvlation of PTEN.

  5. Molecular pathways associated with stress resilience and drug resistance in the chronic mild stress rat model of depression: a gene expression study

    DEFF Research Database (Denmark)

    Bergström, Anders; Jayatissa, Magdalena Niepsuj; Andersen, Thomas Thykjær;

    2007-01-01

    The current antidepressant drugs are ineffective in 30 to 40% of the treated patients; hence, the pathophysiology of the disease needs to be further elucidated. We used the chronic mild stress (CMS) paradigm to induce anhedonia, a core symptom of major depression, in rats. A fraction of the animals...... exposed to CMS is resistant to the development of anhedonia; they are CMS resilient. In the CMS-sensitive animals, the induced anhedonic state is reversed in 50% of the animals when treating with escitalopram, whereas the remaining animals are treatment resistant. We used the microarray and the real...... a significant upregulation of apoptotic pathways in the treatment-resistant animals and significantly increased expression levels of genes involved in hippocampal signaling in the CMS-resilient rats. We hypothesize that sensitivity to the stress-induced anhedonia in rats is correlated with the impairment...

  6. Acute treatment with 5-HT3 receptor antagonist, tropisetron, reduces immobility in intact female rats exposed to the forced swim test.

    Science.gov (United States)

    Bravo, Gabriela; Maswood, Sharmin

    2006-10-01

    The effects of tropisetron, a 5-HT3 receptor antagonist, were evaluated in adult Fischer female rats exposed to the Forced Swim Test (FST). Rats selected on the days of proestrus or estrus was immersed in a cylinder of water for 2 consecutive days. Rats were exposed to the FST for 15 min on day 1 (pretest), followed by a 5-min session (test), 24 h later. The proestrous-estrous group consisted of rats that were exposed to the FST on their proestrous stage (pretest); then 24 h later the same rats were exposed to the FST on their estrous stage (test). Rats in the estrous-diestrous group were exposed to the FST on their estrous stage (pretest) and 24 h later on their diestrous stage (test). Rats were injected intraperitoneally with saline or 1.0 or 2.0 mg/kg tropisetron 30 min prior to exposure to the cylinder on the test day. Immobility, swimming, and struggling behaviors were scored for 5 min. There was a significant decline in immobility after treatment with 2.0 mg/kg tropisetron in both groups. In addition, a significant decline in swimming was observed in the estrous rats (proestrous-estrous group) after treatment with 2.0 mg/kg tropisetron. There were no significant effects of tropisetron on struggling in any groups examined.

  7. Fluoxetine induces changes in the testicle and testosterone in adult male rats exposed via placenta and lactation.

    Science.gov (United States)

    Monteiro Filho, Waldo Oliveira; de Torres, Sandra Maria; Amorim, Marleyne José Afonso Accioly Lins; Andrade, Anderson Joel Martino; de Morais, Rosana Nogueira; Tenorio, Bruno Mendes; da Silva Junior, Valdemiro Amaro

    2014-10-01

    Fluoxetine is a selective serotonin reuptake inhibitor used to treat depression in pregnant and nursing women. However, recent studies have shown adverse effects in the male reproductive system after fluoxetine treatment. Aiming to analyze the extent of damage caused by fluoxetine in the testicle and safe doses for treatment during the perinatal period, the present study analyzed the effects of in utero exposure and exposure during lactation to fluoxetine in spermatogenesis of male rat offspring in adulthood. Wistar rat dams were orally treated with fluoxetine (5, 10, and 20 mg/kg) from 13 days of gestation to lactation day 21 and their offspring were analyzed at 90 days old. Results showed a reduction in the weight of testes (16%), epididymis (28%), and seminal glands (18%) in animals exposed to fluoxetine 20 mg/kg compared to the control. Seminal gland weight was also reduced 25% and 30% in animals exposed to 5 mg/kg and 10 mg/kg fluoxetine, respectively. Body weight of animals exposed to 20 mg/kg fluoxetine was reduced from post-natal day 9 to 36 compared to controls but from the post-natal day 9 to 36 there was no statistical difference. The volume of seminiferous epithelium reduced 17% and the total volume of Leydig cells reduced 30% in the group exposed to fluoxetine at 20 mg/kg. Furthermore, Leydig cells volume reduced 29% in the 5 mg/kg group. The length of the seminiferous tubules reduced 17% and daily sperm production per testicle also reduced 18% in animals exposed to the highest dose of fluoxetine compared to controls. The individual area of Leydig cells increased 7% and plasma testosterone increased 49% in animals exposed to fluoxetine at 20 mg/kg. In conclusion, exposure to 20 mg/kg fluoxetine via the placenta and during lactation may change testosterone and testicular parameters important for sperm production and male fertility in adulthood.

  8. The Antidepressant Effect of Angelica sinensis Extracts on Chronic Unpredictable Mild Stress-Induced Depression Is Mediated via the Upregulation of the BDNF Signaling Pathway in Rats

    Directory of Open Access Journals (Sweden)

    Jun Shen

    2016-01-01

    Full Text Available Angelica sinensis (AS, a traditional Chinese herbal medicine, has pharmaceutical effects on menstrual illness, cerebrovascular diseases, cardiovascular diseases, and cognitive impairments. However, until recently, few studies had explored its antidepressant effect. The current study attempts to investigate the effect of AS extracts on chronic unpredictable mild stress- (CUMS- induced depression in rats. Male SD rats were exposed to a CUMS-inducing procedure for 5 weeks, resulting in rodent depressive behaviors that included reduced sucrose consumption and lessened sucrose preference ratios in sucrose preference test, prolonged immobility times and decreased struggling time in force swim test, and decreased locomotor activity in open field test. Moreover, the expression of brain derived neurotrophic factor (BDNF and the phosphorylation of cAMP-response element binding protein (CREB and extracellular signal-regulated protein kinase (ERK 1/2 were markedly decreased in the hippocampus in depressed rats. However, chronically treating the depressed rats with AS (1 g/kg normalized their depression-related behaviors and molecular profiles. In conclusion, in the present study, we show that AS extracts exerted antidepressant effects that were mediated by the BDNF signaling pathway: in AS-treated depressed rats, the expression of the BDNF protein and the phosphorylation of its downstream targets (ERK 1/2, CREB were upregulated in the hippocampus.

  9. Stress sensitivity and resilience in the chronic mild stress rat model of depression; an in situ hybridization study

    DEFF Research Database (Denmark)

    Bergström, A; Jayatissa, M N; Mørk, A;

    2008-01-01

    We used the validated chronic mild stress (CMS) paradigm to induce anhedonia, a core symptom of major depression, in rats. Thirty percent of animals exposed to CMS are resistant to the development of anhedonia, whereas the remaining are responsive, CMS resilient and CMS sensitive, respectively. We...... in stress. Moreover, in the CA3 we found downregulation of vascular endothelial growth factor (VEGF) mRNA in the CMS sensitive group. Downregulation of VEGF suggests impaired hippocampal function, caused by loss of trophic factor neuroprotective support, as part of a previously uncharacterized mechanism...... vasopressin (AVP) in the paraventricular nucleus of the hypothalamus. In particular, HPA axis seems to be activated in the CMS resilient group suggesting other pathways protecting against stress sensitivity. We applied the restraint stress procedure to compare effects of a faster and simpler form of stress...

  10. Proximal tubular bicarbonate reabsorption and PCO2 in chronic metabolic alkalosis in the rat.

    OpenAIRE

    Maddox, D A; Gennari, F J

    1983-01-01

    Studies were undertaken to define the pattern of proximal tubular bicarbonate reabsorption and its relation to tubular and capillary PCO2 in rats with chronic metabolic alkalosis (CMA). CMA was induced by administering furosemide to rats ingesting a low electrolyte diet supplemented with NaHCO3 and KHCO3. Proximal tubular bicarbonate reabsorption and PCO2 were measured in CMA rats either 4-7 or 11-14 d after furosemide injection, in order to study a wide range of filtered bicarbonate loads. A...

  11. STUDY ON INFLAMMATORY CELLS IN BALF OF SMOKE-INDUCED CHRONIC BRONCHITIS RAT MODEL

    Institute of Scientific and Technical Information of China (English)

    李庆云; 黄绍光; 吴华成; 程齐俭; 项轶; 万欢英

    2004-01-01

    Objective To establish a smoke-induced chronic bronchitis rat model and evaluate the pathological change semi-quantitatively, and study the characteristics of the inflammatory cells in the bronchoalveolar lavage fluid (BALF) in various stages. Methods Chronic bronchitis sequential rat model was established by passively inhaling smoke mixture. Experiments were performed in 30 young male Sprague-Dawley rats, which comprised 5 groups in random, i.e.,4 chronic bronchitis model groups and I control group. After stained with hematoxylin and eosin, the specimens were studied by semi-quantitative method to evaluate the morphologic changes in various stages. Meanwhile, the inflammatory cells of the BALF and the activity of myeloperoxidase ( MPO ) of lung tissue were analysed. Results During the process of the chronic bronchitis, the pathologic score was increasing as time went on, and the typical morphologic changes of chronic bronchitis emerged in the group 7 weeks. The total number of inflammatory cells in BALF was increasing as time went on, correlated with the pathologic scores ( P < 0. 01 ).And the percentage of lymphocyte increased as well as positively correlated with pathologic scores ( P < 0. 05 ),whereas that of macrophage decreased and negatively correlated with pathologic scores (P <0. 05). The MPO lever of lung tissue was correlated with the pathologic scores ( P < 0. 01 ). But the percentage of the neutrophil in the BALF was just in a high level during the first week, then it maintained relatively lower. Conclusion Smoke-induced chronic bronchitis is a slowly progressive inflammation process. The model we established is convenient and simple for the longitudinal study on the inflammatory process of chronic bronchitis and the therapy in the early stage. The semi-quantitative evaluation for the pathological change is with much more value. During the inflammatory sequential process of early stage of chronic bronchitis, the cellular characteristics are

  12. Prepubertal chronic stress and ketamine administration to rats as a neurodevelopmental model of schizophrenia symptomatology.

    Science.gov (United States)

    Ram, Edward; Raphaeli, Shani; Avital, Avi

    2013-11-01

    Increased vulnerability to psychiatric disorders, such as schizophrenia, has been associated with higher levels of stress. In the early development of the central nervous system, changes in function of glutamatergic N-Methyl-D-aspartate (NMDA) receptors can possibly result in the development of psychosis, cognitive impairment and emotional dysfunction in adulthood. Thus, in this study we examined the behavioural consequences of the exposure of male rats to chronic stress (postnatal days 30-60) and ketamine administration (postnatal days 41-45); both during a sensitive developmental time window. We found that the locomotor activity of both ketamine and ketamine+chronic stress groups was significantly higher compared with that of the control rats. In contrast, the locomotor activity of the chronic stress group was significantly lower compared with all other groups. Examining anhedonia in the sucrose preference test we found a significantly decreased sucrose intake in both ketamine+chronic stress and the chronic stress groups compared with the control rats. No significant differences were observed in sucrose intake between the control and the ketamine group. The object recognition test revealed that the attention to the novel object was significantly impaired in the ketamine+chronic stress group. Similarly, the ketamine+chronic stress group showed the poorest learning ability in the eight-arm radial maze, starting on the 8th day. Finally, throughout the different pre-pulse intensities, the ketamine+chronic stress group showed impaired PPI compared with all other groups. The results indicate that the combination of prepubertal onset of chronic stress and ketamine may serve as a valid novel animal model for schizophrenia-like symptoms.

  13. Therapeutic effect of DA-9601 on chronic reflux gastritis induced by sodium taurocholate in rats

    Institute of Scientific and Technical Information of China (English)

    Tae Young Oh; Chang Yell Shin; Yong Sung Sohn; Dong Hwan Kim; Byoung Ok Ahn; Eun Bang Lee; Cho Hyun Park

    2005-01-01

    AIM: To investigate the therapeutic effects of DA-9601 on sodium taurocholate (TCA)-induced chronic reflux gastritis in SD rats.METHODS: In this study, we have investigated the therapeutic effects of DA-9601 on chronic erosive and atrophic gastritis induced by 6 mo of TCA administration (5 mmol/L in drinking water) in SD rats. RESULTS: Four weeks of DA-9601 administration (0.065%, 0.216% in rat chow), following the withdrawal of TCA treatment, resulted in a significant decrease in total length of erosions in rats in a dose-dependent manner. Furthermore, the indicators of atrophic gastritis, such as reduced mucosal thickness and reduction in the number of parietal cells, were improved by the administration of DA-9601 in a dose-related manner. DA-9601 also attenuated inflammatory cell infiltration and the proliferation of collagenous fiber in the gastric mucosa. The improvement in the reduction of the gastric mucus was observed in the rats receiving a high dose of DA-9601 (0.216%). The therapeutic effect of DA-9601 on experimental chronic erosive gastritis was superior to that of rebamipide (1.08% in rat chow). Biochemical analyses showed increased mucosal prostaglandin E2 and reduced glutathione levels by DA-9601 treatment. CONCLUSION: We suggest that DA-9601 is apromising agent for the treatment of chronic erosive and atrophic gastritis with an etiological factor of bile reflux. Increasedmucosal prostaglandin E2 and reduced glutathione by DA-9601 treatment may be therapeutic mechanisms for chronic erosive and atrophic gastritis.

  14. Platelet hyperactivity, neurobehavioral symptoms and depression among Indian women chronically exposed to low level of arsenic.

    Science.gov (United States)

    Mukherjee, Bidisha; Bindhani, Banani; Saha, Hirak; Sinha, Dona; Ray, Manas Ranjan

    2014-12-01

    The prevalence of neurobehavioral symptoms (NBS) and depression has been investigated in premenopausal rural women of West Bengal, India enrolled from arsenic (As) endemic (groundwater As 11-50 μg/L; n = 342) and control areas (As level ≤ 10 μg/L; n = 312). The subjective symptoms questionnaire and Beck's 21-point depression inventory-II were used for the detection of NBS and depression, respectively. Platelet P-selectin expression was measured by flow cytometry, plasma neurotransmitter activity with high performance liquid chromatography and groundwater As level by atomic absorption spectroscopy. The As level in groundwater was 2.72 ± 1.18 μg/L in control and 28.3 ± 13.51 μg/L in endemic areas (p memory (69.9 vs. 28.2%, p dopamine level was not significantly different (p>0.05) from that of controls. Moreover, women from endemic areas had 2.3-times more P-selectin-expressing platelets in their circulation (p < 0.001). After controlling the potential confounders, chronic low level As (11-50 μg/L) exposure showed a positive association with the prevalence of neurobehavioral symptoms and depression among Indian women in their child-bearing age. PMID:25451969

  15. Interferon-gamma (IFN-gamma) treatment decreases the inflammatory response in chronic Pseudomonas aeruginosa pneumonia in rats

    DEFF Research Database (Denmark)

    Johansen, H K; Hougen, H P; Rygaard, J;

    1996-01-01

    In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF), we studied whether the inflammatory response could be altered by intraperitoneal treatment with recombinant rat interferon-gamma (rrIFN-gamma). Rats were treated either before or after intratracheal ch...

  16. Effect of intermittent hypoxia on the reproduction of rats exposed to high altitude in the Chilean Altiplano.

    Science.gov (United States)

    Cikutovic, Marcos; Fuentes, Nelson; Bustos-Obregón, Eduardo

    2009-01-01

    Environmental parameters such as the large day-night temperature differences, high light radiation, and low humidity may have a synergistic effect with low oxygen pressure. To evaluate the effects of the exposure to intermittent chronic hypobaric hypoxia (ICHH) in nature on rat reproduction, a group of rats was alternately moved to a location at 3400 meters over sea level (moml) for 7 days and returned the subsequent week to sea level; this procedure was repeated six times. Hematological and reproductive parameters were measured and analyzed. At the end of the experimental protocol, hematocrit and hemoglobin concentrations were significantly greater in the ICHH group compared to the control group (Nx) (p < 0.05). The diameter of the seminiferous tubule and the height of the spermatogenic epithelium in ICHH rats presented a significant decrease in relation to Nx rats (p < 0.05). Consequently, the number of epididymal spermatozoa in the experimental animals decreased compared to normal rats, with no evidence of recovery after 84 days. The offspring of the different matings between normal and hypoxic animals decreased proportionally to hypoxia exposure. The low oxygen and the changes in testicular temperature homeostasis would provide a novel local mechanism to explain the decrease in sperm cell production and the reduced number of puppies born. The alterations of the reproductive parameters of the hypoxic female, plus testicular injuries and diminished sperm in males, result in a significant decrease in the reproductive activity of the animals.

  17. Genetic effects of radon 222 in a population of Drosophila melanogaster chronically exposed

    International Nuclear Information System (INIS)

    It was investigated the mutagenic effect of Radon 222 during a experimental period of 11 generations. In this lapse Drosophila melanogaster larvae line Canton-S were maintained in a radon atmosphere. In each test generation had been extracted males, consequently exposed to radiation which were subjected to a crossing series with a bearer marker genes of according to the Wallace experimental design (1956). Due to the experimental conditions it only was determined the recessive lethal mutations frequency for the second chromosome in the 1,4,7 and 11 generations. Of all study it was conduced in parallel way a non-treated witness population. The concentrations at which was subjected the experimental population varied of generation to generation from 12 ± 2 to 43 ± 5 kBq/m3. Our analysis correspond to lethality determination in 1182 second chromosomes distributed between two populations and the different exposition generations. The study allow to determine the respective frequencies of recessive lethal genes varying according to the population and/or generation between 10.53 and 22.02%. The statistical analysis of data did not show significant differences among the different populations. (Author)

  18. HISTOLOGICAL EFFECTS OF CHRONIC CONSUMPTION OF NUTMEG ON THE LATERAL GENICULATE BODY OF ADULT WISTAR RATS.

    Directory of Open Access Journals (Sweden)

    J.O. Adjene

    2010-01-01

    Full Text Available The effects of chronic consumption of nutmeg commonly used as a spice in various dishes, as components of teas and soft drinks or mixed in milk and alcohol on the lateral geniculate body of adult wistar rats was studied.The rats of both sexes, with average weight of 200g were randomly assigned into treatment and control groups. The rats in the treatment group (n=8 received 2g of nutmeg thoroughly mixed with the feeds on a daily basis for thirty-two days. The control group (n=8 received equal amount of feeds daily without nutmeg added for thirty-two days. The growers mash feeds was obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo State, Nigeria and the rats were given water liberally. The rats were sacrificed on the thirty-three day of the experiment. The lateral geniculate body was carefully dissected out and quickly fixed in 10% formal saline for histological study.The findings indicate that rats in the treated group showed some cellular degenerative changes like sparse cellular population, pyknotic nuclei with some microcystic changes, edema and vacuolations in the stroma of the treated lateral geniculate body as compared to that of the control group.Chronic consumption of nutmeg may therefore have an adverse effect on the visual sensibilities by affecting the microanatomy of the lateral geniculate body of adult wistar rats. It is recommended for further studies aimed at corroborating these observations.

  19. Zinc finger protein A20 protects rats against chronic liver allograft dysfunction

    Institute of Scientific and Technical Information of China (English)

    Jie Yang; Ming-Qing Xu; Lu-Nan Yan; Xiao-Bo Chen; Jiao Liu

    2012-01-01

    AIM:To investigate the effect of zinc finger protein A20 on chronic liver allograft dysfunction in rats.METHODS:Allogeneic liver transplantation from DA rats to Lewis rats was performed.Chronic liver allograft dysfunction was induced in the rats by administering low-dose tacrolimus at postoperative day (POD) 5.Hepatic overexpression of A20 was achieved by recombinant adenovirus (rAd.)-mediated gene transfer administered intravenously every 10 d starting from POD 10.The recipient rats were injected with physiological saline,rAdEasy-A20 (1 x 109 pfu/30 g weight) or rAdEasy (1 x 109 pfu/30 g weight) every 10 d through the tail vein for 3 mo starting from POD 10.Liver tissue samples were harvested on POD 30 and POD 60.RESULTS:Liver-transplanted rats treated with only tacrolimus showed chronic allograft dysfunction with severe hepatic fibrosis.A20 overexpression ameliorated the effects on liver function,attenuated liver allograft fibrosis and prolonged the survival of the recipient rats.Treatment with A20 suppressed hepatic protein production of tumor growth factor (TGF)-β1,interleukin1β,caspase-8,CD40,CD40L,intercellular adhesion molecule-1,vascular cell adhesion molecule-1 and E-selectin.A20 treatment suppressed liver cell apoptosis and inhibited nuclear factor-κB activation of Kupffer cells (KCs),liver sinusoidal endothelial cells (LSECs)and hepatic stellate cells (HSCs),and it subsequently decreased cytokine mRNA expression in KCs and LSECs and reduced the production of TGF-β1 in HSCs.CONCLUSION:A20 might prevent chronic liver allograft dysfunction by re-establishing functional homeostasis of KCs,LSECs and HSCs.

  20. Hippocampal-dependent Pavlovian conditioning in adult rats exposed to binge-like doses of ethanol as neonates.

    Science.gov (United States)

    Lindquist, Derick H

    2013-04-01

    Binge-like postnatal ethanol exposure produces significant damage throughout the brain in rats, including the cerebellum and hippocampus. In the current study, cue- and context-mediated Pavlovian conditioning were assessed in adult rats exposed to moderately low (3E; 3g/kg/day) or high (5E; 5g/kg/day) doses of ethanol across postnatal days 4-9. Ethanol-exposed and control groups were presented with 8 sessions of trace eyeblink conditioning followed by another 8 sessions of delay eyeblink conditioning, with an altered context presented over the last two sessions. Both forms of conditioning rely on the brainstem and cerebellum, while the more difficult trace conditioning also requires the hippocampus. The hippocampus is also needed to gate or modulate expression of the eyeblink conditioned response (CR) based on contextual cues. Results indicate that the ethanol-exposed rats were not significantly impaired in trace EBC relative to control subjects. In terms of CR topography, peak amplitude was significantly reduced by both doses of alcohol, whereas onset latency but not peak latency was significantly lengthened in the 5E rats across the latter half of delay EBC in the original training context. Neither dosage resulted in significant impairment in the contextual gating of the behavioral response, as revealed by similar decreases in CR production across all four treatment groups following introduction of the novel context. Results suggest ethanol-induced brainstem-cerebellar damage can account for the present results, independent of the putative disruption in hippocampal development and function proposed to occur following postnatal ethanol exposure.

  1. Effects of zinc pre-treatment on blood glutathione, serum zinc and kidney histological organisation in male rats exposed to cadmium.

    Science.gov (United States)

    Jemai, Hedya; Lachkar, Hedia Ait; Messaoudi, Imed; Kerkeni, Abdelhamid

    2010-10-01

    The effects of sub-chronic exposure to cadmium (Cd) on the blood glutathione, serum zinc and on the kidney histological organisation in rats as well as the possible protective role of zinc (Zn) are the object of this study. For this purpose, 60 male Wistar rats (8 weeks old) were divided into three groups: the first group was exposed to Cd in the form of CdCl(2), administered in five doses (each of 0.4 mg Cd/kg b.w.) on days 5, 10, 15, 20 and 25, giving a total dose of 2mg Cd/kg b.w., i.p.; the second group was simultaneously exposed to Zn and Cd with the same timeline and the same doses of Cd as the first group but with, in addition, injections of Zn in the form of ZnCl(2), administered in doses of 0.8 mg Zn/kg b.w., giving a total dose of 4 mg Zn/kg b w, i.p.; a control group received 0.5 mL of physiological saline in an identical manner. Intoxication with Cd was followed by a significant decrease in blood glutathione, increase in oxidized glutathione as well as histological damage in kidneys. Pre-treatment with Zn exhibited a protective role against Cd toxicity with a significant decrease in serum zinc content. This fact may be explained by an excessive use of zinc in metallothionein synthesis as a cadmium detoxification agent.

  2. Effect of high-fructose and high-fat diets on pulmonary sensitivity, motor activity, and body composition of brown Norway rats exposed to ozone

    Data.gov (United States)

    U.S. Environmental Protection Agency — pulmonary parameters, BALF biomarkers, body composition, motor activity data collected from rats exposed to ozone after high fructose or high fat diets. This...

  3. Chronic effect of endosulfan on the testicular functions of rat

    Institute of Scientific and Technical Information of China (English)

    K.C.Chitra; C.Latchoumycandane; P,P.Mathur

    1999-01-01

    Aim: To find out the toxic effect of endosulfan on the tesficular function of pubertal rats, Methods: Male rats of pu-bertal age were orally administered endosulfan at a dose of 1.0 mg/kg body weight for 30 days. Twenty-four hours af-ter the last tmagnent, the rats were sacrificed and the testis, epididymis, seminal vesicles and ventral prostate were re-moved and weighed. A 10 % testicular homogenate was prepared for biochemical estimations. Results: In endosul-fan-treated rats, there were a reduction in the body weight and the weights of testis and accessory sex organs, a de-crease in the testicular lactate and pyruvate activities, and in the testicular DNA and RNA concentrations, whereas thetesticular protein concentration was slightly increased; the specific activity of testicular steroidogenic enzyme, 33OH-steroid dehydrogenase and the ascorbic acid level were decreased, which were correlated with a decrease in steroidoge-nesis. The lysosomal enzyme acid phosphatase and brush-border enzyme alkaline phosphatase activities were also de-creased in the testis of treated rats. Conclusion: In puhertal rats, endosulfan treaanent inhibits the testicular functions.(Asian J Androl 1999 Dec; 1 : 203 - 206)

  4. Stimulation-Evoked Dopamine Release in the Nucleus Accumbens Following Cocaine Administration in Rats Perinatally Exposed to Polychlorinated Biphenyls

    Science.gov (United States)

    Sable, Helen J. K.

    2013-01-01

    Exposure to polychlorinated biphenyls (PCBs) alters brain dopamine (DA) concentrations and DA receptor/transporter function, suggesting the reinforcing properties of drugs of abuse acting on the DA system may be affected by PCB exposure. Female Long-Evans rats were orally exposed to 0, 3, or 6mg/kg/day PCBs from 4 weeks prior to breeding until litters were weaned on postnatal day 21. In vivo fixed potential amperometry (FPA) was used in adult anesthetized offspring to determine whether perinatal PCB exposure altered (1) presynaptic DA autoreceptor (DAR) sensitivity, (2) electrically evoked nucleus accumbens (NAc) DA efflux following administration of cocaine, and (3) the rate of depletion of presynaptic DA stores. One adult male and female littermate were tested using FPA following a single injection of cocaine (20mg/kg ip), whereas a second adult male and female littermate were tested following the last of seven daily cocaine injections of the same dose. The carbon fiber recording microelectrode was positioned in the NAc core, and DA oxidation currents (i.e., DA release) evoked by brief stimulation of the medial forebrain bundle (MFB) were quantified before and after administration of cocaine. PCB-exposed rats exhibited enhanced stimulation-evoked DA release (relative to baseline) following a single injection of cocaine. Although nonexposed controls exhibited typical DA sensitization following repeated cocaine administration, this effect was attenuated in PCB-exposed rats. In addition, DAR sensitivity was higher (males only), and the rate of depletion of presynaptic DA stores was greater in PCB-exposed animals relative to nonexposed controls. These results indicate that perinatal PCB exposure can modify DA synaptic transmission in the NAc in a manner previously shown to alter the reinforcing properties of cocaine. PMID:23912914

  5. The effect of oxidative stress in myocardial cell injury in mice exposed to chronic intermittent hypoxia

    Institute of Scientific and Technical Information of China (English)

    LIU Jian-nan; ZHANG Jie-xin; LIU gan; QIU Yan; YANG Di; YIN Guo-yong; ZHANG Xi-long

    2010-01-01

    Background Obstructive sleep apnea syndrome (OSAS) is an important risk factor for cardiovascular diseases. Chronic intermittent hypoxia (CIH) is considered to be one of the most important causes of cardiovascular diseases in OSA patients. This repeated hypoxia and reoxygenation cycle is similar to hypoxia-reperfusion injury, which initiates oxidative stress. In this study, we observed cardiocytes injury induced by CIH and the effect of N-acetylcysteine (NAC). Methods Thirty ICR mice were randomly assigned to 3 groups: control, CIH and NAC (CIH+NAC) groups. Malondialdehyde (MDA) and superoxide dismutase (SOD) of cardiocyte homogenates were measured. Serum lipids were measured by an instrument method. Serum cardiac troponin I (cTnl) was detected by enzyme-linked immunosorbent assays (ELISA). Myocardium pathological sections were observed.Results (1) The SOD activity and MDA concentration of cardiocyte homogenates in the CIH group were significantly higher than in other groups (P <0.005). The MDA concentration of the NAC group was lower than that of the control group (P <0.01). (2) The serum cTnl concentration of the CIH and NAC groups was significantly higher than that of the control group (P<0.01). (3) Serum triglyceride levels in the NAC group were lower than in the other groups (P<0.01), while there were no significant differences in low density lipoprotein and high density lipoprotein among the three groups. (4) The degeneration of myocardium, transverse striation blurred, and fabric effusion were observed in tissue sections in the CIH and NAC groups. However, normal tissue was found in the control group.Conclusion The oxidative stress induced by CIH can injure cardiocytes and the injury effect can be partially inhibited by NAC.

  6. Gene expression profile of human lung epithelial cells chronically exposed to single-walled carbon nanotubes

    Science.gov (United States)

    Chen, Dongquan; Stueckle, Todd A.; Luanpitpong, Sudjit; Rojanasakul, Yon; Lu, Yongju; Wang, Liying

    2015-01-01

    A rapid increase in utility of engineered nanomaterials, including carbon nanotubes (CNTs), has raised a concern over their safety. Based on recent evidence from animal studies, pulmonary exposure of CNTs may lead to nanoparticle accumulation in the deep lung without effective clearance which could interact with local lung cells for a long period of time. Physicochemical similarities of CNTs to asbestos fibers may contribute to their asbestos-like carcinogenic potential after long-term exposure, which has not been well addressed. More studies are needed to identify and predict the carcinogenic potential and mechanisms for promoting their safe use. Our previous study reported a long-term in vitro exposure model for CNT carcinogenicity and showed that 6-month sub-chronic exposure of single-walled carbon nanotubes (SWCNT) causes malignant transformation of human lung epithelial cells. In addition, the transformed cells induced tumor formation in mice and exhibited an apoptosis resistant phenotype, a key characteristic of cancer cells. Although the potential role of p53 in the transformation process was identified, the underlying mechanisms of oncogenesis remain largely undefined. Here, we further examined the gene expression profile by using genome microarrays to profile molecular mechanisms of SWCNT oncogenesis. Based on differentially expressed genes, possible mechanisms of SWCNT-associated apoptosis resistance and oncogenesis were identified, which included activation of pAkt/p53/Bcl-2 signaling axis, increased gene expression of Ras family for cell cycle control, Dsh-mediated Notch 1, and downregulation of apoptotic genes BAX and Noxa. Activated immune responses were among the major changes of biological function. Our findings shed light on potential molecular mechanisms and signaling pathways involved in SWCNT oncogenic potential.

  7. Nicotinic receptor blockade decreases fos immunoreactivity within orexin/hypocretin-expressing neurons of nicotine-exposed rats.

    Science.gov (United States)

    Simmons, Steven J; Gentile, Taylor A; Mo, Lili; Tran, Fionya H; Ma, Sisi; Muschamp, John W

    2016-11-01

    Tobacco smoking is the leading cause of preventable death in the United States. Nicotine is the principal psychoactive ingredient in tobacco that causes addiction. The structures governing nicotine addiction, including those underlying withdrawal, are still being explored. Nicotine withdrawal is characterized by negative affective and cognitive symptoms that enhance relapse susceptibility, and suppressed dopaminergic transmission from ventral tegmental area (VTA) to target structures underlies behavioral symptoms of nicotine withdrawal. Agonist and partial agonist therapies help 1 in 4 treatment-seeking smokers at one-year post-cessation, and new targets are needed to more effectively aid smokers attempting to quit. Hypothalamic orexin/hypocretin neurons send excitatory projections to dopamine (DA)-producing neurons of VTA and modulate mesoaccumbal DA release. The effects of nicotinic receptor blockade, which is commonly used to precipitate withdrawal, on orexin neurons remain poorly investigated and present an attractive target for intervention. The present study sought to investigate the effects of nicotinic receptor blockade on hypothalamic orexin neurons using mecamylamine to precipitate withdrawal in rats. Separate groups of rats were treated with either chronic nicotine or saline for 7-days at which point effects of mecamylamine or saline on somatic signs and anxiety-like behavior were assessed. Finally, tissue from rats was harvested for immunofluorescent analysis of Fos within orexin neurons. Results demonstrate that nicotinic receptor blockade leads to reduced orexin cell activity, as indicated by lowered Fos-immunoreactivity, and suggest that this underlying cellular activity may be associated with symptoms of nicotine withdrawal as effects were most prominently observed in rats given chronic nicotine. We conclude from this study that orexin transmission becomes suppressed in rats upon nicotinic receptor blockade, and that behavioral symptoms associated

  8. Oxidative stress in testicular tissues of rats exposed to cigarette smoke and protective effects of caffeic acid phenethyl ester

    Institute of Scientific and Technical Information of China (English)

    Hüseyin Ozyurt; Hidir Pekmez; Bekir Suha Parlaktas; Ilter Kus; Birsen Ozyurt; Mustafa Sarsllmaz

    2006-01-01

    Aim: To show the oxidative stress after cigarette smoke exposure in rat testis and to evaluate the effects of caffeic acid phenethyl ester (CAPE). Methods: Twenty-one rats were divided into three groups of seven. Animals in Group Ⅰwere used as control. Rats in Group Ⅱ were exposed to cigarette smoke only (4 x 30 min/d) and rats in Group Ⅲall the rats were killed and the levels of nitric oxide (NO) and anti-oxidant enzymes such as superoxide-dismutase,catalase and glutathione peroxidase (GSH-Px) and the level of malondialdehyde were studied in the testicular tissues of rats with spectrophotometric analysis. Results: There was a significant increase in catalase and superoxide-dismutase activities in Group Ⅱ when compared to the controls, but the levels of both decreased after CAPE administration in Group Ⅲ. GSH-Px activity was decreased in Group Ⅱ but CAPE caused an elevation in GSH-Px activity in Group Ⅲ.The difference between the levels of GSH-Px in Group Ⅰ and Group Ⅱ was significant, but the difference between groups Ⅱ and Ⅲ was not significant. Elevation of malondialdehyde after smoke exposure was significant and CAPE caused a decrease to a level which was not statistically different to the control group. A significantly increased level of NO after exposure to smoke was reversed by CAPE administration and the difference between NO levels in groups Ⅰ and Ⅲ was statistically insignificant. Conclusion: Exposure to cigarette smoke causes changes in the oxidative enzyme levels in rat testis, but CAPE can reverse these harmful effects.

  9. Rats offspring exposed to Ipomoea Carnea and handling during gestation: neurochemical evaluation

    Directory of Open Access Journals (Sweden)

    Aline Schwarz

    2007-05-01

    Full Text Available The present study evaluated the central monoamine levels of male and female adult rat offspring exposed orally by gavage to 0.0, 0.7, 3.0 and 15.0 mg/kg I. carnea aqueous extract daily, from gestation day (GD 5 to GD 21. Several alterations in the monoamine activity systems were observed. However, the major differences were noted between the 0.0 mg/kg and the no gavage control groups, showing that alterations showing that alterations were not due to the alterations to the aqueous extract. The control data showed that gavage and handling of dams were stressful enough to produce a significant decline in 3,4-dihydroxyphenylacetic acid (DOPAC and an increase in vanilmandelic acid (VMA, indicating decreased dopamine (DA and enhanced norepinephrine (NE activity, respectively.Estudo anterior realizado em filhotes de ratas tratadas diariamente por gavage com 0,0, 0,7, 3,0 e 15,0 mg/kg de uma solução aquosa obtida de folhas frescas da Ipomoea carnea, do dia 5 ao dia 21 da gestação, mostrou poucas alterações comportamentais na prole em vida adulta. O presente estudo teve como objetivo avaliar a atividade e níveis das monoaminas cerebrais nas proles masculina e feminina expostas ao mesmo tratamento acima descrito. As maiores alterações encontradas, entretanto, foram entre os grupos 0,0 mg/kg e controle negativo (no gavage, impedindo a atribuição das alterações encontradas à solução aquosa. O dados resultantes do grupo controle sugerem que o estresse provocado pela gavage e pelo manuseio das fêmeas enquanto prenhes é suficiente para produzir um importante declínio nos níveis do ácido 3,4 dihidroxifenilacético (DOPAC e um não menos importante aumento nos níveis do ácido vanilmandélico (VMA, promovendo maior atividade do sistema noradrenérgico (NE.

  10. Basolateral amygdala lesion inhibits the development of pain chronicity in neuropathic pain rats.

    Directory of Open Access Journals (Sweden)

    Zheng Li

    Full Text Available BACKGROUND: Chronicity of pain is one of the most interesting questions in chronic pain study. Clinical and experimental data suggest that supraspinal areas responsible for negative emotions such as depression and anxiety contribute to the chronicity of pain. The amygdala is suspected to be a potential structure for the pain chronicity due to its critical role in processing negative emotions and pain information. OBJECTIVE: This study aimed to investigate whether amygdala or its subregions, the basolateral amygdala (BLA and the central medial amygdala (CeA, contributes to the pain chronicity in the spared nerve injury (SNI-induced neuropathic pain model of rats. METHODOLOGY/PRINCIPAL FINDINGS: (1 Before the establishment of the SNI-induced neuropathic pain model of rats, lesion of the amygdaloid complex with stereotaxic injection of ibotenic acid (IBO alleviated mechanical allodynia significantly at days 7 and 14, even no mechanical allodynia at day 28 after SNI; Lesion of the BLA, but not the CeA had similar effects; (2 however, 7 days after SNI when the neuropathic pain model was established, lesion of the amygdala complex or the BLA or the CeA, mechanical allodynia was not affected. CONCLUSION: These results suggest that BLA activities in the early stage after nerve injury might be crucial to the development of pain chronicity, and amygdala-related negative emotions and pain-related memories could promote pain chronicity.

  11. Copper balance and ceruloplasmin in chronic hepatitis in a Wilson disease animal model, LEC rats

    Energy Technology Data Exchange (ETDEWEB)

    Komatsu, Yutaka; Ogra, Yasumitsu; Suzuki, Kazuo T. [Graduate School of Pharmaceutical Sciences, Chiba University, Inage, Chiba 263-8522 (Japan)

    2002-09-01

    In an animal model of Wilson disease, Long-Evans rats with cinnamon-colored coat (LEC rats), copper (Cu) accumulates in the liver with age up to the onset of acute hepatitis owing to a hereditary defective transporter for the efflux of Cu, ATP7B. The plasma Cu concentration is low in LEC rats because of the excretion of apo-ceruloplasmin (apo-Cp). However, toward and after the onset of chronic hepatitis, plasma Cu concentration increases in the form of holo-Cp, while the liver Cu concentration is maintained at a constant level without the occurrence of fulminant hepatitis. In the present study, the material balance of Cu was studied in LEC rats with chronic hepatitis in order to elucidate the mechanisms underlying the increase of holo-Cp in plasma and the maintenance of Cu at a constant level in the liver. The relationship between the Cu concentration and ferroxidase activity of Cp was analyzed in the plasma of LEC rats of different ages and of Wistar rats fed a Cu-deficient diet for different durations. Cu was suggested to be delivered to Cp in an all-or-nothing manner, resulting in the excretion of fully Cu-occupied holo-Cp (Cu{sub 6}-Cp) or totally Cu-unoccupied Cu{sub 0}-Cp (apo-Cp), but not partially Cu-occupied Cu{sub n}-Cp (where n=1-5). The increase of holo-Cp in acute and chronic hepatitis in LEC rats was explained by the delivery of Cu, accumulating in the non-metallothionein-bound form, to Cp outside the Golgi apparatus of the liver. The plasma Cu concentration and ferroxidase activity were proposed to be specific indicators of the appearance of non-metallothionein-bound Cu in the liver of LEC rats. (orig.)

  12. Development of chronic allograft rejection and arterial hypertension in Brown Norway rats after renal transplantation.

    Science.gov (United States)

    Vaskonen, T; Mervaala, E; Nevala, R; Soots, A; Krogerus, L; Lähteenmäki, T; Karppanen, H; Vapaatalo, H; Ahonen, J

    2000-01-01

    The cardiovascular and renal pathophysiology associated with chronic renal allograft rejection under triple drug immunosuppressive treatment was studied using a recently developed model (Brown Norway (BN) rats) in a 6-week experiment. Renal transplantation was performed to 10-week-old rats in a rat strain combination of Dark Agouti (DA) --> BN. The right kidney was removed from another group of BN rats (uninephrectomized). A triple drug treatment comprising cyclosporine (10 mg/kg subcutaneously, s.c.), azathioprine (2 mg/kg s.c.) and methylprednisolone (1.6 mg/kg s.c.) was given to each rat daily for 6 weeks. A control group underwent no operations nor drug treatment. After the transplantation, the systolic blood pressure in this group was increased from 116 +/- 2 to 166 +/- 2 mmHg, while in the uninephrectomized group the rise was from 115 +/- 4 to 146 +/- 4 mmHg, and no change was observed in the blood pressures of the control group. The vascular relaxation responses of mesenteric arterial rings in vitro to acetylcholine were inhibited in both the transplantation group and the uninephrectomized group as compared with the control group, but few significant differences were found in the contraction responses to noradrenaline and potassium chloride. Graft histology was examined after 6 weeks, quantified by using the chronic allograft damage index (CADI). Changes specific to a chronic rejection reaction were observed in the allografts (CADI mean 6.0) but no injuries were seen in the rats' own kidneys (CADI mean 1.2). Our findings show that allograft rejection in BN rats after renal transplantation is associated with the development of arterial hypertension. The combination of cyclosporine, methylprednisolone and azathioprine also rises blood pressure in uninephrectomized BN rats. The hypertensive effects of the drug treatment and graft rejection are associated with endothelial dysfunction.

  13. The impact of chronic stress on the rat brain lipidome

    OpenAIRE

    Oliveira, Tiago Gil; Chan, Robin B.; Bravo, Francisca Vaz; Miranda, André; Silva, Rita Ribeiro; Zhou, Bowen; Marques, Fernanda; Pinto, Vítor; Cerqueira, João José; Di Paolo, Gilbert; Sousa, Nuno

    2015-01-01

    Chronic stress is a major risk factor for several human disorders that affect modern societies. The brain is a key target of chronic stress. In fact, there is growing evidence indicating that exposure to stress affects learning and memory, decision making and emotional responses, and may even predispose for pathological processes, such as Alzheimer’s disease (AD) and depression. Lipids are a major constituent of the brain, and specifically signaling lipids have been shown to regulate brain fu...

  14. Maternal separation in early life modifies anxious behavior and Fos and glucocorticoid receptor expression in limbic neurons after chronic stress in rats: effects of tianeptine.

    Science.gov (United States)

    Trujillo, Verónica; Durando, Patricia E; Suárez, Marta M

    2016-01-01

    Early-life adversity can lead to long-term consequence persisting into adulthood. Here, we assess the implications of an adverse early environment on vulnerability to stress during adulthood. We hypothesized that the interplay between early and late stress would result in a differential phenotype regarding the number of neurons immunoreactive for glucocorticoid receptor (GR-ir) and neuronal activity as assessed by Fos immunoreactivity (Fos-ir) in brain areas related to stress responses and anxiety-like behavior. We also expected that the antidepressant tianeptine could correct some of the alterations induced in our model. Male Wistar rats were subjected to daily maternal separation (MS) for 4.5 h during the first 3 weeks of life. As adults, the rats were exposed to chronic stress for 24 d and they were treated daily with tianeptine (10 mg/kg intraperitoneal) or vehicle (isotonic saline). Fos-ir was increased by MS in all structures analyzed. Chronic stress reduced Fos-ir in the hippocampus, but increased it in the paraventricular nucleus. Furthermore, chronic stress increased GR-ir in hippocampus (CA1) and amygdala in control non-MS rats. By contrast, when MS and chronic stress were combined, GR-ir was decreased in these structures. Additionally, whereas tianeptine did not affect Fos-ir, it regulated GR-ir in a region-dependent manner, in hippocampus and amygdala opposing in some cases the stress or MS effects. Furthermore, tianeptine reversed the MS- or stress-induced anxious behavior. The interplay between MS and chronic stress observed indicates that MS rats have a modified phenotype, which is expressed when they are challenged by stress in later life.

  15. Skeletal growth and long-term bone turnover after enterocystoplasty in a chronic rat model

    DEFF Research Database (Denmark)

    Gerharz, E.W.; Gasser, J.A.; Mosekilde, Li.;

    2003-01-01

    OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment, colocystopl...

  16. Chronic stress and social housing differentially affect neurogenesis in male and female rats

    NARCIS (Netherlands)

    Westenbroek, Christel; Boer, Johan A. den; Veenhuis, Maarten; Horst, Gert J. ter

    2004-01-01

    Stress plays an important role in the development of affective disorders. Women show a higher prevalence for these disorders than men. The course of a depression is thought to be positively influenced by social support. We have used a chronic stress model in which rats received foot-shocks daily for

  17. THERMOREGULATION IN THE RAT DURING CHRONIC, DIETARY EXPOSURE TO CHLORPYRIFOS, AN ORGANOPHOSPHATE INSECTICIDE.

    Science.gov (United States)

    Administration of chlorpyrifos (CHP) at a dose of 25 to 80 mg/kg (p.o.) To rats results in hypothermia followed by a fever lasting for several days. To understand if chronic, low level exposure to CHP affects thermoregulation in a comparable manner to acute administration, male L...

  18. EFFECTS OF CHRONIC EXERCISE CONDITIONING ON THERMAL RESPONSES TO LIPOPOLYSACCHARIDE AND TURPENTINE ABSCESS IN FEMALE RATS.

    Science.gov (United States)

    Chronic exercise conditioning has been shown to alter basal thermoregulatory processes as well as the response to inflammatory agents. Two such agents, lipopolysaccharide (LPS) and turpentine (TPT) are inducers of fever in rats. LPS, given intraperitoneally (i.p.), involves a sys...

  19. Physiological and behavioral effects of chronic intracerebroventricular infusion of corticotropin-releasing factor in the rat

    NARCIS (Netherlands)

    Buwalda, B; deBoer, SF; VanKalkeren, AA; Koolhaas, JM; Kalkeren, A.A. van

    1997-01-01

    The present study was conducted to investigate the Long-term effects of chronic elevation of centrally circulating levels of corticotropin-releasing factor (CRF) on behavior and physiology. For this purpose ovine CRF was infused continuously far a period of 10 days into the lateral ventricle of rats

  20. Renoprotective effects of the AGE-inhibitor pyridoxamine in experimental chronic allograft nephropathy in rats

    NARCIS (Netherlands)

    Waanders, Femke; van den Berg, Else; Nagai, Ryoji; van Veen, Ingrid; Navis, Gerjan; van Goor, Harry

    2008-01-01

    Background. Advanced glycation end products (AGEs) are involved in diabetic nephropathy (DN). The AGE formation inhibitor pyridoxamine (PM) is renoprotective in DN and in normoglycaemic obese Zucker rats. In chronic allograft nephropathy (CAN), renal AGE accumulation occurs as well. Methods. To inve

  1. Spironolactone ameliorates transplant vasculopathy in renal chronic transplant dysfunction in rats

    NARCIS (Netherlands)

    Waanders, Femke; Rienstra, Heleen; Boer, Mark Walther; Zandvoort, Andre; Rozing, Jan; Navis, Gerjan; van Goor, Harry; Hillebrands, Jan-Luuk

    2009-01-01

    Waanders F, Rienstra H, Walther Boer M, Zandvoort A, Rozing J, Navis G, van Goor H, Hillebrands JL. Spironolactone ameliorates transplant vasculopathy in renal chronic transplant dysfunction in rats. Am J Physiol Renal Physiol 296: F1072-F1079, 2009. First published February 25, 2009; doi:10.1152/aj

  2. HYPOTHALAMIC BLOOD-FLOW REMAINS UNALTERED FOLLOWING CHRONIC NITRIC-OXIDE SYNTHASE BLOCKADE IN RATS

    NARCIS (Netherlands)

    BENYO, Z; SZABO, C; STUIVER, BT; BOHUS, B; SANDOR, P

    1995-01-01

    The effect of the chronic oral application of N-G-nitro-L-arginine methyl eater (L-NAME), a potent inhibitor of nitric oxide (NO) production, was studied on hypothalamic blood flow (HBF) and hypothalamic nitric oxide synthase (NOS) activity in rats. L-NAME was dissolved in the drinking water, in a c

  3. Perinatal and chronic hypothyroidism impair behavioural development in male and female rats.

    NARCIS (Netherlands)

    Wijk, van N.; Rijntjes, E.; Heijning, van de B.J.

    2008-01-01

    Perinatal and chronic hypothyroidism impair behavioural development in male and female rats. EXP PHYSIOL 00(0) 000-000, 0000. - A lack of thyroid hormone, i.e. hypothyroidism, during early development results in multiple morphological and functional alterations in the developing brain. In the presen

  4. Correlation between light scattering signal and tissue reversibility in rat brain exposed to hypoxia

    Science.gov (United States)

    Kawauchi, Satoko; Sato, Shunichi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

    2010-02-01

    Light scattering signal is a potential indicator of tissue viability in brain because cellular and subcellular structural integrity should be associated with cell viability in brain tissue. We previously performed multiwavelength diffuse reflectance measurement for a rat global ischemic brain model and observed a unique triphasic change in light scattering at a certain time after oxygen and glucose deprivation. This triphasic scattering change (TSC) was shown to precede cerebral ATP exhaustion, suggesting that loss of brain tissue viability can be predicted by detecting scattering signal. In the present study, we examined correlation between light scattering signal and tissue reversibility in rat brain in vivo. We performed transcranial diffuse reflectance measurement for rat brain; under spontaneous respiration, hypoxia was induced for the rat by nitrogen gas inhalation and reoxygenation was started at various time points. We observed a TSC, which started at 140 +/- 15 s after starting nitrogen gas inhalation (mean +/- SD, n=8). When reoxygenation was started before the TSC, all rats survived (n=7), while no rats survived when reoxygenation was started after the TSC (n=8). When reoxygenation was started during the TSC, rats survived probabilistically (n=31). Disability of motor function was not observed for the survived rats. These results indicate that TSC can be used as an indicator of loss of tissue reversibility in brains, providing useful information on the critical time zone for treatment to rescue the brain.

  5. Assessment of anti-depressant effect of nelumbinis semen on rats under chronic mild stress and its subchronic oral toxicity in rats and beagle dogs

    Directory of Open Access Journals (Sweden)

    Chung Hwan-Suck

    2012-05-01

    Full Text Available Abstract Background Previously, we examined the antidepressant effects of Nelumbinis Semen (NS. In this study, we assessed the anti-depressant effects of NS in the forced swimming test and chronic mild stress (CMS models of depression and its oral toxicity in rats and dogs. Methods In the forced swimming test, NS was intraperitoneally injected before 24 h, 5 h and 1 h of forced swimming test. And the rats were forced to swim for 5 min, the duration of immobility was observed. In CMS models, animals were exposed to a variety of CMS for 8 weeks in order to induce depression-like symptoms. They were treated with NS for the last four weeks of the 8-week CMS and then an open field test was conducted. The anti-depression effects were evaluated based on a measured index, which consisted of visiting counts, start latency, rearing number and grooming time. In the toxicological studies, NS was administered to rats by gavages for 13 weeks at doses of 0, 500, 1000, and 2000 mg/kg/day. To assess the toxicity of NS in beagle dogs, NS was administered orally for 28 days at doses of 0, 500, 1000, 2000 and 4000 mg/kg/day. Results 400 mg/kg of NS had the lowest immobility times in forced swimming test. And NS significantly reversed the decreased visiting counts, rearing number and grooming time caused by CMS. In addition, NS treatment significantly decreased the start latency. No treatment-related toxicity was detected during 13 weeks administration in rats and 28 days administration in dogs. Conclusions Based on the results of this study and previous reports that have examined the anti-depressive effects of NS, NS holds great promise for use in the treatment of depression without causing any adverse effects or toxicities.

  6. Greenhouse gas fluxes from salt marshes exposed to chronic nutrient enrichment

    Science.gov (United States)

    Chmura, Gail L.; Kellman, Lisa; van Ardenne, Lee; Guntenspergen, Glenn R.

    2016-01-01

    We assessed the impact of nutrient additions on greenhouse gas fluxes using dark static chambers in a microtidal and a macrotidal marsh along the coast of New Brunswick, Canada approximately monthly over a year. Both were experimentally fertilized for six years with varying levels of N and P. For unfertilized, N and NPK treatments, average yearly CO2 emissions (which represent only respiration) at the microtidal marsh (13, 19, and 28 mmoles CO2 m-2 hr-1, respectively) were higher than at the macrotidal marsh (12, 15, and 19 mmoles m-2 hr-1, respectively, with a flux under the additional high N/low P treatment of 21 mmoles m-2 hr-1). Response of CH4 to fertilization was more variable. At the macrotidal marsh average yearly fluxes were 1.29, 1.26, and 0.77 μmol CH4 m-2 hr-1 with control, N, and NPK treatments, respectively and 1.21 μmol m-2 hr-1 under high N/low P treatment. At the microtidal marsh CH4fluxes were 0.23, 0.16, and -0.24 μmol CH4 m-2 hr-1 in control, N, and NPK and treatments, respectively. Fertilization changed soils from sinks to sources of N2O. Average yearly N2O fluxes at the macrotidal marsh were -0.07, 0.08, and 1.70, μmol N2O m-2 hr-1 in control, N, NPK and treatments, respectively and 0.35 μmol m-2 hr-1 under high N/low P treatment. For the control, N, and NPK treatments at the microtidal marsh N2O fluxes were -0.05, 0.30, and 0.52 μmol N2O m-2 hr-1, respectively. Our results indicate that N2O fluxes are likely to vary with the source of pollutant nutrients but emissions will be lower if N is not accompanied by an adequate supply of P (e.g., atmospheric deposition vs sewage or agricultural runoff). With chronic fertilization the global warming potential of the increased N2O emissions may be enough to offset the global cooling potential of the C sequestered by salt marshes.

  7. Greenhouse Gas Fluxes from Salt Marshes Exposed to Chronic Nutrient Enrichment.

    Science.gov (United States)

    Chmura, Gail L; Kellman, Lisa; van Ardenne, Lee; Guntenspergen, Glenn R

    2016-01-01

    We assessed the impact of nutrient additions on greenhouse gas fluxes using dark static chambers in a microtidal and a macrotidal marsh along the coast of New Brunswick, Canada approximately monthly over a year. Both were experimentally fertilized for six years with varying levels of N and P. For unfertilized, N and NPK treatments, average yearly CO2 emissions (which represent only respiration) at the microtidal marsh (13, 19, and 28 mmoles CO2 m(-2) hr(-1), respectively) were higher than at the macrotidal marsh (12, 15, and 19 mmoles m(-2) hr(-1), respectively, with a flux under the additional high N/low P treatment of 21 mmoles m(-2) hr(-1)). Response of CH4 to fertilization was more variable. At the macrotidal marsh average yearly fluxes were 1.29, 1.26, and 0.77 μmol CH4 m(-2) hr(-1) with control, N, and NPK treatments, respectively and 1.21 μmol m(-2) hr(-1) under high N/low P treatment. At the microtidal marsh CH4 fluxes were 0.23, 0.16, and -0.24 μmol CH4 m(-2) hr(-1) in control, N, and NPK and treatments, respectively. Fertilization changed soils from sinks to sources of N2O. Average yearly N2O fluxes at the macrotidal marsh were -0.07, 0.08, and 1.70, μmol N2O m(-2) hr(-1) in control, N, NPK and treatments, respectively and 0.35 μmol m(-2) hr(-1) under high N/low P treatment. For the control, N, and NPK treatments at the microtidal marsh N2O fluxes were -0.05, 0.30, and 0.52 μmol N2O m(-2) hr(-1), respectively. Our results indicate that N2O fluxes are likely to vary with the source of pollutant nutrients but emissions will be lower if N is not accompanied by an adequate supply of P (e.g., atmospheric deposition vs sewage or agricultural runoff). With chronic fertilization the global warming potential of the increased N2O emissions may be enough to offset the global cooling potential of the C sequestered by salt marshes. PMID:26914333

  8. Greenhouse Gas Fluxes from Salt Marshes Exposed to Chronic Nutrient Enrichment.

    Directory of Open Access Journals (Sweden)

    Gail L Chmura

    Full Text Available We assessed the impact of nutrient additions on greenhouse gas fluxes using dark static chambers in a microtidal and a macrotidal marsh along the coast of New Brunswick, Canada approximately monthly over a year. Both were experimentally fertilized for six years with varying levels of N and P. For unfertilized, N and NPK treatments, average yearly CO2 emissions (which represent only respiration at the microtidal marsh (13, 19, and 28 mmoles CO2 m(-2 hr(-1, respectively were higher than at the macrotidal marsh (12, 15, and 19 mmoles m(-2 hr(-1, respectively, with a flux under the additional high N/low P treatment of 21 mmoles m(-2 hr(-1. Response of CH4 to fertilization was more variable. At the macrotidal marsh average yearly fluxes were 1.29, 1.26, and 0.77 μmol CH4 m(-2 hr(-1 with control, N, and NPK treatments, respectively and 1.21 μmol m(-2 hr(-1 under high N/low P treatment. At the microtidal marsh CH4 fluxes were 0.23, 0.16, and -0.24 μmol CH4 m(-2 hr(-1 in control, N, and NPK and treatments, respectively. Fertilization changed soils from sinks to sources of N2O. Average yearly N2O fluxes at the macrotidal marsh were -0.07, 0.08, and 1.70, μmol N2O m(-2 hr(-1 in control, N, NPK and treatments, respectively and 0.35 μmol m(-2 hr(-1 under high N/low P treatment. For the control, N, and NPK treatments at the microtidal marsh N2O fluxes were -0.05, 0.30, and 0.52 μmol N2O m(-2 hr(-1, respectively. Our results indicate that N2O fluxes are likely to vary with the source of pollutant nutrients but emissions will be lower if N is not accompanied by an adequate supply of P (e.g., atmospheric deposition vs sewage or agricultural runoff. With chronic fertilization the global warming potential of the increased N2O emissions may be enough to offset the global cooling potential of the C sequestered by salt marshes.

  9. Chronic ethanol inhibits receptor-stimulated phosphoinositide hydrolysis in rat liver slices

    Energy Technology Data Exchange (ETDEWEB)

    Gonzales, R.A.; Crews, F.T. (Department of Pharmacology, University of Texas, Austin (USA))

    1991-03-01

    The effects of chronic ethanol feeding on norepinephrine (NE)- and arginine-vasopressin (AVP)-stimulated phosphoinositide (PI) hydrolysis in rat liver slices was determined. The maximum NE-stimulated PI response was significantly reduced by 40% in liver slices from 8-month-old rats which had been treated for 5 months with a liquid diet containing ethanol compared to pair-fed controls. The maximum AVP-stimulated PI response was decreased by 39% in liver slices from the ethanol-fed rats compared to control. EC50 values for NE- and AVP-stimulated PI hydrolysis in liver slices were not affected by the chronic ethanol treatment. Similar reductions in the maximal NE- and AVP-stimulated PI hydrolysis (28% and 27%, respectively) were found in 22-month-old rats which had been maintained on an ethanol containing diet for 5 months compared to pair-fed controls. The binding of (3H)prazosin and (3H)AVP to liver plasma membranes from 8-month-old ethanol-fed rats was not significantly different from binding to liver membranes from sucrose-fed controls. Our data suggest that chronic ethanol ingestion may lead to a reduction in PI-linked signal transduction in liver.

  10. BDNF and COX-2 participate in anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress.

    Science.gov (United States)

    Wang, Jun-Ming; Yang, Lian-He; Zhang, Yue-Yue; Niu, Chun-Ling; Cui, Ying; Feng, Wei-Sheng; Wang, Gui-Fang

    2015-11-01

    Catalpol, a major compound in Rehmannia glutinosa with both medicinal and nutritional values, has been previously confirmed to shorten the duration of immobility in mice exposed to tail suspension and forced swimming tests. This study attempted to examine the anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress (CUMS) by involving brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (COX-2). CUMS-exposed rats were given catalpol daily (5, 10, and 20mg/kg, ig) or a reference drug, fluoxetine hydrochloride (FH, 10mg/kg, ig), at 5 weeks after starting the CUMS procedure. Sucrose preference test was performed to observe depression-like behavior, and serum and brain tissues were used for neurochemical and fluorescent quantitative reverse transcription PCR analysis. CUMS induced depression-like behavior, whereas catalpol and FH administration attenuated this symptom. Moreover, CUMS caused excessively elevated levels of serum corticosterone, an index of hypothalamic-pituitary-adrenal (HPA) axis hyperactivation, in a manner attenuated by catalpol and FH administration. Catalpol administration also further decreased BDNF activities, downregulated the mRNA expression of BDNF and tropomyosin-related kinase B (TrkB), and reversed the excessive elevation in the activities and mRNA expression levels of COX-2 and prostaglandin E2 (PGE2) in the hippocampus and frontal cortex of rats undergoing CUMS. Results indicate that catalpol can ameliorate CUMS-induced depression-like behavior, and suggest its mechanisms may partially be ascribed to restoring HPA axis dysfunctions, upregulating BDNF expression and its cognate receptor TrkB, and downregulating COX-2 expression, thereby reducing PGE2 levels in the brain. PMID:26255123

  11. Vitamin E Mitigates Chronic Chlorpyrifos-Induced Oxidative Changes in Pituitary Glands and Testes in Wistar Rats

    Directory of Open Access Journals (Sweden)

    M. Shittu

    2012-01-01

    Full Text Available Problem statement: The sperm counts of men have declined by about 50% in the last few decades. The contribution of environmental contaminants to this decline cannot be overemphasized. Pesticide is one of the most pervasive environmental chemical contaminants that have been of increased use due to the compelling need to feed the ever-growing world human and animal population and protect their health. Chlorpyrifos (CPF, a widely used Organophosphate (OP insecticide has been reported to alter male reproductive hormones and semen characteristics. Apart from acetyl cholinesterase inhibition, the induction of oxidative stress is one of the molecular mechanisms implicated in CPF poisoning. Approach: The present study was aimed at evaluating the effect of vitamin E in mitigating oxidative damage to the pituitary gland and the testis, induced by chronic CPF administration in Wistar rats. Methodology: Twenty adult male Wistar rats divided into 4 groups of 5 rats in each group were used for this study. Group I received soya oil (2 mL kg-1, while Group II was administered vitamin E (75 mg kg-1; Group III was administered CPF only (10.6 mg kg-1~1/8th LD50, while group IV was pretreated with vitamin E (75 mg kg-1 and exposed to CPF (10.6 mg kg-1 30 min later. The regimens were administered orally by gavages once daily for a period of 15 weeks. At the end of the treatment period, the rats were sacrificed and the pituitary glands and testicular tissues were assayed for the concentrations of Malonaldehyde (MDA and the activities of Superoxide Dismutase (SOD and Catalane (CAT. Results: The result showed that the increase in concentrations of pituitary and testicular MDA and a decrease in the activities of SOD and CAT recorded in the group exposed to CPF were ameliorated by pretreatment with vitamin E. Conclusion: This indicates that vitamin E mitigates reproductive toxicity induced by chronic CPF exposure due to its protective antioxidant activity on pituitary

  12. Effects of niacin on nitric oxide synthase expression in rat lungs exposed to silica

    Institute of Scientific and Technical Information of China (English)

    WANG Shixin; DU Haike; ZHANG Xizhen; CAI Shaoxi; FAN Huaquan; WANG Chang'en

    2004-01-01

    The aim of this study was to evaluate the effects of niacin in diet on the expression of nitric oxide synthase (NOS) in rat lungs of the animal model of silicosis established by direct tracheal instillation of silica particles into rat lungs surgically. The niacin concentration in serum was analyzed by high performance liquid chromatography (HPLC). The expression of inducible nitric oxide synthase (iNOS) protein in paraffin-embedded lung sections was determined by streptavidin/peroxidase (SP) staining. Quantitative analysis by Image-Pro Plus was also performed on the expression of iNOS. The results showed that niacin concentration in serum of the niacin-treated rats was significantly higher than that in the control and silica-treated rats. After 7 days of silica instillation, iNOS integrated optical density (IOD) in rat lungs and total NOS and iNOS activities in bronchoalveolar lavage fluid (BALF) in silica-treated rats rose by 273420.75, 2.61 units/mL and 1.89 units/mL respectively, when compared with those in the control rats. Niacin treatment significantly reduced silica-induced iNOS IOD in rat lung tissues and total NOS and iNOS activities in BALF supernatant by 248292.35, 1.50 units/mL and 0.91 units/mL, respectively, as compared with those in silica-treated rats. Therefore, niacin can effectively attenuate the pathological expression of NOS in rat lung tissues induced by silica particles.

  13. Chronic inhalation toxicity and carcinogenicity studies on β-chloroprene in rats and hamsters

    NARCIS (Netherlands)

    Trochimowicz, H.J.; Löser, E.; Feron, V.J.; Clary, J.J.; Valentine, R.

    1998-01-01

    Three groups of 100 Wistar rats and Syrian golden hamsters of each sex were exposed by inhalation to 0, 10, or 50 ppm (v/v) β-chloroprene for 6 h/day, 5 days a week for up to 24 and 18 too, respectively. To maintain the chemical integrity of this highly reactive material in the exposure chambers, β-

  14. Ultrastructure alterations of retinal photoreceptors of the black rat,Rattus rattus exposed to certain heavy metals

    Directory of Open Access Journals (Sweden)

    Elsayed F. A. El-Dawi¹ and Naima I. Naguib²

    2010-12-01

    Full Text Available Aim of work: This study was designed to investigate the impact of lead and cadmium on the retinal photoreceptors of rats. Material &Methods: Adult black rats, Rattus rattus, were selected and divided into control and exposed groups. The exposed group was housed in industrial car batteries room containing fumes of lead and cadmium. The retina prepared for scanning and transmission electron microscopy. Results: The scanning electron microscopy revealed different lead-cadmium changes represented by gradual increasing in spaces between segments of the photoreceptors, associated with swelling of their inner segments and accompanied with rupture, degeneration and decreased numbers of some rods and cones in the outer segments. Disorganization, shortening, a decrease in number of the photoreceptors and a great deformity were the characteristic changes after prolonged exposure to the heavy metals. The aforementioned damages of the photoreceptors were confirmed at the ultrastructural level using transmission electron microscope in the form of progressive disorganization, shortening, swelling, widening of the intradiscal spaces, vacuolization and degeneration of the lamellae of the outer segments (OS, followed by the damage of mitochondria of the inner segments(IS. Excessive penetration of the processes of the pigmented epithelium (PE filled with pigments of different shapes and sizes between the damaged segments were noted. These pathological changes were considered the first symptoms in the retinal toxicity. Conclusion: The present results are alarming and call for further investigations to elucidate the impact of exposure to these heavy metals for longer periods on the rat vision and eye structure.

  15. Polymorphism of mitochondria in rat auriclar contractive cardiomyocites under the chronic alcoholic intoxication

    Directory of Open Access Journals (Sweden)

    Dunaev A.V.

    2007-01-01

    Full Text Available A number of the questions related to the reactions of mitochondrial apparatus of atrial cardiomyocites under the chronic alcoholization were dissolved in this study. The purpose of the study was to analyze morphological reactions of mi-tochondrial apparatus of atrial contractive cardiomyocites in rats on the chronic alcoholic poisoning. Modeling of the chronic alcoholic poisoning in rats was realized by daily introduction of ethyl alcohol per os in dosage 2-3,5 mg/g of rat weight dur-ing 30 days. Morphological research comprised both light and electronic microscopy of myocardium of right and left atria, right and left auricles, and also interatrial septum. Stereological estimation of several indexes was carried out: the compact-ness of mitochondria, numeral compactness of mitohondria, surface area of external mitochondrial membrane, compactness of mitochondrial cristae, number of mitochondrial cristae, surface area of internal mitochondrial membrane, degree of cristae orientation, coefficient of mitochondrial sphericity, volume of mitochondrium, quantitative correlation of types of mitochon-dria. It was shown that the reaction of different types of mitochondria on development of chronic alcoholization in atrial con-tractive cardiomyocites depends on the structural-metabolic type of mitochondria. Under the chronic alcoholic poisoning the moderate diffuse reduction of mitochondrial apparatus of contractive cardiomyocites takes place that is accompanied by the prolonged renewal of high-energy mitochondria and causes energetical limitation of contractive function of atrial myocar-dium.

  16. Effects of chronic delta-9-THC treatment on cardiac beta-adrenoceptors in rats

    Energy Technology Data Exchange (ETDEWEB)

    Evans, E.B.; Seifen, E.; Kennedy, R.H.; Kafiluddi, R.; Paule, M.G.; Scallet, A.C.; Ali, S.F.; Slikker, W. Jr.

    1987-10-01

    This study was designed to determine if chronic treatment with delta-9-tetrahydrocannabinol (THC) alters cardiac beta-adrenoceptors in the rat. Following daily oral administration of 10 or 20 mg/kg THC or an equivalent volume of control solvent for 90 days, rats were sacrificed, and sarcolemmal membranes were prepared from ventricular myocardium. Beta-adrenoceptor density and binding affinity estimated with (-)(/sup 3/H)dihydroalprenolol; a beta-adrenergic antagonist, were not significantly affected by treatment with THC when compared to vehicle controls. These results suggest that the tolerance to cardiovascular effects of THC which develops during chronic exposure in the rat is not associated with alterations in cardiac beta-adrenoceptors as monitored by radiolabeled antagonist binding.

  17. Neuropeptide Y and leptin receptor expression in the hypothalamus of rats with chronic immobilization stress

    Institute of Scientific and Technical Information of China (English)

    Shaoxian Wang; Jiaxu Chen; Guangxin Yue; Minghua Bai; Meijing Kou; Zhongye Jin

    2013-01-01

    In this study, Sprague-Dawley rats were immobilized to a frame for 3 hours a day for 21 days to establish a model of chronic immobilization stress. The body weight and food intake of rats subjected to chronic immobilization stress were significantly decreased compared with the control group. Dual-labeling immunofluorescence revealed that the expression of leptin receptor and the co-localization coeffient in these leptic receptor neurons in the arcuate nucleus of the hypothalamus were both upregulated, while the number of neuropeptide Y neurons was decreased. Chronic immobilization stress induced high expression of leptin receptor in the arcuate nucleus and suppressed the synthesis and secretion of neuropeptide Y, thereby disrupting the pathways in the arcuate nucleus that regulate feeding behavior, resulting in diminished food intake and reduced body weight.

  18. Coral reefs chronically exposed to river sediment plumes in the southwestern Caribbean: Rosario Islands, Colombia.

    Science.gov (United States)

    Restrepo, Juan D; Park, Edward; Aquino, Samia; Latrubesse, Edgardo M

    2016-05-15

    Politicians do not acknowledge the devastating impacts riverine sediments can have on healthy coral reef ecosystems during environmental debates in Caribbean countries. Therefore, regional and/or local decision makers do not implement the necessary measures to reduce fluvial sediment fluxes on coral reefs. The Magdalena River, the main contributor of continental fluxes into the Caribbean Sea, delivers water and sediment fluxes into the Rosario Islands National Park, an important marine protected area in the southwestern Caribbean. Until now, there is no scientific consensus on the presence of sediment fluxes from the Magdalena River in the coral reefs of the Rosario Islands. Our hypothesis is that high sediment and freshwater inputs from the Magdalena have been present at higher acute levels during the last decade than previously thought, and that these runoff pulses are not flashy. We use in-situ calibrated MODIS satellite images to capture the spatiotemporal variability of the distribution of suspended sediment over the coral reefs. Furthermore, geochemical data are analyzed to detect associated sedimentation rates and pollutant dispersion into the coastal zone. Results confirm that turbidity levels have been much higher than previous values presented by national environmental authorities on coral reefs off Colombia over the last decade. During the 2003-2013-period most of the Total Suspended Sediments (TSS) values witnessed in the sampled regions were above 10mg/l, a threshold value of turbidity for healthy coral reef waters. TSS concentrations throughout the analyzed time were up to 62.3mg/l. Plume pulses were more pronounced during wet seasons of La Niña events in 2002-2003, 2007-2008, and 2009-2010. Reconstructed time series of MODIS TSS indicates that coral reef waters were exposed to river plumes between 19.6 and 47.8% of the entire period of analysis (2000-2013). Further analyses of time series of water discharge and sediment load into the coastal zone

  19. Coral reefs chronically exposed to river sediment plumes in the southwestern Caribbean: Rosario Islands, Colombia.

    Science.gov (United States)

    Restrepo, Juan D; Park, Edward; Aquino, Samia; Latrubesse, Edgardo M

    2016-05-15

    Politicians do not acknowledge the devastating impacts riverine sediments can have on healthy coral reef ecosystems during environmental debates in Caribbean countries. Therefore, regional and/or local decision makers do not implement the necessary measures to reduce fluvial sediment fluxes on coral reefs. The Magdalena River, the main contributor of continental fluxes into the Caribbean Sea, delivers water and sediment fluxes into the Rosario Islands National Park, an important marine protected area in the southwestern Caribbean. Until now, there is no scientific consensus on the presence of sediment fluxes from the Magdalena River in the coral reefs of the Rosario Islands. Our hypothesis is that high sediment and freshwater inputs from the Magdalena have been present at higher acute levels during the last decade than previously thought, and that these runoff pulses are not flashy. We use in-situ calibrated MODIS satellite images to capture the spatiotemporal variability of the distribution of suspended sediment over the coral reefs. Furthermore, geochemical data are analyzed to detect associated sedimentation rates and pollutant dispersion into the coastal zone. Results confirm that turbidity levels have been much higher than previous values presented by national environmental authorities on coral reefs off Colombia over the last decade. During the 2003-2013-period most of the Total Suspended Sediments (TSS) values witnessed in the sampled regions were above 10mg/l, a threshold value of turbidity for healthy coral reef waters. TSS concentrations throughout the analyzed time were up to 62.3mg/l. Plume pulses were more pronounced during wet seasons of La Niña events in 2002-2003, 2007-2008, and 2009-2010. Reconstructed time series of MODIS TSS indicates that coral reef waters were exposed to river plumes between 19.6 and 47.8% of the entire period of analysis (2000-2013). Further analyses of time series of water discharge and sediment load into the coastal zone

  20. Evaluation of Krebs cycle enzymes in the brain of rats after chronic administration of antidepressants.

    Science.gov (United States)

    Scaini, Giselli; Santos, Patricia M; Benedet, Joana; Rochi, Natália; Gomes, Lara M; Borges, Lislaine S; Rezin, Gislaine T; Pezente, Daiana P; Quevedo, João; Streck, Emilio L

    2010-05-31

    Several works report brain impairment of metabolism as a mechanism underlying depression. Citrate synthase and succinate dehydrogenase are enzymes localized within cells in the mitochondrial matrix and are important steps of Krebs cycle. In addition, citrate synthase has been used as a quantitative enzyme marker for the presence of intact mitochondria. Thus, we investigated citrate synthase and succinate dehydrogenase activities from rat brain after chronic administration of paroxetine, nortriptiline and venlafaxine. Adult male Wistar rats received daily injections of paroxetine (10mg/kg), nortriptiline (15mg/kg), venlafaxine (10mg/kg) or saline in 1.0mL/kg volume for 15 days. Twelve hours after the last administration, the rats were killed by decapitation, the hippocampus, striatum and prefrontal cortex were immediately removed, and activities of citrate synthase and succinate dehydrogenase were measured. We verified that chronic administration of paroxetine increased citrate synthase activity in the prefrontal cortex, hippocampus, striatum and cerebral cortex of adult rats; cerebellum was not affected. Chronic administration of nortriptiline and venlafaxine did not affect the enzyme activity in these brain areas. Succinate dehydrogenase activity was increased by chronic administration of paroxetine and nortriptiline in the prefrontal cortex, hippocampus, striatum and cerebral cortex of adult rats; cerebellum was not affected either. Chronic administration of venlafaxine increased succinate dehydrogenase activity in prefrontal cortex, but did not affect the enzyme activity in cerebellum, hippocampus, striatum and cerebral cortex. Considering that metabolism impairment is probably involved in the pathophysiology of depressive disorders, an increase in these enzymes by antidepressants may be an important mechanism of action of these drugs.

  1. Characteristics of Optic Nerve Damage Induced by Chronic Intraocular Hypertension in Rat

    Institute of Scientific and Technical Information of China (English)

    Jiantao Wang; Jian Ge; A.A. Sadun; T.T. Lam

    2004-01-01

    Purpose:To set up the Sharma's chronic intraocular hypertension model and investigate the intraocular pressure (lOP) as well as the optic nerve damage of this model in rat.Methods:The operations of the chronic intraocular hypertension model were performed as described by Sharma in 60 male Lewis albino rats. IOP was measured using the TonoPen XL immediately after surgery and then at 5 day, 2 week or 4 week intervals. Cresyl violet staining of whole-mounted retinas was used to label retinal ganglion cells (RGCs),then RGCs were counted. Paraphenylenediamine (PPD) staining was performed in the semi-thin cross sections of optic nerve of rat, in order to know whether the axons of optic nerve were degenerated or not. Results:There were 47 rats with higher IOP after the episcleral veins cauterized in 60rats. The ratio of elevated IOP was 78.3%. The IOPs were stable in 4 weeks. After cresyl violet staining, the RGCs loss was 11.0% and 11.3% was found in the central and peripheral retina respectively after 2 weeks of increased IOP. After 4 weeks of increased lOP, the loss of RGCs was 17% for the central retina and 24.6% for the peripheral retina. In the retinas without higher IOP, there was no loss of RGCs. PPD staining showed that optic nerve of rat with about 5.3% damage of axons located at the superior temporal region. Region of affected optic nerve 1 mm posterior to the globe by light microscope showed evidence of damaged axons with axonal swelling and myelin debris.Conclusion:Sharma's chronic intraocular hypertension model is a reproducible and effective glaucoma model, which mimics human glaucoma with chronically elevation IOP and induced RGCs loss and damage of optic nerve. Eye Science 2004;20:25-29.

  2. Renal Actions of Neutral Endopeptidase Inhibition in Rats with Chronic Heart Failure

    Directory of Open Access Journals (Sweden)

    Amr M. Abbas

    2010-01-01

    Full Text Available Problem statement: We aim to evaluate the effects of acute and chronic inhibition of Neutral EndoPeptidase (NEP, by ONO-9902, on plasma and renal NEP gene expression, hemodynamic and renal parameters in rats with Chronic Heart Failure (CHF following left Coronary Artery Ligation (CAL. Approach: Forty eight male Sprague-Dawley rats (220-240 g were divided into sham and CAL groups. Myocardial infarction was induced by left CAL. All rats were further subdivided into untreated and orally treated with ONO-9902 (300 mg kg-1 day-1 from the 1st to 6th weeks after the operation. At the 1st and 6th weeks after the operation, gene expression of plasma and renal NEP, plasma ANP, cGMP and aldosterone concentrations, urine volume, Na and ANP excretion, creatinine clearance and renal cGMP generation were measured. Results: CAL leads to sodium and water retention, increased renal NEP gene expression, plasma ANP and aldosterone and decreased renal cGMP generation and plasma NEP gene expression. Acute treatment of CAL rats by ONO-9902, at the 1st week after the operation, inhibited plasma and renal NEP gene expression with increased plasma ANP, which caused diuresis, natriuresis and increased renal cGMP generation. Moreover, chronic treatment of those rats by ONO-9902 decreased plasma and renal NEP gene expression, plasma aldosterone, increased plasma ANP but non significantly, and caused diuresis, natriuresis with increased renal cGMP generation. GFR was not significantly changed before or after treatment. Conclusion: Chronic treatment with NEP inhibitor decreases Na and water retention in rats with CHF by enhancing ANP action and suppressing aldosterone secretion. So, ONO-9902 may offer a new therapeutic approach in patients with CHF.

  3. Effects of Electroacupuncture at Auricular Concha Region on the Depressive Status of Unpredictable Chronic Mild Stress Rat Models

    OpenAIRE

    Ru-Peng Liu; Ji-Liang Fang; Pei-Jing Rong; Yufeng Zhao; Hong Meng; Hui Ben; Liang Li; Zhan-Xia Huang; Xia Li; Ying-Ge Ma; Bing Zhu

    2013-01-01

    To explore new noninvasive treatment options for depression, this study investigated the effects of electroacupuncture (EA) at the auricular concha region (ACR) of depression rat models. Depression in rats was induced by unpredictable chronic mild stress (UCMS) combined with isolation for 21 days. Eighty male Wistar rats were randomly assigned into four groups: normal, UCMS alone, UCMS with EA-ACR treatment, and UCMS with EA-ear-tip treatment. Rats under inhaled anesthesia were treated once d...

  4. Chronic Arsenic Exposure-Induced Oxidative Stress is Mediated by Decreased Mitochondrial Biogenesis in Rat Liver.

    Science.gov (United States)

    Prakash, Chandra; Kumar, Vijay

    2016-09-01

    The present study was executed to study the effect of chronic arsenic exposure on generation of mitochondrial oxidative stress and biogenesis in rat liver. Chronic sodium arsenite treatment (25 ppm for 12 weeks) decreased mitochondrial complexes activity in rat liver. There was a decrease in mitochondrial superoxide dismutase (MnSOD) activity in arsenic-treated rats that might be responsible for increased protein and lipid oxidation as observed in our study. The messenger RNA (mRNA) expression of mitochondrial and nuclear-encoded subunits of complexes I (ND1 and ND2) and IV (COX I and COX IV) was downregulated in arsenic-treated rats only. The protein and mRNA expression of MnSOD was reduced suggesting increased mitochondrial oxidative damage after arsenic treatment. There was activation of Bax and caspase-3 followed by release of cytochrome c from mitochondria suggesting induction of apoptotic pathway under oxidative stress. The entire phenomenon was associated with decrease in mitochondrial biogenesis as evident by decreased protein and mRNA expression of nuclear respiratory factor 1 (NRF-1), nuclear respiratory factor 2 (NRF-2), peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), and mitochondrial transcription factor A (Tfam) in arsenic-treated rat liver. The results of the present study indicate that arsenic-induced mitochondrial oxidative stress is associated with decreased mitochondrial biogenesis in rat liver that may present one of the mechanisms for arsenic-induced hepatotoxicity. PMID:26767369

  5. Comparison of the Adulthood Chronic Stress Effect on Hippocampal BDNF Signaling in Male and Female Rats.

    Science.gov (United States)

    Niknazar, Somayeh; Nahavandi, Arezo; Peyvandi, Ali Asghar; Peyvandi, Hassan; Akhtari, Amin Shams; Karimi, Mohsen

    2016-08-01

    Studies show that gender plays an important role in stress-related disorders, and women are more vulnerable to its effect. The present study was undertaken to investigate differences in the change in expression of brain-derived neurotrophic factor (BDNF), and its tyrosine intracellular kinase-activating receptor (TrkB) genes in the male and female rats' hippocampus (HPC) under chronic mild repeated stress (CMRS) conditions. In this experiment, male and female Wistar rats were randomly divided into two groups: the CMRS and the control group. To induce stress, a repeated forced swimming paradigm was employed daily for adult male and female rats for 21 days. At the end of the stress phase, elevated plus maze (EPM) was used for measuring the stress behavioral effects. Serum corticosterone level was measured by ELISA. BDNF and TrkB gene methylation and protein expression in the HPC were detected using real-time PCR and Western blotting. Chronic stress in the adolescence had more effects on anxiety-like behavior and serum corticosterone concentration in female rats than males. Furthermore, stressed female rats had higher methylation levels and following reduced protein expression of BDNF but not TrkB compared to stressed male rats. These findings suggest that in exposure to a stressor, sex differences in BDNF methylation may be root cause of decreased BDNF levels in females and may underlie susceptibility to pathology development. PMID:26189832

  6. Carcinogenicity study on butylated hydroxytoluene (BHT) in Wistar rats exposed in utero

    DEFF Research Database (Denmark)

    Olsen, P.; Meyer, Otto A.; Bille, N.;

    1986-01-01

    the controls, the extent of the reduction being dose related; the effect, which persisted throughout the study, was most pronounced in the males. The survival of BHT-treated F1 rats of both sexes was significantly better than that of the controls. No significant changes attributable to BHT treatment were found...... detected when the F1 rats were more than 2 yr old. Tumours were found in many other organs of some of the treated rats, but their incidence was not significantly different from that in controls. The role of BHT in the development of hepatocellular tumours requires further elucidation....

  7. Expression of Rho GDIα in rat osteoblasts intermittently exposed to parathyroid hormone in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Zu-feng SUN; Hui JIANG; Zheng-qin YE; Bing JIA; Xiao-le ZHANG; Ke-qin ZHANG

    2009-01-01

    Aim:To investigate the mechanism of the bone-forming effects of intermittent parathyroid hormone (PTH) administration and to search for novel molecules of bone anabolism via the PTH signaling pathway.Methods:Primary cultures of rat osteoblasts (ROBs) were divided into an intermittent PTH-treated group (Itm) and a control group (Ctr).imitating the pharmacokinetics of intermittent PTH administration in vivo,the ROBs in the Itm group were exposed to PTH for 6 h in a 24-h incubation cycle,and the ROBs in the Ctr group were exposed to vehicle for the entire incubation cycle.The cells were collected at 6 h and 24 h of the final cycle,and the proteins in the Itm and Ctr groups were analyzed by two-dimensional electrophoresis (2-DE) coupled with peptide mass fingerprinting and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) to detect proteins that were differentially expressed.The proteins with the most significant changes in vitro were validated by immunohistochemistry (IHC) in a rat model.Results:The proteomics analysis indicated that a total of 26 proteins were up- or down-regulated in the Itm group compared with the Ctr group at 6 h and 24 h;among these,15 proteins were successfully identified.These proteins mainly belong to the cytoskeleton and molecular chaperone protein families,and most of these have anti-apoptotic effects in various cells.Rho GDP-dissociation inhibitor α (RhoGDla) and vimentin were the most significantly changed proteins.Further studies by IHC showed that the expression of RhoGDIα in ROBs was significantly higher in PTH-treated sham-operated rats than in vehicle-treated sham-operated rats,but the difference was not significant between PTH-treated and vehicle-treated OVX rats.Vimentin expression was not changed in either PTH-treated shamoperated rats or PTH-treated OVX rats.Conclusion:Our research suggests that intermittent PTH treatment induces changes in expression of many proteins in ROBs in vitro

  8. Erythrocyte osmotic fragility and lipid peroxidation following chronic co-exposure of rats to chlorpyrifos and deltamethrin, and the beneficial effect of alpha-lipoic acid

    Directory of Open Access Journals (Sweden)

    Chidiebere Uchendu

    2014-01-01

    Full Text Available The present study aimed to evaluate the effect of chronic co-exposure to chlorpyrifos (CPF and deltamethrin (DLT on erythrocyte osmotic fragility, lipid peroxidation and the ameliorative effect of alpha-lipoic acid (ALA on erythrocyte fragility. Thirty-six male Wistar rats divided into six groups of six rats each were used for the study. Groups I (S/oil and II (ALA were given soya oil (2 ml/kg and ALA (60 mg/kg, respectively. Rats in group III (DLT and IV (CPF were exposed to DLT (6.25 mg/kg and CPF (4.75 mg/kg (1/20th of the previously determined LD50 of 125 mg/kg and 95 mg/kg, respectively, over a period of 48 h. Rats in group V (CPF + DLT were co-exposed to CPF (4.75 mg/kg and DLT (6.25 mg/kg, while those in group VI (ALA + CPF + DLT were pretreated with ALA (60 mg/kg and then co-exposed to CPF and DLT, 45 min later. The treatments were administered by gavage once daily for a period of 16 weeks. Blood collected at the end of the experimental period were analyzed for erythrocyte osmotic fragility and malondialdehyde (MDA concentration. The study showed that chronic co-exposure to CPF and DLT resulted in an increase in erythrocyte fragility and MDA concentration which were ameliorated by supplementation with alpha-lipoic acid. The study concluded that repeated co-exposure to CPF and DLT elevated erythrocyte fragility probably due to increased lipid peroxidation, and pretreatment with alpha-lipoic acid ameliorated these alterations.

  9. Quantification of epithelial cell differentiation in mammary glands and carcinomas from DMBA- and MNU-exposed rats.

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    Deepak Sharma

    Full Text Available Rat mammary carcinogenesis models have been used extensively to study breast cancer initiation, progression, prevention, and intervention. Nevertheless, quantitative molecular data on epithelial cell differentiation in mammary glands of untreated and carcinogen-exposed rats is limited. Here, we describe the characterization of rat mammary epithelial cells (RMECs by multicolor flow cytometry using antibodies against cell surface proteins CD24, CD29, CD31, CD45, CD49f, CD61, Peanut Lectin, and Thy-1, intracellular proteins CK14, CK19, and FAK, along with phalloidin and Hoechst staining. We identified the luminal and basal/myoepithelial populations and actively dividing RMECs. In inbred rats susceptible to mammary carcinoma development, we quantified the changes in differentiation of the RMEC populations at 1, 2, and 4 weeks after exposure to mammary carcinogens DMBA and MNU. DMBA exposure did not alter the percentage of basal or luminal cells, but upregulated CD49f (Integrin α6 expression and increased cell cycle activity. MNU exposure resulted in a temporary disruption of the luminal/basal ratio and no CD49f upregulation. When comparing DMBA- or MNU-induced mammary carcinomas, the RMEC differentiation profiles are indistinguishable. The carcinomas compared with mammary glands from untreated rats, showed upregulation of CD29 (Integrin β1 and CD49f expression, increased FAK (focal adhesion kinase activation especially in the CD29hi population, and decreased CD61 (Integrin β3 expression. This study provides quantitative insight into the protein expression phenotypes underlying RMEC differentiation. The results highlight distinct RMEC differentiation etiologies of DMBA and MNU exposure, while the resulting carcinomas have similar RMEC differentiation profiles. The methodology and data will enhance rat mammary carcinogenesis models in the study of the role of epithelial cell differentiation in breast cancer.

  10. Chronic loss of melanin-concentrating hormone affects motivational aspects of feeding in the rat.

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    Joram D Mul

    Full Text Available Current epidemic obesity levels apply great medical and financial pressure to the strenuous economy of obesity-prone cultures, and neuropeptides involved in body weight regulation are regarded as attractive targets for a possible treatment of obesity in humans. The lateral hypothalamus and the nucleus accumbens shell (AcbSh form a hypothalamic-limbic neuropeptide feeding circuit mediated by Melanin-Concentrating Hormone (MCH. MCH promotes feeding behavior via MCH receptor-1 (MCH1R in the AcbSh, although this relationship has not been fully characterized. Given the AcbSh mediates reinforcing properties of food, we hypothesized that MCH modulates motivational aspects of feeding.Here we show that chronic loss of the rat MCH-precursor Pmch decreased food intake predominantly via a reduction in meal size during rat development and reduced high-fat food-reinforced operant responding in adult rats. Moreover, acute AcbSh administration of Neuropeptide-GE and Neuropeptide-EI (NEI, both additional neuropeptides derived from Pmch, or chronic intracerebroventricular infusion of NEI, did not affect feeding behavior in adult pmch(+/+ or pmch(-/- rats. However, acute administration of MCH to the AcbSh of adult pmch(-/- rats elevated feeding behavior towards wild type levels. Finally, adult pmch(-/- rats showed increased ex vivo electrically evoked dopamine release and increased limbic dopamine transporter levels, indicating that chronic loss of Pmch in the rat affects the limbic dopamine system.Our findings support the MCH-MCH1R system as an amplifier of consummatory behavior, confirming this system as a possible target for the treatment of obesity. We propose that MCH-mediated signaling in the AcbSh positively mediates motivational aspects of feeding behavior. Thereby it provides a crucial signal by which hypothalamic neural circuits control energy balance and guide limbic brain areas to enhance motivational or incentive-related aspects of food consumption.

  11. Chinese green tea consumption reduces oxidative stress, inflammation and tissues damage in smoke exposed rats

    Directory of Open Access Journals (Sweden)

    Wajdy Al-Awaida

    2014-10-01

    Conclusion: Exposure of albino rat model to cigarette smoke caused oxidative stress, altered the cellular antioxidant defense system, induced apoptosis in lung tissue, inflammation and tissues damage, which could be prevented by supplementation of CGT.

  12. Systemic physiology and neuroapoptotic profiles in young and adult rats exposed to surgery

    DEFF Research Database (Denmark)

    Ibrahim, Rami Mossad; Krammer, Caspar Weel; Hansen, Tom Giedsing;

    2015-01-01

    neuroapoptosis as well as systemic homeostasis. Here we explored this possibility by performing dorsal skin flap surgery in young and adult rats under four distinct currently used anaesthesia regimens. METHODS: Young (21-days) and adult (2 months) male Sprague-Dawley rats were randomized to 150min exposure...... in experimental groups receiving dexmedetomidine, while propofol administration was associated with increased systemic lactate levels and metabolic acidosis. A substantial difference in anaesthesia/surgery-induced neuroapoptosis was found between young and adult rats in several brain regions. Combination...... and adult spontaneously breathing rats undergoing surgery. These observations further enlighten the need for detailed physiological monitoring under these experimental conditions. Although some statistically significant differences in activated caspase-3 profiles were detected between experimental groups...

  13. Recruitment of hypothalamic orexin neurons after formalin injections in adult male rats exposed to a neonatal immune challenge

    Directory of Open Access Journals (Sweden)

    Erin Jane Campbell

    2015-03-01

    Full Text Available Exposure to early life physiological stressors, such as infection, is thought to contribute to the onset of psychopathology in adulthood. In animal models, injections of the bacterial immune challenge, lipopolysaccharide (LPS, during the neonatal period has been shown to alter both neuroendocrine function and behavioural pain responses in adulthood. Interestingly, recent evidence suggests a role for the lateral hypothalamic peptide orexin in stress and nociceptive processing. However, whether neonatal LPS exposure affects the reactivity of the orexin system to formalin-induced inflammatory pain in later life remains to be determined. Male Wistar rats (n=13 were exposed to either LPS or saline (0.05mg/kg, i.p on postnatal days (PND 3 and 5. On PND 80-97, all rats were exposed to a subcutaneous hindpaw injection of 2.25% formalin. Following behavioural testing, animals were perfused and brains processed for Fos-protein and orexin immunohistochemistry. Rats treated with LPS during the neonatal period exhibited decreased licking behaviours during the interphase of the formalin test, the period typically associated with the active inhibition of pain, and increased grooming responses to formalin in adulthood. Interestingly, these behavioural changes were accompanied by an increase in the percentage of Fos-positive orexin cells in the dorsomedial and perifornical hypothalamus in LPS-exposed animals. Similar increases in Fos-protein were also observed in stress and pain sensitive brain regions that receive orexinergic inputs. These findings highlight a potential role for orexin in the behavioural responses to pain and provide further evidence that early life stress can prime the circuitry responsible for these responses in adulthood.

  14. Chronic Sleep Disturbance Impairs Glucose Homeostasis in Rats

    NARCIS (Netherlands)

    Barf, R. Paulien; Meerlo, Peter; Scheurink, Anton J. W.

    2010-01-01

    Epidemiological studies have shown an association between short or disrupted sleep and an increased risk for metabolic disorders. To assess a possible causal relationship, we examined the effects of experimental sleep disturbance on glucose regulation in Wistar rats under controlled laboratory condi

  15. Sympathoadrenal dysfunction in rats with chronic neurogenic hypertension

    OpenAIRE

    Dominiak, P; Kees, Frieder K.; Grobecker, H

    1985-01-01

    Compared to sham-operated controls 5 weeks after surgery neurogenic hypertensive rats with sino-aortic baroreceptor deafferentation had higher blood pressure, higher plasma noradrenaline and adrenaline levels, lower heart noradrenaline concentrations, higher adrenomedullary adrenaline levels and increased cardiac intraventricular pressure (dp/dtmax).

  16. Blood-brain barrier permeability in rats exposed to electromagnetic fields used in wireless communication

    OpenAIRE

    Persson, Bertil R.; Leif G Salford; Brun, Arne

    1997-01-01

    iological effects of radio frequency electromagnetic fields (EMF) on the blood-brain barrier (BBB) have been studied in Fischer 344 rats of both sexes. The rats were not anaesthetised during the exposure. All animals were sacrificed by perfusion–fixation of the brains under chloralhydrate anaesthesia after the exposure. The brains were perfused with saline for 3–4 minutes, and thereafter perfusion fixed with 4% formaldehyde for 5–6 minutes. Whole coronal sections of the brains were d...

  17. Carcinogenicity study on butylated hydroxytoluene (BHT) in Wistar rats exposed in utero

    DEFF Research Database (Denmark)

    Olsen, P.; Meyer, Otto A.; Bille, N.;

    1986-01-01

    Groups of 60, 40, 40 and 60 F0 Wistar rats of each sex were fed a semi-synthetic diet containing butylated hydroxytoluene (BHT) in concentrations to provide intakes of 0, 25, 100 or 500 mg/kg body weight/day, respectively. The F0 rats were mated and groups of 100, 80, 80 or 100 F1 rats of each sex...... were formed from 40, 29, 30 and 44 litters, respectively. After weaning, the highest dose (500 mg BHT/kg/day) was lowered to 250 mg/kg/day for the F1 rats. The numbers of litters of ten or more pups at birth decreased with increasing BHT dose. At weaning, treated F1 rats had lower body weights than the...... controls, the extent of the reduction being dose related; the effect, which persisted throughout the study, was most pronounced in the males. The survival of BHT-treated F1 rats of both sexes was significantly better than that of the controls. No significant changes attributable to BHT treatment were found...

  18. Effects of caloric restriction on learning and recovery of a spatial task in rats exposed to acute stress

    Directory of Open Access Journals (Sweden)

    Lamprea Rodríguez, Marisol

    2009-06-01

    Full Text Available The purpose of the present study was to describe the effects of caloric restriction on spatial learning and recovery in the Barnes maze in animals experimentally stressed before recovery of the spatial task. Male Wistar rats were exposed for two months to one of two conditions: ad libitum (AL or intermittent fasting (IF. Both groups were exposed then to an experimental form of acute stress, induced by movement restriction for 4 hours. IF subjects had better performance in learning tasks during the acquisition trials but required more time to complete the task after the stressor was applied. These results are discussed in light of previous data reported in the literature emphasizing differences in the instruments used to evaluate spatial learning and its interaction with experimentally induced stress.

  19. Association between polymorphisms in arsenic metabolism genes and urinary arsenic methylation profiles in girls and boys chronically exposed to arsenic.

    Science.gov (United States)

    Recio-Vega, Rogelio; González-Cortes, Tania; Olivas-Calderón, Edgar; Clark Lantz, R; Jay Gandolfi, A; Michel-Ramirez, Gladis

    2016-08-01

    Disease manifestations or susceptibilities often differ among individuals exposed to the same concentrations of arsenic (As). These differences have been associated with several factors including As metabolism, sex, age, genetic variants, nutritional status, smoking, and others. This study evaluated the associations between four As metabolism-related gene polymorphisms/null genotypes with urinary As methylation profiles in girls and boys chronically exposed to As. In a total of 332 children aged 6-12 years, the frequency of AS3MT, GSTO1, GSTT1, and GSTM1 polymorphisms/null genotypes and As urinary metabolites were measured. The results revealed that total As and monomethyl metabolites of As (MMA) levels were higher in boys than in girls. No differences in the frequency of the evaluated polymorphisms were found between girls and boys. In AS3MT-Met287Thr carriers, %MMA levels were higher and second methylation levels (defined as dimethylarsinic acid divided by MMA) were lower. In children with the GSTM1 null genotype, second methylation levels were higher. In boys, a positive association between the AS3MT-Met287Thr polymorphism with %MMA and between the GSTO1-Glu155del and As(v) was found; whereas, a negative relationship was identified between AS3MT-Met287Thr and second methylation profiles. In girls, a positive association was found between the GSTO1-Ala140Asp polymorphism with second methylation levels. In conclusion, our data indicate that gender, high As exposure levels, and polymorphisms in the evaluated genes negatively influenced As metabolism. Environ. Mol. Mutagen. 57:516-525, 2016. © 2016 Wiley Periodicals, Inc.

  20. DJ1 Expression Downregulates in Neuroblastoma Cells (SK-N-MC Chronically Exposed to HIV-1 and Cocaine.

    Directory of Open Access Journals (Sweden)

    Upal eRoy

    2015-07-01

    Full Text Available Background: HIV-associated neurological disorder (HAND has long been recognized as a consequence of Human Immunodeficiency Virus (HIV infection in the brain. The pathology of HAND gets more complicated with the recreational drug use such as cocaine. Recent studies have suggested multiple genetic influences involved in the pathology of addiction and HAND but only a fraction of the entire genetic risk has been investigated so far. In this regard, role of DJ1 protein (a gene linked to autosomal recessive early-onset Parkinson’s disease in regulating dopamine transmission and reactive oxygen species (ROS production in neuronal cells will be worth investigating in HIV-1 and cocaine exposed microenvironment. Being a very abundant protein in the brain, DJ1 could serve as a potential marker for early detection of HIV-1 and/or cocaine related neurological disorder.Methods: In vitro analysis was done to observe the effect of HIV-1 and/or cocaine on DJ1 protein expression in neuroblastoma cells (SK-N-MC. Gene expression and protein analysis of DJ1 was done on the HIV infected and/or cocaine treated SK-N-MC and compared to untreated cells using real time PCR, Western Blot and flow cytometry.Results: Gene expression and protein analysis indicated that there was a significant decrease in DJ1 expression in SK-N-MC chronically exposed to HIV-1 and/or cocaine.Conclusion: This is the first study to establish that DJ1 expression level in the neuronal cells significantly decreased in presence of HIV-1and/or cocaine indicating oxidative stress level of dopamine neurons.

  1. Hepatoprotective Effect Of Silyamarin In Individuals Chronically Exposed To Hydrogen Sulfide; Modulating Influence Of TNF-Α Cytokine Genetic Polymorphism

    Directory of Open Access Journals (Sweden)

    Vahideh Montazeri

    2013-04-01

    Full Text Available Background and the purpose of the study:Silymarin, a standardized extract of the milk thistle (Silybum marianum, is believed to exert some of its hepatoprotective effects though inhibition of free radicals and inflammation. In this study the effect of some pro- and anti-inflammatory cytokines and also antioxidant genes polymorphisms on the hepatoprotective effects of silymarin in the occupationally exposed individuals to hydrogen sulfide (H2S in the sour natural gas refinery was investigated.Methods:We genotyped seven polymorphisms in six genes reported by others as modifiers of oxidative stress (NQO1, mEPXH1, GSTT1 and GSTM1 and inflammation (TNF-α and TGF-β1 for an association in effect of decreasing in liver function tests (LFTs. The LFTs of 77 sour gas refinery workers were measured before and after administration of silymarin (140 mg, three times per day for 1 month.Results:A significant reduction of blood AST, ALT and ALP was observed after 30 days of consumption (p < 0.001. The decreasing effect of silymarin on ALT in the subjects with high producer genotype (A allele carriers was less than low producers. There were no significant associations between TGF-β1 and the studied genes of oxidative stress pathway and the effectiveness of silymarin.Conclusion:This is the first report about the effectiveness of silymarin in the subjects exposed chronically to H2S. Meanwhile, the modulatory effect of TNF-α on the effectiveness of silymarin might be used for individualize therapy

  2. Estrogen intervention in microvascular morphology and choline acetyltransferase expression in rat hippocampal neurons in chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Zhenjun Yang; Hongwei Yan; Guomin Zhang; Zhihong Chen; Jingfeng Xue

    2011-01-01

    We observed dynamic changes in microvessels and a protective effect of estrogen on chronic cerebral ischemia ovariectomized rat models established through permanent occlusion of bilateral carotid arteries at 7, 14 and 21 days. The results revealed that estrogen improved microvasculature in the hippocampus of chronic cerebral ischemic rats, upregulated Bcl-2 protein expression, downregulated Bax protein expression, increased choline acetyltransferase expression in hippocampal cholinergic neurons, and suppressed hippocampal neuronal apoptosis. These findings indicate that estrogen can protect hippocampal neurons in rats with chronic cerebral ischemia.

  3. Changes in blood sugar content of dogs exposed to chronic gamma radiation for 6 years. [Combined effects of physical stress, heat stress, and acute radiation stress

    Energy Technology Data Exchange (ETDEWEB)

    Akhunov, A.A.

    1978-10-26

    There have not been many studies of blood sugar concentration in animals exposed to chronic gamma radiation, and the results thereof are contradictory. Therefore, data on blood sugar levels in dogs during a 6-year exposure to gamma radiation and after discontinuation thereof are reported.

  4. Systemic and Vascular Alterations in Rat models Exposed to Libby Amphibole

    Science.gov (United States)

    Acute pulmonary injury and chronic diseases can impact systemic vasculature and extra pulmonary organ systems due to the hemodynamic properties of the pulmonary capillary network that allows mediators to release into the circulation. Exposure to Libby amphibole (LA) is associated...

  5. Rats with high or low sociability are differently affected by chronic variable stress.

    Science.gov (United States)

    Tõnissaar, M; Herm, L; Eller, M; Kõiv, K; Rinken, A; Harro, J

    2008-04-01

    Depression is strongly related to social behavior. We have previously shown that social behavior of rats is individually stable. The purpose of the present study was to compare the sensitivity of animals with different sociability to chronic variable stress (CVS). Four social interaction tests were performed with 60 single-housed male Sprague-Dawley rats. Twenty rats with the lowest and 20 with the highest average social activity time were selected as low sociability (LS) and high sociability (HS) rats, respectively. Both groups were further divided into control and stress groups with equal average body weight. The CVS procedure lasted for 3 weeks. The stressors applied were cold water and wet bedding, imitation of injection, stroboscopic light, movement restriction in a small cage, tail pinch with a clothespin, and strong illumination during the predicted dark phase. In HS-rats, but not in LS-rats, CVS reduced sucrose intake compared with baseline after 3 weeks, suggesting that HS-rats are more vulnerable to anhedonia elicited by CVS. LS-animals were more anxious in the social interaction and open field tests, but stress eliminated differences with HS-animals in the social interaction test and increased their activity in the forced swimming test. In LS-rats stress increased ex vivo dopamine levels and reduced 5-HT levels in the frontal cortex, suggesting that the increased behavioral activity after stress may be related to increased impulsivity. This study thus revealed that animals with high sociability trait are more vulnerable to anhedonia elicited by chronic stress in conditions of single housing. PMID:18343596

  6. Effects of Exercise on Behavior and Peripheral Blood Lymphocyte Apoptosis in a Rat Model of Chronic Fatigue Syndrome

    Institute of Scientific and Technical Information of China (English)

    邹军; 苑建齐; 吕爽; 屠嘉衡

    2010-01-01

    This study examined the effects of exercise on behavior and peripheral blood leukocyte apoptosis in a rat model of chronic fatigue syndrome(CFS).Thirty-six healthy male Sprague-Dawley rats were equally randomized into 3 groups:the control group,CFS model group and the exercise group in terms of body weight.A total of 25 rats entered the final statistical analysis due to 11 deaths during the study.CFS model was established by subjecting the rats in CFS model group and exercise group to electric shock,chronic...

  7. Effects of exposing rats to 100% oxygen at 450 and 600 mm Hg on in vitro liver and adipose tissue lipid synthesis.

    Science.gov (United States)

    Feller, D. D.; Neville, E. D.; Talarico, K. S.

    1972-01-01

    Male rats (260-285 gm) were exposed to 100% oxygen at 450 or 600 mm Hg for 1 to 4 days. Rats maintained at 450 mm Hg ate 92% the amount of food eaten by ad libitum controls maintained at sea level conditions. At 600 mm Hg, the food intake was 77% of the ad libitum controls. No difference was found in the plasma level of glucose, free fatty acids, and corticosterone between oxygen exposed rats and their respective pair-fed controls. The in vitro conversion of acetate into fatty acids by adipose tissue from rats exposed at 450 mm Hg for 2, 3, or 4 days was significantly increased above pair-fed controls and ad libitum controls. Increasing the oxygen pressure to 600 mm Hg abolished this increase, and in fact, reversed the increased synthesis to a significant decrease for the 4-day exposure.

  8. Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats

    Indian Academy of Sciences (India)

    Ashok Iyyaswamy; Sheeladevi Rathinasamy

    2012-09-01

    This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

  9. Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats.

    Science.gov (United States)

    Iyyaswamy, Ashok; Rathinasamy, Sheeladevi

    2012-09-01

    This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

  10. Magnetic resonance imaging of the normal and chronically injured adult rat spinal cord in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Guizar-Sahagun, G. (Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Clinical Research in Neurology and Neurosurgery, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Inst. Mexicano del Seguro Social, Mexico City (Mexico)); Rivera, F. (Centro de Investigacion del Proyecto Camina, Mexico City (Mexico)); Babinski, E. (Centro de Investigacion del Proyecto Camina, Mexico City (Mexico)); Berlanga, E. (Dept. of Magnetic Resonance Imaging, Hospital Angeles del Pedregal, Mexico City (Mexico)); Madrazo, M. (Dept. of Magnetic Resonance Imaging, Hospital Angeles del Pedregal, Mexico City (Mexico)); Franco-Bourland, R. (Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Biochemistry, Inst. Nacional de la Nutricion, Mexico City (Mexico)); Grijalva, I. (Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Clinical Research in Neurology and Neurosurgery, Hospital de Especialidades, Centro Medico Nacional Siglo

    1994-08-01

    We assessed the capacity of MRI to show and characterise the spinal cord (SC) in vivo in normal and chronically injured adult rats. In the chronically injured animals the SC was studied by MRI and histological examination. MRI was performed at 1.5 T, using gradient-echo and spin-echo (SE) sequences, the latter with and without gadolinium-DTPA (Gd-DTPA). Several positions were tried for good alignment and to diminish interference by respiratory movements. Images of the SC were obtained in sagittal, coronal, and axial planes. Normal SC was observed as a continuous intensity in both sequences, although contrast resolution was better using SE; it was not possible to differentiate the grey and white matter. Low signal was seen in the damaged area in chronically injured rats, which corresponded to cysts, trabeculae, mononuclear infiltrate, and fibroglial wall on histological examination. Gd-DTPA failed to enhance the SC in normal or chronically injured rats. It did, however, cause enhancement of the lesion after acute SC injury. (orig.)

  11. Chronic stress induces ageing-associated degeneration in rat Leydig cells

    Institute of Scientific and Technical Information of China (English)

    Fei-Fei Wang; Qian Wang; Yong Chen; Qiang Lin; Hui-Bao Gao; Ping Zhang

    2012-01-01

    Several studies have suggested that stress and ageing exert inhibitory effects on rat Leydig cells.In a pattern similar to the normal process of Leydig cell ageing,stress-mediated increases in glucocorticoid levels inhibit steroidogenic enzyme expression that then results in decreased testosterone secretion.We hypothesized that chronic stress accelerates the degenerative changes associated with ageing in Leydig cells.To test this hypothesis,we established a model of chronic stress to evaluate stress-induced morphological and functional alterations in Brown Norway rat Leydig cells; additionally,intracellular lipofuscin levels,reactive oxygen species (ROS)levels and DNA damage were assessed.The results showed that chronic stress accelerated ageing-related changes:ultrastructural alterations associated with ageing,cellular lipofuscin accumulation,increased ROS levels and more extensive DNA damage were observed.Additionally,testosterone levels were decreased.This study sheds new light on the idea that chronic stress contributes to the degenerative changes associated with ageing in rat Leydig cells in vivo.

  12. An improved strategy for evaluating the extent of chronic arterial baroreceptor denervation in conscious rats

    Directory of Open Access Journals (Sweden)

    M. Rodríguez-Martínez

    2010-11-01

    Full Text Available There is no index or criterion of aortic barodenervation, nor can we differentiate among rats that have suffered chronic sham, aortic or sino-aortic denervation. The objective of this study was to develop a procedure to generate at least one quantitative, reproducible and validated index that precisely evaluates the extent of chronic arterial barodenervation performed in conscious rats. Data from 79 conscious male Wistar rats of about 65-70 days of age with diverse extents of chronic arterial barodenervation and used in previous experiments were reanalyzed. The mean arterial pressure (MAP and the heart rate (HR of all rats were measured systematically before (over 1 h and after three consecutive iv bolus injections of phenylephrine (PHE and sodium nitroprusside (SNP. Four expressions of the effectiveness of barodenervation (MAP lability, PHE ratio, SNP ratio, and SNP-PHE slope were assessed with linear fixed models, three-level average variance, average separation among levels, outlier box plot analysis, and overlapping graphic analysis. The analysis indicated that a neither MAP lability nor SNP-PHE slope was affected by the level of chronic sodium intake; b even though the Box-Cox transformations of both MAP lability [transformed lability index (TLI] and SNP-PHE slope [transformed general sensitivity index (TGSI, {((3-(ΔHRSNP-ΔHRPHE/ΔMAPSNP-ΔMAPPHE-0.4-1/-0.04597}] could be two promising indexes, TGSI proved to be the best index; c TLI and TGSI were not freely interchangeable indexes for this purpose. TGSI ranges that permit differentiation between sham (10.09 to 11.46, aortic (8.40 to 9.94 and sino-aortic (7.68 to 8.24 barodenervated conscious rats were defined.

  13. Serum and tissue lipids in rats exposed to chronic irradiation with uneven daily doses. Part 2

    International Nuclear Information System (INIS)

    The animals were irradiated continuously for a period of 10 days with a total dose of 9 Gy. Combined hyperlipemia, the accumulation of triacylglycerols in the bone tissue, and a decreased content of triacylglycerols and phospholipids in the thymus were observed. Serum and tissue lipids returned to normal slowly, the accumulation of triacylglycerols in the bone tissue went back to normal only on day 240 after irradiation. (M.D.)

  14. Paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats

    OpenAIRE

    Khedr LH; Nassar NN; El-Denshary ES; Abdel-tawab AM

    2015-01-01

    Lobna H Khedr, Noha N Nassar, Ezzeldin S El-Denshary, Ahmed M Abdel-tawab 1Department of Pharmacology, Faculty of Pharmacy, Misr International University, 2Department of Pharmacology, Faculty of Pharmacy, Cairo University, 3Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt Abstract: The molecular mechanisms underlying stress-induced depression have not been fully outlined. Hence, the current study aimed at testing the link between behavioral changes in chro...

  15. Myocardial metabolism of pantothenic acid in chronically diabetic rats.

    Science.gov (United States)

    Beinlich, C J; Naumovitz, R D; Song, W O; Neely, J R

    1990-03-01

    Transport and metabolism of [3H]pantothenic acid ([3H]Pa) was investigated in hearts from control and streptozotocin-induced diabetic rats. In isolated perfused hearts from control animals, the transport of [3H]Pa was linear over 3 h of perfusion when 11 mM glucose was the only exogenous substrate. The in vitro transport of [3H]Pa by hearts from 48-h diabetic rats was reduced by 65% compared to controls and was linear over 2 h of perfusion with no further accumulation of Pa during the third hour. The defect in transport observed in vitro could be corrected by in vivo treatment with 4 U Lente insulin/day for 2 days. In vitro addition of insulin in the presence of 11 mM glucose or 11 mM glucose plus 1.2 mM palmitate had no effect on [3H]Pa transport in hearts from 48-h diabetic rats during 3 h of perfusion. Accumulation of [3H]Pa was not inhibited by inclusion of 0.7 mM amino acids, 1 mM carnitine, 50 microM mersalic acid or 1 mM panthenol, pantoyllactone or pantoyltaurine. Uptake was inhibited by 1 mM nonanoic, octanoic or heptanoic acid, 0.1 mM biotin or 0.25 mM probenecid, suggesting a requirement for the terminal carboxyl group for transport. Transport of pantothenic acid was reduced in hearts from diabetic rats within 24 h of injection of streptozotocin. In vitro accumulation of [3H]Pa decreased to 10% of control 1 week after streptozotocin injection and then remained at 30% of the control value over 10 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2141362

  16. Circulating and tissue catecholamines in rats with chronic neurogenic hypertension

    OpenAIRE

    Dominiak, P; Kees, Frieder K.; Grobecker, H

    1986-01-01

    To study the role of peripheral catecholamines in plasma and different tissues in neurogenic hypertension we measured directly blood pressure, maximum rate of left ventricular pressure rise (dp/dtmax) and heart rate through an aortic catheter 5 weeks after total sino-aortic baroreceptor deafferentation in male Sprague-Dawley rats. Blood samples were collected through the same catheter to determine plasma catecholamine concentrations. Blood pressure and dp/dtmax were significantly higher in ne...

  17. Effect of estrogen on plasma ceruloplasmin level in rats exposed to acute stress

    Directory of Open Access Journals (Sweden)

    Ganaraja B

    2004-04-01

    Full Text Available BACKGROUND: Plasma ceruloplasmin, a copper containing protein, belongs to a class called acute phase proteins. Reduced level of ceruloplasmin was associated with Wilson′s disease and Menke′s kinky hair disease in man, primarily affecting copper metabolism. Stress was known to increase Ceruloplasmin. Several stress associated changes were commonly observed in women at menopause and also those who underwent overiectomy. Present experiment investigated the effect of estrogen on ceruloplasmin level in acute stress. AIMS: To assess the estradiol induced changes in plasma ceruloplasmin concentration on exposure of the rats to acute stress. SETTINGS AND DESIGN: Acute stress was induced by forcing the rats to swim till exhaustion. The rats were overiectomised bilaterally to remove the primary source of sex hormones. And hormone replacement was done later. MATERIAL AND METHODS: Wistar albino female rats were used. Acute stress was induced before overiectomy, following recovery from surgery, and again after Estradiol Valerate injection (for 10 days in same group of rats. The plasma ceruloplasmin was estimated immediately after stress during each stage - that is preoperative control, stressed control, after overiectomy and then following treatment with Estradiol Valerate. STATISTICAL ANALYSIS USED: Paired sample T test was applied to analyze the findings. Results: We found lowest ceruloplasmin level after stress in overiectomised animals, while on substitution of estradiol the trend appeared to be reversed. CONCLUSION: The result suggested a direct effect of estrogen on hepatic ceruloplasmin production/release and this could account for some of the beneficial effects of hormone replacement therapy.

  18. Ovariectomy-induced chronic abdominal hypernociception in rats: Relation with brain oxidative stress

    Directory of Open Access Journals (Sweden)

    Bárbara B. Garrido-Suárez

    2015-12-01

    Full T