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Sample records for pregnant sprague-dawley rats

  1. Systemic candidiasis in Sprague-Dawley rats.

    Science.gov (United States)

    Schmidt, A

    1996-01-01

    A reproducible model of a generalized Candida albicans infection was established in rats to allow a precise evaluation of the efficacy of antifungal compounds. In contrast to the intravenous C. albicans model in mice, which serves as a primary model for in vivo efficacy studies of antimycotic compounds, the infectious process in Sprague-Dawley rats is more severely spread into organs other than the kidneys, such as brain, heart, liver, lung, retina and spleen. Apart from a severe granulomatous nephritis beginning 1 day after infection, we observed a severe pneumonitis 3 days after infection with a mass of extravasal erythrocytes in the interstitium and the alveolar space. In addition, multiple nodular lesions could be observed in the brain, heart, liver, retina and spleen on the first day after infection. Lethality was 100% within 1 week, the majority of deaths occurring from 5 to 7 days. Antifungal therapy with amphotericin B or fluconazole led to long-term survival over 4 months, which could not be achieved in mice.

  2. Neuronal Function in Male Sprague Dawley Rats During Normal Ageing.

    Science.gov (United States)

    Idowu, A J; Olatunji-Bello, I I; Olagunju, J A

    2017-03-06

    During normal ageing, there are physiological changes especially in high energy demanding tissues including the brain and skeletal muscles. Ageing may disrupt homeostasis and allow tissue vulnerability to disease. To establish an appropriate animal model which is readily available and will be useful to test therapeutic strategies during normal ageing, we applied behavioral approaches to study age-related changes in memory and motor function as a basis for neuronal function in ageing in male Sprague Dawley rats. 3 months, n=5; 6 months, n=5 and 18 months, n=5 male Sprague Dawley Rats were tested using the Novel Object Recognition Task (NORT) and the Elevated plus Maze (EPM) Test. Data was analyzed by ANOVA and the Newman-Keuls post hoc test. The results showed an age-related gradual decline in exploratory behavior and locomotor activity with increasing age in 3 months, 6 months and 18 months old rats, although the values were not statistically significant, but grooming activity significantly increased with increasing age. Importantly, we established a novel finding that the minimum distance from the novel object was statistically significant between 3 months and 18 months old rats and this may be an index for age-related memory impairment in the NORT. Altogether, we conclude that the male Sprague Dawley rat show age-related changes in neuronal function and may be a useful model for carrying out investigations into the mechanisms involved in normal ageing.

  3. Keishibukuryogan is not carcinogenic in Sprague-Dawley rats

    OpenAIRE

    Kanitani, Masanao; Nishimura, Nobuo; Edamoto, Hiroshi; Kase, Yoshio

    2016-01-01

    Keishibukuryogan is a traditional Japanese medicine widely administered to patients with menopausal symptoms. Because humans use it on a long-term basis, we believed that a carcinogenicity study was warranted. We orally administered keishibukuryogan (TJ-25) extract powder to 6-week-old Sprague-Dawley rats [Crl:CD(SD)], which were divided into four dosage groups-0 (water for injection), 100, 500 and 2,500 mg/kg/day for 24 months. We found that TJ-25 did not affect the survival rate of either s...

  4. Increased radiosensitivity of cerebral capillaries in neonatal Gunn rats as compared to Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Landolt, R.; Arn, D.

    1979-01-01

    The extent of petechial haemorrhages of the cerebral cortex examined between 14 hours and 4 days after X-irradiation to the head was compared in Sprague-Dawley and homozygous Gunn rats with congenital hyperbilirubinaemia. Animals 1 to 2 days old received single doses of either 250, 500 or 750 rad. By means of a special scoring scale the degree of the damage to the micro vasculature was semi-quantitatively estimated. In both strains a significant difference in effect was obtained between 250 and 500 rad, but not between 500 and 750 rad. The shape of the dose-effect curve in Gunn rats was similar to that of Sprague-Dawley rats, but displaced upwards. In Gunn rats the effect of 250 rad was greater that that of 750 rad in Sprague-Dawley rats. Possible radiosensitizing mechanisms are discussed with reference to the literature and these results. (author)

  5. Dietary (n-6 : n-3 Fatty Acids Alter Plasma and Tissue Fatty Acid Composition in Pregnant Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Amira Abdulbari Kassem

    2012-01-01

    Full Text Available The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO: 50% cod liver oil (CLO (1 : 1, 84% SBO: 16% CLO (6 : 1, 96% SBO: 4% CLO (30 : 1. Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat.

  6. Dietary (n-6 : n-3) fatty acids alter plasma and tissue fatty acid composition in pregnant Sprague Dawley rats.

    Science.gov (United States)

    Kassem, Amira Abdulbari; Abu Bakar, Md Zuki; Yong Meng, Goh; Mustapha, Noordin Mohamed

    2012-01-01

    The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO): 50% cod liver oil (CLO) (1 : 1), 84% SBO: 16% CLO (6 : 1), 96% SBO: 4% CLO (30 : 1). Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat.

  7. Dietary (n-6 : n-3) Fatty Acids Alter Plasma and Tissue Fatty Acid Composition in Pregnant Sprague Dawley Rats

    Science.gov (United States)

    Kassem, Amira Abdulbari; Abu Bakar, Md Zuki; Yong Meng, Goh; Mustapha, Noordin Mohamed

    2012-01-01

    The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO): 50% cod liver oil (CLO) (1 : 1), 84% SBO: 16% CLO (6 : 1), 96% SBO: 4% CLO (30 : 1). Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat. PMID:22489205

  8. Diverse basal and stress-related phenotypes of Sprague Dawley rats from three vendors

    NARCIS (Netherlands)

    Pecoraro, Norman; Ginsberg, Abigail B.; Warne, James P.; Gomez, Francisca; la Fleur, Susanne E.; Dallman, Mary F.

    2006-01-01

    Based on observed phenotypic differences in growth and ACTH responses to stress in Sprague Dawley rats obtained from different vendors, we ran head-to-head comparisons on rats obtained from three different vendors, Harlan, Charles River, and Simonsen, with respect to baseline phenotypic differences

  9. Wheel running decreases palatable diet preference in Sprague-Dawley rats

    OpenAIRE

    Moody, Laura; Liang, Joy; Choi, Pique P.; Moran, Timothy H.; Liang, Nu-Chu

    2015-01-01

    Physical activity has beneficial effects on not only improving some disease conditions but also by preventing the development of multiple disorders. Experiments in this study examined the effects of wheel running on intakes of chow and palatable diet e.g. high fat (HF) or high sucrose (HS) diet in male and female Sprague Dawley rats. Experiment 1 demonstrated that acute wheel running results in robust HF or HS diet avoidance in male rats. Although female rats with running wheel...

  10. Transplacentally transmitted congenital brucellosis due to brucella abortus biotype 1 in sprague-dawley rats

    International Nuclear Information System (INIS)

    Rahman, M.S.; Baek, B.K.

    2008-01-01

    In the investigation on the transplacentally transmitted congenital brucellosis due to Brucella abortus biotype 1 in Sprague- Dawley rats, neither any stillbirth, abortion or premature birth nor any abnormality of fetus was observed in the infected group or in the control group. B. abortus biotype was isolated from the fetus of infected rats only. Only one band of 498 base pair DNA was obtained in polymerase chain reaction products from DNA of the fetuses of infected SD rats. (author)

  11. Sprague-Dawley and Fischer Female Rats Differ in Acute Effects of Fluoxetine on Sexual Behavior

    Science.gov (United States)

    Miryala, C.S.J.; Hiegel, C.; Uphouse, L.

    2012-01-01

    Introduction The selective serotonin reuptake inhibitor (SSRI), fluoxetine, leads to sexual dysfunction in a substantial proportion of women. In studies with the Fischer inbred rat, the 5-HT1A receptor has been implicated in this sexual dysfunction. Whether this association with 5-HT1A receptors holds for other rat strains is not known. Aim The effects of acute fluoxetine on sexual behavior in two strains of rats that differ in their response to a 5-HT1A receptor agonist were examined. Whether the strain difference is comparable in naturally cycling and hormonally primed, ovariectomized rats was determined. Main Outcome Measures Lordosis to mount ratios, lordosis quality, and proceptive behaviors were quantified. Sprague-Dawley and Fischer females were compared on each of these measures. The IC50 for inhibition of lordosis behavior was determined. Methods Proestrous rats and ovariectomized rats, hormonally primed with estradiol benzoate and progesterone, were treated with varying doses of fluoxetine. Sexual behavior was examined before and after treatment with the SSRI. Results In both the intact and the hormonally-primed, ovariectomized model, Sprague-Dawley females were less sensitive to the effects of fluoxetine on sexual behavior. In both groups, fluoxetine showed dose-dependency in behavioral inhibition, but a higher dose was required for Sprague-Dawley than for Fischer females. Naturally cycling, proestrous rats required a higher dose of fluoxetine than hormonally-primed ovariectomized rats to produce significant inhibition of sexual behavior. Thus, the strain difference in the response to fluoxetine does not parallel strain differences in the response to a 5-HT1A receptor agonist. Conclusions Acute treatment with fluoxetine inhibits lordosis behavior in both Fischer and Sprague-Dawley females and the strain difference cannot be explained by reported strain differences in the response to a 5-HT1A receptor agonist. Fluoxetine’s inhibition of female rat

  12. Oxidized LDL Is Strictly Limited to Hyperthyroidism Irrespective of Fat Feeding in Female Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Sieglinde Zelzer

    2015-05-01

    Full Text Available Metabolic dysfunctions might play a crucial role in the pathophysiology of thyroid dysfunctions. This study aimed to investigate the impact of a controlled diet (normal versus high fat feeding on hypothyroid and hyperthyroid Sprague Dawley rats. Female Sprague Dawley rats (n = 66 were grouped into normal diet (n = 30 and high-fat diet (n = 36 groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3 treatment, respectively. After 12 weeks of treatment metabolic parameters, such as oxidized LDL (oxLDL, malondialdehyde (MDA, 4-hydroxynonenal (HNE, the lipid profile, body weight and food intake parameters were analyzed. Successfully induced thyroid dysfunctions were shown by T3 levels, both under normal and high fat diet. Thyroid dysfunctions were accompanied by changes in calorie intake and body weight as well as in the lipid profile. In detail, hypothyroid rats showed significantly decreased oxLDL levels, whereas hyperthyroid rats showed significantly increased oxLDL levels. These effects were seen under high fat diet and were less pronounced with normal feeding. Taken together, we showed for the first time in female SD rats that only hyper-, but not hypothyroidism, is associated with high atherogenic oxidized LDL irrespective of normal or high-fat diet in Sprague Dawley rats.

  13. Oxidized LDL Is Strictly Limited to Hyperthyroidism Irrespective of Fat Feeding in Female Sprague Dawley Rats.

    Science.gov (United States)

    Zelzer, Sieglinde; Mangge, Harald; Pailer, Sabine; Ainoedhofer, Herwig; Kieslinger, Petra; Stojakovic, Tatjana; Scharnagl, Hubert; Prüller, Florian; Weghuber, Daniel; Datz, Christian; Haybaeck, Johannes; Obermayer-Pietsch, Barbara; Trummer, Christian; Gostner, Johanna; Gruber, Hans-Jürgen

    2015-05-21

    Metabolic dysfunctions might play a crucial role in the pathophysiology of thyroid dysfunctions. This study aimed to investigate the impact of a controlled diet (normal versus high fat feeding) on hypothyroid and hyperthyroid Sprague Dawley rats. Female Sprague Dawley rats (n = 66) were grouped into normal diet (n = 30) and high-fat diet (n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment metabolic parameters, such as oxidized LDL (oxLDL), malondialdehyde (MDA), 4-hydroxynonenal (HNE), the lipid profile, body weight and food intake parameters were analyzed. Successfully induced thyroid dysfunctions were shown by T3 levels, both under normal and high fat diet. Thyroid dysfunctions were accompanied by changes in calorie intake and body weight as well as in the lipid profile. In detail, hypothyroid rats showed significantly decreased oxLDL levels, whereas hyperthyroid rats showed significantly increased oxLDL levels. These effects were seen under high fat diet and were less pronounced with normal feeding. Taken together, we showed for the first time in female SD rats that only hyper-, but not hypothyroidism, is associated with high atherogenic oxidized LDL irrespective of normal or high-fat diet in Sprague Dawley rats.

  14. Neuronal Function in Male Sprague Dawley Rats During Normal ...

    African Journals Online (AJOL)

    olayemitoyin

    appropriate animal model which is readily available and will be useful to test therapeutic ... and locomotor activity with increasing age in 3 months, 6 months and 18 months old rats, although the values were not ... The mean life expectancy has.

  15. Neurolaena lobata L. promotes wound healing in Sprague Dawley rats

    OpenAIRE

    Nayak, Bijoor Shivananda; Ramlogan, Surrin; Chalapathi Rao, AV; Maharaj, Sandeep

    2014-01-01

    Background: The leaves of the Neurolaena lobata (Asteraceae) plant are used to control diabetes and heal wounds and infections. Aim: The ethanolic extract of N. lobata leaf was evaluated for its ability to heal inflicted wounds in rats using the excision wound model. Materials and Methods: Animals were divided into three groups of six each. Test group animals were treated topically with an ethanolic extract of N. lobata (1:1 with petroleum jelly, 100 mg/kg/day). Standard and control group ani...

  16. Anticancer Potential of Nutraceutical Formulations in MNU-induced Mammary Cancer in Sprague Dawley Rats

    OpenAIRE

    Pitchaiah, Gummalla; Akula, Annapurna; Chandi, Vishala

    2017-01-01

    Background: Nutraceuticals help in combating some of the major health problems of the century including cancer, and ?nutraceutical formulations? have led to the new era of medicine and health. Objective: To develop different nutraceutical formulations and to assess the anticancer potential of nutraceutical formulations in N-methyl-N-nitrosourea (MNU)-induced mammary cancer in Sprague Dawley rats. Materials and Methods: Different nutraceutical formulations were prepared using fine powders of a...

  17. Spontaneous Renal Tumors Suspected of Being Familial in Sprague-Dawley Rats

    OpenAIRE

    Kudo, Kayoko; Hoshiya, Toru; Nakazawa, Tomomi; Saito, Tsubasa; Shimoyama, Natsumi; Suzuki, Isamu; Tamura, Kazutoshi; Seely, John Curtis

    2012-01-01

    Spontaneous renal tubule tumors (RTTs), with a distinctive morphological phenotype, were present in three Sprague-Dawley rats, 1 male and 2 females, out a total of 120 animals of each sex from untreated and placebo control groups in a 2-year carcinogenicity study. One female had one carcinoma, adenoma and hyperplasia, and the other female had five adenomas and many hyperplastic lesions; the male case had one carcinoma. From these cases, a biological continuum of hyperplasia, adenoma and carci...

  18. Developmental Neurotoxicity Study of Dietary Bisphenol A in Sprague-Dawley Rats

    OpenAIRE

    Stump, Donald G.; Beck, Melissa J.; Radovsky, Ann; Garman, Robert H.; Freshwater, Lester L.; Sheets, Larry P.; Marty, M. Sue; Waechter, John M.; Dimond, Stephen S.; Van Miller, John P.; Shiotsuka, Ronald N.; Beyer, Dieter; Chappelle, Anne H.; Hentges, Steven G.

    2010-01-01

    This study was conducted to determine the potential of bisphenol A (BPA) to induce functional and/or morphological effects to the nervous system of F1 offspring from dietary exposure during gestation and lactation according to the Organization for Economic Cooperation and Development and U.S. Environmental Protection Agency guidelines for the study of developmental neurotoxicity. BPA was offered to female Sprague-Dawley Crl:CD (SD) rats (24 per dose group) and their litters at dietary concent...

  19. Neurolaena lobata L. promotes wound healing in Sprague Dawley rats.

    Science.gov (United States)

    Nayak, Bijoor Shivananda; Ramlogan, Surrin; Chalapathi Rao, Av; Maharaj, Sandeep

    2014-07-01

    The leaves of the Neurolaena lobata (Asteraceae) plant are used to control diabetes and heal wounds and infections. The ethanolic extract of N. lobata leaf was evaluated for its ability to heal inflicted wounds in rats using the excision wound model. Animals were divided into three groups of six each. Test group animals were treated topically with an ethanolic extract of N. lobata (1:1 with petroleum jelly, 100 mg/kg/day). Standard and control group animals were treated with mupirocin and petroleum jelly, respectively. Treatment was given for 13 days and the wound area was measured on alternate days. Parameters of healing assessed were the rate of wound contraction, period of epithelialization and hydroxyproline content. Antimicrobial activity of the extract was observed against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. Phytochemical analysis of the extract showed the presence of saponins, tannins, alkaloids and flavanoids. Extract-treated animals exhibited 87% reduction in the wound area over 13 days when compared with the control (78%) and standard (83%) groups (P lobata as a pharmacotherapy for wound healing.

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

    Science.gov (United States)

    2014-05-10

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

  1. The Effect of 2.45 GHz Microwave Radiation on Brain Cell Apoptosis in Sprague Dawley Rats

    International Nuclear Information System (INIS)

    Wan Saffiey Wan Abdullah; Rozaimah Abdul Rahim; Zulkifli Yusof

    2016-01-01

    Microwave radiation is a part of non-ionizing electromagnetic radiations present in the environment and is now being perceived as health risks. The study was performed to investigate the effect of 2.45 GHz microwave radiation on brain cell apoptosis in Sprague Dawley rat. In the research done, 32 Sprague Dawley rat were used and divided into four groups; control group, G1 (1 month exposure), G2 (2 months exposure) and G3 (3 months exposure). The presence of apoptotic activity in control group was compared molecularly with exposed group through DNA ladder test. Each exposed group were irradiated in GTEM cell at frequency of 2.45 GHz located at RF/ MW laboratory. There was presence of necrotic instead of apoptotic activity in brain cell and increase in weight of Sprague Dawley rat. Therefore the effect of 2.45GHz microwave radiation shown no presence of apoptosis and increase in weight of Sprague Dawley rat. (author)

  2. Fluoxetine augments ventilatory CO2 sensitivity in Brown Norway but not Sprague Dawley rats

    OpenAIRE

    Hodges, Matthew R.; Echert, Ashley E.; Puissant, Madeleine M.; Mouradian, Gary C.

    2013-01-01

    The Brown Norway (BN; BN/NHsdMcwi) rat exhibits a deficit in ventilatory CO2 sensitivity and a modest serotonin (5-HT) deficiency. Here, we tested the hypothesis that the selective serotonin reuptake inhibitor fluoxetine would augment CO2 sensitivity in BN but not Sprague Dawley (SD) rats. Ventilation during room air or 7 % CO2 exposure was measured before, during and after 3 weeks of daily injections of saline or fluoxetine (10 mg/kg/day) in adult male BN and SD rats. Fluoxetine had minimal ...

  3. Characterization of dynamic changes in vascular reactivity following treatment with carmustine in Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Rawson, C.L.

    1985-01-01

    Carmustine, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), is a highly effective anti-cancer drug and bone marrow suppressant agent in humans and animals. Pilot studies demonstrated that BCNU induced a time- and dose-dependent supersensitivity to norepinephrine (NE) in rat caudal arteries after a single dose. The studies presented in this thesis were performed to determine the mechanism for this supersensitivity. Male Sprague-Dawley rats were administered a single dose of BCNU (25 mg/kg, i.p.) on day 0. On day 7 a proximal section of caudal artery was doubly cannulated and perfused intraluminally with Krebs bicarbonate physiological buffer. These studies demonstrated that the supersensitivity induced by BCNU treatment was pre-junctional. Denervation of caudal arteries with 6-hydroxydopamine led to a significant decrease in the EC 50 for NE in caudal arteries from control rats but not BCNU treated rats. The EC 50 for NE in control-denervated arterial segments was not statistically different from BCNU-denervated or BCNU-nondenervated segments. Metabolism of [ 3 H] NE to its 5 primary metabolites, as determined by thin layer chromatography, and uptake of [ 3 H] NE were significantly lower in caudal arteries taken from BCNU treated rats. These data demonstrate that a pre-junctional mechanism was responsible for vascular supersensitivity to NE after BCNU treatment in caudal arteries from Sprague-Dawley rats

  4. Assessment of female reproductive endpoints in Sprague-Dawley rats developmentally exposed to Diuron: potential ovary toxicity.

    Science.gov (United States)

    Grassi, Tony Fernando; Guerra, Marina Trevisan; Perobelli, Juliana Elaine; de Toledo, Fabíola Choqueta; da Silva, Denise Salioni; De Grava Kempinas, Wilma; Barbisan, Luís Fernando

    2011-10-01

    Diuron is widely used in agriculture but its deleterious effects on the reproductive system and mammary gland are still poorly understood. This study evaluated whether early-life-stage exposure to Diuron alters puberty onset or susceptibility to mammary carcinogenesis in female Sprague-Dawley rats. Pregnant rats received basal diet or diet containing Diuron at 500, 750, and 1,250 ppm, from gestational day 12 to the end of lactation (postnatal day 21 [PND21]). After weaning, female offspring continued receiving basal diet or diet containing Diuron until PND 51. At PND 51, female Sprague-Dawley offspring received a single dose of 50 mg/kg b.w. of 7,12-dimethylbenz(a)anthracene (DMBA) for initiation of mammary carcinogenesis. The animals were sacrificed on PND 51, 75, and 226 to 233 (week 25) for mammary gland morphology, reproductive organs and tumor analysis, respectively. There were no significant differences among groups on vaginal opening, estrous cycle, mammary morphology, or carcinogenesis. However, reductions in ovary weight and corpora lutea were observed at PND 75 in the group treated with Diuron at 1,250 ppm. The findings suggesting that Diuron exposure (1,250 ppm) may have been potentially toxic to the ovaries. © 2011 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    1993-01-01

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

  6. [Construction and functional identification of eukaryotic expression vector carrying Sprague-Dawley rat MSX-2 gene].

    Science.gov (United States)

    Yang, Xian-Xian; Zhang, Mei; Yan, Zhao-Wen; Zhang, Ru-Hong; Mu, Xiong-Zheng

    2008-01-01

    To construct a high effective eukaryotic expressing plasmid PcDNA 3.1-MSX-2 encoding Sprague-Dawley rat MSX-2 gene for the further study of MSX-2 gene function. The full length SD rat MSX-2 gene was amplified by PCR, and the full length DNA was inserted in the PMD1 8-T vector. It was isolated by restriction enzyme digest with BamHI and Xhol, then ligated into the cloning site of the PcDNA3.1 expression plasmid. The positive recombinant was identified by PCR analysis, restriction endonudease analysis and sequence analysis. Expression of RNA and protein was detected by RT-PCR and Western blot analysis in PcDNA3.1-MSX-2 transfected HEK293 cells. Sequence analysis and restriction endonudease analysis of PcDNA3.1-MSX-2 demonstrated that the position and size of MSX-2 cDNA insertion were consistent with the design. RT-PCR and Western blot analysis showed specific expression of mRNA and protein of MSX-2 in the transfected HEK293 cells. The high effective eukaryotic expression plasmid PcDNA3.1-MSX-2 encoding Sprague-Dawley Rat MSX-2 gene which is related to craniofacial development can be successfully reconstructed. It may serve as the basis for the further study of MSX-2 gene function.

  7. Lipofundin 20% induces hyperlipidemia and oxidative stress in male Sprague Dawley rats

    Directory of Open Access Journals (Sweden)

    L DelgadoRoche

    2012-06-01

    Full Text Available Lipofundin is a lipid emulsion used in parenteral nutrition. One of adverse effects reported for this kind of pharmaceutical products is the capacity to induce oxidative stress, which is an important contributor of many diseases, such as cardiovascular diseases. The aim of the present work was to evaluate the effects of Lipofundin administration on lipid profile and serum redox biomarkers, in order to determine if both events are responsible for the undesirable effects of this lipid emulsion. Male Sprague Dawley rats were intravenously administered with 2 mL/kg of Lipofundin 20% daily, for 8 days. Then, serum lipid profile and redox biomarkers were spectrophotometrically determined. A significant increase (p<0,05 of serum lipids and biomolecules damages was observed at the end of the experiment, while a reduction of antioxidant capacity was also detected in treated rats compared with controls. Our data demonstrated that Lipofundin 20% induces hyperlipidemia, which promotes an oxidative stress state in Sprague Dawley rats. [Vet. World 2012; 5(3.000: 133-137

  8. Acute and subchronic toxicity studies of methanol extract of Polygonum minus leaves in Sprague Dawley rats.

    Science.gov (United States)

    Christapher, Parayil Varghese; Parasuraman, Subramani; Asmawi, Mohd Zaini; Murugaiyah, Vikneswaran

    2017-06-01

    Medicinal plant preparations may contain high levels of toxic chemical constituents to potentially cause serious harm to animals and/or humans. Thus, toxicity studies are important to assess the toxic effects of plant derived products. Polygonum minus is used traditionally for different ailments in Southeast Asia. This study was conducted to establish the acute and subchronic toxicity profile of the methanol extract of P. minus leaves. The acute toxicity study showed that the methanol extract of P. minus is safe even at the highest dose tested of 2000 mg/kg in female Sprague Dawley rats. There were no behavioural or physiological changes and gross pathological abnormalities observed. The subchronic toxicity study of methanol extract of P. minus at 250, 500, 1000 and 2000 mg/kg were conducted in both sexes of Sprague Dawley rats. There were no changes observed in the extract treated animal's body weight, food and water intake, motor coordination, behaviour and mental alertness. The values of haematological and biochemical parameters were not different between the treated and control animals. The relative organ weights of extract-treated animals did not differ with that of control animals. Based on the present findings, the methanol extract of P. minus leaves could be considered safe up to the dose of 2000 mg/kg. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Spontaneous renal tumors suspected of being familial in sprague-dawley rats.

    Science.gov (United States)

    Kudo, Kayoko; Hoshiya, Toru; Nakazawa, Tomomi; Saito, Tsubasa; Shimoyama, Natsumi; Suzuki, Isamu; Tamura, Kazutoshi; Seely, John Curtis

    2012-12-01

    Spontaneous renal tubule tumors (RTTs), with a distinctive morphological phenotype, were present in three Sprague-Dawley rats, 1 male and 2 females, out a total of 120 animals of each sex from untreated and placebo control groups in a 2-year carcinogenicity study. One female had one carcinoma, adenoma and hyperplasia, and the other female had five adenomas and many hyperplastic lesions; the male case had one carcinoma. From these cases, a biological continuum of hyperplasia, adenoma and carcinoma could be recognized. The tumors were present in the renal cortex and appeared as solid lobulated growths with occasional central necrosis. The lobules were divided by a small amount of fibrovascular tissue. Occasionally the larger tumors contained a cystic area. Tumor cells appeared distinctive and exhibited variable amounts of eosinophilic/amphophilic and vacuolated cytoplasm. Nuclei were round to oval with a prominent nucleolus. Mitotic figures were uncommon, and no distant metastasis was noted. The tumors were seen as multiple and bilateral lesions in two animals and had no apparent relationship to chronic progressive nephropathy (CPN). Foci of tubule hyperplasia were also noted to contain the same type of cellular morphology. The morphological and biological features of these 3 cases resembled the amphophilic-vacuolar (AV) variant of RTT that has been posited to be of familial origin. This is a report of spontaneous familial renal tumors in Sprague-Dawley rats from Japan.

  10. 90 days bioassay in sprague-dawley rats exposed to 20KHz magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung-Ho [College of Veterinary Medicine, Chonnam National Univ. Kwangju (Korea, Republic of); Song, Ji-Eun; Lee, Yun-Sil [Korea Cancer Center Hospital, Seoul (Korea, Republic of); Pack, Jeong-Ki [ETRI, Daejon (Korea, Republic of); Yoo, Done-SIk [College of Engineering, Daejon (Korea, Republic of)

    2002-07-01

    Sprague Dawley rats (20 rats/group [10 males, 10 females] in sham and magnetic field exposed groups) were exposed in carrousel irradiator to an 20 KHz magnetic field for 8 hrs/day, 5 days/week, for 90 days. Urine analysis (pH, SG, protein, ketone body, RBC, WBC, glucose, bilirubin, and urobilinogen), blood analysis (WBC, RBC, HGB; henoglubin concentration, HCT; hematocrit, MCV; mean corpuscular volume, MCH; mean corpuscular hemoglobin, MCHC; mean corpuscular hemoglobin concentration, and PLT; platelet or thrombocyte count), blood biochemistry (total protein, blood urea nitrogen, creatinine, glucose, total bilirubin, total cholesterol, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase), histopathological analysis for organs such as liver, kidney, testis, ovary, spleen, brain, heart, and lung were performed. When compared to the sham control rats, there were no significant differences in above analysis of magnetic field exposed rats. From the results, there were no significant differences between control and exposed fetus.

  11. Anticancer Potential of Nutraceutical Formulations in MNU-induced Mammary Cancer in Sprague Dawley Rats.

    Science.gov (United States)

    Pitchaiah, Gummalla; Akula, Annapurna; Chandi, Vishala

    2017-01-01

    Nutraceuticals help in combating some of the major health problems of the century including cancer, and 'nutraceutical formulations' have led to the new era of medicine and health. To develop different nutraceutical formulations and to assess the anticancer potential of nutraceutical formulations in N-methyl-N-nitrosourea (MNU)-induced mammary cancer in Sprague Dawley rats. Different nutraceutical formulations were prepared using fine powders of amla, apple, garlic, onion, papaya, turmeric, and wheat grass with and without cow urine distillate. Total phenolic content, acute oral toxicity, and microbial load of nutraceutical formulations were assessed. The anticancer potential of nutraceutical formulations was evaluated against MNU-induced mammary cancer in female Sprague Dawley rats. Improvement in total phenolic content was significant ( P safe to use in animals. Microbial load was within the limits. Significant longer tumor-free days ( P apple, garlic, onion, papaya, turmeric, and wheat grass with and without cow urine distillate. Total phenolic content, acute oral toxicity, and microbial load of nutraceutical formulations were assessed. The anticancer potential of nutraceutical formulations was evaluated against MNU-induced mammary cancer in female Sprague Dawley rats. Improvement in total phenolic content was observed after self-fortification process. Toxicity studies showed that the nutraceutical formulations were safe to use in animals. Microbial load was within the limits. Longer tumor-free days, lower tumor incidence, lower tumor multiplicity and tumor burden were observed for nutraceutical formulation-treated groups. This suggests that combination of whole food-based nutraceuticals acted synergistically in the prevention of mammary cancer. Further, the process of fortification enhanced the anticancer potential of nutraceutical formulations. Abbreviations used: HMNU: N-methyl-N-nitrosourea, CAM: Complementary and Alternative Medicine, NF: Nutraceutical

  12. Serum Acetyl Cholinesterase as a Biomarker of Arsenic Induced Neurotoxicity in Sprague-Dawley Rats

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    Paul B. Tchounwou

    2005-04-01

    Full Text Available Arsenic is an environmental toxicant, and one of the major mechanisms by which it exerts its toxic effect is through an impairment of cellular respiration by inhibition of various mitochondrial enzymes, and the uncoupling of oxidative phosphorylation. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Recent studies have pointed out that arsenic toxicity is associated with the formation of reactive oxygen species, which may cause severe injury/damage to the nervous system. The main objective of this study was to conduct biochemical analysis to determine the effect of arsenic trioxide on the activity of acetyl cholinesterase; a critical important nervous system enzyme that hydrolyzes the neurotransmitter acetylcholine. Four groups of six male rats each weighing an average 60 + 2 g were used in this study. Arsenic trioxide was intraperitoneally administered to the rats at the doses of 5, 10, 15, 20mg/kg body weight (BW, one dose per 24 hour given for five days. A control group was also made of 6 animals injected with distilled water without chemical. Following anaesthesia, blood specimens were immediately collected using heparinized syringes, and acetyl cholinesterase detection and quantification were performed in serum samples by spectrophotometry. Arsenic trioxide exposure significantly decreased the activity of cholinesterase in the Sprague-Dawley rats. Acetyl cholinesterase activities of 6895 + 822, 5697 + 468, 5069 + 624, 4054 + 980, and 3158 + 648 U/L were recorded for 0, 5, 10, 15, and 20 mg/kg, respectively; indicating a gradual decrease in acetyl cholinesterase activity with increasing doses of arsenic. These findings indicate that acetyl

  13. Oral and intravenous pharmacokinetics of taurine in sprague-dawley rats

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Bjerg, Maria; Ulaganathan, Nithiya

    2017-01-01

    Taurine is involved in various physiological processes, and one of the most abundant amino acids in human. The aim was to investigate the mechanism for intestinal absorption of taurine in vivo using also in vitro mechanistic studies. Taurine absorption was measured in male Sprague-Dawley rats at 10...... (BCH) (200 mg/kg). BCH is not an inhibitor of PAT1 or the taurine transporter, TauT, hence it was included as a negative control. In vitro studies investigating the transport mechanism of taurine were conducted in human intestinal Caco-2 cells. The pharmacokinetic investigations showed that intestinal...... taurine absorption was not saturable at the investigated doses, but that the time (tmax) to reach the maximal plasma concentration (Cmax) increased with dose. Furthermore, Sar and Pro, but not BCH, decreased taurine Cmax. In vitro it was clearly shown that PAT1 mediated the cellular uptake of taurine...

  14. Distribution of PDE8A in the nervous system of the Sprague-Dawley rat

    DEFF Research Database (Denmark)

    Kruse, Lars Schack; Møller, Morten; Kruuse, Christina

    2011-01-01

    in the brain of adult male Sprague-Dawley rats and in the trigeminal ganglion. PDE8A was confined to neuronal perikaryal cytoplasm and to processes extending from those perikarya. The neurons exhibiting PDE8A-immunoreactivity were widely distributed in the forebrain, brain stem, and cerebellum. Strongly...... immunoreactive neurons were located in the olfactory bulb, the septal area, zona incerta, and reticular nucleus of the thalamus. Less immunoreactivity was seen in the hippocampus and cerebral cortex. Intense staining was detected in both the substantia nigra and the sensory trigeminal nucleus. In cerebellum PDE8....... The localization of the cAMP degrading PDE8A may indicate a role for PDE8A in cAMP signaling related to pain transmission, motor function, cognition and olfaction....

  15. Sex differences in MDMA-induced toxicity in Sprague-Dawley rats

    Science.gov (United States)

    Asl, Sara Soleimani; Mehdizadeh, Mehdi; Shahraki, Soudabeh Hamedi; Artimani, Tayebeh; Joghataei, Mohammad Taghi

    2015-01-01

    Summary Recent evidence demonstrates that female subjects show exaggerated responses to 3,4-methylenedioxymethamphetamine (MDMA) compared with males. The aim of our study was to evaluate sex differences and the role of endogenous gonadal hormones on the effects of MDMA. Fifty-six intact and gonadectomized male and female Sprague-Dawley rats were randomly assigned to either MDMA (5 mg/kg) or saline treatment. Learning and memory were assessed using the Morris water maze (MWM). The expression of Bax and Bcl-2 in the hippocampus was detected by Western blotting. Behavioral analysis showed that MDMA led to memory impairment in both male and female rats. The female rats showed more sensitivity to impairment than the males, as assessed using all the memory parameters in the MWM. Ovariectomy attenuated the MDMA-induced memory impairment. By contrast, orchiectomized rats showed more impairment than MDMA-treated intact male rats. Bcl-2 and Bax were down-regulated and up-regulated in MDMA-treated male and female rats, respectively. MDMA treatment in the orchiectomized rats led to up-regulation of Bax and down-regulation of Bcl-2. Ovariectomy attenuated the MDMA-induced up-regulation of Bax and caused more expression of Bcl-2 compared with what was observed in the MDMA-treated intact female rats. In summary, female rats showed exaggerated responses to the effects of MDMA and this may be explained by endogenous gonadal hormones. PMID:26415786

  16. Fluoxetine augments ventilatory CO2 sensitivity in Brown Norway but not Sprague Dawley rats.

    Science.gov (United States)

    Hodges, Matthew R; Echert, Ashley E; Puissant, Madeleine M; Mouradian, Gary C

    2013-04-01

    The Brown Norway (BN; BN/NHsdMcwi) rat exhibits a deficit in ventilatory CO2 sensitivity and a modest serotonin (5-HT) deficiency. Here, we tested the hypothesis that the selective serotonin reuptake inhibitor fluoxetine would augment CO2 sensitivity in BN but not Sprague Dawley (SD) rats. Ventilation during room air or 7% CO2 exposure was measured before, during and after 3 weeks of daily injections of saline or fluoxetine (10mg/(kgday)) in adult male BN and SD rats. Fluoxetine had minimal effects on room air breathing in BN and SD rats (p>0.05), although tidal volume (VT) was reduced in BN rats (peffects of fluoxetine on CO2 sensitivity in SD rats, but fluoxetine increased minute ventilation, breathing frequency and VT during hypercapnia in BN rats (pCO2 response was reversible upon withdrawal of fluoxetine. Brain levels of biogenic amines were largely unaffected, but 5-HIAA and the ratio of 5-HIAA/5-HT were reduced (peffective 5-HT reuptake inhibition. Thus, fluoxetine increases ventilatory CO2 sensitivity in BN but not SD rats, further suggesting altered 5-HT system function may contribute to the inherently low CO2 sensitivity in the BN rat. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Effects of prolonged agmatine treatment in aged male Sprague-Dawley rats.

    Science.gov (United States)

    Rushaidhi, M; Zhang, H; Liu, P

    2013-03-27

    Increasing evidence suggests that altered arginine metabolism contributes to cognitive decline during ageing. Agmatine, decarboxylated arginine, has a variety of pharmacological effects, including the modulation of behavioural function. A recent study demonstrated the beneficial effects of short-term agmatine treatment in aged rats. The present study investigated how intraperitoneal administration of agmatine (40mg/kg, once daily) over 4-6weeks affected behavioural function and neurochemistry in aged Sprague-Dawley rats. Aged rats treated with saline displayed significantly reduced exploratory activity in the open field, impaired spatial learning and memory in the water maze and object recognition memory relative to young rats. Prolonged agmatine treatment improved animals' performance in the reversal test of the water maze and object recognition memory test, and significantly suppressed age-related elevation in nitric oxide synthase activity in the dentate gyrus of the hippocampus and prefrontal cortex. However, this prolonged supplementation was unable to improve exploratory activity and spatial reference learning and memory in aged rats. These findings further demonstrate that exogenous agmatine selectively improves behavioural function in aged rats. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Thymoquinone ameliorates lead-induced brain damage in Sprague Dawley rats.

    Science.gov (United States)

    Radad, Khaled; Hassanein, Khaled; Al-Shraim, Mubarak; Moldzio, Rudolf; Rausch, Wolf-Dieter

    2014-01-01

    The present study aims to investigate the protective effects of thymoquinone, the major active ingredient of Nigella sativa seeds, against lead-induced brain damage in Sprague-Dawley rats. In which, 40 rats were divided into four groups (10 rats each). The first group served as control. The second, third and fourth groups received lead acetate, lead acetate and thymoquinone, and thymoquinone only, respectively, for one month. Lead acetate was given in drinking water at a concentration of 0.5 g/l (500 ppm). Thymoquinone was given daily at a dose of 20mg/kg b.w. in corn oil by gastric tube. Control and thymoquinone-treated rats showed normal brain histology. Treatment of rats with lead acetate was shown to produce degeneration of endothelial lining of brain blood vessels with peri-vascular cuffing of mononuclear cells consistent to lymphocytes, congestion of choroid plexus blood vessels, ischemic brain infarction, chromatolysis and neuronal degeneration, microglial reaction and neuronophagia, degeneration of hippocampal and cerebellar neurons, and axonal demyelination. On the other hand, co-administration of thymoquinone with lead acetate markedly decreased the incidence of lead acetate-induced pathological lesions. Thus the current study shed some light on the beneficial effects of thymoquinone against neurotoxic effects of lead in rats. Copyright © 2013 Elsevier GmbH. All rights reserved.

  19. Toxicity Evaluation of Graphene Oxide in Kidneys of Sprague-Dawley Rats

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    Anita K. Patlolla

    2016-03-01

    Full Text Available Recently, graphene and graphene-related materials have attracted a great deal of attention due their unique physical, chemical, and biocompatibility properties and to their applications in biotechnology and medicine. However, the reports on the potential toxicity of graphene oxide (GO in biological systems are very few. The present study investigated the response of kidneys in male Sprague-Dawley rats following exposure to 0, 10, 20 and 40 mg/Kg GO for five days. The results showed that administration of GOs significantly increased the activities of superoxide dismutase, catalase and glutathione peroxidase in a dose-dependent manner in the kidneys compared with control group. Serum creatinine and blood urea nitrogen levels were also significantly increased in rats intoxicated with GO compared with the control group. There was a significant elevation in the levels of hydrogen peroxide and lipid hydro peroxide in GOs-treated rats compared to control animals. Histopathological evaluation showed significant morphological alterations of kidneys in GO-treated rats compared to controls. Taken together, the results of this study demonstrate that GO is nephrotoxic and its toxicity may be mediated through oxidative stress. In the present work, however, we only provided preliminary information on toxicity of GO in rats; further experimental verification and mechanistic elucidation are required before GO widely used for biomedical applications.

  20. Phage FR38 Treatment on Sprague Dawley Rat Inferred from Blood Parameters and Organ Systems

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    DEWI SARTIKA

    2012-09-01

    Full Text Available The ability of phage FR38 to lysis indigenous Salmonella P38 from feces of diarrheal patient has been studied. However, effects of phage FR38 on organ system were not revealed as yet. This study was conducted to observe the effect of phage FR38 on blood chemistry, kidney functions, and liver functions. Twelve Sprague-Dawley rats were used as a model for this study that were divided into two groups; (i control and (ii treated group with phage FR38. For treated phage group, each rat was administered by 5 ml/kg bw of 1.59•107 pfu/ml of phage intragastric. The blood parameters were analysed on day 16. The results revealed that body and organs weight, erythrocyte, hematocrit, hemoglobin, leukocyte, total protein, creatinine, SGOT, and SGPT of phage treatment rats were not significantly different with the control rats on day 16 (P > 0.05. Therefore, this study showed was no effect of phage FR38 on body weight, blood chemistry, kidney and liver functions of the rat (P > 0.05.

  1. Phage FR38 Treatment on Sprague Dawley Rat Inferred from Blood Parameters and Organ Systems

    Directory of Open Access Journals (Sweden)

    DEWI SARTIKA

    2012-09-01

    Full Text Available The ability of phage FR38 to lysis indigenous Salmonella P38 from feces of diarrheal patient has been studied. However, effects of phage FR38 on organ system were not revealed as yet. This study was conducted to observe the effect of phage FR38 on blood chemistry, kidney functions, and liver functions. Twelve Sprague-Dawley rats were used as a model for this study that were divided into two groups; (i control and (ii treated group with phage FR38. For treated phage group, each rat was administered by 5 ml/kg bw of 1.59-107 pfu/ml of phage intragastric. The blood parameters were analysed on day 16. The results revealed that body and organs weight, erythrocyte, hematocrit, hemoglobin, leukocyte, total protein, creatinine, SGOT, and SGPT of phage treatment rats were not significantly different with the control rats on day 16 (P > 0.05. Therefore, this study showed was no effect of phage FR38 on body weight, blood chemistry, kidney and liver functions of the rat (P > 0.05.

  2. Variation in nocturnality and circadian activity rhythms between photoresponsive F344 and nonphotoresponsive Sprague Dawley rats

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    Johnson Cynthia E

    2008-09-01

    Full Text Available Abstract Background Variation in circadian rhythms and nocturnality may, hypothetically, be related to or independent of genetic variation in photoperiodic mediation of seasonal changes in physiology and behavior. We hypothesized that strain variation in photoperiodism between photoperiodic F344 rats and nonphotoperiodic Harlan Sprague Dawley (HSD rats might be caused by underlying variation in clock function. We predicted that HSD rats would have more activity during the day or subjective day, longer free-running rhythms, poor entrainment to short day length, and shorter duration of activity, traits that have been associated with nonphotoperiodism in other laboratory rodent species, relative to F344 rats. An alternative hypothesis, that differences are due to variation in melatonin secretion or responses to melatonin, predicts either no such differences or inconsistent combinations of differences. Methods We tested these predictions by examining activity rhythms of young male F344 and HSD rats given access to running wheels in constant dark (DD, short day length (L8:D16; SD, and long day length (L16:D8; LD. We compared nocturnality (the proportion of activity during night or subjective night, duration of activity (alpha, activity onset and offset, phase angle of entrainment, and free running rhythms (tau of F344 and HSD rats. Results HSD rats had significantly greater activity during the day, were sometimes arrhythmic in DD, and had significantly longer tau than F344 rats, consistent with predictions. However, HSD rats had significantly longer alpha than F344 rats and both strains entrained to SD, inconsistent with predictions. Conclusion The ability of HSD rats to entrain to SD, combined with longer alpha than F344 rats, suggests that the circadian system of HSD rats responds correctly to SD. These data offer best support for the alternative hypothesis, that differences in photoresponsiveness between F344 and HSD rats are caused by non

  3. Effect of melatonin supplementation on pregnancy outcome in Wistar-Kyoto and Sprague-Dawley rats.

    Science.gov (United States)

    Singh, Harbindar Jeet; Saleh, Hisham Ibrahim; Gupalo, Sergey; Omar, Effat

    2013-04-25

    Although melatonin supplementation is known to influence numerous physiological functions, little is however known of its effects on pregnancy outcome. This study investigated the effects of melatonin supplementation on pregnancy outcome in Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats aged 12-13 weeks. Upon confirmation of proestrus, each female rat was housed overnight with a male of the same strain. On the next morning, following confirmation of mating (vaginal smear), WKY female rats were isolated into individual metabolic cages and given 0, 25, 50 or 100 mg/kg per day of melatonin in drinking water from day 1 of pregnancy to day 21 postpartum. SD females were given 0 or 100 mg/kg per day of melatonin. Maternal weight, duration of pregnancy, litter size, birth weight and body weight of pups up to day 42, and pup mortality were recorded. Data were analyzed using ANOVA for repeated measures. Compared to controls, maternal weight gain during pregnancy was significantly lower in melatonin-supplemented dams (P melatonin-supplemented dams (P melatonin (P melatonin was significantly lower than controls (P melatonin respectively, and all pup deaths occurred after day 21 of weaning. The results suggest that melatonin supplementation during antenatal and postpartum period appears to adversely affect litter size, pup growth and mortality in WKY and SD rats. The precise mechanism causing the death is not clear.

  4. Status Epilepticus due to Intraperitoneal Injection of Vehicle Containing Propylene Glycol in Sprague Dawley Rats

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    Evon S. Ereifej

    2017-01-01

    Full Text Available Published reports of status epilepticus due to intraperitoneal injection containing propylene glycol in rats are sparse. In fact, there are no reports specifying a maximum safe dose of propylene glycol through intraperitoneal administration. We report here a case of unexpected seizures in Sprague Dawley rats after receiving an intraperitoneal injection containing propylene glycol. Nine-week-old, 225–250 gram male rats were reported to experience tremor progressing to seizures within minutes after given injections of resveratrol (30 mg/kg dissolved in a 40 : 60 propylene glycol/corn oil vehicle solution by direct intraperitoneal (IP slow bolus injection or via a preplaced intraperitoneal catheter. The World Health Organization suggests a maximum dose of 25 mg/kg/day of propylene glycol taken orally and no more than 25 mg/dL in blood serum, whereas the animals used in our study got a calculated maximum 0.52 g/kg (25 times lower dose. Blood tests from the seizing rat support a diagnosis of hemolysis and lactic acidosis which may have led to the seizures, all of which appeared to be a consequence of the propylene glycol administration. These findings are consistent with oral and intravenous administration of propylene glycol toxicity as previously reported in other species, including humans. To our knowledge, this report represents the first published case of status epilepticus due to an IP injection containing propylene glycol.

  5. Characterization of Diabetic Neuropathy in the Zucker Diabetic Sprague-Dawley Rat: A New Animal Model for Type 2 Diabetes

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    Eric P. Davidson

    2014-01-01

    Full Text Available Recently a new rat model for type 2 diabetes the Zucker diabetic Sprague-Dawley (ZDSD/Pco was created. In this study we sought to characterize the development of diabetic neuropathy in ZDSD rats using age-matched Sprague-Dawley rats as a control. Rats were examined at 34 weeks of age 12 weeks after the onset of hyperglycemia in ZDSD rats. At this time ZDSD rats were severely insulin resistant with slowing of both motor and sensory nerve conduction velocities. ZDSD rats also had fatty livers, elevated serum free fatty acids, triglycerides, and cholesterol, and elevated sciatic nerve nitrotyrosine levels. The corneas of ZDSD rats exhibited a decrease in subbasal epithelial corneal nerves and sensitivity. ZDSD rats were hypoalgesic but intraepidermal nerve fibers in the skin of the hindpaw were normal compared to Sprague-Dawley rats. However, the number of Langerhans cells was decreased. Vascular reactivity of epineurial arterioles, blood vessels that provide circulation to the sciatic nerve, to acetylcholine and calcitonin gene-related peptide was impaired in ZDSD rats. These data indicate that ZDSD rats develop many of the neural complications associated with type 2 diabetes and are a good animal model for preclinical investigations of drug development for diabetic neuropathy.

  6. Effect of thiazolidinedione treatment on resistin levels in insulin resistant sprague dawley rats

    International Nuclear Information System (INIS)

    Yousaf, I.; Hameed, W.; Rajput, T.A.

    2015-01-01

    Insulin resistance is manifested by decreased effect of fixed quantity of insulin on glucose metabolism leading to type 2 diabetes mellitus. Visceral obesity has been positively correlated with insulin resistance but its mechanism is not fully defined. Insulin resistance may be the consequence of adipocytokines including visfatin and resistin. This study was designed to see the effect of thiazolidinediones on levels of resistin in insulin resistant rats. Methods: Ninety Sprague Dawley rats were randomly divided into three groups. Group I served as control. Rats in Group II and III were made insulin resistant diabetics. Group III was treated with rosiglitazone after development of diabetes. Plasma glucose, serum triglycerides, HDL, TG:HDL ratio and serum resistin levels were analysed. Results: Body weight and plasma glucose were significantly increased (p<0.05) along with TG:HDL ratio (p<0.05) in group II and group III at the end of 4th week. Serum resistin levels also increased significantly (p<0.05) in group II and III at the end of 4th week. Treatment of group III with rosiglitazone led to improvement in insulin resistance with decrease in serum resistin levels (p<0.05). Conclusion: Increased serum resistin level indicates insulin resistance and impending hyperglycaemia. Thiazolidinediones augment sensitivity of insulin to restore normoglycaemia by decreasing serum resistin level. (author)

  7. Oral toxicity evaluation of kefir-isolated Lactobacillus kefiranofaciens M1 in Sprague-Dawley rats.

    Science.gov (United States)

    Owaga, E E; Chen, M J; Chen, W Y; Chen, C W; Hsieh, R H

    2014-08-01

    Lactobacilli kefiranofaciens M1 has shown novel immunomodulation and anti-allergy probiotic attributes in cell and animal models. An acute oral toxicity assessment of L. kefiranofaciens M1 was evaluated in Sprague-Dawley rats. The rats were randomly assigned to four groups (12 rats/sex/group): the low dose group was orally gavaged with L. kefiranofaciens M1 at 3.0×10(8)cfu/kg bw while the medium dose and high dose groups received 9.0×10(9)cfu/kg bw and 1.8×10(10)cfu/kg bw, respectively, for 28days. The control group received phosphate buffer saline. The body weights were measured weekly while blood samples were collected for haematology and serum biochemistry tests. Histopathology of the organs (heart, liver, kidney, adrenal glands, spleen, ovary, testis), and urinalysis were conducted on study termination. The body weight gain of the L. kefiranofaciens M1 and control groups were comparable during the administration period. Overall, L. kefiranofaciens M1 did not induce adverse effects on haematology, serum biochemistry, and urinalysis parameters. Gross and microscopic histopathology of the organs revealed no toxicity effect of L. kefiranofaciens M1. In conclusion, 1.8×10(10)cfu/kg bw of L. kefiranofaciens M1 was considered as the no-observed-adverse-effect-level (NOAEL), which was the highest dose tested in the present study. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Whole-body metabolism varies across the estrous cycle in Sprague-Dawley rats.

    Science.gov (United States)

    Parker, G C; McKee, M E; Bishop, C; Coscina, D V

    2001-10-01

    Food intake in rats and other mammals is lowest at estrus and highest at diestrus. While much is known about the effects of different estrous phases on energy intake, as well as some of the metabolic effects the associated hormones exert, little has been reported about changes in whole-body metabolism that accompany those phases. This study investigates how energy expenditure (EE) and respiratory quotient (RQ) vary in intact female Sprague-Dawley rats (n=12) tested mid-light cycle over 2 h on days associated with estrus vs. diestrus. Rats showed small but reliable decreases in body weight on days associated with estrus, but not diestrus. EE was significantly increased by approximately 21% on the day associated with estrus compared to diestrus. At the same time, RQ was significantly decreased by approximately 7% on the day associated with estrus, indicating a relative shift to fat over carbohydrate as the energy substrate to support energetic needs. Future investigations of ingestive processes can integrate the present findings to investigate how gender differences in feeding and metabolism contribute to regulatory behaviors.

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

    Science.gov (United States)

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

    2011-01-01

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

  10. The Effect of Alium Satium Extract on the Glomerular Diameter of STZ -induced Sprague dawley Rats

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    Susilorini Susilorini

    2013-06-01

    Full Text Available Hyperglycemia exert toxic effect in kidney.The aim of this study was to investigate the short term effect of ethanolic extract of garlic in preventing nephropathy following streptozotocin (STZ induced rats. Twenty male Sprague dawley rats were randomly divided into 4 group, all group induced induced by single dose intraperitoneal injection of 40 mg kg-1 of streptozotocin (STZ. Treatment with 3 doses ethanolic extract of garlic (0,1; 0,25; 0,5 mg kg-1 day-1 was followed for 14 days, then the left kidneys were excised and histhopathological studies were carried out using scanner 3D Hitech and Panoramic view software. Statistical analysis have been done using non parametric analysis Kruskall Wallis. The study revealed that glomerular diameter of the treatment rats was significantly different from the control group (p=0,0001. Increasing doses didn’t make difference. The ethanolic extract of garlic (Allium sativum influences the diameter glomeruli but increasing doses has no effect on the glomerular diameter.

  11. Red Palm Oil Attenuates Lead Acetate Induced Testicular Damage in Adult Male Sprague-Dawley Rats

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    A. I. Jegede

    2015-01-01

    Full Text Available To study the protective effect of Red Palm Oil (RPO on testicular damage induced by administration of lead acetate on male Sprague-Dawley rats, 28 rats divided into four groups of 7 animals each were used. They were administered orally with RPO (1 mL and 2 mL and lead acetate (i.p. 6 mg/kg body weight/day, respectively. Treatment was conducted for 8 weeks, and 24 hrs after the last treatment the rats were sacrificed using cervical dislocation. Sperms collected from epididymis were used for seminal fluid analyses; while the testes sample was used for ROS and oxidative enzyme activities assessment. Statistical analysis was carried out using GraphPad Prism 5.02 statistical analysis package. Administration of lead acetate increased generation of reactive oxygen species (ROS significantly (p<0.05 as evidenced by the elevated value of H2O2 and LPO and decreased GSH level. Also there was reduced epididymal sperm count, poor grade of sperm motility, and lower percentage of normal sperm morphology significantly. Coadministration with RPO, however, has a protective effect against lead toxicity by decreasing H2O2 production, increased GSH level, and increased sperm qualities especially. This shows that RPO has a potential to attenuate the toxic effect of lead on testicular cells preventing possible resultant male infertility.

  12. Variations in lead isotopic abundances in Sprague-Dawley rat tissues: possible reason of formation.

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    Duojian Liu

    Full Text Available It has been reported in previous research that the lead isotopic composition of blood, urine and feces samples statistically differed from the given lead sources in Sprague-Dawley (SD rats. However, the reason for this phenomenon is still unclear. An animal experiment was performed to investigate the lead isotope fractionation in diverse biological samples (i.e., lungs, liver, kidneys, bone and to explore the possible reasons. SD rats were intratracheally instilled with lead acetate at the concentrations of 0, 0.02, 0.2, and 2 mg/kg body weight. Biological samples were collected for lead isotope analysis using an inductively coupled plasma mass spectrometry (ICP-MS. Significant differences are observed in lead isotope abundances among the diverse biological samples. The lead isotope abundances ((206Pb, (207Pb and (208Pb in diverse biological samples show different degrees and directions of departure from the given lead source. The results suggest that differences in enrichment or depletion capacity for each lead isotope in the various tissues might lead to the variation in lead isotopic abundances in tissues. Moreover, a nonlinear relationship between the blood lead level and the lead isotope abundances in liver and bone is observed. When the whole-blood level is higher than 50 ng/mL, the lead isotopic compositions of biological samples tend to be the same. Thus, the data support the speculation of a fractionation functional threshold.

  13. Subchronic Toxicity Study of Standardized Methanolic Extract of Mitragyna Speciosa Korth in Sprague-Dawley Rats

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    Mohd Ulul Ilmie Ahmad Nazri

    2015-06-01

    Full Text Available Mitragyna speciosa Korth, or better known as ketum, has long been used by traditional folk around Southeast Asia to prevent fatigue from working under hot tropical weather and as a replacement of opium, which can then cause addiction. To date, no findings have been reported of the toxic effect of ketum subchronically (28 days. Hence, the aim of this study was to investigate the toxicity of subchronic effect of standardised methanolic extract of ketum (SMEMS in Sprague-Dawley rats. Rats were orally administered with 100, 200, and 500 mg/kg of SMEMS for 28 days. Body weights were recorded daily. They were terminated at day 28 to obtain data for haematology, biochemistry, and histopathology of the brain, liver, kidney, lung, heart, sciatic nerve, and spinal cord. The SMEMS affected body weight compared to control group. Biochemistry findings showed that liver and kidney were affected with the abnormal values in AST, creatinine, globulin, glucose, total protein, and urea. However, SMEMS produced toxic effect more to liver, kidney, and lung than other organs as observed histopathologically. The results suggested subchronic exposure of ketum is toxic to the physiology of the animals.

  14. In vivo mammary tumourigenesis in the Sprague-Dawley rat and microdosimetric correlates

    International Nuclear Information System (INIS)

    Dicello, J F; Christian, A; Cucinotta, F A

    2004-01-01

    Standard methods for risk assessments resulting from human exposures to mixed radiation fields in Space consisting of different particle types and energies rely upon quality factors. These are generally defined as a function of linear energy transfer (LET) and are assumed to be proportional to the risk. In this approach, it is further assumed that the risks for single exposures from each of the radiation types add linearly. Although risks of cancer from acute exposures to photon radiations have been measured in humans, quality factors for protons and ions of heavier atomic mass are generally inferred from animal and/or cellular data. Because only a small amount of data exists for such particles, this group has been examining tumourigenesis initiated by energetic protons and iron ions. In this study, 741 female Sprague-Dawley rats were irradiated or sham irradiated at approximately 60 days of age with 250 MeV protons, 1 GeV/nucleon iron ions or both protons and iron ions. The results suggest that the risk of mammary tumours in the rats sequentially irradiated with 1 GeV/nucleon 56 Fe ions and 250 MeV protons is less than additive. These data in conjunction with earlier results further suggest that risk assessments in terms of only mean LETs of the primary cosmic rays may be insufficient to accurately evaluate the relative risks of each type of particle in a radiation field of mixed radiation qualities

  15. Oral exposure to low-dose of nonylphenol impairs memory performance in Sprague-Dawley rats.

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    Kawaguchi, Shinichiro; Kuwahara, Rika; Kohara, Yumi; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

    2015-02-01

    Nonylphenol ethoxylate (NPE) is a non-ionic surfactant, that is degraded to short-chain NPE and 4-nonylphenol (NP) by bacteria in the environment. NP, one of the most common environmental endocrine disruptors, exhibits weak estrogen-like activity. In this study, we investigated whether oral administration of NP (at 0.5 and 5 mg/kg doses) affects spatial learning and memory, general activity, emotionality, and fear-motivated learning and memory in male and female Sprague-Dawley (SD) rats. SD rats of both sexes were evaluated using a battery of behavioral tests, including an appetite-motivated maze test (MAZE test) that was used to assess spatial learning and memory. In the MAZE test, the time required to reach the reward in male rats treated with 0.5 mg/kg NP group and female rats administered 5 mg/kg NP was significantly longer than that for control animals of the corresponding sex. In other behavioral tests, no significant differences were observed between the control group and either of the NP-treated groups of male rats. In female rats, inner and ambulation values for animals administered 0.5 mg/kg NP were significantly higher than those measured in control animals in open-field test, while the latency in the group treated with 5 mg/kg NP was significantly shorter compared to the control group in step-through passive avoidance test. This study indicates that oral administration of a low-dose of NP slightly impairs spatial learning and memory performance in male and female rats, and alters emotionality and fear-motivated learning and memory in female rats only.

  16. Geraniin Protects High-Fat Diet-Induced Oxidative Stress in Sprague Dawley Rats

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    Alexis Panny Y. S. Chung

    2018-03-01

    Full Text Available Geraniin, a hydrolysable polyphenol derived from Nephelium lappaceum L. fruit rind, has been shown to possess significant antioxidant activity in vitro and recently been recognized for its therapeutic potential in metabolic syndrome. This study investigated its antioxidative strength and protective effects on organs in high-fat diet (HFD-induced rodents. Rats were fed HFD for 6 weeks to induce obesity, followed by 10 and 50 mg/kg of geraniin supplementation for 4 weeks to assess its protective potential. The control groups were maintained on standard rat chows and HFD for the same period. At the 10th week, oxidative status was assessed and the pancreas, liver, heart and aorta, kidney, and brain of the Sprague Dawley rats were harvested and subjected to pathological studies. HFD rats demonstrated changes in redox balance; increased protein carbonyl content, decreased levels of superoxide dismutase, glutathione peroxidase, and glutathione reductase with a reduction in the non-enzymatic antioxidant mechanisms and total antioxidant capacity, indicating a higher oxidative stress (OS index. In addition, HFD rats demonstrated significant diet-induced changes particularly in the pancreas. Four-week oral geraniin supplementation, restored the OS observed in the HFD rats. It was able to restore OS biomarkers, serum antioxidants, and the glutathione redox balance (reduced glutathione/oxidized glutathione ratio to levels comparable with that of the control group, particularly at dosage of 50 mg geraniin. Geraniin was not toxic to the HFD rats but exhibited protection against glucotoxicity and lipotoxicity particularly in the pancreas of the obese rodents. It is suggested that geraniin has the pharmaceutical potential to be developed as a supplement to primary drugs in the treatment of obesity and its pathophysiological sequels.

  17. Pharmacokinetics of bisphenol A in neonatal and adult Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Doerge, Daniel R.; Twaddle, Nathan C.; Vanlandingham, Michelle; Fisher, Jeffrey W.

    2010-01-01

    Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure. The current study used LC/MS/MS to measure serum pharmacokinetics of aglycone (active) and conjugated (inactive) BPA in adult and neonatal Sprague-Dawley rats by oral and injection routes. Deuterated BPA was used to avoid issues of background contamination. Linear pharmacokinetics were observed in adult rats treated orally in the range of 0-200 μg/kg bw. Evidence for enterohepatic recirculation of conjugated, but not aglycone, BPA was observed in adult rats. Significant inverse relationships were observed between postnatal age and measures of internal exposures to aglycone BPA and its elimination. In neonatal rats treated orally, internal exposures to aglycone BPA were substantially lower than from subcutaneous injection. The results reinforce the critical role for first-pass Phase II metabolism of BPA in gut and liver after oral exposure that attenuates internal exposure to the aglycone form in rats of all ages. The internal exposures to aglycone BPA observed in adult and neonatal rats following a single oral dose of 100 μg/kg bw are inconsistent with effects mediated by classical estrogen receptors based on binding affinities. However, an impact on alternative estrogen signaling pathways that have higher receptor affinity cannot be excluded in neonatal rats. These findings emphasize the importance of matching aglycone BPA internal dosimetry with receptor affinities in experimental animal studies reporting toxicity.

  18. Female Sprague Dawley Rats Show Impaired Spatial Memory in the 8-Arm Radial Maze under Dim Blue and Red Light

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    Michael Pirchl

    2010-01-01

    Full Text Available Light intensity and wavelength strongly influence mood and cognition in humans and rodent animal models. The aim of the present study was to explore if dim white (7.6–17.7 lux , blue (1.3–2.3 lux, and red light (0.8–1.4 lux affect spatial memory of male and female Sprague Dawley rats in the 8-arm radial maze. Our data show that spatial memory significantly improved within 5 daily learning sessions (each 5 trials under dim white light, which was not different between male and female rats. However, dim blue and red light significantly reduced spatial learning of female rats in the 8-arm radial maze in the last training session (session 5. In conclusion, we suggest that female Sprague Dawley rats show reduced learning under blue and red light.

  19. Wheel running decreases palatable diet preference in Sprague-Dawley rats.

    Science.gov (United States)

    Moody, Laura; Liang, Joy; Choi, Pique P; Moran, Timothy H; Liang, Nu-Chu

    2015-10-15

    Physical activity has beneficial effects on not only improving some disease conditions but also by preventing the development of multiple disorders. Experiments in this study examined the effects of wheel running on intakes of chow and palatable diet e.g. high fat (HF) or high sucrose (HS) diet in male and female Sprague-Dawley rats. Experiment 1 demonstrated that acute wheel running results in robust HF or HS diet avoidance in male rats. Although female rats with running wheel access initially showed complete avoidance of the two palatable diets, the avoidance of the HS diet was transient. Experiment 2 demonstrated that male rats developed decreased HF diet preferences regardless of the order of diet and wheel running access presentation. Running associated changes in HF diet preference in females, on the other hand, depended on the testing schedule. In female rats, simultaneous presentation of the HF diet and running access resulted in transient complete HF diet avoidance whereas running experience prior to HF diet access did not affect the high preference for the HF diet. Ovariectomy in females resulted in HF diet preference patterns that were similar to those in male rats during simultaneous exposure of HF and wheel running access but similar to intact females when running occurred before HF exposure. Overall, the results demonstrated wheel running associated changes in palatable diet preferences that were in part sex dependent. Furthermore, ovarian hormones play a role in some of the sex differences. These data reveal complexity in the mechanisms underlying exercise associated changes in palatable diet preference. Published by Elsevier Inc.

  20. Probiotic Amelioration of Azotemia in 5/6th Nephrectomized Sprague-Dawley Rats

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    Natarajan Ranganathan

    2005-01-01

    Full Text Available The present study was to test the hypothesis that selected bacteria instilled into the gastrointestinal tract could help in converting nitrogenous wastes accumulated due to renal insufficiency into nontoxic compounds; thereby, ameliorating the biochemical imbalance. Herein we describe a prospective, blinded, placebo-controlled pilot study, using 5/6th nephrectomized Sprague Dawley rat as a chronic renal failure model. The study group consisted of 36 nephrectomized and 7 non-nephrectomized (control rats. After two-week nephrectomy stabilization, cohorts of six nephrectomized rats were fed casein-based diet plus one of the following regimens: (A Control, (B Placebo (casein-based diet without probiotics, (C Bacillus pasteurii, (D Sporolac®, (E Kibow cocktail, (F CHR Hansen Cocktail, and (G ECONORMTM. Subsequently, blood (retro-orbital and urine (collected for measurements of blood urea-nitrogen and creatinine respectively, body weight and bacterial counts (feces were obtained at regular intervals. The study end-points were to determine if any of the probiotic dietary supplements facilitated, (1 decreased blood concentrations of uremic toxins, (2 altered renal function, and (3 prolonged survival. After 16 weeks of treatment, regimens C and D significantly prolonged the life span of uremic rats, in addition to showing a reduction in blood urea-nitrogen levels, concluding that supplementation of probiotic formulation to uremic rats slows the progression of azotemia, which may correlate with prolonged life span of uremic rats. Derivative trials of probiotic treatment of larger animals and humans will further assess the potential role of probiotic formulations in delaying the onset and clinical severity of clinical illness at different stages of renal failure.

  1. Wheel running decreases palatable diet preference in Sprague-Dawley rats

    Science.gov (United States)

    Moody, Laura; Liang, Joy; Choi, Pique P.; Moran, Timothy H.; Liang, Nu-Chu

    2015-01-01

    Physical activity has beneficial effects on not only improving some disease conditions but also by preventing the development of multiple disorders. Experiments in this study examined the effects of wheel running on intakes of chow and palatable diet e.g. high fat (HF) or high sucrose (HS) diet in male and female Sprague Dawley rats. Experiment 1 demonstrated that acute wheel running results in robust HF or HS diet avoidance in male rats. Although female rats with running wheel access initially showed complete avoidance of the two palatable diets, the avoidance of the HS diet was transient. Experiment 2 demonstrated that male rats developed decreased HF diet preferences regardless of the order of diet and wheel running access presentation. Running associated changes in HF diet preference in females, on the other hand, depended on the testing schedule. In female rats, simultaneous presentation of the HF diet and running access resulted in transient complete HF diet avoidance whereas running experience prior to HF diet access did not affect the high preference for the HF diet. Ovariectomy in females resulted in HF diet preference patterns that were similar to those in male rats during simultaneous exposure of HF and wheel running access but similar to intact females when running occurred before HF exposure. Overall, the results demonstrated wheel running associated changes in palatable diet preferences that were in part sex dependent. Furthermore, ovarian hormones play a role in some of the sex differences. These data reveal complexity in the mechanisms underlying exercise associated changes in palatable diet preference. PMID:25791204

  2. Incidence and nature of tumors induced in Sprague-Dawley rats by gamma-irradiation

    International Nuclear Information System (INIS)

    Gross, L.; Dreyfuss, Y.; Faraggiana, T.

    1988-01-01

    In our previous studies carried out on inbred rats of the Sprague-Dawley strain, the tumor incidence was increased following irradiation (150 rads, 5 times, at weekly intervals), from 22 to 93% in females and from 5 to 59% in males. Experiments here reported suggest that 2 consecutive total-body gamma-irradiations of 150 rads each are sufficient to induce in rats the development of tumors, some malignant; 18 of 19 females (94.7%) developed tumors at an average age of 11.4 mo, and seven of the 14 males in this group (50%) developed tumors at an average age of 10.4 mo. In the second group, which received 3 consecutive gamma-irradiations, 20 of 23 females (86.9%) and 5 of 13 males (38.4%) developed tumors at average ages of 9.1 and 7.5 mo, respectively. In the third group, among rats which received 4 consecutive gamma-irradiations, 17 of 19 females (89.4%) and 4 of 12 males (33.3%) developed tumors at average ages of 9.4 and 10.5 mo, respectively. The etiology of tumors either developing spontaneously or induced by irradiation in rats remains to be clarified. Our attempts to detect virus particles by electron microscopy in such tumors or lymphomas have not been successful. As a working hypothesis, we are tempted to theorize that tumors or lymphomas developing spontaneously or induced by gamma irradiation in rats are caused by latent viral agents which are integrated into the cell genome and are cell associated, i.e., not separable from the rat tumor cells by conventional methods thus far used

  3. Evidence for diffuse central retinal edema in vivo in diabetic male Sprague Dawley rats.

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    Bruce A Berkowitz

    Full Text Available Investigations into the mechanism of diffuse retinal edema in diabetic subjects have been limited by a lack of animal models and techniques that co-localized retinal thickness and hydration in vivo. In this study we test the hypothesis that a previously reported supernormal central retinal thickness on MRI measured in experimental diabetic retinopathy in vivo represents a persistent and diffuse edema.In diabetic and age-matched control rats, and in rats experiencing dilutional hyponatremia (as a positive edema control, whole central retinal thickness, intraretinal water content and apparent diffusion coefficients (ADC, 'water mobility' were measured in vivo using quantitative MRI methods. Glycated hemoglobin and retinal thickness ex vivo (histology were also measured in control and diabetic groups. In the dilutional hyponatremia model, central retinal thickness and water content were supernormal by quantitative MRI, and intraretinal water mobility profiles changed in a manner consistent with intracellular edema. Groups of diabetic (2, 3, 4, 6, and 9 mo of diabetes, and age-matched controls were then investigated with MRI and all diabetic rats showed supernormal whole central retinal thickness. In a separate study in 4 mo diabetic rats (and controls, MRI retinal thickness and water content metrics were significantly greater than normal, and ADC was subnormal in the outer retina; the increase in retinal thickness was not detected histologically on sections of fixed and dehydrated retinas from these rats.Diabetic male Sprague Dawley rats demonstrate a persistent and diffuse retinal edema in vivo, providing, for the first time, an important model for investigating its pathogenesis and treatment. These studies also validate MRI as a powerful approach for investigating mechanisms of diabetic retinal edema in future experimental and clinical investigations.

  4. Increased methylglyoxal formation with upregulation of renin angiotensin system in fructose fed Sprague Dawley rats.

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    Indu Dhar

    Full Text Available The current epidemic of obesity and type 2 diabetes is attributed to a high carbohydrate diet, containing mainly high fructose corn syrup and sucrose. More than two thirds of diabetic patients have hypertension. Methylglyoxal is a highly reactive dicarbonyl generated during glucose and fructose metabolism, and a major precursor of advanced glycation end products (AGEs. Plasma methylglyoxal levels are increased in hypertensive rats and diabetic patients. Our aim was to examine the levels of methylglyoxal, mediators of the renin angiotensin system and blood pressure in male Sprague-Dawley rats treated with a high fructose diet (60% of total calories for 4 months. The thoracic aorta and kidney were used for molecular studies, along with cultured vascular smooth muscle cells (VSMCs. HPLC, Western blotting and Q-PCR were used to measure methylglyoxal and reduced glutathione (GSH, proteins and mRNA, respectively. Fructose treated rats developed a significant increase in blood pressure. Methylglyoxal level and protein and mRNA for angiotensin II, AT1 receptor, adrenergic α1D receptor and renin were significantly increased, whereas GSH levels were decreased, in the aorta and/or kidney of fructose fed rats. The protein expression of the receptor for AGEs (RAGE and NF-κB were also significantly increased in the aorta of fructose fed rats. MG treated VSMCs showed increased protein for angiotensin II, AT1 receptor, and α1D receptor. The effects of methylglyoxal were attenuated by metformin, a methylglyoxal scavenger and AGEs inhibitor. In conclusion, we report a strong association between elevated levels of methylglyoxal, RAGE, NF-κB, mediators of the renin angiotensin system and blood pressure in high fructose diet fed rats.

  5. Increased methylglyoxal formation with upregulation of renin angiotensin system in fructose fed Sprague Dawley rats.

    Science.gov (United States)

    Dhar, Indu; Dhar, Arti; Wu, Lingyun; Desai, Kaushik M

    2013-01-01

    The current epidemic of obesity and type 2 diabetes is attributed to a high carbohydrate diet, containing mainly high fructose corn syrup and sucrose. More than two thirds of diabetic patients have hypertension. Methylglyoxal is a highly reactive dicarbonyl generated during glucose and fructose metabolism, and a major precursor of advanced glycation end products (AGEs). Plasma methylglyoxal levels are increased in hypertensive rats and diabetic patients. Our aim was to examine the levels of methylglyoxal, mediators of the renin angiotensin system and blood pressure in male Sprague-Dawley rats treated with a high fructose diet (60% of total calories) for 4 months. The thoracic aorta and kidney were used for molecular studies, along with cultured vascular smooth muscle cells (VSMCs). HPLC, Western blotting and Q-PCR were used to measure methylglyoxal and reduced glutathione (GSH), proteins and mRNA, respectively. Fructose treated rats developed a significant increase in blood pressure. Methylglyoxal level and protein and mRNA for angiotensin II, AT1 receptor, adrenergic α1D receptor and renin were significantly increased, whereas GSH levels were decreased, in the aorta and/or kidney of fructose fed rats. The protein expression of the receptor for AGEs (RAGE) and NF-κB were also significantly increased in the aorta of fructose fed rats. MG treated VSMCs showed increased protein for angiotensin II, AT1 receptor, and α1D receptor. The effects of methylglyoxal were attenuated by metformin, a methylglyoxal scavenger and AGEs inhibitor. In conclusion, we report a strong association between elevated levels of methylglyoxal, RAGE, NF-κB, mediators of the renin angiotensin system and blood pressure in high fructose diet fed rats.

  6. Effects of the phytoestrogen genistein on the development of the reproductive system of Sprague Dawley rats

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    Siti Rosmani Md Zin

    2013-01-01

    Full Text Available OBJECTIVES: Genistein is known to influence reproductive system development through its binding affinity for estrogen receptors. The present study aimed to further explore the effect of Genistein on the development of the reproductive system of experimental rats. METHODS: Eighteen post-weaning female Sprague Dawley rats were divided into the following groups: (i a control group that received vehicle (distilled water and Tween 80; (ii a group treated with 10 mg/kg body weight (BW of Genistein (Gen 10; and (iii a group treated with a higher dose of Genistein (Gen 100. The rats were treated daily for three weeks from postnatal day 22 (P22 to P42. After the animals were sacrificed, blood samples were collected, and the uteri and ovaries were harvested and subjected to light microscopy and immunohistochemical study. RESULTS: A reduction of the mean weekly BW gain and organ weights (uteri and ovaries were observed in the Gen 10 group compared to the control group; these findings were reversed in the Gen 100 group. Follicle stimulating hormone and estrogen levels were increased in the Gen 10 group and reduced in the Gen 100 group. Luteinizing hormone was reduced in both groups of Genistein-treated animals, and there was a significant difference between the Gen 10 and control groups (p<0.05. These findings were consistent with increased atretic follicular count, a decreased number of corpus luteum and down-regulation of estrogen receptors-a in the uterine tissues of the Genistein-treated animals compared to the control animals. CONCLUSION: Post-weaning exposure to Genistein could affect the development of the reproductive system of ovarian-intact experimental rats because of its action on the hypothalamic-pituitary-gonadal axis by regulating hormones and estrogen receptors.

  7. Effects of Nicotine Exposure on In Vitro Metabolism of Chlorpyrifos in Male Sprague-Dawley Rats

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    Lee, Sookwang; Busby, Andrea L.; Timchalk, Charles; Poet, Torka S.

    2009-01-30

    Chlorpyrifos (CPF) is a common organophosphate (OP) insecticide which is metabolized by CYP450s to the neurotoxic metabolite, chlorpyrifos-oxon (CPF-oxon) and a non-toxic metabolite, 3,5,6-trichloro-2-pyridinol (TCP). The objective of this study was to quantify the effect of repeated in vivo nicotine exposures on CPF in vitro metabolism and marker substrate activities in rats. Male Sprague-Dawley rats were dosed subcutaneously with 1 mg nicotine/kg/, for up to 10 days. Animals showed signs of cholinergic crisis after the initial nicotine doses, but exhibited adaptation after a couple days of treatment. Rats were sacrificed on selected days 4 or 24 hr after the last nicotine-treatment. While CYP450 reduced CO spectra were not different across the treatments, the single nicotine dose group showed a 2-fold increase in CYP2E1 marker substrate (p-nitrophenol) activity 24 hr after a single nicotine treatment compared to saline controls. Conversely, repeated nicotine treatments resulted in decreased EROD marker substrate activity 4 hr after the 7th day of treatment. CPF-oxon Vmax and Km did not show significant changes across the different nicotine treatment groups. The Vmax describing the metabolism of CPF to TCP was increased on all groups (days 1, 7, and 10) 24 hr after nicotine treatment but were unchanged 4 hr after nicotine treatment. Results of this in vitro study suggest that repeated nicotine exposure (i.e., from smoking) may result in altered metabolism of CPF. Future in vivo experiments based on these results will be conducted to ascertain the impact of in vivo nicotine exposures on CPF metabolism in rats.

  8. Extremely weak magnetic field exposure may inhibit hippocampal neurogenesis of Sprague Dawley rats

    Science.gov (United States)

    Zhang, B.; Tian, L.; Cai, Y.; Xu, H.; Pan, Y.

    2016-12-01

    Hippocampal neurogenesis occurs throughout life in mammals brains and can be influenced by animals' age as well as environmental factors. Lines of evidences have shown that the magnetic field is an important physics environmental factor influencing many animals' growth and development, and extremely weak magnetic field exposures have been proved having serious adverse effects on the metabolism and behaviors in some animals, but few studies have examined the response of hippocampal neurogenesis to it. In the present study, we experimentally examined the extremely weak magnetic field effects on neurogenesis of the dentate gyrus (DG) of hippocampus of adult Sprague Dawley (SD) rats. Two types of magnetic fields were used, an extremely weak magnetic field (≤ 0.5μT) and the geomagnetic fields (strength 31-58μT) as controls. Thirty-two SD rats (3-weeks old) were used in this study. New cell survival in hippocampus was assessed at 0, 14, 28, and 42 days after a 7-day intraperitoneal injections of 5-bromo-2'-deoxyuridine (BrdU). Meanwhile, the amounts of immature neurons and mature neurons which are both related to hippocampal neurogenesis, as documented by labeling with doublecortin (DCX) and neuron (NeuN), respectively, were also analyzed at 0, 14, 28, and 42 days. Compared with geomagnetic field exposure groups, numbers of BrdU-, DCX-positive cells of DG of hippocampus in tested rats reduces monotonously and more rapidly after 14 days, and NeuN-positive cells significantly decreases after 28days when exposed in the extremely weak magnetic field condition. Our data suggest that the exposure to an extremely weak magnetic field may suppress the neurogenesis in DG of SD rats.

  9. Placental transfer, disposition, and metabolism of a single oral dose of [14CH3S] methamidophos in Sprague Dawley rat

    International Nuclear Information System (INIS)

    Salama, A.K.; Bakry, N.M.; Aly, H.A.; Abou-Donia, M.B.

    1990-01-01

    A single oral dose of 8 mg/kg (8 μci/kg) of [ 14 CH 3 S]methamidophos was administered on day 18 of gestation to pregnant Sprague Dawley rats. Eight groups of three rats were killed after 10 min. and 0.5, 1, 3, 6, 12, 24, 48 hr. At termination, 27.10% of the radioactivity was excreted in the urine, but only 4.19% of the dose was recovered in the feces. Also, 24.59% was recovered as 14 CO 2 , while only 0.11% was detected in expired air as volatile materials. Radiolabeled material was rapidly absorbed and distributed in the tissues with levels in most tissues peaking at one hour. A total of 1.73% of the dose was recovered in the fetus. Methamidophos and its metabolites were analyzed by gas-liquid chromatography/mass spectrometry, thin-layer chromatography and liquid scintillation counting. Methamidophos disappeared biexponentially from tissues and the fetus. The terminal half-lives of methamidophos were 94 and 13.5 hr for plasma and fetus, respectively. The major metabolites in the tissues were monomethyl phosphoramidate and monomethyl phosphate. In addition to these metabolites, phosphoric acid was found in the liver, kidneys, lung, uterus, fetus and urine

  10. Acute and developmental toxicity assessment of erincine A-enriched Hericium erinaceus mycelia in Sprague-Dawley rats.

    Science.gov (United States)

    Li, I-Chen; Chen, Wan-Ping; Chen, Yen-Po; Lee, Li-Ya; Tsai, Yueh-Ting; Chen, Chin-Chu

    2018-01-23

    This study aimed to establish an in vitro model to confirm the efficacy of erinacine A-enriched Hericium erinaceus (EAHE) mycelia and investigate its potential adverse effects in a preclinical experimental setting, including an assessment on the oral administration of EAHE mycelia in acute and prenatal developmental toxicity tests. At a single dose of 5000 mg/kg body weight, EAHE mycelia elicited no death or treatment-related signs of toxicity in ten Sprague-Dawley rats of both sexes during the 14 days of the experimental period. After considering the recommended dose range of EAHE mycelia from the acute toxicity test as well as the therapeutic doses, EAHE mycelia was administered to 66 pregnant rats in the low, medium, and high-dose groups by gavage at 875, 1750, and 2625 mg/kg body weight, respectively. All dams were subjected to a Caesarean section on the 20th day of pregnancy, and the fetuses were examined for any morphological abnormalities. Results indicated that weight of uterus, fetal body weight, number of corpora lutea, implantation sites, pre-implantation loss, and post-implantation loss of the treatment groups and the control group exhibited no statistical difference. In addition, no significant differences were observed in the fetal external, organ, and skeletal examinations. Taken together, it can be concluded that EAHE mycelia is considered safe and practically nontoxic for consumption within the appropriate doses and investigation period in this study.

  11. The hepatic Igf2/H19 locus is not altered in 1-day old pups born to obese-prone Sprague-Dawley rats fed a low protein diet containing adequate folic acid

    Science.gov (United States)

    Gong et al. (Epigenetics, 2010) found, using diets low in folic acid, that compared to an 18% protein diet a 9% protein diet fed to pregnant Sprague-Dawley rats resulted in increased Igf2 and H19 gene expression in the liver of day 0 male offspring. In addition DNA methylation in the Imprinting Cont...

  12. Biological fractionation of lead isotopes in Sprague-Dawley rats lead poisoned via the respiratory tract.

    Directory of Open Access Journals (Sweden)

    Jing Wu

    Full Text Available It was considered that lead isotope ratios did not change during physical, chemical, or biological processes. Thus, lead isotope ratios have been used as fingerprints to identify possible lead sources. However, recent evidence has shown that the lead isotope ratios among different biological samples in human are not always identical from its lead origins in vitro. An animal experiment was conducted to explore the biological fractionation of lead isotopes in biological systems.24 male Sprague-Dawley (SD rats were divided into groups that received acute lead exposure (0, 0.02, 0.2, or 2 mg/kg body weight of lead acetate via the respiratory route every day for 5 days. Biological samples (i.e., blood, urine, and feces were collected for comparison with the lead acetate (test substance and the low-lead animal feed (diet administered to the rats. The lead isotope ratios were determined by inductively coupled plasma mass spectrometry (ICP-MS.There are significant differences (p<0.05 in lead isotope ratios between blood, urine, and feces. Moreover, a nonlinear relationship between the blood lead concentration and the blood lead isotope ratios was observed. There is also a threshold effect to the fractionation function. Only the blood isotope ratio of (204Pb/(206Pb matches the test substance well. As for feces, when (204Pb/(206Pb ratio is considered, there is no significant difference between feces-test substance pairs in medium and high dose group.The biological fractionation of lead isotopes in SD rats was observed. Moreover, there might be a threshold for the biological fractionation of lead isotopes which is depending on whole blood lead level. It is considered to be more reliable that we compared the isotope ratios of potential lead hazards with both blood and feces lead fingerprints especially for (204Pb/(206Pb ratio under high-dose exposure.

  13. Sex differences in the reinstatement of methamphetamine seeking after forced abstinence in Sprague-Dawley rats

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    Jana eKucerova

    2015-07-01

    Full Text Available Preventing relapse to drug abuse is one of the struggles faced by clinicians in order to treat patients with substance use disorders (DSM-5. There is a large body of clinical evidence suggesting differential characteristics of the disorder in men and women which is in line with preclinical findings as well. The aim of this study was to assess differences in relapse-like behavior in methamphetamine (METH seeking after a period of forced abstinence which simulates the real clinical situation very well. Findings from such study might add new insights in gender differences in relapse mechanisms to previous studies, which employ a classical drug or cue-induced reinstatement procedure following the extinction training.Adult male and female Sprague-Dawley rats were used in IV self-administration procedure conducted in operant boxes using nose-poke operandi (Coulborn Instruments, USA. Active nose-poke resulted in activation of the infusion pump to deliver one intravenous infusion of METH (0.08 mg/kg. After baseline drug intake was established (maintenance phase, a period of forced abstinence was initiated and rats were kept singly in their home-cages for 14 days. Finally, one reinstatement session in operant boxes was conducted. Females were found to self-administer significantly lower dose of METH. The relapse rate was assessed as a number of active nose-pokes during the reinstatement session, expressed as a percentage of active nose-poking during the maintenance phase. Females displayed approximately 300 % of active nose-pokes compared to 48 % in males. This indicates higher vulnerability to relapse of METH seeking behavior in female rats. This effect was detected in all females, independently of current phase of their estrous cycle. Therefore, this paradigm using operant drug self-administration and reinstatement of drug-seeking after forced abstinence model can be used for preclinical screening for potential new anti-relapse medications specific for

  14. Biological fractionation of lead isotopes in Sprague-Dawley rats lead poisoned via the respiratory tract.

    Science.gov (United States)

    Wu, Jing; Liu, Duojian; Xie, Qing; Wang, Jingyu

    2012-01-01

    It was considered that lead isotope ratios did not change during physical, chemical, or biological processes. Thus, lead isotope ratios have been used as fingerprints to identify possible lead sources. However, recent evidence has shown that the lead isotope ratios among different biological samples in human are not always identical from its lead origins in vitro. An animal experiment was conducted to explore the biological fractionation of lead isotopes in biological systems. 24 male Sprague-Dawley (SD) rats were divided into groups that received acute lead exposure (0, 0.02, 0.2, or 2 mg/kg body weight of lead acetate) via the respiratory route every day for 5 days. Biological samples (i.e., blood, urine, and feces) were collected for comparison with the lead acetate (test substance) and the low-lead animal feed (diet) administered to the rats. The lead isotope ratios were determined by inductively coupled plasma mass spectrometry (ICP-MS). There are significant differences (pblood, urine, and feces. Moreover, a nonlinear relationship between the blood lead concentration and the blood lead isotope ratios was observed. There is also a threshold effect to the fractionation function. Only the blood isotope ratio of (204)Pb/(206)Pb matches the test substance well. As for feces, when (204)Pb/(206)Pb ratio is considered, there is no significant difference between feces-test substance pairs in medium and high dose group. The biological fractionation of lead isotopes in SD rats was observed. Moreover, there might be a threshold for the biological fractionation of lead isotopes which is depending on whole blood lead level. It is considered to be more reliable that we compared the isotope ratios of potential lead hazards with both blood and feces lead fingerprints especially for (204)Pb/(206)Pb ratio under high-dose exposure.

  15. PROCHLORAZ INHIBITS TESTOSTERONE PRODUCTION AT DOSAGE BELOW THOSE THAT AFFECT ANDROGEN-DEPENDENT ORGAN WEIGHTS OR THE ONSET OF PUBERTY IN THE MALE SPRAGUE DAWLEY RAT

    Science.gov (United States)

    ABSTRACT: Since prochloraz (PCZ) is an imidazole fungicide that inhibits gonadal steroidogenesis and antagonizes the androgen receptor (AR), we hypothesized that pubertal exposure to PCZ would delay male rat reproductive development. Sprague Dawley rats were dosed by gavage with...

  16. Subchronic feeding study of DAS-59122-7 maize grain in Sprague-Dawley rats.

    Science.gov (United States)

    Malley, Linda A; Everds, Nancy E; Reynolds, Julia; Mann, Peter C; Lamb, Ian; Rood, Tracy; Schmidt, Jean; Layton, Raymond J; Prochaska, Lee M; Hinds, Mark; Locke, Mary; Chui, Chok-Fun; Claussen, Fred; Mattsson, Joel L; Delaney, Bryan

    2007-07-01

    59122 is a transgenic maize line containing event DAS-59122-7 that expresses the corn rootworm (CRW) specific pesticidal Cry34Ab1 and Cry35Ab1 proteins from Bacillus thuringiensis (Bt) Berliner strain PS149B1 and the phosphinothricin-N-acetyltransferase (PAT) protein from Streptomyces viridochromogenes for tolerance to the herbicidal ingredient glufosinate-ammonium. For the current study, 59122 maize grain, non-transgenic near-isogenic maize grain (091), and a commercially available non-transgenic reference maize grain (33R77) were grown under conditions simulating commercial farming practices. Adult Sprague-Dawley rats (12/sex/group) were fed diets formulated with 35% maize grain from either 59122, 091, or 33R77, or one of two separate lots of commercially available rodent chow prepared with commercially available corn (35%) in accordance with the standards of Purina Mills Labdiet 5002 for approximately 90 days. All diets possessed similar nutritional and contaminant profiles. The transgenic proteins were detected only in diets prepared with 59122 maize grain and were stable over the course of the study. Compared to control groups, no adverse diet-related differences were observed in rats fed diets formulated with 59122 maize grain with respect to body weight/gain, food consumption/efficiency, clinical signs of toxicity, mortality, ophthalmology, neurobehavioral (FOB and motor activity) assessments, clinical pathology (hematology, clinical chemistry, coagulation, and urinalysis), and pathology (organ weights and gross and microscopic pathology). Results from this study indicate that 59122 maize grain is nutritionally equivalent to and as safe as conventional maize grain.

  17. Anti-inflammatory effect of longan seed extract in carrageenan stimulated Sprague-Dawley rats

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    Ching-Hsiao Lee

    2016-08-01

    Full Text Available Objective(s: Longan seeds have been used as a folk medicine in China. Longan seed extract (LSE is known for antioxidative, antiproliferative, hypoglycemic, and hypouremic effects. However, its anti-inflammatory effect has not been shown. Materials and Methods: In this study, Sprague-Dawley (SD rats were given LSE orally (vehicle, 10, and 30 mg/kg for 3 days to its test anti-inflammatory effect by injecting λ-carrageenan (CARR in the right hind paw or lipopolysaccharide (LPS, IP. For the positive control, animals were given aspirin (20 mg/kg orally and treated likewise. Serum or tissue samples from treated rats were collected after 3 hr of stimulation. Regarding the in vitro study, BV2 microglial cells were stimulated with LPS in the presence of LSE or normal saline for 10 min or 24 hr for Western blot and ELISA assay, respectively. Results: LSE reduced CARR-induced edema in the experimental animals. LSE also reduced LPS/CARR-induced nitric oxide (NO, interleukin-1β (IL1β, IL6, and COX2 productions. These inflammatory factors were also reduced dose dependently by LSE in LPS-stimulated BV2 cells. Furthermore, Western blot analysis revealed that LSE inhibited LPS activated c-Jun NH2-terminal protein kinase (JNK, extracellular signal-regulated kinases (ERKs, and p38 MAP kinases signaling pathways, caspase-3, inducible NO synthase, and COX2 expressions. Conclusion: LSE pretreatment suppressed CARR- and LPS-induced inflammations and these effects might be through the inhibition of MAP kinases signaling pathways and inflammatory factors.

  18. Chronic dietary toxicity and carcinogenicity study with potassium perfluorooctanesulfonate in Sprague Dawley rats

    International Nuclear Information System (INIS)

    Butenhoff, John L.; Chang, Shu-Ching; Olsen, Geary W.; Thomford, Peter J.

    2012-01-01

    Highlights: ► A two-year dietary toxicity and cancer bioassay was conducted with K + PFOS in rats. ► Hepatocellular hypertrophy was the main microscopic non-neoplastic finding. ► Hepatocellular adenoma was increased in males and females fed the high dose. ► Males fed high dose for 1 year had increased thyroid follicular cell adenoma. ► The latter finding is of equivocal relationship to treatment. -- Abstract: To investigate toxicity and neoplastic potential from chronic exposure to perfluorooctanesulfonate (PFOS), a two-year toxicity and cancer bioassay was conducted with potassium PFOS (K + PFOS) in male and female Sprague Dawley rats via dietary exposure at nominal K + PFOS concentrations of 0, 0.5, 2, 5, and 20 μg/g (ppm) diet for up to 104 weeks. Additional groups were fed 20 ppm for the first 52 weeks, after which they were fed control diet through study termination (20 ppm Recovery groups). Scheduled interim sacrifices occurred on Weeks 4, 14, and 53, with terminal sacrifice between Weeks 103 and 106. K + PFOS appeared to be well-tolerated, with some reductions in body weight occurring in treated rats relative to controls over certain study periods. Male rats experienced a statistically significant decreased trend in mortality with significantly increased survival to term at the two highest treatment levels. Decreased serum total cholesterol, especially in males, and increased serum urea nitrogen were consistent clinical chemistry observations that were clearly related to treatment. The principal non-neoplastic effect associated with K + PFOS exposure was in livers of males and females and included hepatocellular hypertrophy, with proliferation of endoplasmic reticulum, vacuolation, and increased eosinophilic granulation of the cytoplasm. Statistically significant increases in hepatocellular adenoma were observed in males (p = 0.046) and females (p = 0.039) of the 20 ppm treatment group, and all of these tumors were observed in rats surviving to

  19. Study of Cyclooxygenase-2 Expression in Sprague Dawley Rat Gastric Cancer Induced by H. Pylori

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    Pooladi A

    2011-01-01

    Full Text Available Background and Objectives: Gastric cancer is one of the most common gastrointestinal tumors; the incidence and mortality of gastric cancer are on the increase nowadays. Helicobacter pylori(H.Pylori causes chronic active gastritis and peptic ulcer disease. Cycloocygenase-2 (COX-2 is the central enzyme in the biosynthetic pathway to prostaglandins. Studies from different laboratories suggested that over-expression of COX-2 was detected in colon and other tumors. To obtain direct evidence concerning this relationship, we investigated the immunohistochemical findings of gastric mucosa using an animal model of gastric cancer induced by H. pylori in sprague dawley rat.Methods: The rats were randomly assigned into three groups(n=5. Those of experimental group2 were given MNU. one week after completion of MNU administration, rats in experimental groups 1 were inoculated with H. pylori three times every other day. Rats in control group(group 3 received neither MNU nor H. pylori. Rats of groups 1, 2, and control group were maintained on standard diets throughout the experiment. Rat were weighed and sacrificed under anesthesia with ether at 20 weeks after infection. One half of the excised stomachs, were fixed in neutral-buffered 10% formalin and were cut into approximately six strips, which were processed by standard methods, embedded in paraffin, sectioned at 6 µm, and stained with hematoxylin and eosin (H&E and immunohistochemistry for Cox-2 protein detection. To confirm H. pylori infection, samples ( 3-mm2 of stomach mucosa transferred to appropriate medium and Colonies were identified by characteristic Gram’s stain morphology, and by urease, catalase, and oxidase activity sample was also placed into the gel of a rapid urease test kit.Results: Data showed a significant decrease of animal body weight in experimental groups compared with control group. Histopathological studies showed severe infiltration of the lamina propria and submucusaal layer by

  20. Study of Cyclooxygenase-2 Expression in Sprague Dawley Rat Gastric Cancer Induced by H. Pylori

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    F Aeini

    2012-05-01

    Full Text Available

    Background and Objectives: Gastric cancer is one of the most common gastrointestinal tumors; the incidence and mortality of gastric cancer are on the increase nowadays. Helicobacter pylori(H.Pylori causes chronic active gastritis and peptic ulcer disease. Cycloocygenase-2 (COX-2 is the central enzyme in the biosynthetic pathway to prostaglandins. Studies from different laboratories suggested that over-expression of COX-2 was detected in colon and other tumors. To obtain direct evidence concerning this relationship, we investigated the immunohistochemical findings of gastric mucosa using an animal model of gastric cancer induced by H. pylori in sprague dawley rat. Methods: The rats were randomly assigned into three groups(n=5. Those of experimental group2 were given MNU. one week after completion of MNU administration, rats in experimental groups 1 were inoculated with H. pylori three times every other day. Rats in control group(group 3 received neither MNU nor H. pylori. Rats of groups 1, 2, and control group were maintained on standard diets throughout the experiment. Rat were weighed and sacrificed under anesthesia with ether at 20 weeks after infection. One half of the excised stomachs, were fixed in neutral-buffered 10% formalin and were cut into approximately six strips, which were processed by standard methods, embedded in paraffin, sectioned at 6 µm, and stained with hematoxylin and eosin (H&E and immunohistochemistry for Cox-2 protein detection. To confirm H. pylori infection, samples ( 3-mm2 of stomach mucosa transferred to appropriate medium  and Colonies were identified by characteristic Gram’s stain morphology, and by urease, catalase, and oxidase activity sample was also placed into the gel of a rapid urease test kit. Results: Data showed a significant decrease of animal body weight in experimental groups compared with control group

  1. Mammary carcinogenesis induced by three consecutive 14 MeV neutron irradiations in Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Jacrot, M.; Mouriquand, J.; Mouriquand, C.

    1978-01-01

    At high doses (400 to 800 rads) the relative biological effectiveness (R.B.E.) of neutrons is two or three times greater than that of X-rays or gamma radiation. The neutron irradiation-induced mammary carcinogenesis threshold, if any, is certainly very low in Sprague-Dawley females. The purpose of this work is to test the possibilities offered by three consecutive 14 MeV neutron irradiations in the mammary carcinogenesis region of Sprague-Dawley rats. The results of these experiments show a hormone-dependence of tumour promotion similar to that observed with chemical carcinogenetic agents. However these tumours, by their recurrences and possible metastases, bear some resemblance to breast cancers in women. Although the tumour induction frequencies seem modest in relation to those obtained with the DMBA model they should nevertheless prove very useful in the study of hormone effects liable to control the appearance of such radioinduced cancers [fr

  2. Effects of adolescent treatment with nicotine, harmane, or norharmane in male Sprague-Dawley rats.

    Science.gov (United States)

    Goodwin, Amy K; Lantz-McPeak, Susan M; Robinson, Bonnie L; Law, C Delbert; Ali, Syed F; Ferguson, Sherry A

    2015-01-01

    The initiation of tobacco use occurs most often in adolescence and may be especially detrimental as the adolescent brain is undergoing substantial development. In addition to nicotine, there are over 9000 other compounds present in tobacco products, including the β-carbolines harmane and norharmane. The present study aimed to determine the long-term effects of adolescent exposure to nicotine (NIC), harmane (HAR), or norharmane (NOR) on locomotor activity, learning and memory, anxiety-like behavior, motor coordination, and monoamine/metabolite concentrations in the striatum and nucleus accumbens of male Sprague-Dawley rats. Beginning on postnatal day (PND) 27 and continuing through PND 55, subjects received twice daily intraperitoneal injections of 1ml/kg saline (CON), 0.5mg NIC/kg, 0.5mg HAR/kg, or 0.5mg NOR/kg. Body weight, food, and water intake were measured daily (PNDs 27-96). Locomotor activity was assessed on PND 40 or 41, PND 55, and PNDs 81 and 82. Other behaviors (anxiety-like behavior, motor coordination, and spatial learning and memory) were assessed at least 25 days after drug exposure ended (PNDs 80-91). On PND 97, subjects were decapitated and the striatum and nucleus accumbens were dissected and frozen for analysis. NIC treatment significantly decreased food intake, but did not alter locomotor activity during or after treatment. HAR and NOR treatment, however, caused significant open field hypoactivity. Motor coordination, water maze performance, and concentrations of monoamines and metabolites in the striatum and nucleus accumbens were unaltered by any drug treatment. These results indicate a long-lasting effect on activity levels from adolescent HAR or NOR treatment; however, there were few long-lasting NIC effects. Given the paucity of data describing effects of HAR or NOR exposure, these data should encourage additional studies of these tobacco constituents as well as constituent combination studies. Published by Elsevier Inc.

  3. Impact of maternal high fat diet on hypothalamic transcriptome in neonatal Sprague Dawley rats.

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    Sanna Barrand

    Full Text Available Maternal consumption of a high fat diet during early development has been shown to impact the formation of hypothalamic neurocircuitry, thereby contributing to imbalances in appetite and energy homeostasis and increasing the risk of obesity in subsequent generations. Early in postnatal life, the neuronal projections responsible for energy homeostasis develop in response to appetite-related peptides such as leptin. To date, no study characterises the genome-wide transcriptional changes that occur in response to exposure to high fat diet during this critical window. We explored the effects of maternal high fat diet consumption on hypothalamic gene expression in Sprague Dawley rat offspring at postnatal day 10. RNA-sequencing enabled discovery of differentially expressed genes between offspring of dams fed a high fat diet and offspring of control diet fed dams. Female high fat diet offspring displayed altered expression of 86 genes (adjusted P-value<0.05, including genes coding for proteins of the extra cellular matrix, particularly Collagen 1a1 (Col1a1, Col1a2, Col3a1, and the imprinted Insulin-like growth factor 2 (Igf2 gene. Male high fat diet offspring showed significant changes in collagen genes (Col1a1 and Col3a1 and significant upregulation of two genes involved in regulation of dopamine availability in the brain, tyrosine hydroxylase (Th and dopamine reuptake transporter Slc6a3 (also known as Dat1. Transcriptional changes were accompanied by increased body weight, body fat and body length in the high fat diet offspring, as well as altered blood glucose and plasma leptin. Transcriptional changes identified in the hypothalamus of offspring of high fat diet mothers could alter neuronal projection formation during early development leading to abnormalities in the neuronal circuitry controlling appetite in later life, hence priming offspring to the development of obesity.

  4. Intratracheal instillation of cerium oxide nanoparticles induces hepatic toxicity in male Sprague-Dawley rats

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    Nalabotu SK

    2011-10-01

    Full Text Available Siva K Nalabotu1,2, Madhukar B Kolli1,2, William E Triest3,4, Jane Y Ma5, Nandini DPK Manne2,6, Anjaiah Katta1,2, Hari S Addagarla2, Kevin M Rice2,6–8, Eric R Blough1,2,6,7,91Department of Pharmacology, Physiology and Toxicology, Marshall University, Joan C Edwards School of Medicine; 2Center for Diagnostic Nanosystems, Marshall University; 3Pathology and Laboratory Medicine Service, Veterans Affairs Medical Center; 4Section of Pathology, Department of Anatomy and Pathology, Joan C Edwards School of Medicine, Marshall University, Huntington; 5Health Effects Laboratory Division, NIOSH, Morgantown; 6Department of Biological Sciences; 7School of Kinesiology, College of Health Professions, Marshall University; 8Biotechnology Department, West Virginia State University; 9Department of Cardiology, Joan C Edwards School of Medicine, Marshall University Huntington, WV, USABackground: Cerium oxide (CeO2 nanoparticles have been posited to have both beneficial and toxic effects on biological systems. Herein, we examine if a single intratracheal instillation of CeO2 nanoparticles is associated with systemic toxicity in male Sprague-Dawley rats.Methods and results: Compared with control animals, CeO2 nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase levels, reduced albumin levels, a diminished sodium-potassium ratio, and decreased serum triglyceride levels (P < 0.05. Consistent with these data, rats exposed to CeO2 nanoparticles also exhibited reductions in liver weight (P < 0.05 and dose-dependent hydropic degeneration, hepatocyte enlargement, sinusoidal dilatation, and accumulation of granular material. No histopathological alterations were observed in the kidney, spleen, and heart. Analysis of serum biomarkers suggested an elevation of acute phase reactants and markers of hepatocyte injury in the rats exposed to CeO2 nanoparticles.Conclusion: Taken together, these data suggest that

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

    Science.gov (United States)

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

    2017-06-01

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

  6. Toxicological characterisation of two novel selective aryl hydrocarbon receptor modulators in Sprague-Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Mahiout, Selma, E-mail: selma.mahiout@helsinki.fi [Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki (Finland); Lindén, Jere [Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki (Finland); Esteban, Javier; Sánchez-Pérez, Ismael [Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Elche, Alicante (Spain); Sankari, Satu [Central Laboratory of the Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki (Finland); Pettersson, Lars [Immunahr AB, Lund (Sweden); Håkansson, Helen [Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm (Sweden); Pohjanvirta, Raimo [Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki (Finland)

    2017-07-01

    The aryl hydrocarbon receptor (AHR) mediates the toxicity of dioxins, but also plays important physiological roles. Selective AHR modulators, which elicit some effects imparted by this receptor without causing the marked toxicity of dioxins, are presently under intense scrutiny. Two novel such compounds are IMA-08401 (N-acetyl-N-phenyl-4-acetoxy-5-chloro-1, 2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide) and IMA-07101 (N-acetyl-N-(4-trifluoromethylphenyl)-4-acetoxy-1, 2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide). They represent, as diacetyl prodrugs, AHR-active metabolites of the drug compounds laquinimod and tasquinimod, respectively, which are intended for the treatment of autoimmune diseases and cancer. Here, we toxicologically assessed the novel compounds in Sprague-Dawley rats, after a single dose (8.75–92.5 mg/kg) and 5-day repeated dosing at the highest doses achievable (IMA-08401: 100 mg/kg/day; and IMA-07101: 75 mg/kg/day). There were no overt clinical signs of toxicity, but body weight gain was marginally retarded, and the treatments induced minimal hepatic extramedullary haematopoiesis. Further, both the absolute and relative weights of the thymus were significantly decreased. Cyp1a1 gene expression was substantially increased in all tissues examined. The hepatic induction profile of other AHR battery genes was distinct from that caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The only marked alterations in serum clinical chemistry variables were a reduction in triglycerides and an increase in 3-hydroxybutyrate. Liver and kidney retinol and retinyl palmitate concentrations were affected largely in the same manner as reported for TCDD. In vitro, the novel compounds activated CYP1A1 effectively in H4IIE cells. Altogether, these novel compounds appear to act as potent activators of the AHR, but lack some major characteristic toxicities of dioxins. They therefore represent promising new selective AHR modulators. - Highlights: • IMA

  7. Effects of Didecyldimethylammonium Chloride (DDAC) on Sprague-Dawley Rats after 13 Weeks of Inhalation Exposure.

    Science.gov (United States)

    Kim, Yong-Soon; Lee, Sung-Bae; Lim, Cheol-Hong

    2017-01-01

    Didecyldimethylammonium chloride (DDAC) is used in many types of biocidal products including tableware, carpets, humidifiers, and swimming pools, etc. In spite of increased chances of DDAC exposure through inhalation, studies on the inhalation toxicity of DDAC are not common even though the toxicity of DDAC might be significantly higher if it were to be administered through routes other than the respiratory system. DDAC aerosols were exposed to Sprague-Dawley rats in whole body exposure chambers for a duration of 13 weeks. The Mass Median Aerodynamic Diameters of the DDAC aerosol were 0.63 μm, 0.81 μm, and 1.65 μm, and the geometric standard deviations were 1.62, 1.65, and 1.65 in the low (0.11 ± 0.06 mg/m 3 ), the middle (0.36 ± 0.20 mg/m 3 ) and the high (1.41 ± 0.71 mg/m 3 ) exposure groups, respectively. Body weight was confirmed to be clearly influenced by exposure to DDAC and mean body weight was approximately 35% lower in the high (1.41 ± 0.71 mg/m 3 ) male group and 15% lower in the high (1.41 ± 0.71 mg/m 3 ) female group compared to that of the control group. In the bronchoalveolar lavage fluid assay, the levels of albumin and lactate dehydrogenase had no effect on DDAC exposure. The lung weight increased for the middle (0.36 ± 0.20 mg/m 3 ) and the high (1.41 ± 0.71 mg/m 3 ) concentrations of the DDAC exposure group, and inflammatory cell infiltration and interstitial pneumonia were partially observed in the lungs of the middle (0.36 ± 0.20 mg/m 3 ) and the high (1.41 ± 0.71 mg/m 3 ) exposure groups. However, severe histopathological symptoms, including proteinosis and/or fibrosis, were not found. Based on the results of the changes in the body weight and lung weight, it is considered that the NOAEL (no-observed adverse effect) level for the 13-week exposure duration is 0.11 mg/m 3 .

  8. Prophylactic Treatment with Cerium Oxide Nanoparticles Attenuate Hepatic Ischemia Reperfusion Injury in Sprague Dawley Rats

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    Nandini D.P.K. Manne

    2017-07-01

    Full Text Available Background: Hepatic ischemia reperfusion is one the main causes for graft failure following transplantation. Although, the molecular events that lead to hepatic failure following ischemia reperfusion (IR are diverse and complex, previous studies have shown that excessive formation of reactive oxygen species (ROS are responsible for hepatic IR injury. Cerium oxide (CeO2 nanoparticles have been previously shown to act as an anti-oxidant and anti-inflammatory agent. Here, we evaluated the protective effects of CeO2 nanoparticles on hepatic ischemia reperfusion injury. Methods: Male Sprague Dawley rats were randomly assigned to one of the four groups: Control, CeO2 nanoparticle only, hepatic ischemia reperfusion (IR group and hepatic ischemia reperfusion (IR plus CeO2 nanoparticle group (IR+ CeO2. Partial warm hepatic ischemia was induced in left lateral and median lobes for 1h, followed by 6h of reperfusion. Animals were sacrificed after 6h of reperfusion and blood and tissue samples were collected and processed for various biochemical experiments. Results: Prophylactic treatment with CeO2 nanoparticles (0.5mg/kg i.v (IR+CeO2 group 1 hour prior to hepatic ischemia and subsequent reperfusion injury lead to a decrease in serum levels of alanine aminotransaminase and lactate dehydrogenase at 6 hours after reperfusion. These changes were accompanied by significant decrease in hepatocyte necrosis along with reduction in several serum inflammatory markers such as macrophage derived chemokine, macrophage inflammatory protein-2, KC/GRO, myoglobin and plasminogen activator inhibitor-1. However, immunoblotting demonstrated no significant changes in the levels of apoptosis related protein markers such as bax, bcl2 and caspase 3 in IR and IR+ CeO2 groups at 6 hours suggesting necrosis as the main pathway for hepatocyte death. Conclusion: Taken together, these data suggest that CeO2 nanoparticles attenuate IR induced cell death and can be used as a prophylactic

  9. Effect of dietary fiber in lowering serum glucose and body weight in sprague dawley rats

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    Muhammad Imran Chohan

    2011-08-01

    Full Text Available Introduction:The present study evaluated the hypoglycemic perspectives and weight loss significance of dietary fiber. Dietary fiber was supplemented in commercial wheat flour (atta for the preparation of chapaties, a staple diet of South Asia. Male Sprague Dawley rats (n = 100 were randomly divided into 4 diet groups (n = 25 per group. The control group was fed basal diet that included commercial wheat flour chapati, cornstarch, corn oil, salt and vitamin mixture in such a way that 10% of the protein was available from the final diet. To the basal diet of other 3 groups, chapaties supplemented with 2% guar gum (GG 2%, 3% guar gum (GG 3% and 5% chickpea + 1% guar gum (CP5%+GG1% were added, respectively. All diets were fed to the rats for a period of 8 weeks to perceive the impact of respective compositions. Rats fed on CP 5% + GG1%, showed maximum glucose reduction (14.57% followed by GG 3% (11.64% and GG 2% (9.60% as compared to control diet. Likewise, rats fed on 3% GG showed maximum decline (7.90% in body weight. It was concluded that chapaties prepared from selected treatments provide an additional dietary fiber that could be supportive for diabetic and obese individuals.Results:The results indicated that addition of dietary fiber influenced the physical characteristics of chapati non-significantly. Maximum glucose concentration was found to be 112.50 mg/dL in control group followed by 101.70 and 99.41 mg/dL in groups fed on guar gum 2% and guar gum 3%, respectively. Lowest glucose concentration (96.11 mg/dL was observed in rats fed on the combination of chickpea 5 %+ guar gum 1%. Maximum serum protein concentration was found to be 6.39 g/dL in rats fed on combination of chickpea 5 % + guar gum 1% whilst the remaining three groups showed non significant variations with respect to each other. Means for serum Functional Foods in Health and Disease 2011; 8:261-278 protein were 6.33, 6.30 and 6.32 g/dL for control, guar gum 3%, and guar gum 2

  10. Female Sprague Dawley Rats Show Impaired Spatial Memory in the 8-Arm Radial Maze under Dim Blue and Red Light

    OpenAIRE

    Pirchl, Michael; Kemmler, Georg; Humpel, Christian

    2010-01-01

    Light intensity and wavelength strongly influence mood and cognition in humans and rodent animal models. The aim of the present study was to explore if dim white (7.6–17.7 lux) , blue (1.3–2.3 lux), and red light (0.8–1.4 lux) affect spatial memory of male and female Sprague Dawley rats in the 8-arm radial maze. Our data show that spatial memory significantly improved within 5 daily learning sessions (each 5 trials) under dim white light, which was not different between male and female rats. ...

  11. Anti-Cataract Potential of Heliotropium indicum Linn on Galactose-Induced Cataract in Sprague-Dawley Rats.

    Science.gov (United States)

    Kyei, Samuel; Koffuor, George A; Ramkissoon, Paul; Abu, Emmanuel K; Sarpong, Josephine F

    2017-03-01

    To evaluate the anti-cataract potential of an aqueous whole plant extract of Heliotropium indicum (HIE) on galactose-induced cataract in Sprague-Dawley rats. Cataract scores were recorded in 3-week-old Sprague-Dawley rats in which cataract was being induced by an oral administration of 1500 mgkg -1 galactose twice daily for 4 weeks, and concurrently being treated with 30, 100, or 300 mgkg -1 HIE daily over the induction period. Fasting blood glucose was monitored at weekly intervals. Changes in body weight as well as total lens protein, lens glutathione, and superoxide dismutase (SOD) were determined initially, and at the end of the experimental period. Crystalline lens weight-to-body-weight ratio was also determined for the various treatment groups at the end of the experimental period. Preliminary phytochemical screening, total antioxidant capacity, and reducing power assays were conducted on HIE. The 30 and 100 mgkg -1 HIE-treated rats recorded significantly lower (p ≤ 0.05-0.001) cataract scores (indicating very significant delays in cataractogenesis by the 3 rd and 4 th weeks of treatment) and blood glucose levels. Rats with delayed cataractogenesis also exhibited significant (p ≤ 0.05-0.001) weight gain, and reduction in lens weight. Total lens proteins glutathione and SOD levels in the crystalline lens were also significantly preserved (p ≤ 0.01-0.001). HIE showed substantial antioxidant capacity and reducing power. The aqueous whole plant extract of Heliotropium indicum delays cataractogenesis at an optimum dose of 30 mgkg -1 in Sprague-Dawley rats.

  12. Effect of dietary carbohydrates on plasma lipoproteins in Sprague-Dawley and LA/N-corpulent rats

    International Nuclear Information System (INIS)

    Ellwood, K.C.

    1989-01-01

    Male Sprague-Dawley rats were fed diets containing 54% carbohydrate as either sucrose (S), fructose (F) or cooked cornstarch (CS) for 5 weeks. Plasma lipoproteins (LP) were isolated by density gradient ultracentrifugation and separated into very low density P (VLDL), low density LP (LDL) and high density LP (HDL) by gel filtration and affinity chromatography. ApoLP E-rich (R 1 and R 2 ) and apoLP E-poor subfractions (NR) of HDL were prepared by heparin-sepharose affinity chromatography. Rats were injected intraperitoneally with 3 H-leucine and sacrificed 2 hours later. Plasma lipoproteins were isolated as described above. The level of 3 H-protein in plasma was greater in Sprague-Dawley rats fed F than those fed S or CS. The amount of 3 H-protein in the chylomicron + VLDL fraction was affected by type of dietary carbohydrate: S > F > CS. Similar studies were conducted with the carbohydrate-sensitive obese and lean LA/N-corpulent rats. Levels of HDL-protein were lower in LA/N-corpulent rats fed S or F than in those fed CS. 3 H-chylomicron + VLDL was higher in rats fed S or F than those fed CS. The concentration of 3 H-protein in plasma and chylomicron + VLDL was greater in obese rats than in lean

  13. Induction of P450 3A1/2 and 2C6 by gemfibrozil in Sprague-Dawley rats.

    Science.gov (United States)

    Liu, Aiming; Yang, Julin; Zhao, Xin; Jiao, Xiaolan; Zhao, Weihong; Ma, Qing; Tang, Zhiyuan; Dai, Renke

    2011-01-01

    Fibrates are a group of peroxisome proliferator-activated receptor α agonists used in the treatment of dyslipidemia; however, they have been reported to cause species-related hepatocarcinogenesis and clinical myotoxicity. Gemfibrozil is one of the most commonly used fibrates, and it shows the highest risk for myotoxicity among the fibrates. The inhibitory drug-drug interaction mechanism associated with gemfibrozil has been explored recently, and the induction of human P450 3A4 and 2C8 has been reported. In this study, in vivo induction of rat P450 by gemfibrozil was studied in Sprague-Dawley rats. After the rats were dosed with gemfibrozil by oral gavage, microsomes were prepared. The metabolic activities of P450 3A1/2, 2C6, and 2D2 were assayed using probe substrates, and the systemic concentration of gemfibrozil during its administration was determined. P450 3A1/2 and 2C6 activities were induced 32-77% in the rats by gemfibrozil when the exposure concentration was in the clinical range. These data indicate that the inducibility of homologous P450 isoforms by gemfibrozil is similar in Sprague-Dawley rats and in humans. Inductive drug-drug interactions and inhibitory actions are involved in the co-administration of gemfibrozil with other drugs, which suggests the relevance for a fibrate-toxicology investigation.

  14. Effects of ascorbic acid and alpha tocopherol supplementation on basal testosterone cortisol ratio in male sprague dawley rats

    International Nuclear Information System (INIS)

    Lodhi, G.M.

    2011-01-01

    Background: Basal testosterone cortisol ratio is considered very important to maintain homeostasis. Increase in this ratio has various beneficial effects on body. In this study we determined the effects of ascorbic acid and alpha tocopherol supplementation on basal testosterone cortisol ratio in male Sprague Dawley rats. Methods: It was quasi experimental study carried out in department of Physiology, Army Medical College Rawalpindi in collaboration with National Institute of Health, Islamabad during October 2006 to September 2007. Forty male Sprague Dawley rats were divided into four groups with ten rats in each group and above mentioned antioxidants supplementation were given along with standard diet for one month. After this, blood samples were taken and analyzed for serum testosterone and cortisol by ELISA and malondialdehyde levels colorimetrically. Data were analysed on SPSS version 13 and p<0.05 was considered significant. Results: There was no significant rise in testosterone cortisol ratio in rats supplemented with single antioxidant; however rats supplemented with combination of ascorbic acid and alpha tocopherol revealed significant rise in testosterone cortisol ratio with a fall in malondialdehyde levels. Conclusions: Synergistic effects of ascorbic acid and alpha tocopherol resulted in a decline in reactive oxygen species induced lipid peroxidation and rise of testosterone cortisol ratio. (author)

  15. Comparación entre dos biomodelos murinos (ratones Balb/c y ratas Sprague Dawley en el ensayo de micronúcleos transplacentarios Comparison between two murine biomodles (Balb/c mice and Sprague Dawley rats in a transplacental micronucleus assay

    Directory of Open Access Journals (Sweden)

    Daniel Francisco Arencibia Arrebola

    2012-03-01

    at 14th, 15th and 16th days of gestation, and 24 h after the last inoculation in mice and 48 h in rats, it proceeded to perform euthanasia in the pregnant animals to obtain the fetal liver samples. Results: the fetuses from Sprague Dawley exhibited smaller cytotoxicity and genotoxicity indexes, and the lowest endogenous micronucleus results. The best results of the cytotoxicity and genotoxicity induction for the high micronucleus formation with cyclophosphamide were found in Sprague Dawley rat fetuses, being more susceptible to the genotoxic damage by this mutagen. The clastogenic transplacental power of cyclophosphamide was confirmed whereas this genotoxicity assay was linked to reproduction toxicology. Conclusions: these results suggest that the Sprague Dawley rats fetuses could be better used as biomodels in this assay when cyclophosphamide is employed as positive control through the way of administration and the studied dosage. It could be similarly used in the evaluation of new antigenotoxic drugs with antigenotoxic effect through transplacental administration

  16. Development of a New Technique for Reconstruction of Hepatic Artery during Liver Transplantation in Sprague-Dawley Rat.

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    Xingmu Liu

    Full Text Available Sleeve anastomosis is the most common technique used to rearterialize orthotopic liver transplants (OLT. However, this technique has a number of disadvantages, including difficulty of performance of the technique visually unaided. We herein describe a novel rearterialized OLT model in the rat.Forty-six male Sprague Dawley rats (300-400 g were used as donors and recipients. Based on Kamada's cuff technique, the new model involved performing a modified "sleeve" anastomosis between the celiac trunk of the donor and common hepatic artery of the recipient to reconstruct blood flow to the hepatic artery. An additional ten male Sprague Dawley rats underwent liver transplantation without artery reconstruction. Liver grafts were retrieved from the two groups and histological examination was performed following surgery.Total mean operating times were ~42 minutes for the donor liver extraction and 57 minutes for the recipient transplantation. Graft preparation took an additional 15 minutes and the time to fix the arterial bracket was ~3 minutes. During transplantation, the anhepatic phase lasted 18 ± 2.5 min and the artery reconstruction only required ~3 minutes. The patency rate was 94.44% and the 4-week survival rate was 90%. Histology indicated obvious fibrosis in the liver grafts without artery reconstruction, while normal histology was observed in the arterialized graft.This new method allows for the surgical procedure to be performed visually unaided with good survival and patency rates and represents an alternative model investigating OLT in rats.

  17. Charles River Sprague Dawley rats lack early age-dependent susceptibility to DMBA-induced mammary carcinogenesis.

    Science.gov (United States)

    Gear, R B; Yan, M; Schneider, J; Succop, P; Heffelfinger, S C; Clegg, D J

    2007-10-04

    Developmental stages of mammary glands influence their susceptibility to initiating events related to carcinogenesis. The "window of susceptibility" to mammary carcinogenesis is classically defined as the time in early puberty when the mammary gland morphology is most sensitive to initiation events. Administration of the polyaromatic hydrocarbon, 7,12-dimethylbenz(a)anthracene (DMBA), in a single oral dose yields maximal mammary tumor formation when administered in this "window". We examined the DMBA treated mammary glands, precursor lesions, and morphology of the uninvolved mammary epithelium for the first 100 days of life for Charles River Sprague Dawley CD(R) IGS. Our goal was to determine the DMBA dose at which 50% of the rats (IC50) developed carcinoma in situ (CIS) within three months of dosing. Here we demonstrate, rather than the classical U-shaped dose curve in which there is maximum sensitivity for DMBA at 50 days, there is an increasing degree of sensitivity with age in the CD(R) IGS rat. Additionally, we report that vehicle-treated animals developed mammary CIS without any known initiator, and 100 day virgin animals demonstrated lactational changes, independent of DMBA exposure or dose. Lastly, we demonstrate this strain of virgin female rats has elevated pituitary prolactin immunoreactivity independent of the level of mammary differentiation. We conclude this strain of Charles River Sprague Dawley rats has prolactin-induced pituitary stimulation, and therefore, the window of susceptibility for mammary tumorigenesis is absent.

  18. The impact of adult vitamin D deficiency on behaviour and brain function in male Sprague-Dawley rats.

    Directory of Open Access Journals (Sweden)

    Jacqueline H Byrne

    Full Text Available BACKGROUND: Vitamin D deficiency is common in the adult population, and this has been linked to depression and cognitive outcomes in clinical populations. The aim of this study was to investigate the effects of adult vitamin D (AVD deficiency on behavioural tasks of relevance to neuropsychiatric disorders in male Sprague-Dawley rats. METHODS: Ten-week old male Sprague-Dawley rats were fed a control or vitamin D deficient diet for 6 weeks prior to, and during behavioural testing. We first examined a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception. We then assessed locomotor response to the psychomimetic drugs, amphetamine and MK-801. Attention and vigilance were assessed using the 5 choice serial reaction time task (5C-SRT and the 5 choice continuous performance task (5C-CPT and, in a separate cohort, working memory was assessed using the delay match to sample (DMTS task. We also examined excitatory and inhibitory neurotransmitters in prefrontal cortex and striatum. RESULTS: AVD-deficient rats were deficient in vitamin D3 (<10 nM and had normal calcium and phosphate levels after 8-10 weeks on the diet. Overall, AVD deficiency was not associated with an altered phenotype across the range of behavioural domains tested. On the 5C-SRT AVD-deficient rats made more premature responses and more head entries during longer inter-trial intervals (ITI than control rats. On the 5C-CPT AVD-deficient rats took longer to make false alarm (FA responses than control rats. AVD-deficient rats had increases in baseline GABA levels and the ratio of DOPAC/HVA within the striatum. CONCLUSIONS: AVD-deficient rats exhibited no major impairments in any of the behavioural domains tested. Impairments in premature responses in AVD-deficient rats may indicate that these animals have specific alterations in striatal systems governing compulsive or reward-seeking behaviour.

  19. Ninety-day oral toxicity study of rice-derived γ-oryzanol in Sprague-Dawley rats.

    Science.gov (United States)

    Moon, Seol-Hee; Kim, Duyeol; Shimizu, Norihito; Okada, Tadashi; Hitoe, Shoketsu; Shimoda, Hiroshi

    2017-01-01

    A 90-day oral toxicity study of γ-oryzanol, a rice-derived triterpenoid ferulate, was performed by oral gavage administration to male and female Sprague-Dawley rats at doses of 0, 1000, and 2000 mg/kg body weight/day. All rats administered γ-oryzanol survived throughout the study period. Both male and female rats showed no toxicologically significant changes of the general signs, examination findings, body weight, food consumption, functional observational battery results, ophthalmological findings, urinalysis, hematology tests, clinical chemistry tests, organ weights, and necropsy findings. Moreover, there were no histopathological changes related to administration of γ-oryzanol in males and females from the 2000 mg/kg body weight/day group. In conclusion, the no observed adverse effect level (NOAEL) of γ-oryzanol exceeded 2000 mg/kg body weight/day for both male and female rats under the conditions of this study.

  20. [Free radical modification of proteins in brain structure of Sprague-Dawley rats and some behaviour indicators after prenatal stress].

    Science.gov (United States)

    V'iushina, A V; Pritvorova, A V; Flerov, M A

    2012-08-01

    We studied the influence of late prenatal stress on free radical oxidation processes in Sprague-Dawley rats cortex, striatum, hippocampus, hypothalamus proteins. It was shown that after prenatal stress most changes were observed in hypothalamus and hippocampus. It was shown that in hypothalamus spontaneous oxidation level increased, but level of induced oxidation decreased, the opposite changes were found in hippocampus. Simultaneously minor changes of protein modification were observed in cortex and striatum. It was shown that prenatal stress changed both correlation of proteins free radical oxidation in studied structures and values of these data regarding to control. In test of "open field" motor activity in rats after prenatal stress decreased and time of freezing and grooming increased; opposite, in T-labyrinth motor activity and time of grooming in rats after prenatal stress increased, but time of freezing decreased.

  1. Determination of human and Sprague-Dawley rat trimethylseleonium ion and total selenium urine concentrations from endogenous body selenium pool by neutron activation analysis

    International Nuclear Information System (INIS)

    Blotcky, A.J.; Claassen, J.P.; Rack, E.P.

    1992-01-01

    This study determined trimethylselenonium ion [TMSe,(CH 3 ) 3 Se + ] and total organic selenium cationic species urinary excretion values for healthy human subjects and Sprague-Dawley rats fed regular diets. The only source of TMSe was from the endogenous selenium body pool. Total selenium concentration in urine was determined by instrumental neutron activation analysis. TMSe and total selenium cationic species concentrations and percent of total selenium urine excretion were determined by chemical neutron activation analysis and coupled anion-cation exchange chromatography and anion-exchange chromatography, respectively. Within experimental error, mean values for TMSe and cationic species as percent selenium were comparable for both human subjects and Sprague-Dawley rats. This study suggested that TMSe excreated in urine by healthy human subjects and Sprague-Dawley rats fed a normal diet is not a minor but a general metabolite of selenium ingested in a normal diet. (author) 27 refs.; 1 fig.; 2 tabs

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

    DEFF Research Database (Denmark)

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

    2018-01-01

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

  3. Potential subchronic food safety of the stacked trait transgenic maize GH5112E-117C in Sprague-Dawley rats.

    Science.gov (United States)

    Han, Shiwen; Zou, Shiying; He, Xiaoyun; Huang, Kunlun; Mei, Xiaohong

    2016-08-01

    The food safety of stacked trait genetically modified (GM) maize GH5112E-117C containing insect-resistance gene Cry1Ah and glyphosate-resistant gene G2-aroA was evaluated in comparison to non-GM Hi-II maize fed to Sprague-Dawley rats during a 90-day subchronic feeding study. Three different dietary concentrations (12.5, 25 and 50 %, w/w) of the GM maize were used or its corresponding non-GM maize. No biologically significant differences in the animals' clinical signs, body weights, food consumption, hematology, clinical chemistry, organ weights and histopathology were found between the stacked trait GM maize groups, and the non-GM maize groups. The results of the 90-day subchronic feeding study demonstrated that the stacked trait GM maize GH5112E-117C is as safe as the conventional non-GM maize Hi-II.

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

    Directory of Open Access Journals (Sweden)

    Izatus Shima Taib

    2013-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  6. Norepinephrine-evoked salt-sensitive hypertension requires impaired renal sodium chloride cotransporter activity in Sprague-Dawley rats.

    Science.gov (United States)

    Walsh, Kathryn R; Kuwabara, Jill T; Shim, Joon W; Wainford, Richard D

    2016-01-15

    Recent studies have implicated a role of norepinephrine (NE) in the activation of the sodium chloride cotransporter (NCC) to drive the development of salt-sensitive hypertension. However, the interaction between NE and increased salt intake on blood pressure remains to be fully elucidated. This study examined the impact of a continuous NE infusion on sodium homeostasis and blood pressure in conscious Sprague-Dawley rats challenged with a normal (NS; 0.6% NaCl) or high-salt (HS; 8% NaCl) diet for 14 days. Naïve and saline-infused Sprague-Dawley rats remained normotensive when placed on HS and exhibited dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide. NE infusion resulted in the development of hypertension, which was exacerbated by HS, demonstrating the development of the salt sensitivity of blood pressure [MAP (mmHg) NE+NS: 151 ± 3 vs. NE+HS: 172 ± 4; P salt-sensitive animals, increased NE prevented dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide, suggesting impaired NCC activity contributes to the development of salt sensitivity [peak natriuresis to hydrochlorothiazide (μeq/min) Naïve+NS: 9.4 ± 0.2 vs. Naïve+HS: 7 ± 0.1; P salt-sensitive component of NE-mediated hypertension, while chronic ANG II type 1 receptor antagonism significantly attenuated NE-evoked hypertension without restoring NCC function. These data demonstrate that increased levels of NE prevent dietary sodium-evoked suppression of the NCC, via an ANG II-independent mechanism, to stimulate the development of salt-sensitive hypertension. Copyright © 2016 the American Physiological Society.

  7. Acute prenatal exposure to ethanol on gestational day 12 elicits opposing deficits in social behaviors and anxiety-like behaviors in Sprague Dawley rats.

    Science.gov (United States)

    Diaz, Marvin R; Mooney, Sandra M; Varlinskaya, Elena I

    2016-09-01

    Our previous research has shown that in Long Evans rats acute prenatal exposure to a high dose of ethanol on gestational day (G) 12 produces social deficits in male offspring and elicits substantial decreases in social preference relative to controls, in late adolescents and adults regardless of sex. In order to generalize the observed detrimental effects of ethanol exposure on G12, pregnant female Sprague Dawley rats were exposed to ethanol or saline and their offspring were assessed in a modified social interaction (SI) test as early adolescents, late adolescents, or young adults. Anxiety-like behavior was also assessed in adults using the elevated plus maze (EPM) or the light/dark box (LDB) test. Age- and sex-dependent social alterations were evident in ethanol-exposed animals. Ethanol-exposed males showed deficits in social investigation at all ages and age-dependent alterations in social preference. Play fighting was not affected in males. In contrast, ethanol-exposed early adolescent females showed no changes in social interactions, whereas older females demonstrated social deficits and social indifference. In adulthood, anxiety-like behavior was decreased in males and females prenatally exposed to ethanol in the EPM, but not the LDB. These findings suggest that social alterations associated with acute exposure to ethanol on G12 are not strain-specific, although they are more pronounced in Long Evans males and Sprague Dawley females. Furthermore, given that anxiety-like behaviors were attenuated in a test-specific manner, this study indicates that early ethanol exposure can have differential effects on different forms of anxiety. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Short-term administration of an aqueous extract of kalanchoe integra var. crenata (Andr.) Cuf leaves produces no major organ damage in Sprague-Dawley rats.

    Science.gov (United States)

    Asiedu-Gyekye, Isaac J; Antwi, Daniel A; Awortwe, Charles; N'guessan, Benoit Banga; Nyarko, Alexander K

    2014-02-03

    Kalanchoe intergra (Ki) leaf extract is an orally administered multipurpose plant medicine in Ghana and other parts of the world for the treatment of ulcers, pain and adenoma of the prostate gland. There is paucity of information concerning its short-term usage. The present study is aimed at conducting histopathological and biochemical studies in a 14-day sub-acute toxicity studies using female Sprague-Dawley rats. Crude extract of Ki leaves was prepared and freeze-dried. A 14-day sub-acute toxicity studies was conducted using 2 week old nulliparous and non-pregnant female Sprague-Dawley rats (120-150g). Reconstituted Ki was administered at a dosage of 900mgkg(-1) (high dose), 300mgkg(-1) with a control group receiving an equivalent volume of distilled water (as vehicle) by gastric lavage. Histopathological studies of major organs and blood chemistry analysis were performed on blood obtained via cardiac puncture into EDTA tubes after euthanisation. There was a significant decrease in urea (p<0.016) and creatinine levels (p<0.001) in both the high and low dose groups. There was an increase in ALP levels (P=0.01) in both the high and low dose groups. ALT and AST rather decreased significantly in both the high and low dose groups (p<0.0001). Histopathological results did not show any abnormalities in all the H&E stained paraffin sections. Thus the photomicrographs of the liver, kidney and heart were within histopathological limits. Ki leaf extract is non-toxic when administered by the oral route over a time period of 14 days at the above doses. © 2013 The Authors. Published by Elsevier Ireland Ltd All rights reserved.

  9. Ninety-day oral toxicity study of rice-derived γ-oryzanol in Sprague-Dawley rats

    Directory of Open Access Journals (Sweden)

    Seol-Hee Moon

    Full Text Available A 90-day oral toxicity study of γ-oryzanol, a rice-derived triterpenoid ferulate, was performed by oral gavage administration to male and female Sprague-Dawley rats at doses of 0, 1000, and 2000 mg/kg body weight/day. All rats administered γ-oryzanol survived throughout the study period. Both male and female rats showed no toxicologically significant changes of the general signs, examination findings, body weight, food consumption, functional observational battery results, ophthalmological findings, urinalysis, hematology tests, clinical chemistry tests, organ weights, and necropsy findings. Moreover, there were no histopathological changes related to administration of γ-oryzanol in males and females from the 2000 mg/kg body weight/day group. In conclusion, the no observed adverse effect level (NOAEL of γ-oryzanol exceeded 2000 mg/kg body weight/day for both male and female rats under the conditions of this study. Keywords: γ-Oryznaol, Rice, Rat, Repeated-dose oral toxicity study, NOAEL

  10. Protective Effects of Tamarillo (Cyphomandra betacea Extract against High Fat Diet Induced Obesity in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Noor Atiqah Aizan Abdul Kadir

    2015-01-01

    Full Text Available This study aims to investigate the protective effect of Cyphomandra betacea in adult male Sprague-Dawley rats fed with high fat diet. Rats were fed on either normal chow or high fat diet for 10 weeks for obesity induction phase and subsequently received C. betacea extract at low dose (150 mg kg−1, medium dose (200 mg kg−1, or high dose (300 mg kg−1 or placebo via oral gavages for another 7 weeks for treatment phase. Treatment of obese rats with C. betacea extracts led to a significant decrease in total cholesterol and significant increase in HDL-C (p<0.05. Also there was a trend of positive reduction in blood glucose, triglyceride, and LDL-C with positive reduction of body weight detected in medium and high dosage of C. betacea extract. Interestingly, C. betacea treated rats showed positive improvement of superoxide dismutase (SOD activity and glutathione peroxidase (GPx activity along with a significant increase of total antioxidant status (TAS (p<0.05. Further, rats treated with C. betacea show significantly lower in TNF-α and IL-6 activities (p<0.05. This study demonstrates the potential use of Cyphomandra betacea extract for weight maintenance and complimentary therapy to suppress some obesity complication signs.

  11. A 4-Week Repeated-Dose Oral Toxicity Study of Bojungikgi-Tang in Crl:CD Sprague Dawley Rats

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    Sae-Rom Yoo

    2017-01-01

    Full Text Available Traditional herbal medicines have been used for centuries in Asian countries. However, recent studies have led to increasing concerns about the safety and toxicity of herbal prescriptions. Bojungikgi-tang (BJIGT, a herbal decoction, has been used in Korea to improve physical strength. To establish the safety information, BJIGT water extract was evaluated in a 4-week repeated-dose oral toxicity test in Crl:CD Sprague Dawley rats. BJIGT was orally administered in daily doses of 0, 500, 1000, and 2000 mg/kg/day for 4 weeks via oral gavage in male and female rats. We examined the mortality, clinical signs, body weight change, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters. No significant changes were observed in mortality, clinical sings, body weight, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters between the control group and the BJIGT-treated groups in the rats of both sexes. The results indicate that BJIGT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. Thus, this concentration is considered the nonobservable effect dose in rats and is appropriate for a 13-week subchronic toxicity study.

  12. Investigation of the Blood Glucose Lowering Potential of the Jamaican Momordica charantia (Cerasee) Fruit in Sprague-Dawley Rats

    Science.gov (United States)

    Burnett, A; McKoy, M-L; Singh, P

    2015-01-01

    ABSTRACT The Momordica charantia (MC) fruit has been documented to possess antidiabetic properties. However, these studies were not without controversy surrounding the blood glucose-lowering ability and the mechanism of action in diabetes therapy. In an effort to evaluate such claims in the Jamaican MC species known as cerasee, aqueous extracts of the unripe fruit were studied in normal and diabetic rats. Normal male Sprague-Dawley rats were divided into groups (n = 6) orally administered distilled water, 10% dimethyl sulfoxide (DMSO) solution, the aqueous extract (400 mg/kg body weight) and glibenclamide (15 mg/kg body weight), respectively prior to assessment of fasting blood glucose (FBG) concentration. The oral glucose tolerance test (OGTT) was conducted in normoglycaemic rats orally administered distilled water, 10% DMSO solution, glibenclamide (15 mg/kg body weight) or aqueous extracts of the fruit (200 and 400 mg/kg body weight). Blood glucose concentration was also monitored in streptozotocin-induced diabetic rats administered the aqueous extract (250 mg/kg body weight) or water vehicle after an overnight fast. The aqueous extracts showed no hypoglycaemic or antidiabetic activity. However, the administration of the aqueous extracts (200 and 400 mg/kg body weight) resulted in significant improvement in glucose tolerance of glucose-primed normoglycaemic rats during the OGTT. These data suggest that the glucose-lowering mechanism of the Jamaican MC fruit species likely involves altered glucose absorption across the gastrointestinal tract. PMID:26624580

  13. Protective role of ginger on lead induced derangement in plasma testosterone and luteinizing hormone levels of male sprague dawley rats

    International Nuclear Information System (INIS)

    Riaz, F.; Ayub, M.; Shaukat, S.

    2011-01-01

    Background: Lead is one of the most serious environmental threats to human health especially in developing countries. It damages multiple body systems including the reproductive system. Ginger's antioxidant and androgenic activity is reported in multiple animal studies. The aim of this study was to investigate the ameliorative effect of Zingiber officinale (ginger) on lead induced derangement in plasma testosterone and luteinizing hormone (LH) levels of male rats. Methods: Sixty adult male Sprague Dawley rats were used in this study in four groups. Group A served as normal control, Group B received 0.3% lead acetate in drinking water, Group C and group D received supplementary 0.5 and 1 gm/Kg bodyweight of ginger respectively along with lead acetate in drinking water. Five rats from each group were sacrificed at the end of 2nd, 4th and 6th weeks. Serum testosterone and LH levels were analysed using ELISA technique. Results: After co administration with different doses of ginger, serum testosterone level which was significantly decreased in lead treated group, showed a significant rise as compared to lead treated group. LH levels which had exhibited no significant change by lead treatment, after co administration with different doses of ginger, again showed no significant change. Conclusion: Oral administration of ginger ameliorated lead induced testicular toxicity in male rats by increasing serum testosterone level at all durations which might be a product of both its androgenic and antioxidant properties. (author)

  14. Effects of sex, age, and fasting conditions on plasma lipidomic profiles of fasted Sprague-Dawley rats.

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    Kosuke Saito

    Full Text Available Circulating lipid molecules reflect biological processes in the body and, thus, are useful tools for preclinical estimation of the efficacy and safety of newly developed drugs. However, background information on profiles of circulating lipid molecules in preclinical animal models is limited. Therefore, we examined the effects of multiple factors such as sex (fasted male vs. female, age (fasted 10 vs. 30 weeks old, and feeding conditions (feeding vs. fasting, 16 vs. 22 hr fasting, 10 AM vs. 4 PM blood collection, on the global profiles of lipid molecules in plasma from Sprague-Dawley rats by using a lipidomic approach. Our assay platform determined 262 lipid molecules (68 phospholipids, 20 sphingolipids, 138 neutral lipids, and 36 polyunsaturated fatty acids and their metabolites in rat plasma. Multivariate discriminant analysis (orthogonal partial least squares discriminant analysis and heat maps of statistically significant lipid molecules revealed that the plasma lipid profiles in rats are predominantly influenced by feeding conditions, followed by sex and age. In addition, the fasting duration (16 vs. 22 hr fasting or the time of blood collection (10 AM vs. 4 PM blood collection has limited or no contribution on the profiles of lipid molecules in rat plasma. Our results provide useful, fundamental information for exploring and validating biomarkers in future preclinical studies and may help to establish regulatory standards for such studies.

  15. Acute, reproductive toxicity and two-generation teratology studies of a standardized quassinoid-rich extract of Eurycoma longifolia Jack in Sprague-Dawley rats.

    Science.gov (United States)

    Low, Bin-Seng; Das, Prashanta Kumar; Chan, Kit-Lam

    2014-07-01

    The roots of Eurycoma longifolia Jack are popularly sought as herbal medicinal supplements to improve libido and general health amongst the local ethnic population. The major quassinoids of E. longifolia improved spermatogenesis and fertility but toxicity studies have not been well documented. The reproductive toxicity, two generation of foetus teratology and the up-and-down acute toxicity were investigated in Sprague-Dawley rats orally treated with quassinoid-rich E. longifolia extract (TAF273). The results showed that the median lethal dose (LD50 ) of TAF273 for female and male rats was 1293 and >2000 mg/kg, respectively. Fertility index and litter size of the TAF273 treated were significantly increased when compared with those of the non-treated animals. The TAF273-treated dams decreased in percentage of pre-implantation loss, post-implantation loss and late resorption. No toxic symptoms were observed on the TAF273-treated pregnant female rats and their foetuses were normal. The no-observed adverse effect level (NOAEL) obtained from reproductive toxicity and teratology studies of TAF273 in rats was 100 mg/kg body weight/day, being more than 10-fold lower than the LD50 value. Thus, any human dose derived from converting the rat doses of 100 mg/kg and below may be considered as safe for further clinical studies. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Analysis of testosterone effects on sonic hedgehog signaling in juvenile, adolescent and adult sprague dawley rat penis.

    Science.gov (United States)

    Bond, Christopher W; Angeloni, Nicholas L; Podlasek, Carol A

    2010-03-01

    Smooth muscle apoptosis is a major contributing factor to erectile dysfunction (ED) development in prostatectomy and diabetic patients and animal models. A critical regulator of penile smooth muscle and apoptosis is Sonic hedgehog (SHH). The SHH protein is decreased in ED models and SHH treatment of cavernous nerve (CN) injured rats prevents smooth muscle apoptosis. A close association between androgen deficiency and ED has been suggested in the literature, but few studies have examined the molecular effects on penile smooth muscle and on known signaling mechanisms that regulate morphology. Aim. Examine testosterone and SHH interaction in eugonadal adult, adolescent and juvenile rats by performing castration studies and treatment with supraphysiological testosterone. The eugonadal adult Sprague Dawley rats were either treated with testosterone for 7 or 14 days (N = 14) or were castrated for 4 or 7 days (N = 12). The juvenile rats were treated with testosterone for 8 days (N = 7). The adolescent rats were castrated and sacrificed at P88 (N = 8). The control rats had empty vehicle (N = 22) or sham surgery (N = 20). The active form of SHH protein and mRNA were quantified by semi-quantitative immunohistochemical analysis and real-time reverse transcriptase polymerase chain reaction (RT-PCR). Testosterone treatment did not alter SHH signaling in juvenile rats. Shh mRNA increased 3.2-fold and SHH protein increased 1.2-fold in rats castrated during puberty. In adult rats, castration decreased Shh mRNA 3.2-fold but did not alter SHH protein. Testosterone supplement in adult rats increased Shh mRNA 2.3-fold and decreased SHH protein 1.3-fold. SHH signaling is independent of testosterone in normal juvenile rats and is sensitive to testosterone during adolescence, while testosterone supplement in the adult adversely impacts SHH signaling in a very similar manner to that observed with CN injury.

  17. Voluntary Binge Consumption of Ethanol in a Sweetened, Chocolate-Flavored Solution by Male and Female Adolescent Sprague Dawley Rats.

    Science.gov (United States)

    Hosová, Dominika; Spear, Linda Patia

    2017-03-01

    The still maturing adolescent brain may be particularly vulnerable to lasting consequences of ethanol (EtOH) exposure. Yet, human adolescents are the age group most likely to engage in binge drinking (a pattern of drinking leading to blood EtOH concentrations (BECs) of 80 mg/dl or greater). Most studies to date assessing the long-term effects of adolescent EtOH exposure in outbred rodent populations have either used experimenter-administered EtOH to produce BECs in the binge range or assessed voluntary intake of EtOH at well below binge levels. Beginning with a modified schedule-induced polydipsia (SIP) procedure, this study examined the suitability of several approaches to induce voluntary binge-like consumption during adolescence in an outbred rat strain. Adolescent male and female Sprague Dawley rats were food deprived to 85% projected free-feeding weights beginning on postnatal day (P) 24 and were given 30 minutes of access to 10% EtOH in chocolate Boost ® or Boost ® alone daily from P28 to P41 (followed later by their daily allocation of food). Animals were tested within operant chambers (Exp. 1a, 1b and Exp. 2) or home and novel cages (Exp. 3). Animals received either scheduled delivery of banana pellets to examine SIP (Exp. 1a,b) or massed pellet presentation (Exp. 2 and Exp. 3). Blood samples were collected via the lateral tail vein on P33 and P41. Intakes produced BECs frequently in the binge range (>80 mg/dl) and modeled binge-like consumption patterns, with high consumption days typically followed by 1 to 2 days of lower consumption; this variability was less evident with Boost ® alone. Consumption was not schedule induced and was generally high across all studies, although consumption in males appeared to be particularly pronounced when animals were tested in the presence of their cage mate. Binge-like patterns of EtOH consumption were produced using these procedures in adolescent Sprague Dawley rats of both sexes and may prove to be a useful

  18. Comprehensive behavioural analysis of Long Evans and Sprague-Dawley rats reveals differential effects of housing conditions on tests relevant to neuropsychiatric disorders.

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    Karly M Turner

    Full Text Available Genetic (G and environmental (E manipulations are known to alter behavioural outcomes in rodents, however many animal models of neuropsychiatric disorders only use a restricted selection of strain and housing conditions. The aim of this study was to examine GxE interactions comparing two outbred rat strains, which were housed in either standard or enriched cages. The strains selected were the albino Sprague-Dawley rat, commonly used for animal models, and the other was the pigmented Long Evans rat, which is frequently used in cognitive studies. Rats were assessed using a comprehensive behavioural test battery and included well-established tests frequently employed to examine animal models of neuropsychiatric diseases, measuring aspects of anxiety, exploration, sensorimotor gating and cognition. Selective strain and housing effects were observed on a number of tests. These included increased locomotion and reduced pre-pulse inhibition in Long Evans rats compared to Sprague Dawley rats; and rats housed in enriched cages had reduced anxiety-like behaviour compared to standard housed rats. Long Evans rats required fewer sessions than Sprague Dawley rats to learn operant tasks, including a signal detection task and reversal learning. Furthermore, Long Evans rats housed in enriched cages acquired simple operant tasks faster than standard housed Long Evans rats. Cognitive phenotypes in animal models of neuropsychiatric disorders would benefit from using strain and housing conditions where there is greater potential for both enhancement and deficits in performance.

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

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    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.

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

    Science.gov (United States)

    Abey, Nosarieme Omoregie

    2018-06-01

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

  1. A Pilot Study on Single-dose Toxicity Testing of Scolopendrid Pharmacopuncture in Sprague-Dawley Rats

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    Ilhong Son

    2014-06-01

    Full Text Available Objectives:This study was performed to analyze single dose toxicity and the lethal dose of Scolopendrid Pharmacopuncture in rats. Methods:All experiments were conducted at the Korea Testing & Research Institute (KTR, an institution authorized to perform non-clinical studies, under the regulations of Good Laboratory Practice (GLP. Sprague-Dawley rats were chosen for the pilot study. Doses of Scolopendrid pharmacopuncture, 0.1, 0.5, and 1.0 mL, were administered to the experimental group, and 1.0 mL doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethic Committee. Results:No deaths or abnormalities occurred in any of the groups. No significant changes in the weight, hematological parameters or clinical chemistry were noted between the control group and the experimental group. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. Conclusion:The above findings suggest Scolopendrid Pharmacopuncture is a relatively safe to use for treatment. Further studies on the subject should be conducted to yield more concrete evidence.

  2. Identification of proteins involved in the pancreatic exocrine by exogenous ghrelin administration in Sprague-Dawley rats.

    Science.gov (United States)

    Lee, Kyung-Hoon; Wang, Tao; Jin, Yong-Cheng; Lee, Sang-Bum; Oh, Jin-Ju; Hwang, Jin-Hee; Lim, Ji-Na; Lee, Jae-Sung; Lee, Hong-Gu

    2014-01-01

    The aims of study were to investigate the effects of intraperitoneal (i.p.) infusion of ghrelin on pancreatic α-amylase outputs and the responses of pancreatic proteins to ghrelin that may relate to the pancreatic exocrine. Six male Sprague-Dawley rats (300 g) were randomly divided into two groups, a control group (C, n = 3) and a treatment group (T, 10.0μg/kg BW, n = 3). Blood samples were collected from rat caudal vein once time after one hour injection. The concentrations of plasma ghrelin, cholecystokinin (CCK) and alfa-amylase activity were evaluated by enzyme immunoassay (EIA) kit. Two-dimensional gel electrophoresis (2-DE) analysis was conducted to separate the proteins in pancreas tissue. Results showed that the i.p. infusion of ghrelin at doses of 10.0 μg/kg body weight (BW) increased the plasma ghrelin concentrations (p = 0.07) and elevated the plasma CCK level significantly (p amylase activity tended to increase. The proteomics analysis indicated that some pancreatic proteins with various functions were up- or down- regulated compared with control group. In conclusion, ghrelin may have role in the pancreatic exocrine, but the signaling pathway was still not clear. Therefore, much more functional studies focus on these found proteins are needed in the near future.

  3. Dose-rate effects for mammary tumor development in female Sprague-Dawley rats exposed to X and γ radiation

    International Nuclear Information System (INIS)

    Johnson, J.R.; Gragtmans, N.J.; Myers, D.K.; Jones, A.R.

    1989-01-01

    Mammary tumour development was followed in two experiments involving a total of 2229 female Sprague-Dawley rats exposed to various doses of X or γ rays at different dose rates. The data for another 462 rats exposed to tritiated water in one of these experiments were also analyzed. The incidence of adenocarcinomas and fibroadenomas at a given time after exposure increased linearly in proportion to total radiation dose for most groups. However, no significant increase in adenocarcinomas was observed with chronic γ exposures up to 1.1 Gy, and the increase in fibroadenomas observed with chronic gamma exposures at a dose rate of 0.0076 Gy h -1 up to an accumulated dose of 3.3 Gy was small compared to that observed after acute exposures. The incidence of all mammary tumors increased almost linearly with the log of dose rate in the range 0.0076 to 26.3 Gy h -1 for 3 Gy total dose of gamma rays. The effects of X rays appeared to be less influenced by dose rate than were the effects of γ rays. (author)

  4. 4-Vinylcyclohexene Diepoxide (VCD) Inhibits Mammary Epithelial Differentiation and Induces Fibroadenoma Formation in Female Sprague Dawley Rats

    Science.gov (United States)

    Wright, Laura E.; Frye, Jennifer B.; Lukefahr, Ashley L.; Marion, Samuel L.; Hoyer, Patricia B.; Besselsen, David G.; Funk, Janet L.

    2011-01-01

    4-Vinylcyclohexene diepoxide (VCD), an occupational chemical that targets ovarian follicles and accelerates ovarian failure in rodents, was used to test the effect of early-onset reproductive senescence on mammary fibroadenoma formation. One-month female Sprague Dawley rats were dosed with VCD (80 mg/kg or 160 mg/kg) and monitored for 22 months for persistent estrus and tumor development. Only high-dose VCD treatment accelerated the onset of persistent estrus relative to controls. However, both doses of VCD accelerated mammary tumor onset by 5 months, increasing incidence to 84% (vs. 38% in controls). Tumor development was independent of time in persistent estrus, 17β-estradiol, androstenedione and prolactin. Delay in VCD administration until after completion of mammary epithelial differentiation (3 months) did not alter tumor formation despite acceleration of ovarian senescence. VCD administration to 1-month rats acutely decreased mammary alveolar bud number and expression of β-casein, suggesting that VCD’s tumorigenic effect requires exposure during mammary epithelial differentiation. PMID:21621605

  5. Effect of Piper sarmentosum Extract on the Cardiovascular System of Diabetic Sprague-Dawley Rats: Electron Microscopic Study

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    Zar Chi Thent

    2012-01-01

    Full Text Available Although Piper sarmentosum (PS is known to possess the antidiabetic properties, its efficacy towards diabetic cardiovascular tissues is still obscured. The present study aimed to observe the electron microscopic changes on the cardiac tissue and proximal aorta of experimental rats treated with PS extract. Thirty-two male Sprague-Dawley rats were divided into four groups: untreated control group (C, PS-treated control group (CTx, untreated diabetic group (D, and PS-treated diabetic group (DTx. Intramuscular injection of streptozotocin (STZ, 50 mg/kg body weight was given to induce diabetes. Following 28 days of diabetes induction, PS extract (0.125 g/kg body weight was administered orally for 28 days. Body weight, fasting blood glucose, and urine glucose levels were measured at 4-week interval. At the end of the study, cardiac tissues and the aorta were viewed under transmission electron microscope (TEM. DTx group showed increase in body weight and decrease in fasting blood glucose and urine glucose level compared to the D group. Under TEM study, DTx group showed lesser ultrastructural degenerative changes in the cardiac tissues and the proximal aorta compared to the D group. The results indicate that PS restores ultrastructural integrity in the diabetic cardiovascular tissues.

  6. Molecular basis for the effects of zinc deficiency on spermatogenesis: An experimental study in the Sprague-dawley rat model

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    Alexander E Omu

    2015-01-01

    Full Text Available Introduction: The objective of this study is to investigate the molecular mechanisms underlying the effects of zinc deficiency on spermatogenesis in the Sprague-Dawley (SD rat. Materials and Methods: Three groups of eight adult male SD rats were maintained for 4 weeks on a normal diet as control, zinc deficient diet and zinc deficient diet with zinc supplementation of 28 mg zinc/kg body weight respectively. Using standard techniques, the following parameters were compared between the three groups of experimental animals at the end of 4 weeks: (a Serum zinc, magnesium (Mg, copper (Cu, selenium (Se and cadmium (Cd, (b serum sex hormones, malondialdehyde (MDA, superoxide dismutase (SOD and glutathione peroxidase (GPX, (c interleukin-4 (IL-4, tumor necrosis factor-alpha (TNF-α, Bcl-2, Bax and caspase-3 expression in the testes, (d assessment of apoptosis of testicular cells using electron microscopy and (e testicular volume and histology using the orchidometer and Johnsen score, respectively. Results: The zinc deficient group showed a reduction of testicular volume, serum concentrations of Zn, Cu, Se, Mg, SOD, GPX, IL-4, Bcl-2 and testosterone (P < 0.05, as well as increased levels of serum Cd, MDA and tissue TNF-α, Bax, caspase-3 and apoptosis of the germ cells (P < 0.05 compared with control and zinc supplementation groups. Conclusion: Zinc deficiency is associated with impaired spermatogenesis because of reduced testosterone production, increased oxidative stress and apoptosis. These findings suggest that zinc has a role in male reproduction.

  7. Effects of applying anchovy (Stolephorus insularis) substrates on the microhardness of tooth enamel in Sprague-Dawley rats

    Science.gov (United States)

    Hendrik, Y. C.; Puspitawati, R.; Gunawan, H. A.

    2017-08-01

    Anchovies (Stolephorus insularis) contain high levels of fluor in the form of CaF2. The aim of this study is to analyze changes in tooth enamel microhardness after application of anchovy substrates by feeding or as a topical fluoridation material. An in vivo study of the lower left incisors of nine Sprague-Dawley rats was conducted. The sample was comprised of baseline and treatment groups, including feeding application, topical application, negative control feeding, and negative control topical groups. The treatment groups were given 5% anchovy substrates through feeding and topical applications. After treatment, tooth samples were extracted from each of the rats for examination, and statistical analyses were performed after determining hardness numbers for enamel surfaces using Vickers microhardness tester. Vickers hardness numbers (VHNs) for anchovy substrate application and consumption by feeding (440.3 ± 24.72) were higher than for the negative control (315.80 ± 17.51). VHNs for the topical application group were higher than for the negative control (347.28 ± 28.56) and for the feeding group. The use of anchovy as a fluoridation material in form of topical application is potentially an effective method for increasing the microhardness of the tooth enamel surface

  8. Common handling procedures conducted in preclinical safety studies result in minimal hepatic gene expression changes in Sprague-Dawley rats.

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    Yudong D He

    Full Text Available Gene expression profiling is a tool to gain mechanistic understanding of adverse effects in response to compound exposure. However, little is known about how the common handling procedures of experimental animals during a preclinical study alter baseline gene expression. We report gene expression changes in the livers of female Sprague-Dawley rats following common handling procedures. Baseline gene expression changes identified in this study provide insight on how these changes may affect interpretation of gene expression profiles following compound exposure. Rats were divided into three groups. One group was not subjected to handling procedures and served as controls for both handled groups. Animals in the other two groups were weighed, subjected to restraint in Broome restrainers, and administered water via oral gavage daily for 1 or 4 days with tail vein blood collections at 1, 2, 4, and 8 hours postdose on days 1 and 4. Significantly altered genes were identified in livers of animals following 1 or 4 days of handling when compared to the unhandled animals. Gene changes in animals handled for 4 days were similar to those handled for 1 day, suggesting a lack of habituation. The altered genes were primarily immune function related genes. These findings, along with a correlating increase in corticosterone levels suggest that common handling procedures may cause a minor immune system perturbance.

  9. Behavioral Phenotyping of Juvenile Long-Evans and Sprague-Dawley Rats: Implications for Preclinical Models of Autism Spectrum Disorders.

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    Katherine M Ku

    Full Text Available The laboratory rat is emerging as an attractive preclinical animal model of autism spectrum disorder (ASD, allowing investigators to explore genetic, environmental and pharmacological manipulations in a species exhibiting complex, reciprocal social behavior. The present study was carried out to compare two commonly used strains of laboratory rats, Sprague-Dawley (SD and Long-Evans (LE, between the ages of postnatal day (PND 26-56 using high-throughput behavioral phenotyping tools commonly used in mouse models of ASD that we have adapted for use in rats. We detected few differences between young SD and LE strains on standard assays of exploration, sensorimotor gating, anxiety, repetitive behaviors, and learning. Both SD and LE strains also demonstrated sociability in the 3-chamber social approach test as indexed by spending more time in the social chamber with a constrained age/strain/sex matched novel partner than in an identical chamber without a partner. Pronounced differences between the two strains were, however, detected when the rats were allowed to freely interact with a novel partner in the social dyad paradigm. The SD rats in this particular testing paradigm engaged in play more frequently and for longer durations than the LE rats at both juvenile and young adult developmental time points. Results from this study that are particularly relevant for developing preclinical ASD models in rats are threefold: (i commonly utilized strains exhibit unique patterns of social interactions, including strain-specific play behaviors, (ii the testing environment may profoundly influence the expression of strain-specific social behavior and (iii simple, automated measures of sociability may not capture the complexities of rat social interactions.

  10. Skeletal effect of casein and whey protein intake during catch-up growth in young male Sprague-Dawley rats.

    Science.gov (United States)

    Masarwi, Majdi; Gabet, Yankel; Dolkart, Oleg; Brosh, Tamar; Shamir, Raanan; Phillip, Moshe; Gat-Yablonski, Galia

    2016-07-01

    The aim of the present study was to determine whether the type of protein ingested influences the efficiency of catch-up (CU) growth and bone quality in fast-growing male rats. Young male Sprague-Dawley rats were either fed ad libitum (controls) or subjected to 36 d of 40 % food restriction followed by 24 or 40 d of re-feeding with either standard rat chow or iso-energetic, iso-protein diets containing milk proteins - casein or whey. In terms of body weight, CU growth was incomplete in all study groups. Despite their similar food consumption, casein-re-fed rats had a significantly higher body weight and longer humerus than whey-re-fed rats in the long term. The height of the epiphyseal growth plate (EGP) in both casein and whey groups was greater than that of rats re-fed normal chow. Microcomputed tomography yielded significant differences in bone microstructure between the casein and whey groups, with the casein-re-fed animals having greater cortical thickness in both the short and long term in addition to a higher trabecular bone fraction in the short term, although this difference disappeared in the long term. Mechanical testing confirmed the greater bone strength in rats re-fed casein. Bone quality during CU growth significantly depends on the type of protein ingested. The higher EGP in the casein- and whey-re-fed rats suggests a better growth potential with milk-based diets. These results suggest that whey may lead to slower bone growth with reduced weight gain and, as such, may serve to circumvent long-term complications of CU growth.

  11. Perfluorooctane Sulfonate-Induced Hepatic Steatosis in Male Sprague Dawley Rats Is Not Attenuated by Dietary Choline Supplementation.

    Science.gov (United States)

    Bagley, Bradford D; Chang, Shu-Ching; Ehresman, David J; Eveland, Alan; Zitzow, Jeremiah D; Parker, George A; Peters, Jeffrey M; Wallace, Kendall B; Butenhoff, John L

    2017-12-01

    Perfluorooctane sulfonate (PFOS) is an environmentally persistent chemical. Dietary 100 ppm PFOS fed to male mice and rats for 4 weeks caused hepatic steatosis through an unknown mechanism. Choline deficient diets can cause hepatic steatosis. A hepatic choline:PFOS ion complex was hypothesized to cause this effect in mice. This study tested whether dietary choline supplementation attenuates PFOS-induced hepatic steatosis in rats. Sprague Dawley rats (12/sex/group) were fed control, choline supplemented (CS), 100 ppm PFOS, or 100 ppm PFOS + CS diets for 3 weeks. Male rats fed both PFOS-containing diets had decreased serum cholesterol and triglycerides (TGs) on days 9, 16, and/or 23 and increased hepatic free fatty acids and TG (ie, steatosis). Female rats fed both PFOS diets had decreased serum cholesterol on days 9 and 16 and decreased hepatic free fatty acid and TG at termination (ie, no steatosis). Liver PFOS concentrations were similar for both sexes. Liver choline concentrations were increased in male rats fed PFOS (±CS), but the increase was lower in the PFOS + CS group. Female liver choline concentrations were not altered by any diet. These findings demonstrate a clear sex-related difference in PFOS-induced hepatic steatosis in the rat. Additional evaluated mechanisms (ie, nuclear receptor activation, mRNA upregulation, and choline kinase activity inhibition) did not appear to be involved in the hepatic steatosis. Dietary PFOS (100 ppm) induced hepatic steatosis in male, but not female, rats that was not attenuated by choline supplementation. The mechanism of lipid accumulation and the sex-related differences warrant further investigation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Longitud del ciclo estral en ratas Sprague Dawley tratadas in útero con extracto de Roystonea regia Estrus cycle length in Sprague Dawley rats in uterus using Roystonea regia extract

    Directory of Open Access Journals (Sweden)

    Ariadne Gutiérrez Martínez

    2009-12-01

    Full Text Available El D-004 consiste en una mezcla de ácidos grasos que inhibe significativamente la hiperplasia prostática inducida por testosterona en roedores. El objetivo del presente estudio fue evidenciar los posibles efectos adversos sobre el ciclo estral de hembras F1 expuestas in útero al D-004. Se utilizaron ratas Sprague Dawley, distribuidas aleatoriamente en 4 grupos: un control y 3 tratados con D-004 a las dosis de 500, 750 y 1 000 mg/kg; las hembras recibieron la administración de la dosis por vía oral desde 15 días antes del apareo y hasta el fin de la lactancia. A una hembra por camada de la generación F1 se le estudió la citología vaginal y se calculó la longitud aproximada del ciclo, la cual no se vio afectada ya que no existieron diferencias significativas (p= 0,1537 entre los grupos tratados y el control. Estos resultados indican que el D-004 no reveló alteraciones del ciclo estral de las crías hembras expuestas in útero.D-004 is a mix of fatty acids inhibiting significantly Testosterone- induced prostatic hyperplasia in rodents. The aim of present paper was to demonstrate the potential side effects on estrus cycle of F1 female rats exposed in uterus to D-004. We used Sprague Dawley rats, distributed randomly in 4 groups: a control one and another three treated with D-004 at a dosage of 500, 750 and 1 000 mg/kg; in the female rats we administered the dose by mouth from the 15 days before mating, and up to breast feeding termination. In each female rat by litter of F1 generation, the vaginal cytology was studied, and we estimated the approximate length of cycle, remained un-affected since there were not significant differences (p= 0,1537 among treatment groups and the control one. These results show that D-004 fails to reveals alterations in the estrum cycle of female litters exposed in uterus.

  13. Isoflurane and ketamine:xylazine differentially affect intraocular pressure-associated scotopic threshold responses in Sprague-Dawley rats.

    Science.gov (United States)

    Choh, Vivian; Gurdita, Akshay; Tan, Bingyao; Feng, Yunwei; Bizheva, Kostadinka; McCulloch, Daphne L; Joos, Karen M

    2017-10-01

    Amplitudes of electroretinograms (ERG) are enhanced during acute, moderate elevation of intraocular pressure (IOP) in rats anaesthetised with isoflurane. As anaesthetics alone are known to affect ERG amplitudes, the present study compares the effects of inhalant isoflurane and injected ketamine:xylazine on the scotopic threshold response (STR) in rats with moderate IOP elevation. Isoflurane-anaesthetised (n = 9) and ketamine:xylazine-anaesthetised (n = 6) rats underwent acute unilateral IOP elevation using a vascular loop anterior to the equator of the right eye. STRs to a luminance series (subthreshold to -3.04 log scotopic cd s/m 2 ) were recorded from each eye of Sprague-Dawley rats before, during, and after IOP elevation. Positive STR (pSTR) amplitudes for all conditions were significantly smaller (p = 0.0001) for isoflurane- than for ketamine:xylazine-anaesthetised rats. In addition, ketamine:xylazine was associated with a progressive increase in pSTR amplitudes over time (p = 0.0028). IOP elevation was associated with an increase in pSTR amplitude (both anaesthetics p ketamine:xylazine and isoflurane were similar (66.3 ± 35.5 vs. 54.2 ± 24.1 µV, respectively). However, the fold increase in amplitude during IOP elevation was significantly higher in the isoflurane- than in the ketamine:xylazine-anaesthetised rats (16.8 ± 29.7x vs. 2.1 ± 2.7x, respectively, p = 0.0004). The anaesthetics differentially affect the STRs in the rat model with markedly reduced amplitudes with isoflurane compared to ketamine:xylazine. However, the IOP-associated enhancement is of similar absolute magnitude for the two anaesthetics, suggesting that IOP stress and anaesthetic effects operate on separate retinal mechanisms.

  14. Repeated Intramuscular-dose Toxicity Test of Water-soluble Carthami Flos (WCF Pharmacopuncture in Sprague-Dawley Rats

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    Yoo-min Choi

    2015-03-01

    Full Text Available Objectives: Water-soluble carthami flos (WCF is a new mixture of Carthami flos (CF pharmacopuncture. We conducted a 4-week toxicity test of repeated intramuscular injections of WCF in Sprague-Dawley rats. Methods: Forty male and 40 female rats were divided into 4 groups of 10 male and 10 female SD rats: The control group received 0.5 mL/animal/day of normal saline whereas the three experimental groups received WCF at doses of 0.125, 0.25, and 0.5 mL/animal/day, respectively. For 4 weeks, the solutions were injected into the femoral muscle of the rats alternating from side to side. Clinical signs, body weights, and food consumption were observed; opthalmological examinations and urinalyses were performed. On day 29, blood samples were taken for hematological and clinical chemistry analyses. Then, necropsy was conducted in all animals to observe weights and external and histopathological changes in the bodily organs. All data were tested using a statistical analysis system (SAS. Results: No deaths were observed. Temporary irregular respiration was observed in male rats of the experimental group for the first 10 days. Body weights, food consumptions, opthalmological examinations, urinalyses, clinical chemistry analyses, organ weights and necropsy produced no findings with toxicological meaning. In the hematological analysis, delay of prothrombin time (PT was observed in male rats of the 0.25- and the 0.5-mL/animal/day groups. In the histopathological test, a dose-dependent inflammatory cell infiltration into the fascia and panniculitis in perimuscular tissues was observed in all animals of the experimental groups. However, those symptoms were limited to local injection points. No toxicological meanings, except localized changes, were noted. Conclusion: WCF solution has no significant toxicological meaning, but does produce localized symptoms. No observed adverse effect level (NOAEL of WCF in male and female rats is expected for doses over 0.5 mL/animal/day.

  15. Predictors of ethanol consumption in adult Sprague-Dawley rats: relation to hypothalamic peptides that stimulate ethanol intake.

    Science.gov (United States)

    Karatayev, Olga; Barson, Jessica R; Carr, Ambrose J; Baylan, Jessica; Chen, Yu-Wei; Leibowitz, Sarah F

    2010-06-01

    To investigate mechanisms in outbred animals that increase the propensity to consume ethanol, it is important to identify and characterize these animals before or at early stages in their exposure to ethanol. In the present study, different measures were examined in adult Sprague-Dawley rats to determine whether they can predict long-term propensity to overconsume ethanol. Before consuming 9% ethanol with a two-bottle choice paradigm, rats were examined with the commonly used behavioral measures of novelty-induced locomotor activity and anxiety, as assessed during 15 min in an open-field activity chamber. Two additional measures, intake of a low 2% ethanol concentration or circulating triglyceride (TG) levels after a meal, were also examined with respect to their ability to predict chronic 9% ethanol consumption. The results revealed significant positive correlations across individual rats between the amount of 9% ethanol ultimately consumed and three of these different measures, with high scores for activity, 2% ethanol intake, and TGs identifying rats that consume 150% more ethanol than rats with low scores. Measurements of hypothalamic peptides that stimulate ethanol intake suggest that they contribute early to the greater ethanol consumption predicted by these high scores. Rats with high 2% ethanol intake or high TGs, two measures found to be closely related, had significantly elevated expression of enkephalin (ENK) and galanin (GAL) in the hypothalamic paraventricular nucleus (PVN) but no change in neuropeptide Y (NPY) in the arcuate nucleus (ARC). This is in contrast to rats with high activity scores, which in addition to elevated PVN ENK expression showed enhanced NPY in the ARC but no change in GAL. Elevated ENK is a common characteristic related to all three predictors of chronic ethanol intake, whereas the other peptides differentiate these predictors, with GAL enhanced with high 2% ethanol intake and TG measures but NPY related to activity. 2010 Elsevier

  16. Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats

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    Yu, Hong-Ren; Tain, You-Lin; Sheen, Jiunn-Ming; Tiao, Mao-Meng; Chen, Chih-Cheng; Kuo, Ho-Chang; Hung, Pi-Lien; Hsieh, Kai-Sheng; Huang, Li-Tung

    2016-01-01

    Overexposure to prenatal glucocorticoid (GC) disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF) diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14–21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF), and prenatal dexamethasone exposure plus a postnatal HF diet (DHF). The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ) production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming. PMID:27669212

  17. Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats

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    Hong-Ren Yu

    2016-09-01

    Full Text Available Overexposure to prenatal glucocorticoid (GC disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14–21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF, and prenatal dexamethasone exposure plus a postnatal HF diet (DHF. The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming.

  18. NMR-based metabolomics reveals urinary metabolome modifications in female Sprague-Dawley rats by cranberry procyanidins.

    Science.gov (United States)

    Liu, Haiyan; Tayyari, Fariba; Edison, Arthur S; Su, Zhihua; Gu, Liwei

    2016-08-01

    A (1)H NMR global metabolomics approach was used to investigate the urinary metabolome changes in female rats gavaged with partially purified cranberry procyanidins (PPCP) or partially purified apple procyanidins (PPAP). After collecting 24-h baseline urine, 24 female Sprague-Dawley rats were randomly separated into two groups and gavaged with PPCP or PPAP twice using a dose of 250 mg extracts per kilogram body weight. The 24-h urine samples were collected after the gavage. Urine samples were analyzed using (1)H NMR. Multivariate analyses showed that the urinary metabolome in rats was modified after administering PPCP or PPAP compared to baseline urine metabolic profiles. 2D (1)H-(13)C HSQC NMR was conducted to assist identification of discriminant metabolites. An increase of hippurate, lactate and succinate and a decrease of citrate and α-ketoglutarate were observed in rat urine after administering PPCP. Urinary levels of d-glucose, d-maltose, 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid, formate and phenol increased but citrate, α-ketoglutarate and creatinine decreased in rats after administering PPAP. Furthermore, the NMR analysis showed that the metabolome in the urine of rats administered with PPCP differed from those gavaged with PPAP. Compared to PPAP, PPCP caused an increase of urinary excretion of hippurate but a decrease of 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid and phenol. These metabolome changes caused by cranberry procyanidins may help to explain its reported health benefits and identify biomarkers of cranberry procyanidin intake. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Rashid, A.; Ayub, M.

    2011-01-01

    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)

  20. Repeated Dose 28-Days Oral Toxicity Study of Carica papaya L. Leaf Extract in Sprague Dawley Rats

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    Hussin Muhammad

    2012-04-01

    Full Text Available Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from ‘Sekaki’ C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.

  1. Intravascular streaming and variable delivery to brain following carotid artery infusions in the Sprague-Dawley rat

    International Nuclear Information System (INIS)

    Saris, S.C.; Wright, D.C.; Oldfield, E.H.; Blasberg, R.G.

    1988-01-01

    Intracarotid artery infusions in animals are commonly performed in studies of the blood-brain barrier and in chemotherapy trials. Implicit in the analysis of these experiments is that the infusate will be distributed to the territory of the internal carotid artery in a manner that is proportional to blood flow. Fifteen Sprague-Dawley rats were studied to determine if poor infusate mixing with blood due to intravascular streaming occurred during intracarotid artery drug infusions and if it could be eliminated with fast retrograde infusion. In three experimental groups, a radiolabeled flow tracer-- 14 C-iodoantipyrine (IAP)--was infused retrograde through the external carotid artery into the common carotid artery at slow, medium, and fast rates (0.45, 1.5, and 5.0 ml/min). In a control group, IAP was injected intravenously (i.v.). Local isotope concentrations in the brain were determined by quantitative autoradiography, and the variability of isotope delivery was assessed in the frontoparietal cortex, temporal cortex, and caudate putamen of all animals. Streaming phenomena were manifest in all selected anatomic areas after the slow and medium rates of intraarterial infusion. After fast intracarotid infusion or i.v. injection, there was uniform distribution of isotope in the same brain regions

  2. The effect of anchovy substrate application to fluor retention rate on Sprague Dawley rat tooth email (in vivo)

    Science.gov (United States)

    Zabrina, S.; Puspitawati, R.; Gunawan, H. A.

    2017-08-01

    Usage of anchovies (Stolephorus insularis), which contain a high fluoride concentration in a CaF2 compound, needs to be examined as a topical fluoridative agent. Aim: To study the effects of an anchovy substrate application, either by chewing or smearing, in increasing fluoride retention of enamel. Fourteen Sprague Dawley rats were divided into five groups: baseline, experimental (feeding and smearing), and negative controls. After 15 days, lower incisor teeth were extracted and fluoride retention on the enamel surface was measured using EDX. Data were analyzed by the independent samples t-test, the Mann-Whitney U test, and the Kruskal-Wallis test. There was a significant increase in fluoride retention on enamel from the experimental groups compared to the negative control group (p < 0.05). Fluoride retention levels of the experimental feeding group (6.823%) were slightly higher than those of the experimental smearing group (6.783%), though the difference was not statistically significant (p < 0.05). Anchovy substrate application, either by chewing or smearing, increases fluoride retention on tooth enamel.

  3. Glucometabolic effects of single and repeated exposure to forced-swimming stressor in Sprague-Dawley rats.

    Science.gov (United States)

    Morakinyo, Ayodele Olufemi; Iranloye, Bolanle Olubusola; Ogunsola, Oluseyi Abimbola

    2018-04-01

    We aimed to evaluate the effects of a single (acute) and repeated (chronic) exposure to forced-swimming stressor on glucose tolerance, insulin sensitivity, lipid profile and glycogen content in male rats. Thirty adult male Sprague-Dawley rats (12 weeks old) were divided randomly into five groups: control group, single exposure (SE) to forced-swim stressor, repeated exposure to forced-swim stressor for 7 days (RE7), 14 days (RE14) and 28 days (RE28). Glucose tolerance test and Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) were undertaken on fasting rats to obtain glucose and insulin profiles. ELISA was performed to assess plasma insulin and corticosterone levels. Total cholesterol, triglyceride, high- and low-density lipoproteins, hepatic and skeletal glycogen content were also determined. Repeated exposure to stressor induced glucose intolerance and insulin resistance in the experimental rats. Results showed that all RE groups exhibited a significantly higher area under the curve compared with others (p=0.0001); similarly, HOMA-IR increased (p=0.0001) in all RE groups compared with control. Prolonged exposure to stressor significantly increased the plasma insulin and corticosterone levels but decreased the glycogen content in the liver and skeletal muscle when compared with the control group. Additionally, chronic stressor significantly increased the total cholesterol and triglyceride levels, however, acute stressor produced significantly elevated high-density lipoproteins level. In conclusion, repeated exposure to forced-swimming stressor induced glucose intolerance and insulin resistance in rats by disrupting the insulin sensitivity as well as heightening the glycogenolysis in the liver and skeletal muscle. Acute stressor was unable to cause glucose intolerance and insulin resistance but it appears that may have a positive effect on the lipid metabolism.

  4. Developmental exposure to paraquat and maneb can impair cognition, learning and memory in Sprague-Dawley rats.

    Science.gov (United States)

    Li, Bai; He, Xi; Sun, Yan; Li, Baixiang

    2016-10-20

    Paraquat and maneb are identified environmental pollutants. Combined exposure to paraquat and maneb is a latent risk factor for many diseases, particularly those of the central nervous system, including Parkinson's disease and Alzheimer's disease. Hippocampus is the key structure in memory formation and babies are more sensitive to environmental stimuli than adults, so we investigated the neurotoxicity of paraquat and maneb on the hippocampi of rat pups. Female and male Sprague-Dawley rats were mated (female : male = 2 : 1) every night for a week. The gravid rats were randomly divided into three groups (one control and two experimental groups). A mixed solution of paraquat-maneb was administered twice a week by lavage at a dose of 10 or 15 mg kg(-1) bodyweight (containing 30 or 45 mg kg(-1) bodyweight maneb, respectively) from day 6 after pregnancy till ablactation. Maternal weight gain and offspring bodyweights were not affected by the drugs. However, behavioral tests showed that reaction latency and mistake frequency increased after treatment. Intuitively, we found significant changes in the hippocampal neurons in the morphological observation. Taking into account the interaction of the related genes in the cAMP-PKA-CREB pathway, we used a variety of methods to detect the gene and protein levels. Reduced expression of cAMP and related genes and proteins in the hippocampus and serum was also observed. These results indicate that PQ-MB stimulates cAMP to reduce the production of PKA, thus reducing the phosphorylation of CREB and inhibiting the activation of other elements (BDNF, C-JUN, and C-FOS). These changes lead to hippocampal damage and impaired abilities (learning, cognition, and memory). Our results demonstrate that PQ-MB induces hippocampal toxicity in the early life of rats, and they thus provide a theoretical foundation for further investigation of the bathypelagic mechanism involved and measures that can be taken to avoid PQ-MB neurotoxicity.

  5. Lansoprazole increases testosterone metabolism and clearance in male Sprague-Dawley rats: implications for leydig cell carcinogenesis

    International Nuclear Information System (INIS)

    Coulson, Michelle; Gibson, G. Gordon; Plant, Nick; Hammond, Tim; Graham, Mark

    2003-01-01

    Leydig cell tumours (LCTs) are frequently observed during rodent carcinogenicity studies, however, the significance of this effect to humans remains a matter of debate. Many chemicals that produce LCTs also induce hepatic cytochromes P450 (CYPs), but it is unknown whether these two phenomena are causally related. Our aim was to investigate the existence of a liver-testis axis wherein microsomal enzyme inducers enhance testosterone metabolic clearance, resulting in a drop in circulating hormone levels and a consequent hypertrophic response from the hypothalamic-pituitary-testis axis. Lansoprazole was selected as the model compound as it induces hepatic CYPs and produces LCTs in rats. Male Sprague-Dawley rats were dosed with lansoprazole (150 mg/kg/day) or vehicle for 14 days. Lansoprazole treatment produced effects on the liver consistent with an enhanced metabolic capacity, including significant increases in relative liver weights, total microsomal CYP content, individual CYP protein levels, and enhanced CYP-dependent testosterone metabolism in vitro. Following intravenous administration of [ 14 C]testosterone, lansoprazole-treated rats exhibited a significantly smaller area under the curve and significantly higher plasma clearance. Significant reductions in plasma and testicular testosterone levels were observed, confirming the ability of this compound to perturb androgen homeostasis. No significant changes in plasma LH, FSH, or prolactin levels were detected under our experimental conditions. Lansoprazole treatment exerted no marked effects on testicular testosterone metabolism. In summary, lansoprazole treatment induced hepatic CYP-dependent testosterone metabolism in vitro and enhanced plasma clearance of radiolabelled testosterone in vivo. These effects may contribute to depletion of circulating testosterone levels and hence play a role in the mode of LCT induction in lansoprazole-treated rats

  6. A probiotic strain of L. acidophilus reduces DMH-induced large intestinal tumors in male Sprague-Dawley rats.

    Science.gov (United States)

    McIntosh, G H; Royle, P J; Playne, M J

    1999-01-01

    Probiotic bacteria strains were examined for their influence on 1,2-dimethylhydrazine (DMH)-induced intestinal tumors in 100 male Sprague-Dawley rats. Lactobacillus acidophilus (Delvo Pro LA-1), Lactobacillus rhamnosus (GG), Bifidobacterium animalis (CSCC1941), and Streptococcus thermophilus (DD145) strains were examined for their influence when added as freeze-dried bacteria to an experimental diet based on a high-fat semipurified (AIN-93) rodent diet. Four bacterial treatments were compared: L. acidophilus, L. acidophilus + B. animalis, L. rhamnosus, and S. thermophilus, the bacteria being added daily at 1% freeze-dried weight (10(10) colony-forming units/g) to the diet. Trends were observed in the incidence of rats with large intestinal tumors for three treatments: 25% lower than control for L. acidophilus, 20% lower for L. acidophilus + B. animalis and L. rhamnosus treatments, and 10% lower for S. thermophilus. Large intestinal tumor burden was significantly lower for treated rats with L. acidophilus than for the control group (10 and 3 tumors/treatment group, respectively, p = 0.05). Large intestinal tumor mass index was also lower for the L. acidophilus treatment than for control (1.70 and 0.10, respectively, p L. acidophilus, no adenocarcinomas were present in the colons. Pulsed-field gel electrophoresis of bacterial chromosomal DNA fragments was used to differentiate introduced (exogenous) bacterial strains from indigenous bacteria of the same genera present in the feces. Survival during gut passage and displacement of indigenous lactobacilli occurred with introduced L. acidophilus and L. rhamnosus GG during the probiotic treatment period. However, introduced strains of B. animalis and S. thermophilus were not able to be isolated from feces. It is concluded that this strain of L. acidophilus supplied as freeze-dried bacteria in the diet was protective, as seen by a small but significant inhibition of tumors within the rat colon.

  7. Heating Pad Performance and Efficacy of 2 Durations of Warming after Isoflurane Anesthesia of Sprague-Dawley Rats (Rattus norvegicus).

    Science.gov (United States)

    Zhang, Emily Q; Knight, Cameron G; Pang, Daniel Sj

    2017-11-01

    Anesthetic agents depress thermoregulatory mechanisms, causing hypothermia within minutes of induction of general anesthesia. The consequences of hypothermia include delayed recovery and increased experimental variability. Even when normothermia is maintained during anesthesia, hypothermia may occur during recovery. The primary aim of this study was to identify an effective warming period for maintaining normothermia during recovery. Adult male (n = 8) and female (n = 9) Sprague-Dawley rats were randomized to 30 min (post30) or 60 min (post60) of warming after recovery from anesthesia. During a 40-min anesthetic period, normothermia (target, 37.5 ± 1.1 °C) was maintained by manual adjustment of an electric heating pad in response to measured rectal temperatures (corrected to estimate core body temperature). Warming was continued in a recovery cage according to treatment group. Rectal temperature was measured for a total of 120 min after anesthesia. Heating pad performance was assessed by measuring temperatures at various sites over its surface. One female rat in the post30 group was excluded from analysis. Normothermia was effectively maintained during and after anesthesia without significant differences between groups. In the post60 group, core temperature was slightly but significantly increased at 90 and 100 min compared with baseline. One rat in each treatment group became hyperthermic (>38.6 °C) during recovery. During recovery, the cage floor temperature required approximately 30 min to stabilize. The heating pad produced heat unevenly over its surface, and measured temperatures frequently exceeded the programmed temperature. Providing 30 min of warming immediately after anesthesia effectively prevented hypothermia in rats. Shorter warming periods may be useful when recovery cages are preheated.

  8. Assessment of bioaccumulation, neuropathology, and neurobehavior following subchronic (90 days) inhalation in Sprague-Dawley rats exposed to manganese phosphate.

    Science.gov (United States)

    Normandin, Louise; Carrier, Gaétan; Gardiner, Phillip F; Kennedy, Greg; Hazell, Alan S; Mergler, Donna; Butterworth, Roger F; Philippe, Suzanne; Zayed, Joseph

    2002-09-01

    Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline. It has been suggested that the combustion products of MMT containing Mn, such as manganese phosphate, could cause neurological symptoms similar to Parkinson's disease in humans. The aim of this work was to investigate the exposure-response relationship of bioaccumulation, neuropathology, and neurobehavior following a subchronic inhalation exposure to manganese phosphate in Sprague-Dawley male rats. Rats were exposed 6 h/day, 5 days/week for 13 consecutive weeks at 30, 300, or 3000 microg/m(3) Mn phosphate and compared to controls. Some rats were implanted with chronic EMG electrodes in the gastrocnemius muscle of the hind limb to assess tremor at the end of Mn exposure. Spontaneous motor activity was measured for 36 h using a computerized autotrack system. Rats were then sacrificed by exsanguination and Mn level in different brain tissues and other organs was determined by instrumental neutron activation analysis. Neuronal cell counts were obtained by assessing the sum of five grid areas for the caudate/putamen and the sum of two adjacent areas for the globus pallidus. Increased manganese concentrations were observed in all tissues of the brain and was dose-dependent in olfactory bulb and caudate/putamen. In fact, beginning with the highest level of exposure (3000 microg/m(3)) and ending with the control group, Mn concentrations in the olfactory bulb were 2.47 vs 1.28 vs 0.77 vs 0.64 ppm (P Locomotor activity assessment and tremor assessment did not reveal in neurobehavioral changes between the groups. Our results reinforce the hypothesis that the olfactory bulb and caudate/putamen are the main brain tissues for Mn accumulation after subchronic inhalation exposure.

  9. Placental and milk transfer, disposition and elimination of a single oral dose of [14C acetyl] acephate in Sprague Dawley rats

    International Nuclear Information System (INIS)

    Bakry, N.M.; Salama, A.K.; Abou-Donia, M.B.

    1991-01-01

    A single oral dose of 40 mg/kg (6.4 μCi/kg) of [ 14 C acetyl]acephate was administered on day 18 of gestation to pregnant Sprague Dawley rats. Eight groups of three rats were killed after 10 min and 0.5, 1, 3, 6, 12, 24, and 48 hr. At the end of the 48 hr experimental period, a total of 22.38% of the dose was exhaled as carbon dioxide, while only 1.25% and 0.60% of the dose were eliminated in the urine and feces, respectively. Trace amount (0.03% of the dose) was recovered in expired air as volatile materials. Radioactive acephate was rapidly absorbed and distributed in the tissues, with levels in most tissues reaching a peak concentration within 1 to 3 hr. The highest concentration of radioactivity was present in the maternal stomach followed by the liver. A total of 0.72% of the dose was recovered in the fetus. In another study, a single oral dose of 40 mg/kg [ 14 C acetyl]acephate was administered to the dams right after delivery. Nursing and suckling groups were killed at intervals of 1, 3, 6, 12, 24, 36, and 48 hr after dosing. Generally, the highest concentrations of radioactivity were present in the stomach, small intestine, liver, lung, and kidneys. A total of 0.96% of the dose was recovered in the sucklings

  10. Effect of method of euthanasia on sperm motility of mature Sprague-Dawley rats.

    Science.gov (United States)

    Stutler, Shannon A; Johnson, Eric W; Still, Kenneth R; Schaeffer, David J; Hess, Rex A; Arfsten, Darryl P

    2007-03-01

    Euthanasia is one of the most commonly performed procedures in laboratory animal settings. The method of euthanasia may affect experimental results in studies using animals and must be compatible with research objectives including subsequent tissue analyses. Our present study was performed to evaluate the effects of 7 euthanasia methods on sperm motility in mature rats. Rats were euthanized using CO2, 2 commercially available euthanasia solutions (Beuthanasia-D and Sleepaway), and 4 volatile anesthetics (enflurane, halothane, isoflurane, and sevoflurane). Rats euthanized by rapid decapitation alone served as negative controls, and a-chlorohydrin-treated rats euthanized by rapid decapitation were positive controls for sperm impairment. For 5 of these methods, we also measured time to ataxia, recumbency, respiratory arrest, and no auscultable heartbeat. Immediately after euthanasia of each rat, distal caudal epididymides were removed; 1 was processed for automated sperm motility analysis, and the other was frozen for subsequent concentration analysis. Time to all measured parameters was less for volatile anesthetics than for Beuthanasia-D. Times to last respiration and no heartbeat were less for halothane and isoflurane than for enflurane and sevoflurane. Percentage motile sperm did not differ significantly between methods. Percentage progressively motile sperm did not vary significantly between methods except for Beuthanasia-D, for which it was significantly less than the negative control value. Specific sperm motion parameters for each euthanasia method except CO2 and Sleepaway varied significantly from the negative control. Our results indicate that the method of euthanasia is an important consideration when rat sperm motility parameters must be evaluated.

  11. Results of long-term carcinogenicity bioassays on Coca-Cola administered to Sprague-Dawley rats.

    Science.gov (United States)

    Belpoggi, Fiorella; Soffritti, Morando; Tibaldi, Eva; Falcioni, Laura; Bua, Luciano; Trabucco, Francesca

    2006-09-01

    Coca-Cola was invented in May 1886 in Atlanta, Georgia by a pharmacist who, by accident or design, mixed carbonated water with the syrup of sugar, phosphoric acid, caffeine, and other natural flavors to create what is known as "the world's favorite soft drink." Coca-Cola is currently sold in more than 200 countries and in early 2000, the company sold its 10 billionth unit case of Coca-Cola branded products. Given the worldwide consumption of Coca-Cola, a project of experimental bioassays to study its long-term effects when administered as substitute for drinking water on male and female Sprague-Dawley rats was planned and executed. The objective of the project was to study whether and how long-term consumption of Coca-Cola affects the basic tumorigram of test animals. The bioassays were performed on rats beginning at different ages, namely: (a) on males and females exposed since embryonic life or from 7 weeks of age; and (b) on males and females exposed from 30, 39, or 55 weeks of age. Overall, the project included 1999 rats. During the biophase, data were collected on fluid and feed consumption, body weight, and survival. Animals were kept under observation until spontaneous death and underwent complete necropsy. The results indicate: (a) an increase in body weight in all treated animals; (b) a statistically significant increase of the incidence in females, both breeders and offspring, bearing malignant mammary tumors; (c) a statistically significant increase in the incidence of exocrine ademonas of the pancreas in both male and female breeders and offspring; and (d) an increased incidence, albeit not statistically significant, of pancreatic islet cell carcinomas in females, a malignant tumor which occurs very rarely in our historical controls. On the basis of the results of this study, excessive consumption of regular soft-drinks should be generally discouraged, in particular for children and adolescents.

  12. Single Intramuscular-dose Toxicity of Water soluble Carthmi-Flos herbal acupuncture (WCF in Sprague-Dawley Rats

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    Lee Hyung-geol

    2014-03-01

    Full Text Available Objectives: This experiment was conducted to examine the toxicity of WCF (Water soluble Carthmi-Flos herbal acupuncture by administering a single intramuscular dose of WCF in 6-week-old, male and female Sprague-Dawley rats and to find the lethality dose for WCF. Methods: The experiment was conducted at Biotoxtech according to Good Laboratory Practices under a request by the Korean Pharmacopuncture Institute. This experiment was performed based on the testing standards of “Toxicity Test Standards for Drugs” by the Ministry of Food and Drug Safety. Subjects were divided into 4 groups: 1 control group in which normal saline was administered and 3 test groups in which 0.1, 0.5 or 1.0 mL of WCF was administered; a single intramuscular dose was injected into 5 males and 5 females in each group. General symptoms and body weights were observed/measured for 14 days after injection. At the end of the observation period, hematological and clinical chemistry tests were performed, followed by necropsy and histopathological examinations of the injected sections. Results: No mortalities were observed in any group. Also, symptoms, body weight, hematology, clinical chemistry and necropsy were not affected. However, histopathological examination of the injected part in one female in the 1.0-mL group showed infiltration of mononuclear cells and a multi-nucleated giant cell around eosinophilic material. Conclusion: Administration of single intramuscular doses of WCF in 3 groups of rats showed that the approximate lethal dose of WCF for all rats was in excess of 1.0 mL, as no mortalities were observed for injections up to and including 1.0 mL.

  13. Islet inflammation, hemosiderosis, and fibrosis in intrauterine growth-restricted and high fat-fed Sprague-Dawley rats.

    Science.gov (United States)

    Delghingaro-Augusto, Viviane; Madad, Leili; Chandra, Arin; Simeonovic, Charmaine J; Dahlstrom, Jane E; Nolan, Christopher J

    2014-05-01

    Prenatal and postnatal factors such as intrauterine growth restriction (IUGR) and high-fat (HF) diet contribute to type 2 diabetes. Our aim was to determine whether IUGR and HF diets interact in type 2 diabetes pathogenesis, with particular attention focused on pancreatic islet morphology including assessment for inflammation. A surgical model of IUGR (bilateral uterine artery ligation) in Sprague-Dawley rats with sham controls was used. Pups were fed either HF or chow diets after weaning. Serial measures of body weight and glucose tolerance were performed. At 25 weeks of age, rat pancreases were harvested for histologic assessment. The birth weight of IUGR pups was 13% lower than that of sham pups. HF diet caused excess weight gain, dyslipidemia, hyperinsulinemia, and mild glucose intolerance, however, this was not aggravated further by IUGR. Markedly abnormal islet morphology was evident in 0 of 6 sham-chow, 5 of 8 sham-HF, 4 of 8 IUGR-chow, and 8 of 9 IUGR-HF rats (chi-square, P = 0.007). Abnormal islets were characterized by larger size, irregular shape, inflammation with CD68-positive cells, marked fibrosis, and hemosiderosis. β-Cell mass was not altered by IUGR. In conclusion, HF and IUGR independently contribute to islet injury characterized by inflammation, hemosiderosis, and fibrosis. This suggests that both HF and IUGR can induce islet injury via converging pathways. The potential pathogenic or permissive role of iron in this process of islet inflammation warrants further investigation. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  14. A Study on the Single-dose Oral Toxicity of Super Key in Sprague-Dawley Rats

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    Jinhee Kim

    2015-09-01

    Full Text Available Objectives: This study was performed to analyze the single-dose oral toxicity of the super key (processed sulfur. Methods: All experiments were conducted at Medvill, an institution authorized to perform non-clinical studies, under the Good Laboratory Practice (GLP regulations. In order to investigate the oral toxicity of super key We administered it orally to Sprague-Dawley (SD rats. The SD rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of super key 500 mg/kg, 1,000 mg/kg and 2,000 mg/kg were administered to the experimental groups, and a dose of normal saline solution, 10 mL/kg, was administered to the control group. We examined the survival rates, weights, clinical signs, gross findings and necropsy findings. This study was conducted under the approval of the Institutional Animal Ethics Committee. (Approval number: A01-14018. Results: No deaths or abnormalities occurred in any of the four groups. Although slight decreases in the weights of some female rats were noted, no significant changes in weights or differences in the gross findings between the control group and the experimental groups were observed. To check for abnormalities in organs, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs. Conclusion: The results of this research showed that administration of 500 ─ 2,000 mg/kg of super key did not cause any changes in the weights or in the results of necropsy examinations. Neither did it result in any mortalities. The above findings suggest that treatment with super key is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

  15. Subchronic Toxicities of HZ1006, a Hydroxamate-Based Histone Deacetylase Inhibitor, in Beagle Dogs and Sprague-Dawley Rats

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    Xiaofang Zhang

    2016-11-01

    Full Text Available Histone deacetylase inhibitors (HDACIs, such as vorinostat and panobinostat, have been shown to have active effects on many hematologic malignancies, including multiple myeloma and cutaneous T-cell lymphoma. Hydroxamate-based (Hb HDACIs have very good toxicity profiles and are currently being tested in phases I and II clinical trials with promising results in selected neoplasms, such as bladder carcinoma. One of the Hb-HDACIs, HZ1006, has been demonstrated to be a promising drug for clinical use. The aim of our study was to determine the possible target of toxicity and to identify a non-toxic dose of HZ1006 for clinical use. In our studies, the repeated dosage toxicity of HZ1006 in Beagle dogs and Sprague Dawley (SD rats was identified. Dogs and rats received HZ1006 orally (0–80 and 0–120 mg/kg/day, respectively on a continuous daily dosing agenda for 28 days following a 14-day dosage-free period. HZ1006’s NOAEL (No Observed Adverse Effect Level by daily oral administration for dogs and rats was 5 mg/kg and 60 mg/kg, respectively, and the minimum toxic dose was 20 and 120 mg/kg, respectively. All the side effects indicated that the digestive tract, the male reproductive tract, the respiratory tract and the hematological systems might be HZ1006 toxic targets in humans. HZ1006 could be a good candidate or a safe succedaneum to other existing HDACIs for the treatment of some solid tumor and hematologic malignancies.

  16. Behavioral Effects of Enrichment and Nicotine in Male Sprague Dawley Rats

    Science.gov (United States)

    2008-10-01

    activity, increased habituation to a novel environment, decreased voluntary exercise. Rats in the physically-enriched group had increased voluntary ... voluntary exercise. Environmental enrichment prolonged nicotine’s effects through nicotine cessation. Enrichment’s effects on body weight could not...68 Euthanasia ................................................................................................... 68 DATA ANALYTIC STRATEGY FOR

  17. Effects of gamma radiation on the concentration of 5-hydroxy-L-tryptophan and 5-hydroxytryptamine in presence of radioprotector in Sprague Dawley rats

    International Nuclear Information System (INIS)

    Upadhyay, S.N.; Sharma, Ashok; Nagpal, K.K.; Saini, S.K.

    1997-01-01

    The result of variation of 5-hydroxy-L-tryptophan (HT) and 5-hydroxytryptamine (5-HT) in different tissues of control and gamma-irradiated Sprague Dawley rats with and without a radioprotector β-amino-ethylisothiuronium bromide hydrobromide (AET) combination e.g. (HT+AET) have been studied. The retention of HT, in the tissues studied, decreased after lethal dose (10.5 Gy) but for 5-HT, no such trend was observed after incorporation of HT+AET. A slight tendency of both metabolites to come back to control level was also observed for Sprague Dawley rats. In urine concentration of HT was less compared to 5-HT with a lethal dose (10.5 Gy). After incorporation of HT+AET the turnover rate of HT and 5-HT were found to be maximum when it was injected through intraperitoneal route. (author)

  18. Sub-Acute Toxicity Study of Graphene Oxide in the Sprague-Dawley Rat

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    Yingbo Li

    2016-11-01

    Full Text Available Graphene oxide (GO is an oxidized derivative of graphene used in biotechnology and medicine. The safety of GO is uncertain, so we evaluated its toxicity in male rats. Rat tail veins were injected with 2.5, 5, or 10 mg/kg GO for seven days and behavioral patterns, pathology, and tissue morphology were assessed. Data show that behaviors were not altered according to an open field test and a functional observational battery test, but histopathological analysis indicated that GO caused inflammation of the lung, liver, and spleen. GO also reduced cholesterol, high density lipoprotein (HDL, and low density lipoprotein (LDL. No other organs were modified. Thus, high concentrations of GO are toxic for the lung, liver, and spleen, but the mechanism by which this occurs requires more study.

  19. TOXICOKINETICS OF TREMOROGENIC NATURAL PRODUCTS, HARMANE AND HARMINE, IN MALE SPRAGUE-DAWLEY RATS

    OpenAIRE

    Guan, Yongbiao; Louis, Elan D.; Zheng, Wei

    2001-01-01

    Tremorogenic β-carboline alkaloids are present in foodstuffs and beverages. Acute exposure to β-carboline derivatives causes severe tremor; however, the disposition of these dietary contaminants remains unclear. This study was performed to evaluate toxicokinetics of harmane and harmine, two major β-carboline alkaloids, in rats. Blood concentrations of both toxicants were quantified by high-performance liquid chromatography (HPLC). Following an intravenous injection (0.5 mg/ kg), the concentra...

  20. The gastro protective effects of Cibotium barometz hair on ethanol-induced gastric ulcer in Sprague-Dawley rats.

    Science.gov (United States)

    Al-Wajeeh, Nahla Saeed; Hajerezaie, Maryam; Noor, Suzita Mohd; Halabi, Mohammed Farouq; Al-Henhena, Nawal; Azizan, Ainnul Hamidah Syahadah; Kamran, Sareh; Hassandarvish, Pouya; Shwter, Abdrabuh N; Karimian, Hamed; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen

    2017-01-19

    Cibotium barometz is a medical herb used traditionally in the Malaysian peninsula for several ailments, including gastric ulcer. The aim of this study was assessment the anti-ulcer effects of C. barometz hair on ethanol-induced stomach hemorrhagic abrasions in animals. Seven groups of Sprague Dawley (SD) rats were administered 10% Tween 20 in the normal control and ulcer control groups, and omeprazole 20 mg/kg and 62.5, 125, 250, and 500 mg/kg of C. barometz hair extract in the experimental groups. After 60 min, the normal control group of rats was orally administered 10% Tween 20, while absolute ethanol was orally administered to the groups of ulcer control, omeprazole and experimental groups. Stomachs of the rats were examined macroscopically and histologically. Homogenates of stomachs were used to evaluate endogenous antioxidant enzyme activities. Rats pre-fed with plant extract presented a significant decrease in the sore area, increased pH of gastric contents and preserved stomach wall mucus compared to the ulcer group. Histologically, rats pre-fed with C. barometz hair extract showed mild to moderate disruptions of the surface epithelium while animals pre-fed with absolute ethanol showed severe disruptions of the stomach epithelium with edema and leucocyte penetration of the submucosal layer. A Periodic acid Schiff (PAS) staining revealed that each rat pre-treated with the plant extract displayed an intense uptake of stomach epithelial glycoprotein magenta color compared to the ulcer control group. Immunohistochemical analysis revealed that rats pre-fed with the plant extract showed an up-regulation of the heat shock protein 70 (HSP70) and down-regulation of Bax proteins compared to ulcer control rats. Homogenates of the stomach tissue demonstrated significant increases in the endogenous antioxidant enzymatic activity and decreased lipid peroxidation (MDA) in rats pre-treated with C. barometz hair extract compared with the ulcer control rats. In acute

  1. Spinal NMDA receptor activation constrains inactivity-induced phrenic motor facilitation in Charles River Sprague-Dawley rats.

    Science.gov (United States)

    Streeter, K A; Baker-Herman, T L

    2014-10-01

    Reduced spinal synaptic inputs to phrenic motor neurons elicit a unique form of spinal plasticity known as inactivity-induced phrenic motor facilitation (iPMF). iPMF requires tumor necrosis factor-α (TNF-α) and atypical protein kinase C (aPKC) activity within spinal segments containing the phrenic motor nucleus to stabilize early, transient increases in phrenic burst amplitude into long-lasting iPMF. Here we tested the hypothesis that spinal N-methyl-d-aspartate receptor (NMDAR) activation constrains long-lasting iPMF in some rat substrains. Phrenic motor output was recorded in anesthetized, ventilated Harlan (HSD) and Charles River (CRSD) Sprague-Dawley rats exposed to a 30-min central neural apnea. HSD rats expressed a robust, long-lasting (>60 min) increase in phrenic burst amplitude (i.e., long-lasting iPMF) when respiratory neural activity was restored. By contrast, CRSD rats expressed an attenuated, transient (∼15 min) iPMF. Spinal NMDAR inhibition with DL-2-amino-5-phosphonopentanoic acid (APV) before neural apnea or shortly (4 min) prior to the resumption of respiratory neural activity revealed long-lasting iPMF in CRSD rats that was phenotypically similar to that in HSD rats. By contrast, APV did not alter iPMF expression in HSD rats. Spinal TNF-α or aPKC inhibition impaired long-lasting iPMF enabled by NMDAR inhibition in CRSD rats, suggesting that similar mechanisms give rise to long-lasting iPMF in CRSD rats with NMDAR inhibition as those giving rise to long-lasting iPMF in HSD rats. These results suggest that NMDAR activation can impose constraints on TNF-α-induced aPKC activation after neural apnea, impairing stabilization of transient iPMF into long-lasting iPMF. These data may have important implications for understanding differential responses to reduced respiratory neural activity in a heterogeneous human population. Copyright © 2014 the American Physiological Society.

  2. Arsenic-induced biochemical and genotoxic effects and distribution in tissues of Sprague-Dawley rats

    Science.gov (United States)

    Patlolla, Anita K.; Todorov, Todor I.; Tchounwou, Paul B.; van der Voet, Gijsbert; Centeno, Jose A.

    2012-01-01

    Arsenic (As) is a well documented human carcinogen. However, its mechanisms of toxic action and carcinogenic potential in animals have not been conclusive. In this research, we investigated the biochemical and genotoxic effects of As and studied its distribution in selected tissues of Sprague–Dawley rats. Four groups of six male rats, each weighing approximately 60 ± 2 g, were injected intraperitoneally, once a day for 5 days with doses of 5, 10, 15, 20 mg/kg BW of arsenic trioxide. A control group was also made of 6 animals injected with distilled water. Following anaesthetization, blood was collected and enzyme analysis was performed by spectrophotometry following standard protocols. At the end of experimentation, the animals were sacrificed, and the lung, liver, brain and kidney were collected 24 h after the fifth day treatment. Chromosome and micronuclei preparation was obtained from bone marrow cells. Arsenic exposure significantly increased (p < 0.05) the activities of plasma alanine aminotransferase–glutamate pyruvate transaminase (ALT/GPT), and aspartate aminotransferase–glutamate oxaloacetate transaminase (AST/GOT), as well as the number of structural chromosomal aberrations (SCA) and frequency of micronuclei (MN) in the bone marrow cells. In contrast, the mitotic index in these cells was significantly reduced (p < 0.05). These findings indicate that aminotransferases are candidate biomarkers for arsenic-induced hepatotoxicity. Our results also demonstrate that As has a strong genotoxic potential, as measured by the bone marrow SCA and MN tests in Sprague–Dawley rats. Total arsenic concentrations in tissues were measured by inductively coupled plasma mass spectrometry (ICP-MS). A dynamic reaction cell (DRC) with hydrogen gas was used to eliminate the ArCl interference at mass 75, in the measurement of total As. Total As doses in tissues tended to correlate with specific exposure levels.

  3. Toxicokinetics of tremorogenic natural products, harmane and harmine, in male Sprague-Dawley rats.

    Science.gov (United States)

    Guan, Y; Louis, E D; Zheng, W

    2001-12-21

    Tremorogenic beta-carboline alkaloids are present in foodstuffs and beverages. Acute exposure to beta-carboline derivatives causes severe tremor; however, the disposition of these dietary contaminants remains unclear. This study was performed to evaluate toxicokinetics of harmane and harmine, two major beta-carboline alkaloids, in rats. Blood concentrations of both toxicants were quantified by high-performance liquid chromatography (HPLC). Following an intravenous injection (0.5 mg/kg), the concentration-time profiles of harmane or harmine fit well with a two-compartment model. While both compounds had comparable elimination t 1/2beta (24 and 26 min for harmane and harmine, respectively), the systemic clearance (CLs) for harmine (103.2 ml/kg/ml) was two times greater than that for harmane (52.2 ml/kg/ml). Accordingly, the area under the blood concentration-time curve (AUC) in harmane-treated rats was 2.7-fold greater than that in harmine-treated rats. Harmine appeared to distribute to tissues better than harmane, with a larger volume of distribution (V,d) (3.9 and 1.6 L/kg for harmine and harmane, respectively). After an oral dose (20 mg/kg), the absolute bioavailability (F) was 19% for harmane and 3% for harmine. Harmane was absorbed more slowly (lower Ka), yet more completely (higher Cmax' AUC, and F) than harmine. An oral administration of harmane resulted in blood harmine whose formation accounted for 13% of the ingested harmane, indicating a biotransformation of harmane to harmine. These results suggest that harmane is absorbed into the systemic circulation more completely than harmine. Upon entering the body, harmane can be metabolized to form harmine; the latter may better distribute to the tissue compartment.

  4. The effects of ultrasonic scaling duration and replication on caspase-3 expression of Sprague Dawley rat's pulp cells

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    Archadian Nuryanti

    2015-03-01

    Full Text Available Background: Ultrasonic scaling has been used commonly for stain and calculus removal in dental clinic for over 60years. Previous researches even had proved that ultrasonic scaling may give effects on the surface of tooth root. Ultrasonic wave exposure for 20 seconds or more can increase caspase-3 activity as an indicator of increased apoptotic cells associated with tissue damage. Purpose: This research was aimed to investigate the effects of ultrasonic scaling duration and replication on caspace-3 expression in dental pulp cells. Methods: The samples of this research were 54 male Sprague Dawley rats aged 2 months old divided into 2 groups, each of which consisted of 27 mice. The first group was induced with stain, while the second group was not. Each group was divided into 3 subgroups for ultrasonic scaling 1, 3, and 5 times. Each subgroup was divided into 3 sub-subgroups for duration procedure of 15, 30 and 60 seconds respectively. During scaling process, those rats were anesthetized using 0.1 ml of ketamine and 0.1 ml of xylol added to 2 ml of distilled water injected intramuscularly into their right thigh as much as 0.4 ml. Scaling was done on buccal surface of right first maxillary molar from cervical to occlusal. The teeth were decalcified and embedded in paraffin, then their sagittal plane was cut for thickness of 3µm and painted with immunohystochemistry for detecting caspace-3 expression of cell within dental pulp. Results: The results showed that the duration and replication of ultrasonic scaling procedures affected on the expression of caspace-3 cells as analyzed with Univariate Analisis of Variance test (p<0.05. Conclusion: It can be concluded that duration and replication of ultrasonic scaling procedure on teeth with and without stain enhauced the expression of  caspace-3 in dental pulp cells.

  5. Genotoxicity of Silver Nanoparticles in Lung Cells of Sprague Dawley Rats after 12 Weeks of Inhalation Exposure

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    Hyun Sun Cho

    2013-11-01

    Full Text Available Due to the widespread use of silver nanoparticles in consumer products, the toxicity of silver nanoparticles has also been studied in relation to their application. However, most genotoxicity studies of silver nanoparticles have been performed in vitro. Therefore, this study evaluated the DNA damage to lung cells caused by repeated inhalation of silver nanoparticles. Male Sprague Dawley rats were exposed to silver nanoparticles for 12 weeks in a whole-body inhalation chamber. The animals were divided into one control group and three dose groups that were exposed to silver nanoparticles (14–15 nm diameter at concentrations of 0.66 × 106 particles/cm3 (49 μg/m3, low dose, 1.41 × 106 particles/cm3 (117 μg/m3, middle dose, and 3.24 × 106 particles /cm3 (381 μg/m3, high dose, respectively, for six hours/day over 12 weeks. The rats were sacrificed after the 12-week exposure period and the DNA damage assessed using a Comet assay of cells obtained from the right lungs. The olive tail moment values were 2.93 ± 0.19, 3.81 ± 0.23, 3.40 ± 0.22, and 5.16 ± 0.32 for the control, low-, middle-, and high-dose groups, respectively. Although no dose-dependent results were observed, a significant increase in the level of DNA damage was noted for the high-dose group.

  6. Dietary Selenium as a Modulator of PCB 126–Induced Hepatotoxicity in Male Sprague-Dawley Rats

    Science.gov (United States)

    Lai, Ian K.; Chai, Yingtao; Simmons, Donald; Watson, Walter H.; Tan, Rommel; Haschek, Wanda M.; Wang, Kai; Wang, Bingxuan; Ludewig, Gabriele; Robertson, Larry W.

    2011-01-01

    Homeostasis of selenium (Se), a critical antioxidant incorporated into amino acids and enzymes, is disrupted by exposure to aryl hydrocarbon receptor (AhR) agonists. Here we examined the importance of dietary Se in preventing the toxicity of the most toxic polychlorinated biphenyl congener, 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126), a potent AhR agonist. Male Sprague-Dawley rats were fed a modified AIN-93 diet with differing dietary Se levels (0.02, 0.2, and 2 ppm). Following 3 weeks of acclimatization, rats from each dietary group were given a single ip injection of corn oil (vehicle), 0.2, 1, or 5 μmol/kg body weight PCB 126, followed 2 weeks later by euthanasia. PCB exposure caused dose-dependent increases in liver weight and at the highest PCB 126 dose decreases in whole body weight gains. Hepatic cytochrome P-450 (CYP1A1) activity was significantly increased even at the lowest dose of PCB 126, indicating potent AhR activation. PCB exposure diminished hepatic Se levels in a dose-dependent manner, and this was accompanied by diminished Se-dependent glutathione peroxidase activity. Both these effects were partially mitigated by Se supplementation. Conversely, thioredoxin (Trx) reductase activity and Trx oxidation state, although significantly diminished in the lowest dietary Se groups, were not affected by PCB exposure. In addition, PCB 126–induced changes in hepatic copper, iron, manganese, and zinc were observed. These results demonstrate that supplemental dietary Se was not able to completely prevent the toxicity caused by PCB 126 but was able to increase moderately the levels of several key antioxidants, thereby maintaining them roughly at normal levels. PMID:21865291

  7. A 3D map of the hindlimb motor representation in the lumbar spinal cord in Sprague Dawley rats

    Science.gov (United States)

    Borrell, Jordan A.; Frost, Shawn B.; Peterson, Jeremy; Nudo, Randolph J.

    2017-02-01

    Objective. Spinal cord injury (SCI) is a devastating neurological trauma with a prevalence of about 282 000 people living with an SCI in the United States in 2016. Advances in neuromodulatory devices hold promise for restoring function by incorporating the delivery of electrical current directly into the spinal cord grey matter via intraspinal microstimulation (ISMS). In such designs, detailed topographic maps of spinal cord outputs are needed to determine ISMS locations for eliciting hindlimb movements. The primary goal of the present study was to derive a topographic map of functional motor outputs in the lumbar spinal cord to hindlimb skeletal muscles as defined by ISMS in a rat model. Approach. Experiments were carried out in nine healthy, adult, male, Sprague Dawley rats. After a laminectomy of the T13-L1 vertebrae and removal of the dura mater, a four-shank, 16-channel microelectrode array was inserted along a 3D (200 µm) stimulation grid. Trains of three biphasic current pulses were used to determine evoked movements and electromyographic (EMG) activity. Via fine wire EMG electrodes, stimulus-triggered averaging (StTA) was used on rectified EMG data to determine response latency. Main results. Hindlimb movements were elicited at a median current intensity of 6 µA, and thresholds were significantly lower in ventrolateral sites. Movements typically consisted of whole leg, hip, knee, ankle, toe, and trunk movements. Hip movements dominated rostral to the T13 vertebral segment, knee movements were evoked at the T13-L1 vertebral junction, while ankle and digit movements were found near the rostral L1 vertebra. Whole leg movements spanned the entire rostrocaudal region explored, while trunk movements dominated medially. StTAs of EMG activity demonstrated a latency of ~4 ms. Significance. The derived motor map provides insight into the parameters needed for future neuromodulatory devices.

  8. Impact of low dose prenatal ethanol exposure on glucose homeostasis in Sprague-Dawley rats aged up to eight months.

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    Megan E Probyn

    Full Text Available Excessive exposure to alcohol prenatally has a myriad of detrimental effects on the health and well-being of the offspring. It is unknown whether chronic low-moderate exposure of alcohol prenatally has similar and lasting effects on the adult offspring's health. Using our recently developed Sprague-Dawley rat model of 6% chronic prenatal ethanol exposure, this study aimed to determine if this modest level of exposure adversely affects glucose homeostasis in male and female offspring aged up to eight months. Plasma glucose concentrations were measured in late fetal and postnatal life. The pancreas of 30 day old offspring was analysed for β-cell mass. Glucose handling and insulin action was measured at four months using an intraperitoneal glucose tolerance test and insulin challenge, respectively. Body composition and metabolic gene expression were measured at eight months. Despite normoglycaemia in ethanol consuming dams, ethanol-exposed fetuses were hypoglycaemic at embryonic day 20. Ethanol-exposed offspring were normoglycaemic and normoinsulinaemic under basal fasting conditions and had normal pancreatic β-cell mass at postnatal day 30. However, during a glucose tolerance test, male ethanol-exposed offspring were hyperinsulinaemic with increased first phase insulin secretion. Female ethanol-exposed offspring displayed enhanced glucose clearance during an insulin challenge. Body composition and hepatic, muscle and adipose tissue metabolic gene expression levels at eight months were not altered by prenatal ethanol exposure. Low-moderate chronic prenatal ethanol exposure has subtle, sex specific effects on glucose homeostasis in the young adult rat. As aging is associated with glucose dysregulation, further studies will clarify the long lasting effects of prenatal ethanol exposure.

  9. A THREE-DIMENSIONAL MAP OF THE HINDLIMB MOTOR REPRESENTATION IN THE LUMBAR SPINAL CORD IN SPRAGUE DAWLEY RATS

    Science.gov (United States)

    Borrell, Jordan A.; Frost, Shawn; Peterson, Jeremy; Nudo, Randolph J.

    2016-01-01

    Objective Spinal cord injury (SCI) is a devastating neurological trauma with a prevalence of about 282,000 people living with an SCI in the United States in 2016. Advances in neuromodulatory devices hold promise for restoring function by incorporating the delivery of electrical current directly into the spinal cord grey matter via intraspinal microstimulation (ISMS). In such designs, detailed topographic maps of spinal cord outputs are needed to determine ISMS locations for eliciting hindlimb movements. The primary goal of the present study was to derive a topographic map of functional motor outputs in the lumbar spinal cord to hindlimb skeletal muscles as defined by ISMS in a rat model. Approach Experiments were carried out in nine healthy, adult, male, Sprague Dawley rats. After a laminectomy of the T13-L1 vertebrae and removal of the dura mater, a four-shank, 16-channel microelectrode array was inserted along a three-dimensional (200 µm) stimulation grid. Trains of three biphasic current pulses were used to determine evoked movements and EMG activity. Via fine wire electromyographic (EMG) electrodes, Stimulus-Triggered Averaging (StTA) was used on rectified EMG data to determine response latency. Main results Hindlimb movements were elicited at a median current intensity of 6 µA, and thresholds were significantly lower in ventrolateral sites. Movements typically consisted of whole leg, hip, knee, ankle, toe, and trunk movements. Hip movements dominated rostral to the T13 vertebral segment, knee movements were evoked at the T13-L1 vertebral junction, while ankle and digit movements were found near the rostral L1 vertebra. Whole leg movements spanned the entire rostrocaudal region explored, while trunk movements dominated medially. StTAs of EMG activity demonstrated a latency of ~4 ms. Significance The derived motor map provides insight into the parameters needed for future neuromodulatory devices. PMID:27934789

  10. Effect of autoclave devitalization on autograft incorporation and bone morphogenetic protein of tibia in Sprague-Dawley rats

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    Anak A.G.Y. Asmara

    2014-06-01

    Full Text Available Background: Heating process with autoclave is one of limb salvage modalities that are widely used. but the results are not satisfying, due to mechanical bone fragility. However, considering this treatment modality is widely accepted in terms of financial, religion and sociocultural aspects, we conducted a on study rats treated with resection and reconstruction with autoclave heating method to assess bone healing by sequential radiology, histopathologic osteoblasts count, and bone morphogenetic protein (BMP.Methods: Thirty six Sprague-Dawley rats were divided into two groups with one group being the autoclave group and others served as control group. In both groups, the tibial diaphysis was extracted en bloc for 7 mm. All groups were kept for 8 weeks and treated under the same condition except the autoclave group, where the extracted bones were put into autoclave at 134°C for 15 minutes and refixed again with k-wire. We performed radiological examination at 5th and 8th week using Lane and Sandhu radiological score. After extraction, the tibial bones were inspected for histological pattern using Salked modified score, osteoblast quantity counting and BMP-2 values.Results: There were statistically significant diffences between control and autoclave group on radiological score at 5th (5.12 ± 1.6 g vs 3.21 ± 2.42, p = 0.023 and 8th week (6.06 ± 1.71 vs 4.29 ± 2.53, p = 0.040, histological score between groups (6.06 ± 1.14 vs 4.14 ± 1.99, p = 0.005, osteoblast count (p < 0.001, and BMP-2 expression,  respectively.Conclusion: Autoclave recycling autograft lowered the speed of graft incorporation and BMP-2 expression. Therefore, autoclave recycling autograft as a method of limb salvage surgery must be reevaluated and not considered to be applied for treatment in bone malignancy.  

  11. Inhibitory effect of Coffea arabica bean in testosterone induced prostatic hyperplasia in Sprague-Dawley rats

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    Kristian Alfonso G. Cueto

    2016-05-01

    Full Text Available Benign prostatic hyperplasia (BPH has been described as the uncontrolled prostate gland growth which leads to difficulty in urination. One of the treatment of BPH is saw palmetto lipid extracts which has been shown to inhibit prostate 5 α-reductase and some of its components (lauric acid, myristic acid and oleic acid also inhibit the enzyme. Coffee was also rich in fatty acids namely linoleic acid, oleic acid and palmitic acid. The aim of this research is to investigate whether coffee is effective in preventing testosterone-induced prostatic hyperplasia in rats using testosterone propionate and estradiol valerate. After and before the induction, the rats were tested for prostate specific antigen (PSA . The condition of the prostate gland of the test animals were correlated with the results of the said test and in the histopathologic results. After 14 days of experimentation, animals in the test group significantly decreased their PSA levels as compared to the BPH group. The histomorphology showed that Coffea arabica bean oil inhibited testosterone propionate while estradiol valerate induced prostatic hyperplasia. These findings indicate that Coffee arabica bean oil effectively inhibited the development of BPH. With the proven safety of coffee oil, these findings strongly support the feasibility of using Coffea arabica bean oil therapeutically in treating BPH.

  12. Safety assessment of Maillard reaction products of chicken bone hydrolysate using Sprague-Dawley rats

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    Jin-Zhi Wang

    2016-03-01

    Full Text Available Background: The Maillard reaction products of chicken bone hydrolysate (MRPB containing 38% protein, which is a derived product from chicken bone, is usually used as a flavor enhancer or food ingredient. In the face of a paucity of reported data regarding the safety profile of controversial Maillard reaction products, the potential health effects of MRPB were evaluated in a subchronic rodent feeding study. Methods: Sprague–Dawley rats (SD, 5/sex/group were administered diets containing 9, 3, 1, or 0% of MRPB derived from chicken bone for 13 weeks. Results: During the 13-week treatment period, no mortality occurred, and no remarkable changes in general condition and behavior were observed. The consumption of MRPB did not have any effect on body weight or feed and water consumption. At the same time, there was no significant increase in the weights of the heart, liver, lung, kidney, spleen, small intestine, and thymus in groups for both sexes. Serological examination showed serum alanine aminotransferase in both sexes was decreased significantly, indicating liver cell protection. No treatment-related histopathological differences were observed between the control and test groups. Conclusion: Based on the results of this study, the addition of 9% MRPB in the diet had no adverse effect on both male and female SD rats during the 90-day observation. Those results would provide useful information on the safety of a meaty flavor enhancer from bone residue as a byproduct of meat industry.

  13. Betaine reduces hepatic lipidosis induced by carbon tetrachloride in Sprague-Dawley rats.

    Science.gov (United States)

    Junnila, M; Barak, A J; Beckenhauer, H C; Rahko, T

    1998-10-01

    Carbon tetrachloride-injected rats were given liquid diets with and without betaine for 7 d. Hepatic lipidosis was induced by 4 daily injections of carbon tetrachloride (CCl4). Animals were killed and their livers and blood taken for analysis of betaine, S-adenosylmethionine (SAM), betaine homocysteine methyltransferase (BHMT), triglyceride, alanine aminotransferase and aspartate aminotransferase. Liver samples were also processed and stained for histological examination. Supplemental betaine reduced triglyceride in the liver and centrilobular hepatic lipidosis induced by the CCl4 injections. In both the control and experimental groups receiving betaine, liver betaine, BHMT and SAM were significantly higher than in their respective groups not receiving betaine. This study provides evidence that betaine protects the liver against CCl4-induced lipidosis and may be a useful therapeutic and prophylactic agent in ameliorating the harmful effects of CCl4.

  14. Brief electrical stimulation improves nerve regeneration after delayed repair in Sprague Dawley rats.

    Science.gov (United States)

    Elzinga, Kate; Tyreman, Neil; Ladak, Adil; Savaryn, Bohdan; Olson, Jaret; Gordon, Tessa

    2015-07-01

    Functional recovery after peripheral nerve injury and surgical repair declines with time and distance because the injured neurons without target contacts (chronic axotomy) progressively lose their regenerative capacity and chronically denervated Schwann cells (SCs) atrophy and fail to support axon regeneration. Findings that brief low frequency electrical stimulation (ES) accelerates axon outgrowth and muscle reinnervation after immediate nerve surgery in rats and human patients suggest that ES might improve regeneration after delayed nerve repair. To test this hypothesis, common peroneal (CP) neurons were chronically axotomized and/or tibial (TIB) SCs and ankle extensor muscles were chronically denervated by transection and ligation in rats. The CP and TIB nerves were cross-sutured after three months and subjected to either sham or one hour 20Hz ES. Using retrograde tracing, we found that ES significantly increased the numbers of both motor and sensory neurons that regenerated their axons after a three month period of chronic CP axotomy and/or chronic TIB SC denervation. Muscle and motor unit forces recorded to determine the numbers of neurons that reinnervated gastrocnemius muscle demonstrated that ES significantly increased the numbers of motoneurons that reinnervated chronically denervated muscles. We conclude that electrical stimulation of chronically axotomized motor and sensory neurons is effective in accelerating axon outgrowth into chronically denervated nerve stumps and improving target reinnervation after delayed nerve repair. Possible mechanisms for the efficacy of ES in promoting axon regeneration and target reinnervation after delayed nerve repair include the upregulation of neurotrophic factors. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Disposition and metabolism of glyphosate in the Sprague Dawley rat following oral administration

    International Nuclear Information System (INIS)

    Brewster, D.W.; Warren, J.A.; Hopkins, W.E.

    1991-01-01

    Five groups of male SD rats were administered 14 C-labelled glyphosate, (N-[(phosphonomethyl)glycine]) by gavage at a dose level of 10 mg/kg. Animals were killed 2, 6.3, 28, 96 and 168 hours after dosing and the amount of glyphosate-derived material in various organs and excreta were determined. In addition, the metabolic profile in tissues containing > 1% of the administered dose was evaluated. Approximately 93% of the body burden 2 hours after administration was associated with the GI contents and small intestinal tissue. The total body burden 7 days after administration was ∼1% of the dose. Only the kidneys, small intestine, colon, bone, GI contents, residual carcass contained > 1% of the dose 6 hours after administration and the metabolic profiles of these tissues indicated that ∼100% of the body burden was present as unmetabolized parent material. Glyphosate was rapidly eliminated from these tissues with halflives ranging from 20 to 90 hours. A minor metabolite comprising < 0.1% of the dose was detected in the GI contents and colon tissue of 3 animals. Less than 40% of the administered dose was absorbed from the gut and glyphosate was rapidly eliminated from the body with urine and feces being equally important routes of elimination. The whole body halflife was approximately 52 hours. The results from this study indicate that no toxic metabolites of glyphosate were produced, as there was little evidence of metabolism, and essentially 100% of the body burden was parent glyphosate with no significant persistence of accumulated material

  16. Repeated dose intramuscular injection of the CIMAvax-EGF vaccine in Sprague Dawley rats induces local and systemic toxicity.

    Science.gov (United States)

    Mancebo, A; Casacó, A; González, B; Ledón, N; Sorlozabal, J; León, A; Gómez, D; González, Y; Bada, A M; González, C; Arteaga, M E; Ramírez, H; Fuentes, D

    2012-05-09

    CIMAvax-EGF consists of a human recombinant epidermal growth factor (EGF), coupled to P64k, a recombinant carrier protein from N. meningitis, and Montanide ISA 51 as adjuvant. The vaccine immunization induces a specific antibody production, inhibiting the EGF/EGF-R interaction through EGF deprivation. The objective of this study was to assess the CIMAvax-EGF toxicity in Sprague Dawley rats after intramuscular administration of repeated doses (6 months) and at the same time to determine if rat is a relevant species for studying CIMAvax-EGF vaccine. Rats were randomly distributed into four groups: control, Montanide ISA 51, treated with 1× and 15× of human total dose of the antigen. Animals were immunized weekly during 9 weeks, plus 9 immunizations every 14 days. Rats were inspected daily for clinical signs. Body weight, food consumption, and rectal temperature were measured during the administration of doses. Blood samples were collected for hematological, serum biochemical determinations and EGF titles at the beginning, three months and at the end of experimentation. Gross necropsy and histological examination of tissues were performed on animals at the end of the assay. Vaccine provoked the apparition of antibodies against EGF in the rats, demonstrating rat species relevance in these studies. Body weight gain, food and water consumption were not affected. CIMAvax-EGF and Montanide ISA 51 produced local damage at the administration site, showing multiple cysts and granulomas. Both vaccine-treated groups showed neutrophil elevation, besides an AST increase probably related to the damage at the administration site. Rectal temperature was found to be significantly higher in 15× treated group after immunizations, probably induced by the inflammatory process at the injection site. In summary, the clinical pathology findings together with the body temperature results, appear to be caused by the inflammatory reaction at the administration site of the vaccine, mainly

  17. Endothelin-like action of Pausinystalia yohimbe aqueous extract on vascular and renal regional hemodynamics in Sprague Dawley rats.

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    Ajayi, A A; Newaz, M; Hercule, H; Saleh, M; Bode, C O; Oyekan, A O

    2003-12-01

    The bark of the African tree Pausinystalia yohimbe has been used as a food additive with aphrodisiac and penile erection enhancing properties. The effect of an aqueous extract of P. yohimbe (CCD-X) on renal circulation was assessed in order to test the hypothesis that it possesses additional effects on nitric oxide production and/or endothelin-1 (ET-1)-like actions. In vivo studies with CCD-X in Sprague Dawley rats demonstrated a dose-dependent (1-1000 ng/kg) increase in mean blood pressure (p < 0.001) and an increase in medullary blood flow (MBF) (p < 0.001). Both the pressor action and renal medullary vasodilation were blocked by endothelinA (ETA) receptor antagonist BMS182874 and endothelinB (ETB) receptor antagonist BQ788 in combination. L-Nomega-nitro-l-arginine methyl ester (L-NAME; 10 mg/kg) also inhibited the increase in MBF induced by CCD-X. In vitro studies in isolated perfused kidney and in pressurized renal microvessels confirmed the dose-dependent vasoconstrictor action of this extract. ETA receptor antagonist BQ610 and ETB receptor antagonist BQ788 separately and significantly attenuated the renal vasoconstrictor actions of the extract (p < 0.001 ANOVA). These preliminary observations indicate that, in addition to the alpha-adrenergic antagonist actions that characterize yohimbine, CCD-X possesses endothelin-like actions and affects nitric oxide (NO) production in renal circulation. These findings suggest a strong possibility of post-receptor cross-talk between alpha2-adrenoceptors and endothelin, as well as a direct effect of alpha2-adrenoceptors on renal NO production. (c) 2003 Prous Science

  18. Pituitary Adenylate Cyclase-Activating Polypeptide Disrupts Motivation, Social Interaction, and Attention in Male Sprague Dawley Rats.

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    Donahue, Rachel J; Venkataraman, Archana; Carroll, F Ivy; Meloni, Edward G; Carlezon, William A

    2016-12-15

    Severe or prolonged stress can trigger psychiatric illnesses including mood and anxiety disorders. Recent work indicates that pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in regulating stress effects. In rodents, exogenous PACAP administration can produce persistent elevations in the acoustic startle response, which may reflect anxiety-like signs including hypervigilance. We investigated whether PACAP causes acute or persistent alterations in behaviors that reflect other core features of mood and anxiety disorders (motivation, social interaction, and attention). Using male Sprague Dawley rats, we examined if PACAP (.25-1.0 µg, intracerebroventricular infusion) affects motivation as measured in the intracranial self-stimulation test. We also examined if PACAP alters interactions with a conspecific in the social interaction test. Finally, we examined if PACAP affects performance in the 5-choice serial reaction time task, which quantifies attention and error processing. Dose-dependent disruptions in motivation, social interaction, and attention were produced by PACAP, as reflected by increases in reward thresholds, decreases in social behaviors, and decreases in correct responses and alterations in posterror accuracy. Behavior normalized quickly in the intracranial self-stimulation and 5-choice serial reaction time task tests but remained dysregulated in the social interaction test. Effects on attention were attenuated by the corticotropin-releasing factor receptor-1 antagonist antalarmin but not the κ opioid receptor antagonist JDTic. Our findings suggest that PACAP affects numerous domains often dysregulated in mood and anxiety disorders, but that individual signs depend on brain substrates that are at least partially independent. This work may help to devise therapeutics that mitigate specific signs of these disorders. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. Carcinogenicity of individual and a mixture of dioxin-like compounds in female Harlan Sprague Dawley rats

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    Walker, N.; Nyska, A. [National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Crockett, P. [Constella Group, Research Triangle Park, NC (US)] (and others)

    2004-09-15

    The human health risk posed by exposure to persistent organochlorine pollutants (POPs), including polychlorinated-dioxins (PCDDs), -furans (PCDFs) and - biphenyls (PCBs), present in the food and the environment is one of widespread concern throughout the industrialized world. The dioxin Toxic Equivalency Factor (TEF) approach is currently the most feasible interim approach for assessing and managing the risk posed by exposure to mixtures of these compounds and has been formally adopted by regulatory bodies in many countries, the International Programme on Chemical Safety and the World Health Organization. The TEF methodology is a relative potency scheme that estimates the total exposure and biological effects of a mixture of chemicals based on a common mechanism of action involving an initial binding of the compound to the Aryl hydrocarbon receptor (AhR). An implicit assumption of the TEF methodology is that the combined risk of effects of the different congeners is dose additive. Therefore, the total dioxin toxic equivalents (TEQs) of a mixture of PCDDs, PCDFs, and PCBs may be estimated by the summation of the mass of each compound in the mixture after adjustment for its potency relative to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). While dose additivity is supported for certain mixtures for some biological endpoints in some experimental models, this has never been evaluated for cancer risk. Here we present a summary of four chronic rodent bioassay conducted by the National Toxicology Program (US Department of Health and Human Services) that evaluated the carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3.3',4,4',5- pentachlorobiphenyl (PCB126) and 2,3,4,7,8 pentachlorodibenzofuran (PeCDF) and a mixture of these three dioxin-like compounds in female Harlan Sprague Dawley rats. Data from these studies will be used to test the hypothesis of dose-additivity of carcinogenicity by a defined mixture of dioxin-like compounds.

  20. Apolipoprotein A-V is present in bile and its secretion increases with lipid absorption in Sprague-Dawley rats.

    Science.gov (United States)

    Zhang, Linda S; Sato, Hirokazu; Yang, Qing; Ryan, Robert O; Wang, David Q-H; Howles, Philip N; Tso, Patrick

    2015-12-01

    Apolipoprotein (apo) A-V is a protein synthesized only in the liver that dramatically modulates plasma triglyceride levels. Recent studies suggest a novel role for hepatic apoA-V in regulating the absorption of dietary triglycerides, but its mode of action on the gut remains unknown. The aim of this study was to test for apoA-V in bile and to determine whether its secretion is regulated by dietary lipids. After an overnight recovery, adult male Sprague-Dawley bile fistula rats indeed secreted apoA-V into bile at a constant rate under fasting conditions. An intraduodenal bolus of intralipid (n = 12) increased the biliary secretion of apoA-V but not of other apolipoproteins, such as A-I, A-IV, B, and E. The lipid-induced increase of biliary apoA-V was abolished under conditions of poor lymphatic lipid transport, suggesting that the stimulation is regulated by the magnitude of lipids associated with chylomicrons transported into lymph. We also studied the secretion of apoA-V into bile immediately following bile duct cannulation. Biliary apoA-V increased over time (∼6-fold increase at hour 16, n = 8) but the secretions of other apolipoproteins remained constant. Replenishing luminal phosphatidylcholine and taurocholate (n = 9) only enhanced apoA-V secretion in bile, suggesting that the increase was not due to depletion of phospholipids or bile salts. This is the first study to demonstrate that apoA-V is secreted into bile, introducing a potential route of delivery of hepatic apoA-V to the gut lumen. Our study also reveals the uniqueness of apoA-V secretion into bile that is regulated by mechanisms different from other apolipoproteins. Copyright © 2015 the American Physiological Society.

  1. Study of a 13-weeks, Repeated, Intramuscular Dose, Toxicity Test of Sweet Bee Venom in Sprague-Dawley Rats

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    Hyunmin Kang

    2014-06-01

    Full Text Available Objectives:This study was performed to analyze a 13-week repeated dose toxicity test of Sweet Bee Venom (SBV extracted from bee venom and administered in Sprague-Dawley (SD rats. Methods:Male and female 5-week-old SD rats were treated once daily with SBV (high-dosage group: 0.28 mg/kg; medium-dosage group: 0.14 mg/kg; or low-dosage group: 0.07 mg/kg for 13 weeks. Normal saline was administered to the control group in a similar manner (0.2 mL/kg. We conducted clinical observations, body weight measurements, ophthalmic examinations, urinalyses, hematology and biochemistry tests, and histological observations using hematoxylin and eosin (H&E staining to identify any abnormalities caused by the SBV treatment. Results:During this study, no mortality was observed in any of the experimental groups. Hyperemia and a movement disorder were observed around the area of in all groups that received SBV treatment, with a higher occurrence in rats treated with a higher dosage. Male rats receiving in the high-dosage group showed a significant decrease in weight during the treatment period. Compared to the control group, no significant changes in the ophthalmic parameters, the urine analyses, the complete blood cell count (CBC, and the biochemistry in the groups treated with SBV. Compared to the control group, some changes in organ weights were observed in the medium-and the high-dosage groups, but the low-dosage group showed no significant changes. Histological examination of thigh muscle indicated cell infiltration, inflammation, degeneration, and necrosis of muscle fiber, as well as fibrosis, in both the medium- and the high-dosage groups. Fatty liver change was observed in the periportal area of rats receiving medium and high dosages of SBV. No other organ abnormalities were observed. Conclusion:Our findings suggest that the No Observed Adverse Effect Level (NOAEL of SBV is approximately 0.07 mg/kg in male and female SD rats.

  2. Expresión diferencial de proteínas cardiacas en ratas diabéticas tipo Sprague-Dawley Differential heart protein expression in diabetic type Sprague-Dawley rats

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    Richard Southgate

    Full Text Available Se purificaron proteínas cardiacas a partir de ratas diabéticas y sanas de tipo Sprague-Dawley. Las proteínas fueron fraccionadas por medio de gel de electroforesis de dos dimensiones (2D-PAGE. La separación resultante fue visualizada por tinción con Coomassie azul. Luego de ser convertidas en imagen digital, las proteínas del grupo diabético y del grupo control fueron comparadas y correlacionadas para determinar los niveles de expresión diferenciada. Sesenta de las ciento ochenta proteínas en el gel fueron removidas y digeridas en fragmentos pequeños de péptidos, los cuales se analizaron por medio de espectrometría de masas para determinar la estructura primaria de los péptidos resultantes (secuencia de los aminoácidos. Esta información se registró en una base de datos (http://www.ncbi.nlm.nih.gov/ para determinar la identidad de las proteínas precedentes a los péptidos. Se determinó la identidad de las proteínas expresadas diferencialmente en el tejido cardiaco de ambos grupos; se encontraron varias proteínas expresadas en diferentes niveles a los normales cuando se analizaron los corazones de ratas diabéticas, incluyendo fosfatasa de tiroxina (PTP, Q60998, receptores de lipoproteínas de muy baja densidad (VLDL-R, P98156, perioxidasa de glutation (PHGPx, O70325, transferasa de serina hidroxilamina (SHMT, P50431, adenylyl cyclasa proteína 1 asociada (CAP1, P40124 y teletonina (TELT, O70548.Cardiac proteins were isolated from diabetic and wild type Sprague-Dawley rats, then fractionated by two dimensional gel electrophoresis (2D-PAGE using isoelectric focusing and molecular weight. The resulting protein spots were stained to facilitate detection. After being converted into a digital image, the proteins on the diabetic and wild type gels were matched to each other then compared to determine levels of expression. Sixty of the one hundred and eighty proteins on the gel were removed and digested to produce peptide fragments

  3. Nutritional Ketosis Affects Metabolism and Behavior in Sprague-Dawley Rats in Both Control and Chronic Stress Environments

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    Milene L. Brownlow

    2017-05-01

    Full Text Available Nutritional ketosis may enhance cerebral energy metabolism and has received increased interest as a way to improve or preserve performance and resilience. Most studies to date have focused on metabolic or neurological disorders while anecdotal evidence suggests that ketosis may enhance performance in the absence of underlying dysfunction. Moreover, decreased availability of glucose in the brain following stressful events is associated with impaired cognition, suggesting the need for more efficient energy sources. We tested the hypotheses that ketosis induced by endogenous or exogenous ketones could: (a augment cognitive outcomes in healthy subjects; and (b prevent stress-induced detriments in cognitive parameters. Adult, male, Sprague Dawley rats were used to investigate metabolic and behavioral outcomes in 3 dietary conditions: ketogenic (KD, ketone supplemented (KS, or NIH-31 control diet in both control or chronic stress conditions. Acute administration of exogenous ketones resulted in reduction in blood glucose and sustained ketosis. Chronic experiments showed that in control conditions, only KD resulted in pronounced metabolic alterations and improved performance in the novel object recognition test. The hypothalamic-pituitary-adrenal (HPA axis response revealed that KD-fed rats maintained peripheral ketosis despite increases in glucose whereas no diet effects were observed in ACTH or CORT levels. Both KD and KS-fed rats decreased escape latencies on the third day of water maze, whereas only KD prevented stress-induced deficits on the last testing day and improved probe test performance. Stress-induced decrease in hippocampal levels of β-hydroxybutyrate was attenuated in KD group while both KD and KS prevented stress effects on BDNF levels. Mitochondrial enzymes associated with ketogenesis were increased in both KD and KS hippocampal samples and both endothelial and neuronal glucose transporters were affected by stress but only in the

  4. The gastroprotective effects of hydroalcoholic extract of Monolluma quadrangula against ethanol-induced gastric mucosal injuries in Sprague Dawley rats

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    Ibrahim IAA

    2015-12-01

    Full Text Available Ibrahim Abdel Aziz Ibrahim,1 Mahmood Ameen Abdulla,2 Maryam Hajrezaie,2 Ammar Bader,3 Naiyer Shahzad,1 Saeed S Al-Ghamdi,1 Ahmad S Gushash,4 Mohadeseh Hasanpourghadi5 1Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 2Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Pharmacognosy, Faculty of Pharmacy, Umm Al-Qura University, Makkah, 4College of Arts and Science in Baljurashi, Albaha University, Baljurashi, Saudi Arabia; 5Cell Biology and Drug Discovery Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Abstract: Monolluma quadrangula (Forssk. Plowes is used in Saudi traditional medicines to treat gastric ulcers. The hydroalcoholic extract of M. quadrangula (MHAE was used in an in vivo model to investigate its gastroprotective effects against ethanol-induced acute gastric lesions in rats. Five groups of Sprague Dawley rats were used. The first group was treated with 10% Tween 20 as a control. The other four groups included rats treated with absolute ethanol (5 mL/kg to induce an ulcer, rats treated with 20 mg/kg omeprazole as a reference drug, and rats treated with 150 or 300 mg/kg MHAE. One hour later, the rats were administered absolute ethanol (5 mL/kg orally. Animals fed with MHAE exhibited a significantly increased pH, gastric wall mucus, and flattening of the gastric mucosa, as well as a decreased area of gastric mucosal damage. Histology confirmed the results; extensive destruction of the gastric mucosa was observed in the ulcer control group, and the lesions penetrated deep into the gastric mucosa with leukocyte infiltration of the submucosal layer and edema. However, gastric protection was observed in the rats pre-fed with plant extracts. Periodic acid–Schiff staining of the gastric wall revealed a remarkably intensive uptake of magenta color in the

  5. The effect of developmental vitamin D deficiency in male and female Sprague-Dawley rats on decision-making using a rodent gambling task.

    Science.gov (United States)

    Peak, J N; Turner, K M; Burne, T H J

    2015-01-01

    Developmental vitamin D (DVD) deficiency is a plausible risk factor for schizophrenia that has been associated with behavioural alterations including disruptions in latent inhibition and response inhibition. The rodent gambling task (rGT) assesses risk-based decision-making, which is a key cognitive deficit observed in schizophrenia patients. The primary aim of this study was to examine risk-based decision-making in DVD-deficient and control rats on the rGT. We also evaluated the performance of female Sprague-Dawley rats on the rGT for the first time. Adult male and female Sprague-Dawley rats from control and vitamin D deficient dams were trained to perform the rGT in standard operant chambers and their performance and choice-preferences were assessed. Female rats were significantly faster to reach rGT training criteria compared with male rats and DVD-deficient rats were faster to reach training criteria than control animals. After reaching stable performance on the rGT DVD-deficient and control rats showed a significant preference for the optimal choice-option in the rGT, but there were no significant effects of sex or diet on these responses. DVD deficiency did not alter the decision-making processes on the rGT because no significant changes in choice-preferences were evident. This is the first study to demonstrate that once established, the performance of females is comparable to male Sprague-Dawley rats on the rGT. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  6. Biodistribution of newly synthesized PHEA-based polymer-coated SPION in Sprague Dawley rats as magnetic resonance contrast agent

    Directory of Open Access Journals (Sweden)

    Park J

    2013-10-01

    Full Text Available Junsung Park,1,2,* Wonkyung Cho,1,2,* Hee Jun Park,1,2 Kwang-Ho Cha,1,2 Dae-Chul Ha,2,5 Youn-Woong Choi,5 Ha-Young Lee,3 Sun-Hang Cho,5 Sung-Joo Hwang1,4 1Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea; 2College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea; 3Biomaterials Laboratory, Korea Research Institutes of Chemical Technology, Daejeon, Republic of Korea; 4College of Pharmacy, Yonsei University, Incheon, Republic of Korea; 5Korea United Pharm Inc, Seoul, Republic of Korea *These authors contributed equally to this work Objectives: The purpose of this study was to observe the pharmacokinetic behavior of newly synthesized biocompatible polymers based on polyhydroxyethylaspartamide (PHEA to be used to coat an iron oxide core to make superparamagnetic iron oxide nanoparticles (SPION. Materials and methods: The isotopes [14C] and [59Fe] were used to label the polymer backbone (CLS and iron oxide core (FLS, respectively. In addition, unradiolabeled cold superparamagnetic iron oxide nanoparticles (SPION/ULS were synthesized to characterize particle size by dynamic light scattering, morphology by transmission electron microscopy, and in vivo magnetic resonance imaging (MRI. CLS and FLS were used separately to investigate the behavior of both the synthesized polymer and [Fe] in Sprague Dawley (SD rats, respectively. Because radioactivity of the isotopes was different by β for CLS and γ for FLS, synthesis of the samples had to be separately prepared. Results: The mean particle size of the ULS was 66.1 nm, and the biodistribution of CLS concentrations in various organs, in rank order of magnitude, was liver > kidney > small intestine > other. The biodistribution of FLS concentrations was liver > spleen > lung > other. These rank orders show that synthesized SPION mainly accumulates in the liver. The differences in the distribution were caused by the SPION metabolism. Radiolabeled

  7. Consequences of adolescent ethanol exposure in male Sprague-Dawley rats on fear conditioning and extinction in adulthood

    Science.gov (United States)

    Broadwater, Margaret A.

    Some evidence suggests that adolescents are more vulnerable than adults to alcohol-induced cognitive deficits and that these deficits may persist into adulthood. Five experiments were conducted to assess long-term consequences of ethanol exposure on tone and context Pavlovian fear conditioning in male Sprague-Dawley rats. Experiment 1 examined age-related differences in sensitivity to ethanol-induced disruptions of fear conditioning to a pre-conditioning ethanol challenge. Experiments 2 examined fear conditioning 22 days after early-mid adolescent (P28-48) or adult (P70-90) exposure to 4 g/kg i.g. ethanol or water given every other day (total of 11 exposures). In Experiment 3, mid-late adolescents (P35-55) were exposed in the same manner to assess whether timing of ethanol exposure within the adolescent period would differentially affect later fear conditioning. Experiment 4 assessed the influence of prior adolescent or adult ethanol exposure on the disrupting effects of a pre-conditioning ethanol challenge. In Experiment 5, neurogenesis (doublecortin---DCX) and cholinergic (choline acetyltransferase---ChAT) markers were measured to assess potential long-term ethanol-induced changes in neural mechanisms important for learning and memory. Results indicated that the long-lasting behavioral effects of ethanol exposure varied depending on exposure age, with early-mid adolescent exposed animals showing attenuated context fear retention (a relatively hippocampal-dependent task), whereas mid-late adolescent and adult exposed animals showed slower context extinction (thought to be reliant on the mPFC). Early-mid adolescent ethanol-exposed animals also had significantly less DCX and ChAT expression than their water-exposed counterparts, possibly contributing to deficits in context fear. Tone fear was not influenced by prior ethanol exposure at any age. In terms of age differences in ethanol sensitivity, adolescents were less sensitive than adults to ethanol

  8. Edible Safety Assessment of Genetically Modified Rice T1C-1 for Sprague Dawley Rats through Horizontal Gene Transfer, Allergenicity and Intestinal Microbiota.

    Directory of Open Access Journals (Sweden)

    Kai Zhao

    Full Text Available In this study, assessment of the safety of transgenic rice T1C-1 expressing Cry1C was carried out by: (1 studying horizontal gene transfer (HGT in Sprague Dawley rats fed transgenic rice for 90 d; (2 examining the effect of Cry1C protein in vitro on digestibility and allergenicity; and (3 studying the changes of intestinal microbiota in rats fed with transgenic rice T1C-1 in acute and subchronic toxicity tests. Sprague Dawley rats were fed a diet containing either 60% GM Bacillus thuringiensis (Bt rice T1C-1 expressing Cry1C protein, the parental rice Minghui 63, or a basic diet for 90 d. The GM Bt rice T1C-1 showed no evidence of HGT between rats and transgenic rice. Sequence searching of the Cry1C protein showed no homology with known allergens or toxins. Cry1C protein was rapidly degraded in vitro with simulated gastric and intestinal fluids. The expressed Cry1C protein did not induce high levels of specific IgG and IgE antibodies in rats. The intestinal microbiota of rats fed T1C-1 was also analyzed in acute and subchronic toxicity tests by DGGE. Cluster analysis of DGGE profiles revealed significant individual differences in the rats' intestinal microbiota.

  9. Effects on reproduction in female offspring from Sprague-Dawley rats fed 10% snakeweed (Gutierrezia microcephala) throughout pregnancy and concurrent treatment with safflower oil.

    Science.gov (United States)

    Staley, E C; Smith, G S; Greenberg, J A

    1995-10-01

    Previous studies determined that safflower oil administration provided protection against the embryotoxicity seen following ingestion of 10% snakeweed (Gutierrezia microcephala) throughout pregnancy. Sixty-two young primiparous female rats born in those studies were paired with adult male Sprague-Dawley rats. After 4 d they were removed and carried their litters to term. Observations were made of the presence and extent of reproductive effects attributable to the 10% snakeweed exposure and differences in fecundity that were attributable to dosing with safflower oil or normal saline during the snakeweed exposure. Of the 62 rats, 50 carried litters to term and approximated the reproductive efficiency of normal primiparous Sprague-Dawley rats. There was no significant difference between the fecundity of females born to rats fed the 10% snakeweed and dosed with safflower oil, those born of rats fed snakeweed dosed with normal saline, or those fed a snakeweed-free diet and dosed with normal saline. Regardless of the diet or treatment administered, dams carrying their litters to parturition gave birth to healthy, normo-reproductive offspring. While the toxic principles in Gutierrezia species plants may act as estrogenic or anti-estrogenic compounds, they did not impair fertility in the female offspring of dosed rats.

  10. Edible Safety Assessment of Genetically Modified Rice T1C-1 for Sprague Dawley Rats through Horizontal Gene Transfer, Allergenicity and Intestinal Microbiota.

    Science.gov (United States)

    Zhao, Kai; Ren, Fangfang; Han, Fangting; Liu, Qiwen; Wu, Guogan; Xu, Yan; Zhang, Jian; Wu, Xiao; Wang, Jinbin; Li, Peng; Shi, Wei; Zhu, Hong; Lv, Jianjun; Zhao, Xiao; Tang, Xueming

    2016-01-01

    In this study, assessment of the safety of transgenic rice T1C-1 expressing Cry1C was carried out by: (1) studying horizontal gene transfer (HGT) in Sprague Dawley rats fed transgenic rice for 90 d; (2) examining the effect of Cry1C protein in vitro on digestibility and allergenicity; and (3) studying the changes of intestinal microbiota in rats fed with transgenic rice T1C-1 in acute and subchronic toxicity tests. Sprague Dawley rats were fed a diet containing either 60% GM Bacillus thuringiensis (Bt) rice T1C-1 expressing Cry1C protein, the parental rice Minghui 63, or a basic diet for 90 d. The GM Bt rice T1C-1 showed no evidence of HGT between rats and transgenic rice. Sequence searching of the Cry1C protein showed no homology with known allergens or toxins. Cry1C protein was rapidly degraded in vitro with simulated gastric and intestinal fluids. The expressed Cry1C protein did not induce high levels of specific IgG and IgE antibodies in rats. The intestinal microbiota of rats fed T1C-1 was also analyzed in acute and subchronic toxicity tests by DGGE. Cluster analysis of DGGE profiles revealed significant individual differences in the rats' intestinal microbiota.

  11. Effect of ambient temperature on the thermoregulatory and locomotor stimulant effects of 4-methylmethcathinone in Wistar and Sprague-Dawley rats.

    Directory of Open Access Journals (Sweden)

    M Jerry Wright

    Full Text Available The drug 4-methylmethcathinone (4-MMC; aka, mephedrone, MMCAT, "plant food", "bath salts" is a recent addition to the list of popular recreational psychomotor-stimulant compounds. Relatively little information about this drug is available in the scientific literature, but popular media reports have driven recent drug control actions in the UK and several US States. Online user reports of subjective similarity to 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy" prompted the current investigation of the thermoregulatory and locomotor effects of 4-MMC. Male Wistar and Sprague-Dawley rats were monitored after subcutaneous administration of 4-MMC (1-10 mg/kg using an implantable radiotelemetry system under conditions of low (23°C and high (27°C ambient temperature. A reliable reduction of body temperature was produced by 4-MMC in Wistar rats at 23°C or 27°C with only minimal effect in Sprague-Dawley rats. Increased locomotor activity was observed after 4-MMC administration in both strains with significantly more activity produced in the Sprague-Dawley strain. The 10 mg/kg s.c. dose evoked greater increase in extracellular serotonin, compared with dopamine, in the nucleus accumbens. Follow-up studies confirmed that the degree of locomotor stimulation produced by 10 mg/kg 4-MMC was nearly identical to that produced by 1 mg/kg d-methamphetamine in each strain. Furthermore, hypothermia produced by the serotonin 1(A/7 receptor agonist 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT was similar in each strain. These results show that the cathinone analog 4-MMC exhibits thermoregulatory and locomotor properties that are distinct from those established for methamphetamine or MDMA in prior work, despite recent evidence of neuropharmacological similarity with MDMA.

  12. Resveratrol supplementation rescues pool of growing follicles and ovarian stroma from Cisplatin-induced toxicity on the ovary in Sprague-Dawley rats: An experimental study

    Directory of Open Access Journals (Sweden)

    Gbotolorun Stella Chinwe

    2018-02-01

    Full Text Available Background: Cisplatin is a potent antineoplastic agent for many cancers but causes several levels of gonadal damage. Ovarian toxicity is a major concern of young cancer patients undergoing chemotherapy. Objective: This study sought to examine the effect of Cisplatin and Resveratrol supplementation on ovarian function in Sprague-Dawley rats. Materials and Methods: In this experimental study, 45 cyclic Sprague-Dawley rats with an average weight of 160 gr were divided into 9 groups (n=5/group. Group 1 was used as control and received distilled water. Groups 2 and 9 received Cisplatin only. Groups 3, 4, and 5 received different doses of Resveratrol after a single dose of Cisplatin. Groups 6, 7, and 8 received Resveratrol before Cisplatin. At sacrifice, the ovary was analyzed for histopathology, biochemical indices of oxidation and hormonal assay. Results: Relative and absolute organ weights were notably increased (p=0.001, 0.01 in the prophylactic groups relative to the groups that received Resveratrol after Cisplatin. Also, glutathione, superoxide dismutase and catalase were significantly increased (p=0.047, 0.01, 0.023 in a dose-dependent manner when compared to Cisplatin group only. Malondialdehyde decreased significantly (p=0.001 in the groups that received high dose Resveratrol compared with the control and Cisplatin alone groups. Although oestrogen showed no significant difference within the groups (p=0.48, Resveratrol significantly increased progesterone, follicle stimulating hormone and luteinizing hormone levels (p=0.007, 0.001, 0.006 at high doses when compared with Cisplatin alone groups. Ovarian histoarchitecture was best preserved in the prophylactic groups in a dose-dependent manner. Conclusion: Resveratrol supplementation confers protection and preserves ovarian follicles from Cisplatin toxicity in Sprague-Dawley rats.

  13. Six-month oral toxicity of D-004, a lipid extract from Roystonea regia fruits, in Sprague Dawley rats

    OpenAIRE

    Balia Pardo; Ariadne Gutiérrez; Rafael Gámez; Miriam Noa; Gisela Marrero; Yohany Pérez; Rosa María González; Dayisell Curveco; Haydée García; Eddy Goicochea

    2009-01-01

    El D-004 es un extracto lipídico obtenido del fruto de la palma real (Roystonea regia) que consiste en una mezcla de ácidos grasos, en la cual los ácidos oleico, palmítico, láurico y mirístico son los más abundantes. El tratamiento oral con D-004 inhibe significativamente la hiperplasia prostática inducida por testosterona en roedores. Este ensayo se realizó para investigar la toxicidad inducida por el D-004 en ratas Sprague Dawley (SD). Las ratas de ambos sexos fueron distribuidas al azar en...

  14. Evaluation of 90-day Repeated Dose Oral Toxicity, Glycometabolism, Learning and Memory Ability, and Related Enzyme of Chromium Malate Supplementation in Sprague-Dawley Rats.

    Science.gov (United States)

    Feng, Weiwei; Wu, Huiyu; Li, Qian; Zhou, Zhaoxiang; Chen, Yao; Zhao, Ting; Feng, Yun; Mao, Guanghua; Li, Fang; Yang, Liuqing; Wu, Xiangyang

    2015-11-01

    Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the 90-day oral toxicity of chromium malate in Sprague-Dawley rats. The present study inspected the effect of chromium malate on glycometabolism, glycometabolism-related enzymes, lipid metabolism, and learning and memory ability in metabolically healthy Sprague-Dawley rats. The results showed that all rats survived and pathological, toxic, feces, and urine changes were not observed. Chromium malate did not cause measurable damage on liver, brain, and kidney. The fasting blood glucose, serum insulin, insulin resistance index, C-peptide, hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels of normal rats in chromium malate groups had no significant change when compared with control group and chromium picolinate group under physiologically relevant conditions. The serum and organ content of Cr in chromium malate groups had no significant change compared with control group. No significant changes were found in morris water maze test and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and true choline esterase (TChE) activity. The results indicated that supplementation with chromium malate did not cause measurable toxicity and has no obvious effect on glycometabolism and related enzymes, learning and memory ability, and related enzymes and lipid metabolism of female and male rats. The results of this study suggest that chromium malate is safe for human consumption.

  15. Effect of antioxidant supplementation on lipid peroxidation and antioxidant enzyme activity on exposure to acute restraint stress in sprague dawley rats

    International Nuclear Information System (INIS)

    Lodhi, G.M.; Hussain, M.M.; Aslam, M.

    2012-01-01

    To determine the effects of ascorbic acid (AA) and alpha tocopherol (AT) supplementation on stress induced changes in serum malondialdehyde and serum superoxide dismutase levels in male Sprague Dawley rats. Study design: Quasi experimental study Place and Duration of Study: Department of Physiology, Army Medical College Rawalpindi in collaboration with National Institute of Health, Islamabad during March 2009 to September 2009. Materials and Methods: Eighty male Sprague Dawley rats were divided into five groups with sixteen rats in each group. Group I served as control without stress and group II exposed to restraint stress for 06 hours, group III given ascorbic acid, group IV alpha tocopherol and group V was supplemented with both vitamins along with standard diet for one month. All antioxidant supplemented groups were exposed to restraint stress for six hours. Immediately after stress, the blood samples were analyzed colorimetrically to estimate serum malondialdehyde and superoxide dismutase by commercially available kits. Results: There was no significant fall in serum malondialdehyde in rats supplemented with ascorbic acid alone, however rats supplemented with alpha tocopherol or combination of ascorbic acid and alpha tocopherol revealed significant fall in serum malondialdehyde and increment in superoxide dismutase activity. Conclusions: Alpha tocopherol alone and in combination with ascorbic acid is effective to prevent reactive oxygen species induced increase in lipid peroxidation and fall in super oxide dismutase activity thereby conferring protection against oxidative stress. (author)

  16. Effects of leptin on sperm count and morphology in Sprague-Dawley rats and their reversibility following a 6-week recovery period.

    Science.gov (United States)

    Almabhouh, F A; Osman, K; Siti Fatimah, I; Sergey, G; Gnanou, J; Singh, H J

    2015-09-01

    Altered epididymal sperm count and morphology following leptin treatment has been reported recently. This study examined the effects of 42 days of leptin treatment on sperm count and morphology and their reversibility during a subsequent 56-day recovery period. Twelve-week-old male Sprague-Dawley rats were randomised into four leptin and four saline-treated control groups (n = 6). Intraperitoneal injections of leptin were given daily (60 μg Kg(-1) body weight) for 42 days. Controls received 0.1 ml of 0.9% saline. Leptin-treated animals and their respective age-matched controls were euthanised on either day 1, 21, 42 or 56 of recovery for collection of epididymal spermatozoa. Sperm concentration was determined using a Makler counting chamber. Spermatozoa were analysed for 8-hydroxy-2-deoxyguanosine and DNA fragmentation (Comet assay). Data were analysed using anova. Sperm concentration was significantly lower but fraction of abnormal spermatozoa, and levels of 8-hydroxy-2-deoxyguanosine were significantly higher in leptin-treated rats on day 1 of recovery. Comet assays revealed significant DNA fragmentation in leptin-treated rats. These differences were reduced by day 56 of recovery. It appears that 42 days of leptin treatment to Sprague-Dawley rats has significant adverse effects on sperm count and morphology that reverse following discontinuation of leptin treatment. © 2014 Blackwell Verlag GmbH.

  17. Longitud del ciclo estral en ratas Sprague Dawley tratadas in útero con extracto de Roystonea regia Estrus cycle length in Sprague Dawley rats in uterus using Roystonea regia extract

    OpenAIRE

    Ariadne Gutiérrez Martínez; Rafael Gámez Menéndez; Balia Pardo Acosta; Gisela Marrero Cofiño

    2009-01-01

    El D-004 consiste en una mezcla de ácidos grasos que inhibe significativamente la hiperplasia prostática inducida por testosterona en roedores. El objetivo del presente estudio fue evidenciar los posibles efectos adversos sobre el ciclo estral de hembras F1 expuestas in útero al D-004. Se utilizaron ratas Sprague Dawley, distribuidas aleatoriamente en 4 grupos: un control y 3 tratados con D-004 a las dosis de 500, 750 y 1 000 mg/kg; las hembras recibieron la administración de la dosis por vía...

  18. Sweetpotato- and cereal-based infant foods: protein quality assessment, and effect on body composition using sprague dawley rats as a model.

    Science.gov (United States)

    Amagloh, Francis Kweku; Chiridza, Tracy; Lemercier, Marie-Eve; Broomfield, Anne; Morel, Patrick C H; Coad, Jane

    2015-01-01

    The Protein Digestibility Corrected Amino Acid Score (PDCAAS) of sweetpotato-based complementary foods (OFSP ComFa and CFSP ComFa) and cereal-based infant products (Weanimix and Cerelac) was assessed using 3 wk-old male Sprague Dawley rats weighing between 53-67 g as a model for human infants. Also, the effect of consumption of the infant formulations on lean mass, bone mass content and fat mass was evaluated by Dual-Energy X-ray Absorptiometry (DEXA) using 6 wk-old Sprague Dawley rats (initial weight, 206-229 g). The ComFa products and Weanimix are household-level formulations, and Cerelac is a commercial infant cereal. The true protein digestibility score for Cerelac was 96.27%, and about 1.8% (Pbody composition studies indicate that complementary foods could be formulated from readily available agricultural resources at the household-level to support growth as would a nutritionally adequate industrial-manufactured infant cereal. Nonetheless, it should be noted that the findings of our studies are based on an animal model.

  19. Effects of long-term consumption of high fructose corn syrup containing peach nectar on body weight gain in sprague dawley rats

    Directory of Open Access Journals (Sweden)

    Gulsah OZCAN SINIR

    Full Text Available Abstract High fructose corn syrup (HFCS is one of the most used sweeteners in the food industry. Health concerns regarding the consumption of HFCS-containing foods have developed in parallel with the increasing amount of people who become overweight. This study was conducted to investigate whether HFCS-containing peach nectar (pn-HFCS consumption has more detrimental effects on anthropometrical and biochemical parameters compared with sucrose-containing peach nectar (pn-sucrose. Fifty-day-old Sprague Dawley rats were divided into three groups and were fed (A pn-HFCS + ad libitum chow, (B pn-sucrose + ad libitum chow and (C only ad libitum chow for 7 months. The percentage change in body weight (PCBW, body mass index (BMI, and Lee index were calculated, and serum triglyceride, glucose, insulin and leptin concentrations were measured. The PCBW, BMI, Lee index, serum triglyceride, glucose, insulin and leptin concentrations were insignificant among the three groups. We can suggest that peach nectar consumption resulted in more energy intake than the control and since pn-HFCS group consumed more chow than the pn-sucrose group. The results show that long term daily HFCS or sucrose consumption in peach nectar is not associated with weight gain and does not stimulate metabolic changes in Sprague Dawley rats.

  20. Effects of halothane-nitrous oxide inhalation anesthesia and Inactin on overall renal and tubular function in Sprague-Dawley and Wistar rats

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H; Christensen, P; Leyssac, P P

    1982-01-01

    Real function, plasma renin concentration (PRC) and prostaglandin (PG) excretion rate was studied in groups of Sprague-Dawley (SPRD) and Wistar (WIST) rats anesthetized with either Halothane-N2O or Inactin. Conscious rats were used as controls. A. In Halothane-N2O anesthesia inulin clearance (CIN...... anesthesia indicating that the proximal luminal diameter was constant and independent of CIN. B. Inactin anesthesia CIN was similarly reduced but APR was more depressed (by about 35%). RPF and solute excretion rate decreased only in SPRD rats, while urine flow was significantly reduced in both strains. 1/OT...... prepared rats are more severely depressed by Inactin than by Halothane-N2O anesthesia. The gas anesthesia is equally well tolerated by both strains of rats....

  1. No effect of NOS inhibition on skeletal muscle glucose uptake during in situ hindlimb contraction in healthy and diabetic Sprague-Dawley rats.

    Science.gov (United States)

    Hong, Yet Hoi; Betik, Andrew C; Premilovac, Dino; Dwyer, Renee M; Keske, Michelle A; Rattigan, Stephen; McConell, Glenn K

    2015-05-15

    Nitric oxide (NO) has been shown to be involved in skeletal muscle glucose uptake during contraction/exercise, especially in individuals with Type 2 diabetes (T2D). To examine the potential mechanisms, we examined the effect of local NO synthase (NOS) inhibition on muscle glucose uptake and muscle capillary blood flow during contraction in healthy and T2D rats. T2D was induced in Sprague-Dawley rats using a combined high-fat diet (23% fat wt/wt for 4 wk) and low-dose streptozotocin injections (35 mg/kg). Anesthetized animals had one hindlimb stimulated to contract in situ for 30 min (2 Hz, 0.1 ms, 35 V) with the contralateral hindlimb rested. After 10 min, the NOS inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME; 5 μM) or saline was continuously infused into the femoral artery of the contracting hindlimb until the end of contraction. Surprisingly, there was no increase in skeletal muscle NOS activity during contraction in either group. Local NOS inhibition had no effect on systemic blood pressure or muscle contraction force, but it did cause a significant attenuation of the increase in femoral artery blood flow in control and T2D rats. However, NOS inhibition did not attenuate the increase in muscle capillary recruitment during contraction in these rats. Muscle glucose uptake during contraction was significantly higher in T2D rats compared with controls but, unlike our previous findings in hooded Wistar rats, NOS inhibition had no effect on glucose uptake during contraction. In conclusion, NOS inhibition did not affect muscle glucose uptake during contraction in control or T2D Sprague-Dawley rats, and this may have been because there was no increase in NOS activity during contraction. Copyright © 2015 the American Physiological Society.

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

    Science.gov (United States)

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

    2015-09-01

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

  3. Sweetpotato- and cereal-based infant foods: protein quality assessment, and effect on body composition using sprague dawley rats as a model.

    Directory of Open Access Journals (Sweden)

    Francis Kweku Amagloh

    Full Text Available The Protein Digestibility Corrected Amino Acid Score (PDCAAS of sweetpotato-based complementary foods (OFSP ComFa and CFSP ComFa and cereal-based infant products (Weanimix and Cerelac was assessed using 3 wk-old male Sprague Dawley rats weighing between 53-67 g as a model for human infants. Also, the effect of consumption of the infant formulations on lean mass, bone mass content and fat mass was evaluated by Dual-Energy X-ray Absorptiometry (DEXA using 6 wk-old Sprague Dawley rats (initial weight, 206-229 g. The ComFa products and Weanimix are household-level formulations, and Cerelac is a commercial infant cereal. The true protein digestibility score for Cerelac was 96.27%, and about 1.8% (P<0.0001 higher than that for OFSP ComFa, CFSP ComFa and Weanimix. However, OFSP ComFa had the highest un-truncated PDCAAS by a difference of 4.1%, than CFSP ComFa, and about 20% difference compared with both the Weanimix and Cerelac. All the products investigated had PDCAAS greater than 70%, the minimum protein quality requirement for complementary foods. Among the rats assigned to the four formulations, their bone mass and fat mass composition were not significantly different (P=0.08 and P=0.85, respectively. However, the rats on CFSP ComFa had higher lean mass than those on Cerelac (321.67 vs. 297.19 g; P=0.03. The findings from the PDCAAS and the DEXA-measured body composition studies indicate that complementary foods could be formulated from readily available agricultural resources at the household-level to support growth as would a nutritionally adequate industrial-manufactured infant cereal. Nonetheless, it should be noted that the findings of our studies are based on an animal model.

  4. Preserving Duodenal-Jejunal (Foregut) Transit Does Not Impair Glucose Tolerance and Diabetes Remission Following Gastric Bypass in Type 2 Diabetes Sprague-Dawley Rat Model.

    Science.gov (United States)

    Dolo, Ponnie R; Yao, Libin; Li, Chao; Zhu, Xiaocheng; Shi, Linsen; Widjaja, Jason

    2017-11-02

    Possible mechanisms underlying diabetes remission following Roux-en-Y gastric bypass (RYGB) include eradication of putative factor(s) with duodenal-jejunal bypass. The objective of this study is to observe the effects of duodenal-jejunal transit on glucose tolerance and diabetes remission in gastric bypass rat model. In order to verify the effect of duodenal-jejunal transit on glucose tolerance and diabetes remission in gastric bypass, 22 type 2 diabetes Sprague-Dawley rat models established through high-fat diet and low-dose streptozotocin (STZ) administered intraperitoneally were assigned to one of three groups: gastric bypass with duodenal-jejunal transit (GB-DJT n = 8), gastric bypass without duodenal-jejunal transit (RYGB n = 8), and sham (n = 6). Body weight, food intake, blood glucose, as well as meal-stimulated insulin, and incretin hormone responses were assessed to ascertain the effect of surgery in all groups. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted three and 7 weeks after surgery. Comparing our GB-DJT to the RYGB group, we saw no differences in the mean decline in body weight, food intake, and blood glucose 8 weeks after surgery. GB-DJT group exhibited immediate and sustained glucose control throughout the study. Glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) levels were also significantly increased from preoperative level in the GB-DJT group (p transit does not impede glucose tolerance and diabetes remission after gastric bypass in type-2 diabetes Sprague-Dawley rat model.

  5. Chemopreventive Effects of Germinated Rough Rice Crude Extract in Inhibiting Azoxymethane-Induced Aberrant Crypt Foci Formation in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Elnaz Saki

    2017-01-01

    Full Text Available Chemoprevention has become an important area in cancer research due to low success rate of current therapeutic modalities. Diet plays a vital role in the etiology of cancer. This research was carried out to study the chemopreventive properties of germinated rough rice (GRR crude extract in Sprague-Dawley rats induced with azoxymethane. Germination of rough rice causes significant changes in several chemical compositions of presently bioactive compounds. These compounds may prevent or postpone the inception of cancer. Fifty male Sprague-Dawley rats (6 weeks of age were randomly divided into 5 groups which were (G1 induced with azoxymethane (AOM and not given GRR (positive control, (G2 induced with AOM and given 2000 mg/kg GRR, (G3 induced with AOM and given 1000 mg/kg GRR, (G4 induced with AOM and given 500 mg/kg GRR, and (G5 not induced with AOM and not given GRR crude extract (negative control. To induce colon cancer, rats received two IP injections of AOM in saline (15 mg/kg for two subsequent weeks. Organs were removed and weighed. Aberrant crypt foci (ACF were evaluated histopathologically. β-Catenin expressions were determined by Western blot. Treatment with 2000 mg/kg GRR crude extract not only resulted in the greatest reduction in the size and number of ACF but also displayed the highest percentage of nondysplastic ACF. Treatment with 2000 mg/kg GRR also gave the lowest level of expression in β-catenin. Thus, GRR could be a promising dietary supplement for prevention of CRC.

  6. The Effectiveness of Super Ovulation and Multiple Pregnancies in Sprague Dawley Rat using Morus alba Linn. Fruit

    Directory of Open Access Journals (Sweden)

    Heshu Sulaiman Rahman

    2018-01-01

    Full Text Available The white mulberry, Morus alba L. has been used by several Asian societies for the treatment of infertility. However, there is no evidence that products of the plant can influence ovarian health. Thus, the aim of this study was to determine the effect of the Morus alba fruit extract on the ovarian function of nonpregnant and pregnant rats. The study showed that in rats Morus alba fruit extract stimulates follicular stimulating (FSH and luteinizing hormones (LH, estrogen, and progesterone productions that peaked at 8 days of treatment. The effect was dose-dependent with hormone production increasing with increase in dose of the extract. The Graafian follicles were fully matured, and the number increased with increase in dose of the extract. The uterus of pregnant rats contained several embryos that gave birth to the full-term offspring without abortion or embryonic abnormalities. In conclusion, the Morus alba fruit extract can be used to induce superovulation to cause multiple pregnancies. Thus, the Morus alba fruit extract has potential to be developed into a compound for the treatment of female infertility.

  7. Effects of tributyltin chloride(TBTCl) on seroid hormone and seroidogenic enzymes in Sprague-Dawley male rat

    Energy Technology Data Exchange (ETDEWEB)

    Kang, T.S.; Lee, S.J.; Shin, J.H.; Kim, T.S.; Moon, H.J.; Ki, H.Y.; Bae, H.; Han, S.Y. [Endocrine Toxicology Div., National Inst. of Toxicological Research, Korea FDA, Seoul (Korea); Dong, M.S. [Korea Univ., Seoul (Korea); Yoon, Y.D. [Hanyang Univ., Seoul (Korea)

    2004-09-15

    Tributyltin (TBT), organotin compound is used a wood preservative, a stabilizer of poly-vinyl chloride (PVC), a bactericide, a vermicide, and antifouling agent in maritime paint. TBTCl has been known to bioaccumulate through the food chain and induce imposex in female gastropods. Testosterone was synthesized from cholesterol in Leydig cell. In male rat testes, cholesterol in in the inner membrane of mitochondria is converted to prognenolone by cytochrome P450 side-chain cleavage (P450scc), and prognenolone is consequently converted to progesterone by 3{beta}-hydroxysteroid dehydrogenase (3{beta}a-HSD). Progesterone is converted to testosterone by cytochrome P450 17{alpha}-hydroxylase/C17-20 lyase (P450c17), and 17{beta}-hydroxysteroid dehydrogenase (17{beta}-HSD). Testosterone is converted to estradiol by P450 aromatase. Some studies have been reported that steroidogenic enzyme and steroid hormone were affected by TBT. In a two-generation study of tributyltin chloride, serum estradiol was decreased in F1 and F2 male rats. But serum concentration of testosterone and luteinizing hormone (LH) were not changed in F1 and F2 male rats. When pregnant rats were orally administrated by TBTCl, serum progesterone was decreased and serum estradiol was increased in female litters. Also litters were affected on development of reproductive organs and sexual of differentiation by TBTCl.3 Tributyltin increased serum progesterone in granulosa cells, but serum testosterone and estradiol were diminished.4 TBT has been known that it repressed P450 aromatase activity. In this study, we investigated effect of tributyltin chloride (TBTCl) on the mRNA expression of steroidogenic enzymes and steroid hormone in male rat.

  8. Biological Cleavage of the C–P Bond in Perfluoroalkyl Phosphinic Acids in Male Sprague-Dawley Rats and the Formation of Persistent and Reactive Metabolites

    Science.gov (United States)

    Yeung, Leo W.Y.; Mabury, Scott A.

    2017-01-01

    Background: Perfluoroalkyl phosphinic acids (PFPiAs) have been detected in humans, wildlife, and various environmental matrices. These compounds have been used with perfluoroalkyl phosphonic acids (PFPAs) as surfactants in consumer products and as nonfoaming additives in pesticide formulations. Unlike the structurally related perfluoroalkyl sulfonic and carboxylic acids, little is known about the biological fate of PFPiAs. Objectives: We determined the biotransformation products of PFPiAs and some pharmacokinetic parameters in a rat model. Methods: Male Sprague-Dawley rats received an oral gavage dose of either C6/C8PFPiA, C8/C8PFPiA, or C8PFPA. Blood was sampled over time, and livers were harvested upon sacrifice. Analytes were quantified using ultra-high-performance liquid chromatography–tandem mass spectrometry or gas chromatography–mass spectrometry. Results: PFPiAs were metabolized to the corresponding PFPAs and 1H-perfluoroalkanes (1H-PFAs), with 70% and 75% biotransformation 2 wk after a single bolus dose for C6/C8PFPiA and C8/C8PFPiA, respectively. This is the first reported cleavage of a C-P bond in mammals, and the first attempt, with a single-dose exposure, to characterize the degradation of any perfluoroalkyl acid. Elimination half-lives were 1.9±0.5 and 2.8±0.8 days for C6/C8PFPiA and C8/C8PFPiA, respectively, and 0.95±0.17 days for C8PFPA. Although elimination half-lives were not determined for 1H-PFAs, concentrations were higher than the corresponding PFPAs 48 h after rats were dosed with PFPiAs, suggestive of slower elimination. Conclusions: PFPiAs were metabolized in Sprague-Dawley rats to form persistent PFPAs as well as 1H-PFAs, which contain a labile hydrogen that may undergo further metabolism. These results in rats produced preliminary findings of the pharmacokinetics and metabolism of PFPiAs, which should be further investigated in humans. If there is a parallel between the disposition of these chemicals in humans and rats, then

  9. Soluble Fiber Dextrin and Soluble Corn Fiber Supplementation Modify Indices of Health in Cecum and Colon of Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Maria R. C. de Godoy

    2013-02-01

    Full Text Available The objective of this study was to evaluate health outcomes resulting from dietary supplementation of novel, low-digestible carbohydrates in the cecum and colon of Sprague-Dawley rats randomly assigned to one of four treatment groups for 21 days: 5% cellulose (Control, Pectin, soluble fiber dextrin (SFD, or soluble corn fiber (SCF. Rats fed Pectin had a higher average daily food intake, but no differences in final body weights or rates of weight gain among treatments were observed. No differences were observed in total short-chain fatty acid (SCFA or branched-chain fatty acid (BCFA concentrations in the cecum and colon of rats fed either SFD or SCF. The SFD and SCF treatments increased cecal propionate and decreased butyrate concentrations compared to Control or Pectin. Pectin resulted in increased BCFA in the cecum and colon. Supplementation of SFD and SCF had no effect on cecal microbial populations compared to Control. Consumption of SFD and SCF increased total and empty cecal weight but not colon weight. Gut histomorphology was positively affected by SFD and SCF. Increased crypt depth, goblet cell numbers, and acidic mucin were observed in both the cecum and colon of rats supplemented with SFD, SCF, and Pectin. These novel, low-digestible carbohydrates appear to be beneficial in modulating indices of hindgut morphology when supplemented in the diet of the rat.

  10. 3,5 Diiodo-L-Thyronine (T2 Does Not Prevent Hepatic Steatosis or Insulin Resistance in Fat-Fed Sprague Dawley Rats.

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    Daniel F Vatner

    Full Text Available Thyroid hormone mimetics are alluring potential therapies for diseases like dyslipidemia, nonalcoholic fatty liver disease (NAFLD, and insulin resistance. Though diiodothyronines are thought inactive, pharmacologic treatment with 3,5- Diiodo-L-Thyronine (T2 reportedly reduces hepatic lipid content and improves glucose tolerance in fat-fed male rats. To test this, male Sprague Dawley rats fed a safflower-oil based high-fat diet were treated with T2 (0.25 mg/kg-d or vehicle. Neither 10 nor 30 days of T2 treatment had an effect on weight, adiposity, plasma fatty acids, or hepatic steatosis. Insulin action was quantified in vivo by a hyperinsulinemic-euglycemic clamp. T2 did not alter fasting plasma glucose or insulin concentration. Basal endogenous glucose production (EGP rate was unchanged. During the clamp, there was no difference in insulin stimulated whole body glucose disposal. Insulin suppressed EGP by 60% ± 10 in T2-treated rats as compared with 47% ± 4 suppression in the vehicle group (p = 0.32. This was associated with an improvement in hepatic insulin signaling; insulin stimulated Akt phosphorylation was ~2.5 fold greater in the T2-treated group as compared with the vehicle-treated group (p = 0.003. There was no change in expression of genes thought to mediate the effect of T2 on hepatic metabolism, including genes that regulate hepatic lipid oxidation (ppara, carnitine palmitoyltransferase 1a, genes that regulate hepatic fatty acid synthesis (srebp1c, acetyl coa carboxylase, fatty acid synthase, and genes involved in glycolysis and gluconeogenesis (L-pyruvate kinase, glucose 6 phosphatase. Therefore, in contrast with previous reports, in Sprague Dawley rats fed an unsaturated fat diet, T2 administration failed to improve NAFLD or whole body insulin sensitivity. Though there was a modest improvement in hepatic insulin signaling, this was not associated with significant differences in hepatic insulin action. Further study will be

  11. A 90-day dietary toxicity study of genetically modified rice T1C-1 expressing Cry1C protein in Sprague Dawley rats.

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    Xueming Tang

    Full Text Available In a 90-day study, Sprague Dawley rats were fed transgenic T1C-1 rice expressing Cry1C protein and were compared with rats fed non-transgenic parental rice Minghui 63 and rats fed a basal diet. No adverse effects on animal behavior or weight gain were observed during the study. Blood samples were collected and analyzed, and standard hematological and biochemical parameters were compared. A few of these parameters were found to be significantly different, but were within the normal reference intervals for rats of this breed and age, and were thus not considered to be treatment-related. Following sacrifice, a large number of organs were weighed, and macroscopic and histopathological examinations were performed with no changes reported. The aim of this study was to use a known animal model to determine the safety of the genetically modified (GM rice T1C-1. The results showed no adverse or toxic effects due to T1C-1 rice when tested in this 90-day study.

  12. A 90-day dietary toxicity study of genetically modified rice T1C-1 expressing Cry1C protein in Sprague Dawley rats.

    Science.gov (United States)

    Tang, Xueming; Han, Fangting; Zhao, Kai; Xu, Yan; Wu, Xiao; Wang, Jinbin; Jiang, Lingxi; Shi, Wei

    2012-01-01

    In a 90-day study, Sprague Dawley rats were fed transgenic T1C-1 rice expressing Cry1C protein and were compared with rats fed non-transgenic parental rice Minghui 63 and rats fed a basal diet. No adverse effects on animal behavior or weight gain were observed during the study. Blood samples were collected and analyzed, and standard hematological and biochemical parameters were compared. A few of these parameters were found to be significantly different, but were within the normal reference intervals for rats of this breed and age, and were thus not considered to be treatment-related. Following sacrifice, a large number of organs were weighed, and macroscopic and histopathological examinations were performed with no changes reported. The aim of this study was to use a known animal model to determine the safety of the genetically modified (GM) rice T1C-1. The results showed no adverse or toxic effects due to T1C-1 rice when tested in this 90-day study.

  13. A 90-day safety study in Sprague-Dawley rats fed milk powder containing recombinant human lactoferrin (rhLF) derived from transgenic cloned cattle.

    Science.gov (United States)

    Zhou, Cui; Wang, Jian Wu; Huang, Kun Lun; He, XiaoYun; Chen, Xiu Ping; Sun, Hong; Yu, Tian; Che, Hui Lian

    2011-10-01

    Transgenic cloned animals expressing beneficial human nutritional traits offer a new strategy for large-scale production of some kinds of functional substances. In some cases, the required safety testing for genetically modified (GM) foods do not seem appropriate for human food safety, though regulations do not seem to provide alternatives. A 90-day rat feeding study is the core study for the safety assessment of GM foods. The test material in this 90-day study was prepared nonfat milk powder containing recombinant human lactoferrin (rhLF), which was expressed in transgenic cloned cattle. Groups of 10 male and female Sprague-Dawley rats were given a nutritionally balanced purified diet containing 7.5, 15, or 30% transgenic or conventional milk powder for 90 days. A commercial AIN93G diet was used as an additional control group. Clinical, biological, and pathological parameters were compared between groups. The only significant effect of treatment was higher mean ferritin and Fe(+) concentrations for both male and female rats fed the transgenic milk powder diets, as compared to rats fed nontransgenic milk diets or the commercial diet. The results of the present study are consistent with previous research, which indicates that milk powder containing rhLF derived from healthy transgenic cloned cattle is as safe as conventional milk powder.

  14. Long Term Physiologic and Behavioural Effects of Housing Density and Environmental Resource Provision for Adult Male and Female Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Christopher J. Pinelli

    2017-06-01

    Full Text Available There is considerable interest in refining laboratory rodent environments to promote animal well-being, as well as research reproducibility. Few studies have evaluated the long term impact of enhancing rodent environments with resources and additional cagemates. To that end, male and female Sprague Dawley (SD rats were housed singly (n = 8/sex, in pairs (n = 16/sex, or in groups of four (n = 16/sex for five months. Single and paired rats were housed in standard cages with a nylon chew toy, while group-housed rats were kept in double-wide cages with two PVC shelters and a nylon chew toy and were provided with food enrichment three times weekly. Animal behaviour, tests of anxiety (open field, elevated plus maze, and thermal nociception, and aspects of animal physiology (fecal corticoid levels, body weight, weekly food consumption, organ weights, and cerebral stress signaling peptide and receptor mRNA levels were measured. Significant differences were noted, primarily in behavioural data, with sustained positive social interactions and engagement with environmental resources noted throughout the study. These results suggest that modest enhancements in the environment of both male and female SD rats may be beneficial to their well-being, while introducing minimal variation in other aspects of behavioural or physiologic responses.

  15. Effect of the Combination of Gelam Honey and Ginger on Oxidative Stress and Metabolic Profile in Streptozotocin-Induced Diabetic Sprague-Dawley Rats

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    Nur Fathiah Abdul Sani

    2014-01-01

    Full Text Available Diabetic complications occur as a result of increased reactive oxygen species (ROS due to long term hyperglycaemia. Honey and ginger have been shown to exhibit antioxidant activity which can scavenge ROS. The main aim of this study was to evaluate the antioxidant and antidiabetic effects of gelam honey, ginger, and their combination. Sprague-Dawley rats were divided into 2 major groups which consisted of diabetic and nondiabetic rats. Diabetes was induced with streptozotocin intramuscularly (55 mg/kg body weight. Each group was further divided into 4 smaller groups according to the supplements administered: distilled water, honey (2 g/kg body weight, ginger (60 mg/kg body weight, and honey + ginger. Body weight and glucose levels were recorded weekly, while blood from the orbital sinus was obtained after 3 weeks of supplementation for the estimation of metabolic profile: glucose, triglyceride (TG, superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx, reduced glutathione (GSH: oxidized glutathione (GSSG, and malondialdehyde (MDA. The combination of gelam honey and ginger did not show hypoglycaemic potential; however, the combination treatment reduced significantly (P<0.05 SOD and CAT activities as well as MDA level, while GSH level and GSH/GSSG ratio were significantly elevated (P<0.05 in STZ-induced diabetic rats compared to diabetic control rats.

  16. Effect of the Combination of Gelam Honey and Ginger on Oxidative Stress and Metabolic Profile in Streptozotocin-Induced Diabetic Sprague-Dawley Rats

    Science.gov (United States)

    Abdul Sani, Nur Fathiah; Belani, Levin Kesu; Pui Sin, Chong; Abdul Rahman, Siti Nor Amilah; Zar Chi, Thent; Makpol, Suzana; Yusof, Yasmin Anum Mohd

    2014-01-01

    Diabetic complications occur as a result of increased reactive oxygen species (ROS) due to long term hyperglycaemia. Honey and ginger have been shown to exhibit antioxidant activity which can scavenge ROS. The main aim of this study was to evaluate the antioxidant and antidiabetic effects of gelam honey, ginger, and their combination. Sprague-Dawley rats were divided into 2 major groups which consisted of diabetic and nondiabetic rats. Diabetes was induced with streptozotocin intramuscularly (55 mg/kg body weight). Each group was further divided into 4 smaller groups according to the supplements administered: distilled water, honey (2 g/kg body weight), ginger (60 mg/kg body weight), and honey + ginger. Body weight and glucose levels were recorded weekly, while blood from the orbital sinus was obtained after 3 weeks of supplementation for the estimation of metabolic profile: glucose, triglyceride (TG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH): oxidized glutathione (GSSG), and malondialdehyde (MDA). The combination of gelam honey and ginger did not show hypoglycaemic potential; however, the combination treatment reduced significantly (P < 0.05) SOD and CAT activities as well as MDA level, while GSH level and GSH/GSSG ratio were significantly elevated (P < 0.05) in STZ-induced diabetic rats compared to diabetic control rats. PMID:24822178

  17. Subchronic safety evaluation of CMS-1 (a botanical antihypertensive product derived from Semen Cnidium monnieri) in Sprague-Dawley rats and beagle dogs.

    Science.gov (United States)

    Gong, Xue-Lian; Gao, Ting-Ting; Zhao, Li-Jun; Zhu, Hai; Xia, Zhen-Na; Lu, Wen; Lu, Guo-Cai

    2014-08-01

    CMS-1, mainly composed of imperatorin as its active compound, is a partially purified fraction of a Chinese herbal medicine, Semen Cnidium monnieri. CMS-1 has the potential to be further developed as a new treatment for hypertension. Thus, we studied its toxicity in both Sprague-Dawley rats and beagle dogs. Rats (0-900mg/kg/day) and dogs (0-450mg/kg/day) received CMS-1 orally for 30 consecutive days, followed by a 15-day recovery period. The major target organs of CMS-1 toxicity are the GI (inappetence), liver (hepatocellular necrosis, enzyme elevation), thymus (atrophy), cardiovascular (hypotension), changes in ECG T and P waveforms, elevation of nitrous oxide levels and hematological (RBC parameters disturbances) systems. Most treatment-induced adverse effects were reversible or showed a progressive recovery upon discontinuation of the treatment. The No Observed Adverse Effect Level (NOAEL) was 100mg/kg/day for rats and 50mg/kg/day for dogs. This non-clinical study suggests that clinical monitoring of CMS-1 in patients should focus on the gastrointestinal system, blood tests for liver functions, electrolytes, and blood homeostasis, cardiovascular functions, and immune functions. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Effects of wearing bio-active material coated fabric against γ-irradiation-induced cellular damaged in Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Kang, Jung Ae; Kim, Hye Rim; Yoon, Sun Hye; Nam, Sang Hyun; Park, Sang Hyun; Jang, Beom Su; Go, Kyung Chan; Yang, Gwang Wung; Rho, Young Hwan; Park, Hyo Suk

    2016-01-01

    Ionizing radiation causes cellular damage and death through the direct damage and/or indirectly the production of ROS, which induces oxidative stress. This study was designed to evaluate the in vivo radioprotective effects of a bio-active material coated fabric (BMCF) against γ-irradiation-induced cellular damage in Sprague-Dawley (SD) rats. Healthy male SD rats wore bio-active material coated (concentrations in 10% and 30%) fabric for 7 days after 3 Gy of γ-irradiation. Radioprotective effects were evaluated by performing various biochemical assays including spleen and thymus index, WBC count, hepatic damage marker enzymes [aspartate transaminase (AST) and alanine transaminase (ALT)] in plasma, liver antioxidant enzymes, and mitochondrial activity in muscle. Exposure to γ-irradiation resulted in hepatocellular and immune systemic damage. Gamma-irradiation induced decreases in antioxidant enzymes. However, wearing the BMCF-30% decreased significantly AST and ALT activities in plasma. Furthermore, wearing the BMCF-30% increased SOD (superoxide dismutase) and mitochondrial activity. These results suggest that wearing BMCF offers effective radioprotection against γ-irradiation-induced cellular damage in SD rats

  19. Effects of High-sugar and High-fat Diet on Fat Deposition and Blood Vessel Wall on Sprague Dawley Rats Liver

    Directory of Open Access Journals (Sweden)

    Vera Citra Setiawan Hoei

    2013-11-01

    Full Text Available People nowadays tend to consume more fast food and sweetened beverages. These foods usually contain high amount sugar and fat that have effects on the body including liver.This study was conducted to explore the effects of extensive intake of sugar and fat on blood glucose and  cholesterol level as well as changes in liver. Research was conducted with experimental method using 20 Sprague Dawley rats which were divided into 4 groups; 2 controls and 2 treatments. Rats were given 5 ml sugar or lard alternatively every 2 consecutive days for 1-month and 2-month respectively. Data was retrieved include blood glucose and cholesterol level, fatty liver percentage and blood vessel thickening after intervention through HE staining. The results showed that both 1-month and 2-month intervention group has significant increase in blood glucose and cholesterol level. However, the enhancement of fatty liver percentage and number of thickened blood vessels (p<0.05 were only foundsignificant (p<0.05 in 1-month intervention group.  We concluded that high intake of sugar and fat within 1-monthintervention have significant effects on the rat body including liver. Nevertheless, it was not found significant in 2-months intervention. Further studies are still needed to analyze this incongruent result.Key words: high-sugar diet, high-fat diet, fatty liver, atherosclerosis 

  20. The effect of sibutramine, a serotonin-norepinephrine reuptake inhibitor, on platelets and fibrin networks of male Sprague-Dawley rats: a descriptive study.

    Science.gov (United States)

    van der Schoor, Ciska; Oberholzer, Hester Magdalena; Bester, Megan Jean; van Rooy, Mia-Jeanne

    2014-12-01

    Sibutramine is used in the treatment of obesity due to its ability to influence feelings of hunger and satiety by inhibiting the re-uptake of serotonin and noradrenalin in the central nervous system (CNS). Sibutramine use has been associated with numerous adverse events in particular cardiovascular complications possibly due to the formation of thrombi. This ultrastructural descriptive study investigated the effect of sibutramine on blood coagulation, specifically the effect on morphology of platelets and fibrin networks using scanning electron microscopy. Male Sprague-Dawley rats treated with either a recommended therapeutic dose [low dosage 1.32 mg/kg] or a toxicological higher dose [high dosage 13.2 mg/kg] of sibutramine for 28 days were used and compared to control animals. Blood samples were collected and plasma smears were prepared for platelet evaluation. Following the addition of thrombin to the plasma samples, the morphology of the fibrin clots was evaluated. Platelet evaluation by scanning electron microscopy revealed morphology typical of a prothrombotic state with a characteristic excessive platelet activation in both low-dose (LD) and high-dose (HD) rats. The fibrin clots of sibutramine-treated rats, LD and HD revealed fused thick fibers with thin fibers forming a net-like structure over the thick fibers which differ considerably from the organized structure of the control animals. It can be concluded that sibutramine alters the ultrastructure of platelets and fibrin networks creating a prothrombotic state.

  1. Roles of ROS mediated oxidative stress and DNA damage in 3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide-induced immunotoxicity of Sprague-Dawley rats.

    Science.gov (United States)

    Gao, Hui; Wang, Di; Zhang, Shun; Xu, Mengjing; Yang, Wei; Yan, Peipei; Liu, Yang; Luo, Xiao; Wu, Hailei; Yao, Ping; Yan, Hong; Liu, Liegang

    2015-11-01

    3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide (Quinocetone, QCT) has been broadly used to treat dysentery and promote animal growth in food producing animals. However, its potential toxicity could not been neglected as parts of safety assessment according to the acceptable guidelines for QCT administration. In this study, the immunotoxicity of QCT was investigated in male Sprague-Dawley (SD) rats following a 28-day oral exposure at doses of 0, 50, 800, and 2400 mg/kg/day. The food consumption, body weight gain and relative spleen weight were significantly decreased by QCT in a dose-dependent manner. Treatment of rats with QCT also notably suppressed the T-cell proliferation and natural killer (NK) cell activity, accompanied by intracellular reactive oxygen species (ROS) accumulation, antioxidant system inhibition and DNA damage enhancement. Thus, the primary finding of this study is that QCT exposure (2400 mg/kg/day) could cause immunotoxicity in SD rats due to ROS mediated oxidative stress and DNA damage. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Effects of wearing bio-active material coated fabric against γ-irradiation-induced cellular damaged in Sprague-Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Jung Ae; Kim, Hye Rim; Yoon, Sun Hye; Nam, Sang Hyun; Park, Sang Hyun; Jang, Beom Su [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Go, Kyung Chan; Yang, Gwang Wung; Rho, Young Hwan; Park, Hyo Suk [Research and Development Center, VENTEX Co. Ltd., Seoul (Korea, Republic of)

    2016-09-15

    Ionizing radiation causes cellular damage and death through the direct damage and/or indirectly the production of ROS, which induces oxidative stress. This study was designed to evaluate the in vivo radioprotective effects of a bio-active material coated fabric (BMCF) against γ-irradiation-induced cellular damage in Sprague-Dawley (SD) rats. Healthy male SD rats wore bio-active material coated (concentrations in 10% and 30%) fabric for 7 days after 3 Gy of γ-irradiation. Radioprotective effects were evaluated by performing various biochemical assays including spleen and thymus index, WBC count, hepatic damage marker enzymes [aspartate transaminase (AST) and alanine transaminase (ALT)] in plasma, liver antioxidant enzymes, and mitochondrial activity in muscle. Exposure to γ-irradiation resulted in hepatocellular and immune systemic damage. Gamma-irradiation induced decreases in antioxidant enzymes. However, wearing the BMCF-30% decreased significantly AST and ALT activities in plasma. Furthermore, wearing the BMCF-30% increased SOD (superoxide dismutase) and mitochondrial activity. These results suggest that wearing BMCF offers effective radioprotection against γ-irradiation-induced cellular damage in SD rats.

  3. Increase in Bcl2 expression of penile and prostate cells of Sprague Dawley male rats following treatment with buceng (combination of Pimpinella alpina molk with Eurycoma longifolia Jack

    Directory of Open Access Journals (Sweden)

    Taufiqurrachman Nasihun

    2015-04-01

    Full Text Available Background: Treatment with buceng combination of Eurycoma longifolia Jack and Pimpinella alpine Molk has been proven to increase testosterone level, decrease apoptosis and caspase3 expression. Bcl2 is an antiapoptotic protein found in cytoplasm which inhibits cells apoptosis. This study was aimed to investigate the effect of buceng on Bcl2 expression on penile and prostate tissues of the rats. Methods: In this experimental study, 24 male Sprague Dawley rats of 90 days old, weighing ± 300 grams, were randomly assigned into four groups. Group A, normal rats. Group B, castrated rats and treated with buceng 100 mg/day, per oral (Cast-Bcg; Group C, castrated rats and treated with 2 ml of water as placebo against buceng (Cast-Plac. Group D, castrated rats, treated with mesterolone 6.75 mg/day, per oral, as exogenous testosterone (Cast-Mest. All rats were treated for 30 days. Manova test was used to analyze the different expression of Bcl2 among groups with significance level at p ≤ 0.05. Results: Castration was associated with significant decrease of Bcl2 expression in the penile and prostate tissues (53.0 and 50.9%, respectively compared to normal rats (82.6 and 84.2%, respectively, p < 0.001. Treatment with mesterolone reversed Bcl2 expression (77.1 and 78.1% to a near normal level. The same level of Bcl2 expression was also observed with buceng treatment (73.8 and 78.2%.Conclusion: The treatment with buceng could enhance Bcl2 expression in penile and prostate tissues, comparable to normal rats and mesterolone treated rats.

  4. Early ethanol and water consumption: accumulating experience differentially regulates drinking pattern and bout parameters in male alcohol preferring (P) vs. Wistar and Sprague Dawley rats.

    Science.gov (United States)

    Azarov, Alexey V; Woodward, Donald J

    2014-01-17

    Alcohol-preferring (P) rats develop high ethanol intake over several weeks of water/10% ethanol (10E) choice drinking. However, it is not yet clear precisely what components of drinking behavior undergo modification to achieve higher intake. Our concurrent report compared precisely measured daily intake in P vs. non-selected Wistar and Sprague Dawley (SD) rats. Here we analyze their drinking patterns and bouts to clarify microbehavioral components that are common to rats of different genetic backgrounds, vs. features that are unique to each. Under sole-fluid conditions P, Wistar and SD rats all consumed water at a high initial rate followed by a slow maintenance phase, but 10E - in a distinctly different step-like pattern of evenly distributed bouts. During choice period, 10E vs. water patterns for P rat appeared as an overlap of sole-fluid patterns. The SD rat choice patterns resembled sole-fluid patterns but were less regular. Choice patterns in Wistar differed from both P and SD rats, by consisting of intermixed small frequent episodes of drinking both 10E and water. Wistar and SD rats increased choice ethanol intake by elevating the number of bouts. A key finding was that P rat increased choice ethanol intake through a gradual increase of the bout size and duration, but kept bout number constant. This supports the hypothesis that genetic selection modifies microbehavioral machinery controlling drinking bout initiation, duration, and other pattern features. Precision analysis of drinking patterns and bouts allows differentiation between genetic lines, and provides a venue for study of localized circuit and transmitter influences mediating mesolimbic control over ethanol consumption. © 2013 Elsevier Inc. All rights reserved

  5. The combined toxicity of dibutyl phthalate and benzo(a)pyrene on the reproductive system of male Sprague Dawley rats in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Chen Xuemei [Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016 (China); An Hui; Ao Lin; Sun Lei; Liu Wenbin; Zhou Ziyuan [Department of Hygenic Toxicology, College of Military Preventive Medicine, Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Third Military Medical University, Chongqing 400038 (China); Wang Yingxiong, E-mail: wyx61221@yahoo.com.cn [Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016 (China); Cao Jia, E-mail: caojia1962@126.com [Department of Hygenic Toxicology, College of Military Preventive Medicine, Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Third Military Medical University, Chongqing 400038 (China)

    2011-02-15

    Our previous studies revealed more than 100 pollutants, most of which were endocrine disruptors (EDs) in two Chinese rivers, the Jialing and the Yangtze near Chongqing. Most EDs, such as dibutyl phthalate (DBP) and benzo(a)pyrene (BaP), are known to act individually as reproductive toxicants. However, little is known about the combined toxicity of DBP and BaP. In the current study, male Sprague Dawley rats were subchronically exposed to single doses of DBP (250 mg/kg), single doses of BaP (5 mg/kg) and combined doses of DBP and BaP. Significant adverse effects were observed on the reproductive system, including decreased sperm count, increased production of abnormal sperm, changes in serum testosterone levels and irregular arrangements of the seminiferous epithelium. Biochemical analyses showed that the activities of superoxide dismutase and glutathione peroxidase decreased after exposure to these EDs. Therefore, our data suggest that exposure to DBP and BaP, in either separate or combined doses, can affect the reproductive system of male rats adversely via oxidative stress-related mechanisms. No significant additive effect was observed after combined exposure. These results indicate that exposure to mixtures of EDs have unexpected and elusive effects. Our findings provide preliminary but important data for assessing water safety in China.

  6. The combined toxicity of dibutyl phthalate and benzo(a)pyrene on the reproductive system of male Sprague Dawley rats in vivo

    International Nuclear Information System (INIS)

    Chen Xuemei; An Hui; Ao Lin; Sun Lei; Liu Wenbin; Zhou Ziyuan; Wang Yingxiong; Cao Jia

    2011-01-01

    Our previous studies revealed more than 100 pollutants, most of which were endocrine disruptors (EDs) in two Chinese rivers, the Jialing and the Yangtze near Chongqing. Most EDs, such as dibutyl phthalate (DBP) and benzo(a)pyrene (BaP), are known to act individually as reproductive toxicants. However, little is known about the combined toxicity of DBP and BaP. In the current study, male Sprague Dawley rats were subchronically exposed to single doses of DBP (250 mg/kg), single doses of BaP (5 mg/kg) and combined doses of DBP and BaP. Significant adverse effects were observed on the reproductive system, including decreased sperm count, increased production of abnormal sperm, changes in serum testosterone levels and irregular arrangements of the seminiferous epithelium. Biochemical analyses showed that the activities of superoxide dismutase and glutathione peroxidase decreased after exposure to these EDs. Therefore, our data suggest that exposure to DBP and BaP, in either separate or combined doses, can affect the reproductive system of male rats adversely via oxidative stress-related mechanisms. No significant additive effect was observed after combined exposure. These results indicate that exposure to mixtures of EDs have unexpected and elusive effects. Our findings provide preliminary but important data for assessing water safety in China.

  7. Effect of Injection Minimal Dosages of Depot Medroxyprogesterone acetate (DMPA to Body Weight and Blood Chemistry Male Rat Strain Sprague-Dawley

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    Nukman Moeloek

    2009-11-01

    Full Text Available Many family planning program focus more on men. Until now, vasectomy has been the commonly used method for male contraception. However, this method creates inconvenience such as irreversibility and psychological problems. One of the alternatives contraception is the combination of depot medroxyprogesterone acetate (DMPA and androgen. The minimum dosage of DMPA could suppress testosterone level that leads to reduced spermatogenesis and sperm viability. Nevertheless, until now it is not known whether minimum dosages of DMPA have an effect to body weight and blood chemistry. Therefore, this research aimed at determinate the effect of minimal dosages of DMPA to body mass and blood chemistry using male rats (Rattus norvegicus L. strain Sprague-Dawley as model. This research using completely randomized design, unequal size sample, castration treatments and several doses DMPA (1.25, 0.625, and 0.313 milligram. Injecting of DMPA conducted intramuscularly on week 0 and week 12. Normality/homogeneity Data normality were analyzed before ANOVA test. Then, abnormal data were tested using Kruskal-Wallis test. The result shows that injection of DMPA in various doses do not have an effect on body weight and blood chemistry such as erytrocytes, haemoglobin, hematocrite, HDL, LDL, total cholesterol, SGOT, SGPT and triglyseride (p>0,05. Furthermore, it is concluded that that no effect of minimal dosages of DMPA to body mass and blood chemistry of rat.

  8. Abrogation of carbon tetrachloride-induced hepatotoxicity in Sprague-Dawley rats by Ajwa date fruit extract through ameliorating oxidative stress and apoptosis.

    Science.gov (United States)

    Elsadek, Bakheet; El-Sayed, El-Sayed; Mansour, Ahmed; Elazab, Ayman

    2017-11-01

    Ajwa, a variety of date palme Phoenix dactylifera L., has long been used and considered as one of the most popular fruits in the North Africa and Middle East region. For Muslims this fruit is of religious importance and is mentioned several times in Quran. Besides being a part of the Arabian essential diet, dates have been used traditionally for number of complications. This study aimed to evaluate the possible potential of Ajwa date extract to guard against carbon tetrachloride (CCL4)-induced liver damage in rats. Adult male Sprague-Dawley rats were given Ajwa date extract and silymarin (a standard reference drug) at doses of 300 & 50mg/kg, p.o., respectively for 2 weeks before CCl4 (2 ml/kg, s. c., twice weekly for 8 consecutive weeks), and concomitantly administered with CCl4 for 8 consecutive weeks. Like silymarin, Ajwa date extract produced significant decrease in serum levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total cholesterol, triglycerides (TG) and LDL-cholesterol as well as lipid peroxides measured as malondialdehyde (MDA), hydroxyproline and caspase-3 contents of liver tissue with marked increase in serum albumin, HDL-cholesterol and reduced glutathione (GSH) content as well as enzyme activities of super oxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST). In conclusion, Ajwa date extract afforded significant protection against CCl4-induced hepatocellular injury; an effect that could be attributed to its antioxidant, antiapoptotic and antifibrotic activities.

  9. The Effectivity of Green Coconut Water To Reduce Mercury Level In The Blood And To Improve Blood Profiles And Liver Cells Appearance (Study In Sprague Dawley Rats)

    Science.gov (United States)

    Abdulrzag, Ehmeeda M.; Nur Kristina, Tri; Suwondo, Ari; Sunoko, Henna Rya

    2018-02-01

    When people are exposed to mercury chloride, it can produce a variety of health effects in the blood and liver. Coconut water contains Zn, Fe, Vit. C, Vit B11, Vit. B6, and Se to reduce mercury chloride level in the blood and improve blood profile and liver cells. Aim of this study was to analysis the effect of green coconut water supplementation in overcoming the toxic effect of Hg chlorid in the blood and liver of Sprague dawley rats exposed to Hg chloride. Samples were randomly about 36 animals rats exposed to HgCl2 through forced feeding by 20 mg/kgBW sondage per day for 14 days, which divided into control group, and intervention groups were given fresh green coconut water in each by 6, 8, and 10 mL/kgBW for intervention 7 and 17 days. The result of this study showed that there is a significant effect and the decrease in mercury levels in the blood. There is no significant affect on the hemoglobin level, hematocrit level and platelet count with the treatment of green coconut water in the mice with exposure Hg. There is no significant effect between treatments using green coconut water with SGPT levels; there is a decrease in SGPT levels at the increasing number of doses of green coconut water and the length of treatment.

  10. Effect of a Short-Term and Long-Term Melatonin Administration on Mammary Carcinogenesis in Female Sprague-Dawley Rats Influenced by Repeated Psychoemotional Stress

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    M. Kassayová

    2007-01-01

    Full Text Available The aim of this study was to evaluate the effect of melatonin (MEL on N-methyl-N-nitrosourea (NMU-induced mammary carcinogenesis in female Sprague-Dawley rats exposed to repeated psychoemotional stress - immobilization in boxes. NMU was applied intraperitoneally in two doses each of 50 mg/kg b.w. between 40 - 50 postnatal days. Melatonin was administered in drinking water at a concentration of 4 μg/ml daily from 15:00 h to 8:00 h. The application was initiated 5 days prior to the fi rst NMU dose and lasted 15 days, i.e. during the promotion phase of tumour development, or long-term until the end of the experiment (week 20. Immobilization (2 h per day began on the third day after the second carcinogen application and lasted for 7 consecutive days. Short-term MEL administration to immobilized animals increased incidence by 22%, decreased tumour frequency per animal by 26% and reduced tumour volume gain (by 21% when compared to the immobilized group without MEL application. Decreased frequency per animal by 28% and more than a 40% decrease in tumour volume gain and cumulative volume were the most pronounced changes in the animals drinking MEL until the end of the experiment. Long-term MEL administration reduced the number and size of mammary tumours more markedly than its short-term administration. Melatonin decreased certain attributes of mammary carcinogenesis in female rats influenced by psychoemotional stress.

  11. Safety assessment of freeze-dried powdered Tenebrio molitor larvae (yellow mealworm) as novel food source: Evaluation of 90-day toxicity in Sprague-Dawley rats.

    Science.gov (United States)

    Han, So-Ri; Lee, Byoung-Seok; Jung, Kyung-Jin; Yu, Hee-Jin; Yun, Eun-Young; Hwang, Jae Sam; Moon, Kyoung-Sik

    2016-06-01

    Worldwide demand for novel food source has grown and edible insects are a promising food sources for humans. Tenebrio molitor, as known as yellow mealworm, has advantages of being rich in protein, and easy to raise as a novel food source. The objective of this study was to evaluate subchronic toxicity, including potential hypersensitivity, of freeze-dried powdered T. molitor larvae (fdTML) in male and female Sprague-Dawley rats. The fdTML was administered orally once daily at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 90 days. A toxicological assessment was performed, which included mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings, histopathologic examination and allergic reaction. There were no fdTML- related findings in clinical signs, urinalysis, hematology and serum chemistry, gross examination, histopathologic examination or allergic reaction. In conclusion, the No Observed Adverse Effect Level (NOAEL) for fdTML was determined to be in excess of 3000 mg/kg/day in both sexes of rats under the experimental conditions of this study. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Nonclinical Safety Assessment of Morus alba L. Fruits: Study of 90-D Toxicity in Sprague Dawley Rats and Genotoxicity in Salmonella.

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    Chang, Bo Yoon; Kim, Seon Beom; Lee, Mi Kyeong; Park, Hyun; Kim, Sung Yeon

    2016-05-01

    Morus alba L. is a traditional herb with a long history of consumption, both as an edible fruit and as medicine. However, its safety evaluation has not yet been established. The objective of this study was to evaluate subchronic oral toxicity and genotoxicity of M. alba L. fruits (MFE). The subchronic toxicity after daily oral administration of MFE at 0, 40, 200, and 1000 mg/kg for 90 d was examined in Sprague Dawley (SD) rats. MFE administration did not lead to death, adverse effects, change in food and water consumption, and body weight gain. Significant toxic effects were not found within the parameters of organ weight, biochemical values, and hematological and urine analysis between the control and the MFE group. The genotoxicity of MFE was assayed by Ames test in Salmonella typhimurium strains TA98, TA102, and TA1535. No genotoxicity was found in all the tested strains. Thus in this study, a no-observed-adverse-effect level for MFE in 90 d repeated oral toxicity study in rats was determined to be greater than 1000 mg/kg regardless of gender. The results also suggested that MFE does not have a genotoxicity potential. © 2016 Institute of Food Technologists®

  13. Early ethanol and water intake: choice mechanism and total fluid regulation operate in parallel in male alcohol preferring (P) and both Wistar and Sprague Dawley rats.

    Science.gov (United States)

    Azarov, Alexey V; Woodward, Donald J

    2014-01-17

    The goal of this study was to clarify similar and distinctly different parameters of fluid intake during early phases of ethanol and water choice drinking in alcohol preferring P-rat vs. non-selected Wistar and Sprague Dawley (SD) rats. Precision information on the drinking amounts and timing is needed to analyze micro-behavioral components of the acquisition of ethanol intake and to enable a search for its causal activity patterns within individual CNS circuits. The experiment followed the standard ethanol-drinking test used in P-rat selective breeding, with access to water, then 10% ethanol (10E) as sole fluids, and next to ethanol/water choice. The novelty of the present approach was to eliminate confounding prandial elevations of fluid intake, by time-separating daily food from fluid access. P-rat higher initial intakes of water and 10E as sole fluids suggest adaptations to ethanol-induced dehydration in P vs. Wistar and SD rats. P-rat starting and overall ethanol intake during the choice period were the highest. The absolute extent of ethanol intake elevation during choice period was greatest in Wistar and their final intake levels approached those of P-rat, contrary to the hypothesis that selection would produce the strongest elevation of ethanol intake. The total daily fluid during ethanol/water choice period was strikingly similar between P, Wistar and SD rats. This supports the hypothesis for a universal system that gauges the overall intake volume by titrating and integrating ethanol and water drinking fluctuations, and indicates a stable daily level of total fluid as a main regulated parameter of fluid intake across the three lines in choice conditions. The present findings indicate that a stable daily level of total fluid comprises an independent physiological limit for daily ethanol intake. Ethanol drinking, in turn, stays under the ceiling of this limit, driven by a parallel mechanism of ethanol/water choice. © 2013 Elsevier Inc. All rights reserved.

  14. Comparison of CYP2D metabolism and hepatotoxicity of the myocardial metabolic agent perhexiline in Sprague-Dawley and Dark Agouti rats.

    Science.gov (United States)

    Licari, Giovanni; Somogyi, Andrew A; Milne, Robert W; Sallustio, Benedetta C

    2015-01-01

    1. Perhexiline, a chiral anti-anginal agent, may be useful to develop new cardiovascular therapies, despite its potential hepatotoxicity. 2. This study compared Dark Agouti (DA) and Sprague-Dawley (SD) rats, as models of perhexiline's metabolism and hepatotoxicity in humans. Rats (n = 4/group) received vehicle or 200 mg/kg/d of racemic perhexiline maleate for 8 weeks. Plasma and liver samples were collected to determine concentrations of perhexiline and its metabolites, hepatic function and histology. 3. Median (range) plasma and liver perhexiline concentrations in SD rats were 0.09 (0.04-0.13) mg/L and 5.42 (0.92-8.22) ng/mg, respectively. In comparison, DA rats showed higher (p < 0.05) plasma 0.50 (0.16-1.13) mg/L and liver 24.5 (9.40-54.7) ng/mg perhexiline concentrations, respectively, 2.5- and 3.7-fold higher cis-OH-perhexiline concentrations, respectively (p < 0.05), and lower plasma metabolic ratio (0.89 versus 1.55, p < 0.05). In both strains, the (+):(-) enantiomer ratio was 2:1. Perhexiline increased plasma LDH concentrations in DA rats (p < 0.05), but had no effect on plasma biochemistry in SD rats. Liver histology revealed lower glycogen content in perhexiline-treated SD rats (p < 0.05), but no effects on lipid content in either strain. 4. DA rats appeared more similar to humans with respect to plasma perhexiline concentrations, metabolic ratio, enantioselective disposition and biochemical changes suggestive of perhexiline-induced toxicity.

  15. Development and comparison of a minimally-invasive model of autologous clot pulmonary embolism in Sprague-Dawley and Copenhagen rats

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    Sanapareddy Nina

    2010-02-01

    Full Text Available Abstract Background Experimental models of pulmonary embolism (PE that produce pulmonary hypertension (PH employ many different methods of inducing acute pulmonary occlusion. Many of these models induce PE with intravenous injection of exogenous impervious objects that may not completely reproduce the physiological properties of autologous thromboembolism. Current literature lacks a simple, well-described rat model of autlogous PE. Objective: Test if moderate-severity autologous PE in Sprague-Dawley (SD and Copenhagen (Cop rats can produce persistent PH. Methods blood was withdrawn from the jugular vein, treated with thrombin-Ca++ and re-injected following pretreatment with tranexamic acid. Hemodynamic values, clot weights and biochemical measurements were performed at 1 and 5 days. Results Infusion of clot significantly increased the right ventricular peak systolic pressure to 45-55 mm Hg, followed by normalization within 24 hours in SD rats, and within 5 days in COP rats. Clot lysis was 95% (24 hours and 97% (5 days in SD rats and was significantly lower in COP rats (70%, 24 hours; 87% 5 days. Plasma D-dimer was elevated in surgical sham animals and was further increased 8 hours after pulmonary embolism. Neither strain showed a significant increase in bronchoalveolar chemotactic activity, myeloperoxidase activity, leukocyte infiltration, or chemokine accumulation, indicating that there was no significant pulmonary inflammation. Conclusions Both SD and COP rats exhibited near complete fibrinolysis of autologous clot PE within 5 days. Neither strain developed persistent PH. Experimental models of PE designed to induce sustained PH and a robust inflammatory response appear to require significant, persistent pulmonary vascular occlusion.

  16. The effect of feeding different sugar-sweetened beverages to growing female Sprague-Dawley rats on bone mass and strength.

    Science.gov (United States)

    Tsanzi, Embedzayi; Light, Heather R; Tou, Janet C

    2008-05-01

    Consumption of sugar beverages has increased among adolescents. Additionally, the replacement of sucrose with high fructose corn syrup (HFCS) as the predominant sweetener has resulted in higher fructose intake. Few studies have investigated the effect of drinking different sugar-sweetened beverages on bone, despite suggestions that sugar consumption negatively impacts mineral balance. The objective of this study was to determine the effect of drinking different sugar-sweetened beverages on bone mass and strength. Adolescent (age 35d) female Sprague-Dawley rats were randomly assigned (n=8-9/group) to consume deionized distilled water (ddH2O, control) or ddH2O containing 13% w/v glucose, sucrose, fructose or high fructose corn syrup (HFCS-55) for 8weeks. Tibia and femur measurements included bone morphometry, bone turnover markers, determination of bone mineral density (BMD) and bone mineral content (BMC) by dual energy X-ray absorptiometry (DXA) and bone strength by three-point bending test. The effect of sugar-sweetened beverage consumption on mineral balance, urinary and fecal calcium (Ca) and phosphorus (P) was measured by inductively coupled plasma optical emission spectrometry. The results showed no difference in the bone mass or strength of rats drinking the glucose-sweetened beverage despite their having the lowest food intake, but the highest beverage and caloric consumption. Only in comparisons among the rats provided sugar-sweetened beverage were femur and tibia BMD lower in rats drinking the glucose-sweetened beverage. Differences in bone and mineral measurements appeared most pronounced between rats drinking glucose versus fructose-sweetened beverages. Rats provided the glucose-sweetened beverage had reduced femur and tibia total P, reduced P and Ca intake and increased urinary Ca excretion compared to the rats provided the fructose-sweetened beverage. The results suggested that glucose rather than fructose exerted more deleterious effects on mineral

  17. Study on a 4-Week Recovery Test of Sweet Bee Venom after a 13-Week, Repeated, Intramuscular Dose Toxicity Test in Sprague-Dawley Rats

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    Chungsan Lim

    2014-06-01

    Full Text Available Objectives:This study was performed to check for reversibility in the changes induced by a 13-week, repeated, dose toxicity test of Sweet Bee Venom (SBV in Sprague-Dawley (SD rats. Methods:Fifteen male and 15 female SD rats were treated with 0.28 mg/kg of SBV (high-dosage group and the same numbers of male and female SD rats were treated with 0.2 mL/kg of normal saline (control group for 13 weeks. We selected five male and five female SD rats from the high-dosage group and the same numbers of male and female SD rats from the control group, and we observed these rats for four weeks. We conducted body-weight measurements, ophthalmic examinations, urinalyses and hematology, biochemistry, histology tests. Results:(1 Hyperemia and movement disorder were observed in the 13-week, repeated, dose toxicity test, but these symptoms were not observed during the recovery period. (2 The rats in the high-dose group showed no significant changes in weight compared to the control group. (3 No significant differences in the ophthalmic parameters, urine analyses, complete blood cell counts (CBCs, and biochemistry were observed among the recovery groups. (4 No changes in organ weights were observed during the recovery period. (5 Histological examination of the thigh muscle indicated cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis during the treatment period, but these changes were not observed during the recovery period. The fatty liver change that was observed during the toxicity test was not observed during the recovery period. No other organ abnormalities were observed. Conclusion:The changes that occurred during the 13-week, repeated, dose toxicity test are reversible, and SBV can be safely used as a treatment modality.

  18. Four-week dietary supplementation with 10- and/or 15-fold basal choline caused decreased body weight in Sprague Dawley rats.

    Science.gov (United States)

    Bagley, Bradford D; Chang, Shu-Ching; Ehresman, David J; Eveland, Alan; Parker, George A; Peters, Jeffrey M; Butenhoff, John L

    2017-10-01

    Choline is an essential nutrient utilized for phosphatidylcholine biosynthesis and lipoprotein packaging and secretion. Recently, choline supplementation has been used by athletes and the public for weight loss. However, the potential toxicological impact of choline dietary supplementation requires further investigation. This study examined the effects of choline dietary supplementation in Sprague Dawley rats for 4 weeks. Rats were fed diets containing basal choline levels (control) or 5-, 10-, or 15-fold (5×, 10×, or 15×) basal diet concentration. In groups fed choline-supplemented diets, there were no toxicologically relevant findings in clinical observations, food intake, clinical chemistry, liver weights, or liver histopathology. However, decreased mean body weights (8.5-10.2%) and body weight gains (24-31%) were noted for the 10× choline-supplemented (females only) and 15× choline-supplemented (both sexes) groups relative to the control groups from day 3 onward. These body weight effects were not related to a persistent reduction in average food intake. Serum cholesterol was increased in the 15× choline-supplemented male rats relative to the controls, an expected effect of choline supplementation; however, there were no changes in the serum cholesterol of female rats. Serum choline concentrations were increased in female rats relative to the male rats across all treatment groups. The maximum tolerated dose for male and female rats were the 15× and 10× choline supplements, respectively, based on decreased mean body weight and body weight gains. This study supported the conclusions of a clinical trial that showed a high choline diet can decrease body weight in humans.

  19. Variation in the form of Pavlovian conditioned approach behavior among outbred male Sprague-Dawley rats from different vendors and colonies: sign-tracking vs. goal-tracking.

    Science.gov (United States)

    Fitzpatrick, Christopher J; Gopalakrishnan, Shyam; Cogan, Elizabeth S; Yager, Lindsay M; Meyer, Paul J; Lovic, Vedran; Saunders, Benjamin T; Parker, Clarissa C; Gonzales, Natalia M; Aryee, Emmanuel; Flagel, Shelly B; Palmer, Abraham A; Robinson, Terry E; Morrow, Jonathan D

    2013-01-01

    Even when trained under exactly the same conditions outbred male Sprague-Dawley (SD) rats vary in the form of the Pavlovian conditioned approach response (CR) they acquire. The form of the CR (i.e. sign-tracking vs. goal-tracking) predicts to what degree individuals attribute incentive salience to cues associated with food or drugs. However, we have noticed variation in the incidence of these two phenotypes in rats obtained from different vendors. In this study, we quantified sign- and goal-tracking behavior in a reasonably large sample of SD rats obtained from two vendors (Harlan or Charles River), as well as from individual colonies operated by both vendors. Our sample of rats acquired from Harlan had, on average, more sign-trackers than goal-trackers, and vice versa for our sample of rats acquired from Charles River. Furthermore, there were significant differences among colonies of the same vendor. Although it is impossible to rule out environmental variables, SD rats at different vendors and barriers may have reduced phenotypic heterogeneity as a result of genetic variables, such as random genetic drift or population bottlenecks. Consistent with this hypothesis, we identified marked population structure among colonies from Harlan. Therefore, despite sharing the same name, investigators should be aware that important genetic and phenotypic differences exist among SD rats from different vendors or even from different colonies of the same vendor. If used judiciously this can be an asset to experimental design, but it can also be a pitfall for those unaware of the issue.

  20. Variation in the form of Pavlovian conditioned approach behavior among outbred male Sprague-Dawley rats from different vendors and colonies: sign-tracking vs. goal-tracking.

    Directory of Open Access Journals (Sweden)

    Christopher J Fitzpatrick

    Full Text Available Even when trained under exactly the same conditions outbred male Sprague-Dawley (SD rats vary in the form of the Pavlovian conditioned approach response (CR they acquire. The form of the CR (i.e. sign-tracking vs. goal-tracking predicts to what degree individuals attribute incentive salience to cues associated with food or drugs. However, we have noticed variation in the incidence of these two phenotypes in rats obtained from different vendors. In this study, we quantified sign- and goal-tracking behavior in a reasonably large sample of SD rats obtained from two vendors (Harlan or Charles River, as well as from individual colonies operated by both vendors. Our sample of rats acquired from Harlan had, on average, more sign-trackers than goal-trackers, and vice versa for our sample of rats acquired from Charles River. Furthermore, there were significant differences among colonies of the same vendor. Although it is impossible to rule out environmental variables, SD rats at different vendors and barriers may have reduced phenotypic heterogeneity as a result of genetic variables, such as random genetic drift or population bottlenecks. Consistent with this hypothesis, we identified marked population structure among colonies from Harlan. Therefore, despite sharing the same name, investigators should be aware that important genetic and phenotypic differences exist among SD rats from different vendors or even from different colonies of the same vendor. If used judiciously this can be an asset to experimental design, but it can also be a pitfall for those unaware of the issue.

  1. The type of caloric sweetener added to water influences weight gain, fat mass, and reproduction in growing Sprague-Dawley female rats.

    Science.gov (United States)

    Light, Heather R; Tsanzi, Embedzayi; Gigliotti, Joseph; Morgan, Keri; Tou, Janet C

    2009-06-01

    Caloric sweetened beverages have been suggested to be a major dietary contributor to weight gain, particularly among adolescents. Dietary recommendations are for moderating intakes of added sugars; however, the question remains whether certain types of sugars should be limited. The objective of this study was to determine the effect of drinking different caloric sweetened beverages on the development of adiposity, metabolic, and endocrine disorders. Young (age 28 days) female Sprague-Dawley rats (n = 8-9 rats/group) were randomly assigned to drink either deionized distilled water (ddH2O) or ddH2O sweetened with 13% (w/v) glucose, sucrose, fructose or high fructose corn syrup 55 (HFCS-55) for 8 weeks. Rats drinking caloric sweetened solutions failed to completely compensate for liquid calories ingested by reducing their consumption of solid food. This resulted in greater total energy intake compared to the ddH2O control; however, there was no significant difference in total energy intake between rats drinking sucrose, fructose or HFCS-55. Of the different caloric sweeteners, only rats drinking HFCS-55 had greater (P glucose solution. This may have occurred because drinking HFCS-55 solution promoted a faster body weight gain. Adiposity induced by caloric sweetened water was not accompanied by metabolic disorders indicated by the absence of dyslipidemia and no differences in fasting serum glucose, insulin or C-peptide among the treatment groups. However, rats drinking HFCS-55 showed lengthened estrous cycles due to prolonged estrus. Based on this study, the type of caloric sweetener added to beverages should be considered when making dietary recommendation for reducing excess body weight and related health risk.

  2. Water-Soluble Chitosan Nanoparticles Inhibit Hypercholesterolemia Induced by Feeding a High-Fat Diet in Male Sprague-Dawley Rats

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    Yi Tao

    2011-01-01

    Full Text Available Chitosan, a deacetylated product of chitin, has been demonstrated to lower cholesterol in humans and animals. However, chitosan is not fully soluble in water which would influence absorption in the human intestine. In addition, water-soluble chitosan (WSC has higher reactivity compared to chitosan. The present study was designed to clarify the effects of WSC and water-soluble chitosan nanoparticles (WSC-NPs on hypercholesterolemia induced by feeding a high-fat diet in male Sprague-Dawley rats. WSC-NPs were prepared by the ionic gelation method and the spray-drying technique. The nanoparticles were spherical in shape and had a smooth surface. The mean size of WSC-NPs was 650 nm variing from 500 to 800 nm. Results showed that WSC-NPs reduced the blood lipids and plasma viscosity significantly and increased the serum superoxide dismutase (SOD activities significantly. This paper is the first report of the lipid-lowering effects of WSC-NPs suggesting that the WSC-NPs could be used for the treatment of hypercholesterolemia.

  3. Water-Soluble Chitosan Nanoparticles Inhibit Hypercholesterolemia Induced by Feeding a High-Fat Diet in Male Sprague-Dawley Rats

    International Nuclear Information System (INIS)

    Tao, Y.; Zhang, H.; Gao, B.; Guo, J.; Hu, Y.; Su, Z.

    2011-01-01

    Chitosan, a deacetylated product of chitin, has been demonstrated to lower cholesterol in humans and animals. However, chitosan is not fully soluble in water which would influence absorption in the human intestine. In addition, water-soluble chitosan (WSC) has higher reactivity compared to chitosan. The present study was designed to clarify the effects of WSC and water-soluble chitosan nanoparticles (WSC-NPs) on hypercholesterolemia induced by feeding a high-fat diet in male Sprague-Dawley rats. WSC-NPs were prepared by the ionic gelation method and the spray-drying technique. The nanoparticles were spherical in shape and had a smooth surface. The mean size of WSC-NPs was 650 nm variing from 500 to 800?nm. Results showed that WSC-NPs reduced the blood lipids and plasma viscosity significantly and increased the serum superoxide dismutase (SOD) activities significantly. This paper is the first report of the lipid-lowering effects of WSC-NPs suggesting that the WSC-NPs could be used for the treatment of hypercholesterolemia

  4. [Effect of consumption of bread with amaranth (Amaranthus dubius Mart. ex Thell.) on glycemic response and biochemical parameters in Sprague dawley rats].

    Science.gov (United States)

    Montero-Quintero, Keyla Carolina; Moreno-Rojas, Rafael; Molina, Edgar Alí; Colina-Barriga, Máximo Segundo; Sánchez-Urdaneta, Adriana Beatriz

    2014-11-01

    The incorporation of functional ingredients like amaranth (Amaranthus dubius Mart. ex Thell.) in bread making is a strategy to increase fiber intake, which is associated with beneficial health effects, improving glycemic response and lipid profile. Thirty male Sprague dawley rats were randomized into three groups: diet of bread with 0% amaranth (PA0, control), diet of bread with 10% amaranth (PA10) and bread diet with 20% amaranth (PA20) for determining the feed intake, weight gain, triglyceride, total cholesterol, VLDL-C, LDL-C, HDL-C, protein and postprandial glycemic response. Data were analyzed using a completely randomized with 10 replications analysis, using the comparison test of Tukey for biochemical parameters. Postprandial glycemic response was analyzed by the method of repeated measures over time. The daily intake and weight gain was not affected (P>0.05) in the groups with PA10 and PA20. The concentration of glucose, triglycerides and protein showed statistically significant differences (P>0.05) by the difference in content of amaranth diets. The values of total cholesterol, LDL-C, and atherogenic risk factor index were statistically significant (P. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  5. Investigation of the Anxiolytic and Antidepressant Effects of Curcumin, a Compound From Turmeric (Curcuma longa), in the Adult Male Sprague-Dawley Rat.

    Science.gov (United States)

    Ceremuga, Tomás Eduardo; Helmrick, Katie; Kufahl, Zachary; Kelley, Jesse; Keller, Brian; Philippe, Fabiola; Golder, James; Padrón, Gina

    As the use of herbal medications continues to increase in America, the potential interaction between herbal and prescription medications necessitates the discovery of their mechanisms of action. The purpose of this study was to investigate the anxiolytic and antidepressant effects of curcumin, a compound from turmeric (Curcuma longa), and its effects on the benzodiazepine site of the γ-aminobutyric acid receptor A (GABAA) receptor. Utilizing a prospective, between-subjects group design, 55 male Sprague-Dawley rats were randomly assigned to 1 of the 5 intraperitoneally injected treatment groups: vehicle, curcumin, curcumin + flumazenil, midazolam, and midazolam + curcumin. Behavioral testing was performed using the elevated plus maze, open field test, and forced swim test. A 2-tailed multivariate analysis of variance and least significant difference post hoc tests were used for data analysis. In our models, curcumin did not demonstrate anxiolytic effects or changes in behavioral despair. An interaction of curcumin at the benzodiazepine site of the GABAA receptor was also not observed. Additional studies are recommended that examine the anxiolytic and antidepressant effects of curcumin through alternate dosing regimens, modulation of other subunits on the GABAA receptor, and interactions with other central nervous system neurotransmitter systems.

  6. Evaluation of the toxicological safety of erinacine A-enriched Hericium erinaceus in a 28-day oral feeding study in Sprague-Dawley rats.

    Science.gov (United States)

    Li, I-Chen; Chen, Yen-Lien; Lee, Li-Ya; Chen, Wan-Ping; Tsai, Yueh-Ting; Chen, Chin-Chu; Chen, Chin-Shuh

    2014-08-01

    Natural products have attained great importance as they are believed to be the new alternative medicines for conventional therapy. As numerous studies have proved the tremendous medicinal values of Hericium erinaceus, it is necessary to take into account its safety as well as its risk for the recipient. However, mushroom mycelium has an identity distinct from mushrooms, as two specific classes of compounds, hericenones and erinacines, can only be extracted from both the fruit body and the cultured mycelium, respectively. Therefore, this is the first report on the evaluation of the toxicity of H.erinaceus mycelium, enriched with 5mg/g erinacine A, by a 28-day repeated oral administration study in Sprague-Dawley rats. Three doses of 1 (Low), 2 (Mid) and 3 (High) g/kg body weight/day were selected for the study while distilled water served as control. All animals survived to the end of the study. No abnormal changes were observed in clinical signs. No adverse or test article-related differences were found in urinalysis, haematology and serum biochemistry parameters, between the treatment and control groups. No gross pathological findings and histopathological differences were seen. Therefore, the no-observed-adverse-effect level of erinacine A-enriched H.erinaceus is greater than 3g/kgbody weight/day. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. A review of the incidence and coincidence of uterine and mammary tumors in Wistar and Sprague-Dawley rats based on the RITA database and the role of prolactin.

    Science.gov (United States)

    Harleman, Johannes H; Hargreaves, Adam; Andersson, Håkan; Kirk, Sarah

    2012-08-01

    Wistar rats are frequently selected for use in carcinogenicity studies because of their advantageous survival rate, which is more favorable than other strains such as the Sprague-Dawley (SD) strain. Uterine and mammary tumors are relatively common spontaneous neoplasms of both strains. We examined the incidence and coincidence of uterine tumors and mammary tumors in control animals of both strains within the RITA database. There was a strong inverse relationship between these tumor types in Wistar rats (p 10%.

  8. Stress-dependent changes in neuroinflammatory markers observed after common laboratory stressors are not seen following acute social defeat of the Sprague Dawley rat.

    Science.gov (United States)

    Hueston, Cara M; Barnum, Christopher J; Eberle, Jaime A; Ferraioli, Frank J; Buck, Hollin M; Deak, Terrence

    2011-08-03

    Exposure to acute stress has been shown to increase the expression of pro-inflammatory cytokines in brain, blood and peripheral organs. However, the nature of the inflammatory response evoked by acute stress varies depending on the stressor used and species examined. The goal of the following series of studies was to characterize the consequences of social defeat in the Sprague Dawley (SD) rat using three different social defeat paradigms. In Experiments 1 and 2, adult male SD rats were exposed to a typical acute resident-intruder paradigm of social defeat (60 min) by placement into the home cage of a larger, aggressive Long Evans rat and brain tissue was collected at multiple time points for analysis of IL-1β protein and gene expression changes in the PVN, BNST and adrenal glands. In subsequent experiments, rats were exposed to once daily social defeat for 7 or 21 days (Experiment 3) or housed continuously with an aggressive partner (separated by a partition) for 7 days (Experiment 4) to assess the impact of chronic social stress on inflammatory measures. Despite the fact that social defeat produced a comparable corticosterone response as other stressors (restraint, forced swim and footshock; Experiment 5), acute social defeat did not affect inflammatory measures. A small but reliable increase in IL-1 gene expression was observed immediately after the 7th exposure to social defeat, while other inflammatory measures were unaffected. In contrast, restraint, forced swim and footshock all significantly increased IL-1 gene expression in the PVN; other inflammatory factors (IL-6, cox-2) were unaffected in this structure. These findings provide a comprehensive evaluation of stress-dependent inflammatory changes in the SD rat, raising intriguing questions regarding the features of the stress challenge that may be predictive of stress-dependent neuroinflammation. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Sub-acute Toxicity Study of Tiger Milk Mushroom Lignosus tigris Chon S. Tan Cultivar E Sclerotium in Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Shin Yee Fung

    2016-08-01

    Full Text Available Lignosus also known as Tiger Milk Mushroom, is classified in the family Polyporaceae and mainly consumed for its medicinal properties in Southeast Asia and China. The sclerotium is known as the part with medicinal value and often used by the natives to treat a variety of ailments. Lignosus tigris Chon S. Tan, one of the species of the Malaysia Tiger Milk mushroom, has recently been successfully cultivated in laboratory. Earlier studies have demonstrated the L. tigris cultivar E sclerotia exhibited beneficial biomedicinal properties. This study evaluated the potential toxicity of L. tigris E sclerotia in a 28-day sub-acute oral administration in Sprague Dawley (SD rats. L. tigris E sclerotial powder was administered orally at three different doses of 250, 500 and 1000 mg/kg to the SD rats once daily, consecutively for 28 days. Body weight of the rats was recorded and general behavior, adverse effects and mortality were observed daily throughout the experimental period. At the end of the experiment, blood hematology and biochemistry, relative organ weights and histopathological analysis were performed. Results showed that there were no mortality nor signs of toxicity throughout the 28-day sub-acute toxicity study. Oral administration of the L. tigris E sclerotial powder at daily dose up to 1000 mg/kg had no significant effects in body weight, relative organ weight, blood hematological and biochemistry, gross pathology and histopathology of the organs. L. tigris E sclerotial powder did not cause any treatment-related adverse effect in the rats at different treatment dosages up to 1000 mg/kg. As the lethal dose for the rats is above 1000 mg/kg, the no-observed-adverse-effect level (NOAEL dose is more than 1000 mg/kg.

  10. Behaviour, stress and welfare of Sprague Dawley rats (Rattus norvegicus) on diet board feeding for 24 months

    DEFF Research Database (Denmark)

    Laaksonen, Sakari; Nevalainen, Timo; Ketola, Jukka

    2017-01-01

    .2% less than their AL counterparts. The DB rats of both sexes had 19% increased cage exploration during daytime and 20% reduced grooming during night-time compared to the AL rats. The increased FCMs may indicate slight stress in DB females. The EPM results indicate there was no anxiety due to DB feeding...... at six months. The cage behaviour could point to mild chronic stress in DB rats, but the lack of effect on escape-related behaviour and agonism suggests that there were no substantial welfare problems. DB feeding did not seem to disturb the circadian rhythm. The smaller food requirements of DB females...

  11. The abdominal skin of female Sprague-Dawley rats is more sensitive than the back skin to drug-induced phototoxicity.

    Science.gov (United States)

    Kuga, Kazuhiro; Yasuno, Hironobu; Sakai, Yumi; Harada, Yumiko; Shimizu, Fumi; Miyamoto, Yumiko; Takamatsu, Yuki; Miyamoto, Makoto; Sato, Keiichiro

    2017-11-01

    In vivo phototoxicity studies are important to predict drug-induced phototoxicity in humans; however, a standard methodology has not established. To determine differences in sensitivity to drug-induced phototoxicity among various skin sites, we evaluated phototoxic reactions in the back and abdominal skin of female Sprague-Dawley rats orally dosed with phototoxic drugs (pirfenidone, 8-methoxysoraren, doxycycline, and lomefloxacin) or a non-phototoxic drug (gatifloxacin) followed by solar-simulated light irradiation comprising 18J/cm 2 ultraviolet A. Tissue reactions were evaluated by macroscopic and microscopic examination and immunohistochemistry for γ-H2AX, and tissue concentrations of pirfenidone, doxycycline, and lomefloxacin were measured by tandem mass spectrometry. In addition, the thicknesses of the skin layers at both sites were measured in drug-naïve rats. The abdominal skin showed more severe reactions to all phototoxic drugs than the back skin, whereas the minimal erythema dose in drug-naïve rats and skin concentrations of each drug were comparable between the sites. Furthermore, histopathological lesions and γ-H2AX-positive cells in the abdominal skin were detected in deeper layers than in the back skin. The stratum corneum and dermis in the abdominal skin were significantly thinner than in the back skin, indicating a difference in the depth of light penetration and potentially contributing to the site differences observed in sensitivity to phototoxicity. Gatifloxacin did not induce any phototoxic reactions at either site. In conclusion, the abdominal skin is more sensitive to drug-induced phototoxicity than the back skin and may represent a preferable site for irradiation in this rat phototoxicity model. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Blockade of AT1 type receptors for angiotensin II prevents cardiac microvascular fibrosis induced by chronic stress in Sprague-Dawley rats.

    Science.gov (United States)

    Firoozmand, Lília Taddeo; Sanches, Andrea; Damaceno-Rodrigues, Nilsa Regina; Perez, Juliana Dinéia; Aragão, Danielle Sanches; Rosa, Rodolfo Mattar; Marcondes, Fernanda Klein; Casarini, Dulce Elena; Caldini, Elia Garcia; Cunha, Tatiana Sousa

    2018-04-20

    To test the effects of chronic-stress on the cardiovascular system, the model of chronic mild unpredictable stress (CMS) has been widely used. The CMS protocol consists of the random, intermittent, and unpredictable exposure of laboratory animals to a variety of stressors, during 3 consecutive weeks. In this study, we tested the hypothesis that exposure to the CMS protocol leads to left ventricle microcirculatory remodeling that can be attenuated by angiotensin II receptor blockade. Male Sprague-Dawley rats were randomly assigned into four groups: Control, Stress, Control + losartan, and Stress + losartan (N = 6, each group, losartan: 20 mg/kg/day). The rats were euthanized 15 days after CMS exposure, and blood samples and left ventricle were collected. Rats submitted to CMS presented increased glycemia, corticosterone, noradrenaline and adrenaline concentration, and losartan reduced the concentration of the circulating amines. Cardiac angiotensin II, measured by high-performance liquid chromatography (HPLC), was significantly increased in the CMS group, and losartan treatment reduced it, while angiotensin 1-7 was significantly higher in the CMS losartan-treated group as compared with CMS. Histological analysis, verified by transmission electron microscopy, showed that rats exposed to CMS presented increased perivascular collagen and losartan effectively prevented the development of this process. Hence, CMS induced a state of microvascular disease, with increased perivascular collagen deposition, that may be the trigger for further development of cardiovascular disease. In this case, CMS fibrosis is associated with increased production of catecholamines and with a disruption of renin-angiotensin system balance, which can be prevented by angiotensin II receptor blockade.

  13. Sprague-Dawley rats display metabolism-mediated sex differences in the acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)

    International Nuclear Information System (INIS)

    Fonsart, Julien; Menet, Marie-Claude; Decleves, Xavier; Galons, Herve; Crete, Dominique; Debray, Marcel; Scherrmann, Jean-Michel; Noble, Florence

    2008-01-01

    The use of the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has been associated with unexplained deaths. Male humans and rodents are more sensitive to acute toxicity than are females, including a potentially lethal hyperthermia. MDMA is highly metabolized to five main metabolites, by the enzymes CYP1A2 and CYP2D. The major metabolite in rats, 3,4-methylenedioxyamphetamine (MDA), also causes hyperthermia. We postulated that the reported sex difference in rats is due to a sexual dimorphism(s). We therefore determined (1) the LD50 of MDMA and MDA, (2) their hyperthermic effects, (3) the activities of liver CYP1A2 and CYP2D, (4) the liver microsomal metabolism of MDMA and MDA, (5) and the plasma concentrations of MDMA and its metabolites 3 h after giving male and female Sprague-Dawley (SD) rats MDMA (5 mg.kg -1 sc). The LD50 of MDMA was 2.4-times lower in males than in females. MDMA induced greater hyperthermia (0.9 deg. C) in males. The plasma MDA concentration was 1.3-fold higher in males, as were CYP1A2 activity (twice) and N-demethylation to MDA (3.3-fold), but the plasma MDMA concentration (1.4-fold) and CYP2D activity (1.3-fold) were higher in females. These results suggest that male SD rats are more sensitive to MDMA acute toxicity than are females, probably because their CYP1A2 is more active, leading to higher N-demethylation and plasma MDA concentration. This metabolic pathway could be responsible for the lethality of MDMA, as the LD50 of MDA is the same in both sexes. These data strongly suggest that the toxicity of amphetamine-related drugs largely depends on metabolic differences

  14. Inhalation exposure to chloramine T induces DNA damage and inflammation in lung of Sprague-Dawley rats.

    Science.gov (United States)

    Shim, Ilseob; Seo, Gyun-Baek; Oh, Eunha; Lee, Mimi; Kwon, Jung-Taek; Sul, Donggeun; Lee, Byung-Woo; Yoon, Byung-Il; Kim, Pilje; Choi, Kyunghee; Kim, Hyun-Mi

    2013-01-01

    Chloramine T has been widely used as a disinfectant in many areas such as kitchens, laboratories and hospitals. It has been also used as a biocide in air fresheners and deodorants which are consumer products; however, little is known about its toxic effects by inhalation route. This study was performed to identify the subacute inhalation toxicity of chloramine T under whole-body inhalation exposure conditions. Male and female groups of rats were exposed to chloramine T at concentrations of 0.2, 0.9 and 4.0 mg/m³ for 6 hr/day, 5 days/week during 4 weeks. After 28-day repeated inhalation of chloramine T, there were dose-dependently significant DNA damage in the rat tissues evaluated and inflammation was histopathologically noted around the terminal airways of the lung in both genders. As a result of the expression of three types of antioxidant enzymes (SOD-2, GPx-1, PRX-1) in rat's lung after exposure, there was no significant change of all antioxidant enzymes in the male and female rats. The results showed that no observed adverse effect level (NOAEL) was 0.2 mg/m³ in male rats and 0.9 mg/m³ in female rats under the present experimental condition.

  15. A 90-day subchronic feeding study of genetically modified rice expressing Cry1Ab protein in Sprague-Dawley rats.

    Science.gov (United States)

    Song, Huan; He, Xiaoyun; Zou, Shiying; Zhang, Teng; Luo, Yunbo; Huang, Kunlun; Zhu, Zhen; Xu, Wentao

    2015-04-01

    Bacillus thuringiensis (Bt) transgenic rice line (mfb-MH86) expressing a synthetic cry1Ab gene can be protected against feeding damage from Lepidopteran insects, including Sesamia inferens, Chilo suppressalis, Tryporyza incertulas and Cnaphalocrocis medinalis. Rice flour from mfb-MH86 and its near-isogenic control MH86 was separately formulated into rodent diets at concentrations of 17.5, 35 and 70 % (w/w) for a 90-day feeding test with rats, and all of the diets were nutritionally balanced. In this study, the responses of rats fed diets containing mfb-MH86 were compared to those of rats fed flour from MH86. Overall health, body weight and food consumption were comparable between groups fed diets containing mfb-MH86 and MH86. Blood samples were collected prior to sacrifice and a few significant differences (p < 0.05) were observed in haematological and biochemical parameters between rats fed genetically modified (GM) and non-GM diets. However, the values of these parameters were within the normal ranges of values for rats of this age and sex, thus not considered treatment related. In addition, upon sacrifice a large number of organs were weighed, macroscopic and histopathological examinations were performed with only minor changes to report. In conclusion, these results demonstrated that no toxic effect was observed in the conditions of the experiment, based on the different parameters assessed. GM rice mfb-MH86 is as safe and nutritious as non-GM rice.

  16. Short-chain chlorinated paraffins (SCCPs) induced thyroid disruption by enhancement of hepatic thyroid hormone influx and degradation in male Sprague Dawley rats.

    Science.gov (United States)

    Gong, Yufeng; Zhang, Haijun; Geng, Ningbo; Xing, Liguo; Fan, Jingfeng; Luo, Yun; Song, Xiaoyao; Ren, Xiaoqian; Wang, Feidi; Chen, Jiping

    2018-06-01

    Short-chain chlorinated paraffins (SCCPs) are known to disturb thyroid hormone (TH) homeostasis in rodents. However, the mechanism remains to be fully characterized. In this study, male Sprague Dawley rats received SCCPs (0, 1, 10, or 100mg/kg/day) via gavage once a day for consecutive 28days. Plasma and hepatic TH concentrations, thyrocyte structure, as well as thyroid and hepatic mRNA and protein levels of genes associated with TH homeostasis were examined. Moreover, we performed molecular docking to predict interactions between constitutive androstane receptor (CAR), a key regulator in xenobiotic-induced TH metabolism, with different SCCP molecules. Exposure to SCCPs significantly decreased the circulating free thyroxine (T 4 ) and triiodothyronine (T 3 ) levels, but increased thyroid-stimulating hormone (TSH) levels by a feedback mechanism. Decreased hepatic T 4 and increased hepatic T 3 levels were also seen after 100mg/kg/day SCCPs exposure. SCCPs didn't show any significant effects on the expression of thyroid TH synthesis genes or thyrocyte structure. However, stimulation effects were observed for mRNA and protein levels of hepatic uridine diphosphoglucuronosyl transferase (UGT) 1A1 and organic anion transporter 2, suggesting an accelerated TH metabolism in rat liver. The increased cytochrome P450 2B1 but not 1A1 mRNA and protein levels indicated that the CAR signaling was activated by SCCPs exposure. According to docking analysis, SCCPs form hydrophobic interactions with CAR and the binding affinity shows dependency on chlorine content. Overall, our data showed that CAR implicated enhancement of hepatic TH influx and degradation could be the main cause for SCCPs induced TH deficiency in male rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Bioaccumulation and locomotor effects of manganese phosphate/sulfate mixture in Sprague-Dawley rats following subchronic (90 days) inhalation exposure

    International Nuclear Information System (INIS)

    Salehi, Fariba; Krewski, Daniel; Mergler, Donna; Normandin, Louise; Kennedy, Greg; Philippe, Suzanne; Zayed, Joseph

    2003-01-01

    Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline in Canada. The primary combustion products of MMT are Mn phosphate, Mn sulfate, and a Mn phosphate/Mn sulfate mixture. Concerns have been raised that the combustion products of MMT containing Mn could be neurotoxic, even at low levels of exposure. The objective of this study is to investigate exposure-response relationships for bioaccumulation and locomotor effects following subchronic inhalation exposure to a mixture of manganese phosphates/sulfate mixture. A control group and three groups of 30 male Sprague-Dawley rats were exposed in inhalation chambers for a period of 13 weeks, 5 days per week, 6 h a day. Exposure concentrations were 3000, 300, and 30 μg/m 3 . At the end of the exposure period, locomotor activity and resting time tests were conducted for 36 h using a computerized autotrack system. Rats were then euthanized by exsanguination and Mn concentrations in different tissues (liver, lung, testis, and kidney) and blood and brain (caudate putamen, globus pallidus, olfactory bulb, frontal cortex, and cerebellum) were determined by neutron activation analysis. Increased manganese concentrations were observed in blood, kidney, lung, testis, and in all brain sections in the highest exposure group. Mn in the lung and in the olfactory bulb were dose dependent. Our data indicate that the olfactory bulb accumulated more Mn than other brain regions following inhalation exposure. Locomotor activity was increased at 3000 μg/m 3 , but no difference was observed in resting time among the exposed groups. At the end of the experiment, rats exposed to 300 and 3000 μg/m 3 exhibited significantly decreased body weight in comparison with the control group. Biochemical profiles also revealed some significant differences in certain parameters, specifically alkaline phospatase, urea, and chlorate

  18. Bioaccumulation and locomotor effects of manganese phosphate/sulfate mixture in Sprague-Dawley rats following subchronic (90 days) inhalation exposure.

    Science.gov (United States)

    Salehi, Fariba; Krewski, Daniel; Mergler, Donna; Normandin, Louise; Kennedy, Greg; Philippe, Suzanne; Zayed, Joseph

    2003-09-15

    Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline in Canada. The primary combustion products of MMT are Mn phosphate, Mn sulfate, and a Mn phosphate/Mn sulfate mixture. Concerns have been raised that the combustion products of MMT containing Mn could be neurotoxic, even at low levels of exposure. The objective of this study is to investigate exposure-response relationships for bioaccumulation and locomotor effects following subchronic inhalation exposure to a mixture of manganese phosphates/sulfate mixture. A control group and three groups of 30 male Sprague-Dawley rats were exposed in inhalation chambers for a period of 13 weeks, 5 days per week, 6 h a day. Exposure concentrations were 3000, 300, and 30 microg/m(3). At the end of the exposure period, locomotor activity and resting time tests were conducted for 36 h using a computerized autotrack system. Rats were then euthanized by exsanguination and Mn concentrations in different tissues (liver, lung, testis, and kidney) and blood and brain (caudate putamen, globus pallidus, olfactory bulb, frontal cortex, and cerebellum) were determined by neutron activation analysis. Increased manganese concentrations were observed in blood, kidney, lung, testis, and in all brain sections in the highest exposure group. Mn in the lung and in the olfactory bulb were dose dependent. Our data indicate that the olfactory bulb accumulated more Mn than other brain regions following inhalation exposure. Locomotor activity was increased at 3000 microg/m(3), but no difference was observed in resting time among the exposed groups. At the end of the experiment, rats exposed to 300 and 3000 microg/m(3) exhibited significantly decreased body weight in comparison with the control group. Biochemical profiles also revealed some significant differences in certain parameters, specifically alkaline phospatase, urea, and chlorate.

  19. D-psicose, an epimer of D-fructose, favorably alters lipid metabolism in Sprague-Dawley rats.

    Science.gov (United States)

    Nagata, Yasuo; Kanasaki, Akane; Tamaru, Shizuka; Tanaka, Kazunari

    2015-04-01

    D-Psicose, a C3 epimer of D-fructose, is known to lower body weight and adipose tissue weight and affect lipid metabolism. The precise mechanism remains unknown. It has been reported that D-psicose has a short half-life and is not metabolized in the body. To determine how D-psicose modifies lipid metabolism, rats were fed diets with or without 3% D-psicose for 4 weeks. Rats were decapitated without fasting every 6 h over a period of 24 h. Changes in serum and liver lipid levels, liver enzyme activity, and gene expression were quantified in experiment 1. Rats fed D-psicose had significantly lower serum insulin and leptin levels. Liver enzyme activities involved in lipogenesis were significantly lowered by the D-psicose diet, whereas gene expression of a transcriptional modulator of fatty acid oxidation was enhanced. In experiment 2, feeding the D-psicose diet gave significantly lower body weight (389 ± 3 vs 426 ± 6 g, p vs 25.7 ± 0.4 g/day, p energy expenditure in the light period and fat oxidation in the dark period compared to rats fed the control diet, whereas carbohydrate oxidation was lower. In summary, these results indicate that the D-psicose diet decreases lipogenesis, increases fatty acid oxidation, and enhances 24 h energy expenditure, leading to d-psicose's potential for weight management.

  20. Tomato Juice Consumption Modifies the Urinary Peptide Profile in Sprague-Dawley Rats with Induced Hepatic Steatosis.

    Science.gov (United States)

    Martín-Pozuelo, Gala; González-Barrio, Rocío; Barberá, Gonzalo G; Albalat, Amaya; García-Alonso, Javier; Mullen, William; Mischak, Harald; Periago, María Jesús

    2016-10-26

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in Western countries, with a high prevalence, and has been shown to increase the risk of type 2 diabetes, cardiovascular disease (CVD), etc. Tomato products contain several natural antioxidants, including lycopene-which has displayed a preventive effect on the development of steatosis and CVD. Accordingly, the aim of the present work was to evaluate the effect of tomato juice consumption on the urinary peptide profile in rats with NAFLD induced by an atherogenic diet and to identify potential peptide biomarkers for diagnosis. Urine samples, collected weekly for four weeks, were analyzed by capillary electrophoresis (CE) coupled to a mass spectrometer (MS). A partial least squares-discriminant analysis (PLS-DA) was carried out to explore the association between differential peptides and treatments. Among the 888 peptides initially identified, a total of 55 were obtained as potential biomarkers. Rats with steatosis after tomato juice intake showed a profile intermediate between that of healthy rats and that of rats with induced hepatic steatosis. Accordingly, tomato products could be considered as a dietary strategy for the impairment of NAFLD, although further research should be carried out to develop a specific biomarkers panel for NAFLD.

  1. Salt sensitivity of renin secretion, glomerular filtration rate and blood pressure in conscious Sprague-Dawley rats

    DEFF Research Database (Denmark)

    Isaksson, G L; Stubbe, J; Hansen, Per Lyngs

    2014-01-01

    We hypothesized that in normal rats in metabolic steady state, (i) the plasma renin concentration (PRC) is log-linearly related to Na(+) intake (NaI), (ii) the concurrent changes in mean arterial pressure (MABP) and glomerular filtration rate (GFR) are negligible and (iii) the function PRC...

  2. Tomato Juice Consumption Modifies the Urinary Peptide Profile in Sprague-Dawley Rats with Induced Hepatic Steatosis

    Directory of Open Access Journals (Sweden)

    Gala Martín-Pozuelo

    2016-10-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is the most common liver disorder in Western countries, with a high prevalence, and has been shown to increase the risk of type 2 diabetes, cardiovascular disease (CVD, etc. Tomato products contain several natural antioxidants, including lycopene—which has displayed a preventive effect on the development of steatosis and CVD. Accordingly, the aim of the present work was to evaluate the effect of tomato juice consumption on the urinary peptide profile in rats with NAFLD induced by an atherogenic diet and to identify potential peptide biomarkers for diagnosis. Urine samples, collected weekly for four weeks, were analyzed by capillary electrophoresis (CE coupled to a mass spectrometer (MS. A partial least squares-discriminant analysis (PLS-DA was carried out to explore the association between differential peptides and treatments. Among the 888 peptides initially identified, a total of 55 were obtained as potential biomarkers. Rats with steatosis after tomato juice intake showed a profile intermediate between that of healthy rats and that of rats with induced hepatic steatosis. Accordingly, tomato products could be considered as a dietary strategy for the impairment of NAFLD, although further research should be carried out to develop a specific biomarkers panel for NAFLD.

  3. Bioavailability and mass balance studies of a commercial pentabromodiphenyl ether mixture in male Sprague-Dawley rats.

    Science.gov (United States)

    Huwe, Janice; Hakk, Heldur; Lorentzsen, Margaret

    2007-01-01

    Polybrominated diphenyl ethers (PBDE) are common flame retardants used in polyurethane foam, high impact polystyrene, and textiles which appear to be increasing in the environment and biota. Two PBDE congeners that are particularly prominent in environmental samples are 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and 2,2',4,4',5-pentabromodiphenyl ether (BDE-99). These two congeners are major components in penta-BDE formulations which constitute a minor percentage of the commercial PBDE market. In order to determine the bioavailability and bioconcentration potential of these PBDEs, we have conducted a feeding experiment in rats, dosing with low amounts of a commercial penta-BDE mixture for 21 days to mimic an environmental exposure. The carcasses, livers, and feces from control and dosed rats were quantitated for PBDEs by a high resolution GC-MS isotope dilution method. Between 25% and 50% of each of the dosed congeners was retained in the rats with the liver being a minor depot (commercial mixture. Conclusions from the study suggest that the tetra- to hexa-BDEs present in commercial penta-BDE formulations are largely bioavailable, that bioavailability in the rat is not dependent on the degree of bromination, and that metabolism may occur to a large extent during a chronic exposure.

  4. All-trans retinoic acid protects against arsenic-induced uterine toxicity in female Sprague-Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, A.; Chatterji, U., E-mail: urmichatterji@gmail.com

    2011-12-15

    Background and purpose: Arsenic exposure frequently leads to reproductive failures by disrupting the rat uterine histology, hormonal integrity and estrogen signaling components of the rat uterus, possibly by generating reactive oxygen species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic agent for reversing reproductive disorders. Experimental approach: Rats exposed to arsenic for 28 days were allowed to either recover naturally or were treated simultaneously with ATRA for 28 days or treatment continued up to 56 days. Hematoxylin-eosin double staining was used to evaluate changes in the uterine histology. Serum gonadotropins and estradiol were assayed by ELISA. Expression of the estrogen receptor (ER{alpha}), an estrogen responsive gene vascular endothelial growth factor (VEGF), and cell cycle regulatory proteins, cyclin D1 and CDK4, was assessed by RT-PCR, immunohistochemistry and western blot analysis. Key results: ATRA ameliorated sodium arsenite-induced decrease in circulating estradiol and gonadotropin levels in a dose- and time-dependent manner, along with recovery of luminal epithelial cells and endometrial glands. Concomitant up regulation of ER{alpha}, VEGF, cyclin D1, CDK4 and Ki-67 was also observed to be more prominent for ATRA-treated rats as compared to the rats that were allowed to recover naturally for 56 days. Conclusions and implications: Collectively, the results reveal that ATRA reverses arsenic-induced disruption of the circulating levels of gonadotropins and estradiol, and degeneration of luminal epithelial cells and endometrial glands of the rat uterus, indicating resumption of their functional status. Since structural and functional maintenance of the pubertal uterus is under the influence of estradiol, ATRA consequently up regulated the estrogen receptor and resumed cellular proliferation, possibly by an antioxidant therapeutic approach against arsenic toxicity. Highlights: Black-Right-Pointing-Pointer Arsenic

  5. Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley Rat

    Directory of Open Access Journals (Sweden)

    Roman Smidak

    2017-11-01

    Full Text Available Fragile X mental retardation protein (FMRP encoded by Fragile X mental retardation 1 (FMR1 gene is a RNA-binding regulator of mRNA translation, transport and stability with multiple targets responsible for proper synaptic function. Epigenetic silencing of FMR1 gene expression leads to the development of Fragile X syndrome (FXS that is characterized by intellectual disability and other behavioral problems including autism. In the rat FXS model, the lack of FMRP caused a deficit in hippocampal-dependent memory. However, the hippocampal changes of FMRP in aging rats are not fully elucidated. The current study addresses the changes in FMRP levels in dentate gyrus (DG from young (17 weeks and aging (22 months Sprague – Dawley rats. The aging animal group showed significant decline in spatial reference memory. Protein samples from five rats per each group were analyzed by quantitative proteomic analysis resulting in 153 significantly changed proteins. FMRP showed significant reduction in aging animals which was confirmed by immunoblotting and immunofluorescence microscopy. Furthermore, bioinformatic analysis of the differential protein dataset revealed several functionally related protein groups with individual interactions with FMRP. These include high representation of the RNA translation and processing machinery connected to FMRP and other RNA-binding regulators including CAPRIN1, the members of Pumilio (PUM and CUG-BP, Elav-like (CELF family, and YTH N(6-methyladenosine RNA-binding proteins (YTHDF. The results of the current study point to the important role of FMRP and regulation of RNA processing in the rat DG and memory decline during the aging process.

  6. Gender differences in the metabolism of 1,3-butadiene to butadiene diepoxide in Sprague-Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Thornton-Manning, J.R.; Dahl, A.R.; Bechtold, W.E. [and others

    1995-12-01

    1,3-Butadiene (BD), a gaseous compound used in the production of rubber, is a potent carcinogen in mice and a weak carcinogen in rats. The mechanism of BD-induced carcinogenicity is thought to involve genotoxic effects of its reactive epoxide metabolites butadiene monoepoxide (BDO) and butadiene diepoxide (BDO{sub 2}). Studies in our laboratory have shown that levels of the epoxides, particularly BDO{sub 2}, are greater in mice-the more sensitive species-than rats. While both epoxides are genotoxic in a number of assays, BDO{sub 2} is mutagenic in TK6 human lymphoblastoid cells at concentrations approximately 100-fold lower than BDO. Species differences in carcinogenicity of BD have posed a dilemma to investigators deciding which animal model is most appropriate for BD risk assessment.

  7. Effects of Solutol (Kolliphor) and cremophor in polyethylene glycol 400 vehicle formulations in Sprague-Dawley rats and beagle dogs.

    Science.gov (United States)

    Stokes, Alan H; Kemp, Daniel C; Faiola, Brenda; Jordan, Holly L; Merrill, Christine L; Hailey, James R; Brown, Randy E; Bailey, David W

    2013-01-01

    When conventional vehicles (eg, methylcellulose and water) impart inadequate physical, chemical, and/or biological properties for proper toxicological assessment of test article formulations, nonconventional vehicles may be considered. Often toxicity data for nonconventional vehicle formulations are limited. Studies were conducted to collect toxicity data from a rodent and a non-rodent species given 2 nonconventional vehicles, Solutol HS15/polyethylene glycol (PEG) 400 and Cremophor RH40/PEG 400, with differing formulations and dose volumes (10 mL/kg for rats; 2 or 5 mL/kg for dogs). In rats, both vehicles caused increase in kidney weights (males only) and decrease in thymic weights (males only) without concurrent microscopic findings; altered urine electrolytes, minimally decreased serum electrolytes (males only), and increased serum total cholesterol (females only) were also present. The Cremophor formulation was also associated with increased serum urea (males only) and urine phosphorus: creatinine. For rats given the Solutol formulation, both genders had decreased urine glucose parameters and males had increased urine volume. In dogs, loose/watery feces and emesis were present given either vehicle, and mucus-cell hyperplasia of the ileum was present given the Solutol formulation. Increased red blood cell mass and decreased urine volume in dogs given 30% Solutol/70% PEG 400 (5 mL/kg/d) were likely due to subclinical dehydration and hemoconcentration. For the Cremophor formulations, dose volume-dependent increased incidence of minimal subepithelial gastric hemorrhage was noted in dogs, and dogs given 5 mL/kg/d showed increased serum urea nitrogen. Overall, regardless of the formulation or dose volume, neither vehicle produced overt toxicity in either species, but the Solutol formulation produced fewer effects in rats. Generally, lower dose volumes minimized the severity and/or incidence of findings.

  8. The effects of varied extinction procedures on contingent cue-induced reinstatement in Sprague-Dawley rats.

    Science.gov (United States)

    Buffalari, Deanne M; Feltenstein, Matthew W; See, Ronald E

    2013-11-01

    Cue exposure therapy, which attempts to limit relapse by reducing reactivity to cocaine-paired cues through repeated exposures, has had limited success. The current experiments examined cocaine cue-induced anxiogenesis and investigated whether a model of cue exposure therapy would reduce reinstatement of cocaine seeking in rats with a history of cocaine self-administration. Male rats experienced daily intravenous cocaine self-administration. Rats then experienced exposure to either the self-administration context or the context plus noncontingent presentations of cocaine-paired cues. Immediately following exposure, anxiety-like behavior was measured using elevated plus maze and defensive burying tests. In a second group of rats, self-administration was followed by 7 days of exposure to the context, context + noncontingent cue exposure, lever extinction, or cue + lever extinction. All animals then underwent two contingent cue-induced reinstatement tests separated by 7 days of lever extinction. Exposure to noncontingent cocaine-paired cues in the self-administration context increased anxiety-like behavior on the defensive burying test. Animals that experienced lever + cue extinction displayed the least cocaine seeking on the first reinstatement test, and lever extinction reduced cocaine seeking below context exposure or context + noncontingent cue exposure. All animals had similar levels of cocaine seeking on the second reinstatement test. Noncontingent cue exposure causes anxiety, and noncontingent cue and context exposure are less effective at reducing contingent cue-induced reinstatement than lever or lever + cue extinction. These data indicate that active extinction of the drug-taking response may be critical for reduction of relapse proclivity in former cocaine users.

  9. Effect of autoclave devitalization on autograft incorporation and bone morphogenetic protein of tibia in Sprague-Dawley rats

    OpenAIRE

    Anak A.G.Y. Asmara; Achmad F. Kamal; Nurjati C. Siregar; Marcel Prasetyo

    2014-01-01

    Background: Heating process with autoclave is one of limb salvage modalities that are widely used. but the results are not satisfying, due to mechanical bone fragility. However, considering this treatment modality is widely accepted in terms of financial, religion and sociocultural aspects, we conducted a on study rats treated with resection and reconstruction with autoclave heating method to assess bone healing by sequential radiology, histopathologic osteoblasts count, and bone morphogeneti...

  10. Tocotrienols and Whey Protein Isolates Substantially Increase Exercise Endurance Capacity in Diet -Induced Obese Male Sprague-Dawley Rats

    Science.gov (United States)

    Aguila, Jay; McConell, Glenn K.; McAinch, Andrew J.; Mathai, Michael L.

    2016-01-01

    Background and Aims Obesity and impairments in metabolic health are associated with reductions in exercise capacity. Both whey protein isolates (WPIs) and vitamin E tocotrienols (TCTs) exert favorable effects on obesity-related metabolic parameters. This research sought to determine whether these supplements improved exercise capacity and increased glucose tolerance in diet-induced obese rats. Methods Six week old male rats (n = 35) weighing 187 ± 32g were allocated to either: Control (n = 9), TCT (n = 9), WPI (n = 8) or TCT + WPI (n = 9) and placed on a high-fat diet (40% of energy from fat) for 10 weeks. Animals received 50mg/kg body weight and 8% of total energy intake per day of TCTs and/or WPIs respectively. Food intake, body composition, glucose tolerance, insulin sensitivity, exercise capacity, skeletal muscle glycogen content and oxidative enzyme activity were determined. Results Both TCT and WPI groups ran >50% longer (2271 ± 185m and 2195 ± 265m respectively) than the Control group (1428 ± 139m) during the run to exhaustion test (Pexercise endurance (2068 ± 104m). WPIs increased the maximum in vitro activity of beta-hydroxyacyl-CoA in the soleus muscle (Pexercise endurance by 50% in sedentary, diet-induced obese rats. These positive effects of TCTs and WPIs were independent of body weight, adiposity or glucose tolerance. PMID:27058737

  11. Escitalopram Ameliorates Tau Hyperphosphorylation and Spatial Memory Deficits Induced by Protein Kinase A Activation in Sprague Dawley Rats.

    Science.gov (United States)

    Ren, Qing-Guo; Wang, Yan-Juan; Gong, Wei-Gang; Xu, Lin; Zhang, Zhi-Jun

    2015-01-01

    Here, we investigated the effect of escitalopram pretreatment on protein kinase A (PKA)-induced tau hyperphosphorylation and spatial memory deficits in rats using western blot and behavioral tests, respectively. We demonstrated that escitalopram effectively ameliorated tau hyperphosphorylation and the spatial memory deficits induced by PKA activation. We measured the total and activity-dependent Ser9-phosphorylated levels of glycogen synthase kinase (GSK)-3β in hippocampal extracts. No significant change in the total level of GSK-3β was observed between the different groups. However, compared with forskolin injection alone, pretreatment with escitalopram increased the level of Ser9-phosphorylated GSK-3β. We also demonstrated that escitalopram increased Akt phosphorylation at Ser473 (the active form of Akt). Furthermore, we identified other important kinases and phosphatases, such as protein phosphatase 2A, extracellular signal-regulated kinases 1 and 2, and MAP kinase kinase-1/2, that have previously been reported to play a crucial role in tau phosphorylation; however, we did not detect any significant change in the activation of these kinases or phosphatases in our study. We unexpectedly demonstrated that forskolin caused anxiety-like behavior in rats, and pretreatment with escitalopram did not significantly ameliorate the anxiety-like behavior induced by forskolin. These data provide the first evidence that escitalopram ameliorates forskolin-induced tau hyperphosphorylation and spatial memory impairment in rats; these effects do not occur via the anti-anxiety activity of escitalopram but may involve the Akt/GSK-3β signaling pathway.

  12. Dose-Dependent Effects of Multiple Acute Cocaine Injections on Maternal Behavior and Aggression in Sprague-Dawley Rats

    OpenAIRE

    Johns, Josephine M.; Nelson, Christina J.; Meter, Kathleen E.; Lubin, Deborah A.; Couch, C. Destine; Ayers, Andy; Walker, Cheryl H.

    1998-01-01

    Rat dams, which had no prior drug treatment, were either nontreated controls or were injected subcutaneously 4 times during a 10-day period with a single dose of 30, 15 or 7.5 mg/kg of cocaine hydrochloride HCl, or normal saline. Injections were given immediately postpartum following delivery of their final pup (PPD 1), and again on postpartum day 3 (PPD 3), postpartum day 6 (PPD 6) and postpartum day 10 (PPD 10). Dams were observed 30 min following injections for maternal behavior (MB) towar...

  13. A 5-month toxicity study of the ethanol extract of the leaves of Heliotropium indicum in Sprague Dawley rats after oral administration.

    Science.gov (United States)

    Owolabi, M A; Oribayo, O O; Ukpo, G E; Mbaka, G O; Akindehin, O E

    2015-01-01

    Heliotropium indicum Linn. (Boraginaceae) is used in Nigerian traditional medicine to treat tuberculosis with treatment lasting for 3 months; however, information on its toxicity is scarce. This study investigated the safety of the leaves of Heliotropium indicum after a 5 month oral administration. The leaves of H. indicum were dried; extracted in 70% ethanol and concentrated to dryness. Swiss mice were administered orally with single doses of the extract (0.5 to 12.0 g/kg b.wt /day); mortality was examined for up to 14 days. In another study, the plant material (0.5 to 2.0 g/kg b.wt /day) were administered daily by oral gavage to Sprague Dawley rats. Body weight was monitored weekly, hematological, biochemical and organ parameters were determined at the end of the 1st, 2nd and 5th months of extract administration. The oral administration of the ethanol extract of H. indicum caused dose-dependent mortality. The LD50 was 9.78 g/kg b.wt for the Swiss mice; no harmful effect was observed on the liver and kidney except the testes which exhibited considerable inflammatory changes at the highest dose of 2.0 g/kg b.wt./day after the 5th month treatment. No significant difference (P>0.05) was shown in the enzyme study, marginal increase occurred in some haematological parameters. The increase in body weight of the treated rats after its initial reduction was consistent and significantly different (P<0.05) from their initial body weight. Prolonged administration of the crude leaf extract of H. indicum is considered to be safe and nontoxic at the doses studied. However, there is a probability of a negative effect on the testes at a higher dose of the extract.

  14. Taurine and vitamin E supplementations have minimal effects on body composition, hepatic lipids, and blood hormone and metabolite concentrations in healthy Sprague Dawley rats

    Directory of Open Access Journals (Sweden)

    Allen PS

    2015-10-01

    Full Text Available Portia S Allen,1 Andrew W Brown,2 Michelle M Bohan Brown,3 Walter H Hsu,4 Donald C Beitz1 1Department of Animal Science, Iowa State University, Ames, IA, USA; 2Nutrition Obesity Research Center and Office of Energetics, University of Alabama at Birmingham, Birmingham, AL, USA; 3Department of Biochemistry, Biophysics, and Molecular Biology, 4Department of Biomedical Sciences, Iowa State University, Ames, IA, USA Background: As prescriptions for off-label pharmaceutical use and autonomous administration of over-the-counter nutraceuticals become mainstream, thorough assessments of these compounds are warranted. Objective: To determine the effects of gemfibrozil, rosiglitazone, metformin, taurine, and vitamin E on body composition, hepatic lipids, and metabolic hormone and blood metabolite concentrations in a healthy, outbred rat cohort. Methods: Male Sprague Dawley rats were fed a purified 10 kcal% from fat diet for 56 days and assigned to either the diet alone (control group or the diet plus oral administration of gemfibrozil (34 mg/kg, metformin (500 mg/kg, rosiglitazone (3 mg/kg, taurine (520 mg/kg, or vitamin E (200 mg/kg group. Results: Rosiglitazone administration resulted in a 56% increase in carcass adiposity, cautioning potential prescriptive off-label use. Taurine supplementation had no adverse effects on evaluated parameters. A modest but significant increase in liver triacylglycerol content was observed with vitamin E supplementation compared with control (Δ 17.2 g triacylglycerol/100 g liver lipid. Conclusion: The evaluated pharmaceuticals had effects in a healthy population similar to the reported effects in their target population, and the nutraceuticals had minimal effects on the measured physiological parameters. Keywords: thiazolidinedione, gemfibrozil, metformin, animal model

  15. The Effect of Route, Vehicle, and Divided Doses on the Pharmacokinetics of Chlorpyrifos and its Metabolite Trichloropyridinol in Neonatal Sprague-Dawley Rats

    Energy Technology Data Exchange (ETDEWEB)

    Marty, M. S.; Domoradzki, J. Y.; Hansen, S. C.; Timchalk, Chuck; Bartels, M. J.; Mattsson, Joel L.

    2007-12-01

    There is a paucity of data on neonatal systemic exposure using different dosing paradigms. Male CD (Sprague-Dawley derived) rats at postnatal day (PND) 5 were dosed with chlorpyrifos (CPF, 1 mg/kg) using different routes of exposure, vehicles, and single vs. divided doses. Blood concentrations of CPF and its primary metabolite, trichloropyridinol (TCP), were measured at multiple times through 24 h. Groups included: single gavage bolus vs. divided gavage doses in corn oil (1 vs 3 times in 24 h), single gavage bolus vs. divided gavage doses in rat milk, and subcutaneous administration in DMSO. These data were compared with lactational exposure of PND 5 pups from dams exposed to CPF in the diet at 5 mg/kg/day for four weeks or published data from dams exposed to daily gavage with CPF at 5 mg/kg/day. Maternal blood CPF levels were an order of magnitude lower from dietary exposure than gavage (1.1 vs 14.8 ng/g), and blood CPF levels in PND 5 pups that nursed dietary-exposed or gavage-exposed dams were below the limit of detection. Single gavage doses of 1 mg/kg CPF in corn oil vehicle in pups resulted in CPF blood levels of 49 ng/g, and in milk vehicle about 9 ng/g. Divided doses led to lower peak CPF levels. A bolus dose of 1 mg/kg CPF in DMSO administered sc appeared to have substantially altered pharmacokinetics from orally administered chlorpyrifos. To be meaningful for risk assessment, neonatal studies require attention to the exposure scenario, since route, vehicle, dose and frequency of administration result in different systemic exposure to the test chemical and its metabolites.

  16. The effects of gestational and chronic atrazine exposure on motor behaviors and striatal dopamine in male Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Walters, Jennifer L.; Lansdell, Theresa A.; Lookingland, Keith J.; Baker, Lisa E.

    2015-01-01

    This study sought to investigate the effects of environmentally relevant gestational followed by continued chronic exposure to the herbicide, atrazine, on motor function, cognition, and neurochemical indices of nigrostriatal dopamine (DA) activity in male rats. Dams were treated with 100 μg/kg atrazine, 10 mg/kg atrazine, or vehicle on gestational day 1 through postnatal day 21. Upon weaning, male offspring continued daily vehicle or atrazine gavage treatments for an additional six months. Subjects were tested in a series of behavioral assays, and 24 h after the last treatment, tissue samples from the striatum were analyzed for DA and 3,4-dihydroxyphenylacetic acid (DOPAC). At 10 mg/kg, this herbicide was found to produce modest disruptions in motor functioning, and at both dose levels it significantly lowered striatal DA and DOPAC concentrations. These results suggest that exposures to atrazine have the potential to disrupt nigrostriatal DA neurons and behaviors associated with motor functioning. - Highlights: • Male rats received gestational and chronic exposure to ATZ (10 mg/kg and 100 μg/kg). • ATZ altered locomotor activity and impaired motor coordination. • ATZ lowered striatal DA and DOPAC concentrations. • ATZ produced a potential anxiogenic effect. • ATZ did not impair performance in learning and memory assessments.

  17. The effects of gestational and chronic atrazine exposure on motor behaviors and striatal dopamine in male Sprague-Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Walters, Jennifer L., E-mail: Jennifer.l.walters@wmich.edu [Western Michigan University, Department of Psychology, 1903 W Michigan Ave, Kalamazoo, MI 49008-5439 (United States); Lansdell, Theresa A., E-mail: lansdel1@msu.edu [Michigan State University, Department of Pharmacology and Toxicology, 1355 Bogue Street, East Lansing, MI 48824 (United States); Lookingland, Keith J., E-mail: lookingl@msu.edu [Michigan State University, Department of Pharmacology and Toxicology, 1355 Bogue Street, East Lansing, MI 48824 (United States); Baker, Lisa E., E-mail: lisa.baker@wmich.edu [Western Michigan University, Department of Psychology, 1903 W Michigan Ave, Kalamazoo, MI 49008-5439 (United States)

    2015-12-01

    This study sought to investigate the effects of environmentally relevant gestational followed by continued chronic exposure to the herbicide, atrazine, on motor function, cognition, and neurochemical indices of nigrostriatal dopamine (DA) activity in male rats. Dams were treated with 100 μg/kg atrazine, 10 mg/kg atrazine, or vehicle on gestational day 1 through postnatal day 21. Upon weaning, male offspring continued daily vehicle or atrazine gavage treatments for an additional six months. Subjects were tested in a series of behavioral assays, and 24 h after the last treatment, tissue samples from the striatum were analyzed for DA and 3,4-dihydroxyphenylacetic acid (DOPAC). At 10 mg/kg, this herbicide was found to produce modest disruptions in motor functioning, and at both dose levels it significantly lowered striatal DA and DOPAC concentrations. These results suggest that exposures to atrazine have the potential to disrupt nigrostriatal DA neurons and behaviors associated with motor functioning. - Highlights: • Male rats received gestational and chronic exposure to ATZ (10 mg/kg and 100 μg/kg). • ATZ altered locomotor activity and impaired motor coordination. • ATZ lowered striatal DA and DOPAC concentrations. • ATZ produced a potential anxiogenic effect. • ATZ did not impair performance in learning and memory assessments.

  18. Chemopreventive Activity of Honokiol against 7, 12 - Dimethylbenz[a]anthracene-Induced Mammary Cancer in Female Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Zhenyu Wang

    2017-05-01

    Full Text Available Breast cancer is a predominant cause of death in women across the globe. Chemoprevention by using natural, dietary or synthetic products has been appearing to be a fascinating approach to combat the growing burden of breast cancer. In the current study, we intended to explore the mechanisms of chemopreventive action of honokiol against 7, 12 - dimethylbenz[a]anthracene (DMBA-induced mammary cancer in female Sprague Dawlely (SD rats. We induced mammary cancer in SD rats by administering single dose of DMBA (80 mg/kg through intra gastric route. Chemopreventive effects of honokiol (80 mg/kg, i.p. were confirmed from its ameliorating effect on the DMBA-induced anomalies such as liver marker enzymes, Phases I and II metabolizing enzymes and oxidative stress markers. Further, honokiol reversed the DMBA-induced abnormalities in inflammatory cytokines levels and serum tumor markers. Additionally, histopathological examination of mammary tissue and protein expression analysis of NF-κB revealed that honokiol is effective against DMBA-induced mammary cancer. In summary, the results of our study support the chemopreventive feature of honokiol in mammary cancer.

  19. Vendor-derived differences in injury-induced pain phenotype and pharmacology of Sprague-Dawley rats

    DEFF Research Database (Denmark)

    Kristensen, P J; Heegaard, A M; Kristensen, Sara Hestehave

    2017-01-01

    's adjuvant (CFA) hindpaw inflammation was induced in male SD rats sourced from three to four different vendors, respectively. Neuropathic hypersensitivity was evaluated over 58 days using von Frey filaments, pinprick stimulation and the hot plate test. Pharmacological sensitivity was evaluated by treatment...... with gabapentin (100 mg/kg, p.o.) or morphine (3 mg/kg, s.c.). CFA-induced hyperalgesia and sensitivity to morphine (0.3-6 mg/kg, s.c.) was measured using a digital Randall-Selitto device. In addition, paw weight gain was used as an index of peripheral oedema. RESULTS: Significant differences between the vendor...... to gabapentin varied enormously, the response to morphine was both robust and much more consistent between sub-strains. Despite a similar degree of CFA-induced hypersensitivity, the paw oedema level differed between sub-strains. Here, morphine dose-dependently alleviated the CFA-induced hypersensitivity...

  20. Raphanus sativus cv. Sango Sprout Juice Decreases Diet-Induced Obesity in Sprague Dawley Rats and Ameliorates Related Disorders.

    Directory of Open Access Journals (Sweden)

    Fabio Vivarelli

    Full Text Available Obesity is recognized as a leading global health problem, correlated with an increased risk for several chronic diseases. One strategy for weight control management includes the use of vegetables rich in bioactive compounds to counteract weight gain, improve the antioxidant status and stimulate lipid catabolism.The aim of this study was to investigate the role of Raphanus sativus Sango sprout juice (SSJ, a Brassica extraordinarily rich in anthocyanins (AC and isothiocyanates (ITCs, in a non-genetic model of obesity (high fat diet-HFD induced.Control groups were fed with HFD or regular diet (RD. After a 10-week period, animals were assigned to experimental units and treated by gavage for 28 days as follows: HFD and RD control groups (rats fed HFD or RD and treated with vehicle only and HFD-treated groups (rats fed HFD and treated with 15, 75 or 150 mg/kg b.w. of SSJ. Body weight and food consumption were recorded and serum lipid profile was measured (total cholesterol, triglycerides, and non-esterified fatty acids. Hepatic phase-I, phase-II as well as antioxidant enzymatic activities were assessed.SSJ lowered total cholesterol level, food intake and liver weight compared with HFD rodents. SSJ at medium dose proved effective in reducing body-weight (~19 g reduction. SSJ was effective in up-regulating the antioxidant enzymes catalase,quinone reductase, oxidised glutathione reductase and superoxide dismutase, which reached or exceeded RD levels, as well as the phase II metabolic enzyme UDP-glucuronosyl transferase (up to about 43%. HFD up-regulated almost every cytochrome P450 isoform tested, and a mild down-regulation to baseline was observed after SSJ intervention.This work reveals, for the first time, the antioxidant, hypolipidemic and antiobesity potential of SSJ, suggesting its use as an efficient new functional food/nutraceutical product.

  1. Raphanus sativus cv. Sango Sprout Juice Decreases Diet-Induced Obesity in Sprague Dawley Rats and Ameliorates Related Disorders.

    Science.gov (United States)

    Vivarelli, Fabio; Canistro, Donatella; Sapone, Andrea; De Nicola, Gina Rosalinda; Babot Marquillas, Clara; Iori, Renato; Antonazzo, Ippazio Cosimo; Gentilini, Fabio; Paolini, Moreno

    2016-01-01

    Obesity is recognized as a leading global health problem, correlated with an increased risk for several chronic diseases. One strategy for weight control management includes the use of vegetables rich in bioactive compounds to counteract weight gain, improve the antioxidant status and stimulate lipid catabolism. The aim of this study was to investigate the role of Raphanus sativus Sango sprout juice (SSJ), a Brassica extraordinarily rich in anthocyanins (AC) and isothiocyanates (ITCs), in a non-genetic model of obesity (high fat diet-HFD induced). Control groups were fed with HFD or regular diet (RD). After a 10-week period, animals were assigned to experimental units and treated by gavage for 28 days as follows: HFD and RD control groups (rats fed HFD or RD and treated with vehicle only) and HFD-treated groups (rats fed HFD and treated with 15, 75 or 150 mg/kg b.w. of SSJ). Body weight and food consumption were recorded and serum lipid profile was measured (total cholesterol, triglycerides, and non-esterified fatty acids). Hepatic phase-I, phase-II as well as antioxidant enzymatic activities were assessed. SSJ lowered total cholesterol level, food intake and liver weight compared with HFD rodents. SSJ at medium dose proved effective in reducing body-weight (~19 g reduction). SSJ was effective in up-regulating the antioxidant enzymes catalase, quinone reductase, oxidised glutathione reductase and superoxide dismutase, which reached or exceeded RD levels, as well as the phase II metabolic enzyme UDP-glucuronosyl transferase (up to about 43%). HFD up-regulated almost every cytochrome P450 isoform tested, and a mild down-regulation to baseline was observed after SSJ intervention. This work reveals, for the first time, the antioxidant, hypolipidemic and antiobesity potential of SSJ, suggesting its use as an efficient new functional food/nutraceutical product.

  2. Effects of anti-obesity drugs, phentermine and mahuang, on the behavioral patterns in Sprague-Dawley rat model.

    Science.gov (United States)

    Go, Ryeo-Eun; Hwang, Kyung-A; Kim, Seung-Hee; Lee, Min-Young; Kim, Cho-Won; Jeon, So-Ye; Kim, Yun-Bae; Choi, Kyung-Chul

    2014-06-01

    According to WHO global estimates from 2008, more than 1.4 billion adults were overweight and among them, over 200 million men and 300 million women were obese. Although the main treatment modalities for overweight and obese individuals remain dieting and physical exercise, the synthetic anti-obesity medications have been increasingly used due to their perceived convenience. Generally, anti-obesity medications are classified as appetite suppressants or fat absorption blockers. In the present study, we examined the adverse side-effects in respect of behavior changes of phentermine and Ephedra sinica (mahuang) that are anti-obesity drugs currently distributed to domestic consumers. Phentermine is mainly classified as an anorexing agent and mahuang a thermogenic agent. Because phentermine and mahuang are considered to display effectiveness through the regulation of nerve system, their potential influences of on behavioral changes were examined employing animal experiments. From the results of experiments testing locomotor activity through the use of treadmill, rota-rod, and open field system, phentermine and mahuang were commonly revealed to induce behavioral changes of rats by reducing a motor ability, an ability to cope with an external stimulus, and a sense of balance or by augmenting wariness or excitement. These adverse effects of phenternime and mahuang in behavioral changes need to be identified in humans and anti-obesity medications such as phentermine and mahuang should be prescribed for only obesity where it is anticipated that the benefits of the treatment outweigh their potential risks.

  3. The potential reproductive, neurobehavioral and systemic effects of soluble sodium tungstate exposure in Sprague-Dawley rats

    International Nuclear Information System (INIS)

    McInturf, S.M.; Bekkedal, M.Y.V.; Wilfong, E.; Arfsten, D.; Chapman, G.; Gunasekar, P.G.

    2011-01-01

    The debate on tungsten (W) is fostered by its continuous usage in military munitions. Reports demonstrate W solubilizes in soil and can migrate into drinking water supplies and, therefore, is a potential health risk to humans. This study evaluated the reproductive, systemic and neurobehavioral effects of sodium tungstate (NaW) in rats following 70 days of daily pre-and postnatal exposure via oral gavage to 5, 62.5 and 125 mg/kg/day of NaW through mating, gestation and weaning (PND 0-20). Daily administration of NaW produced no overt evidence of toxicity and had no apparent effect on mating success or offspring physical development. Distress vocalizations were elevated in F 1 offspring from the high dose group, whereas righting reflex showed unexpected sex differences where males demonstrated faster righting than females; however, the effects were not dose-dependent. Locomotor activity was affected in both low and high-dose groups of F 1 females. Low-dose group showed increased distance traveled, more time in ambulatory movements and less time in stereotypic behavior than controls or high dose animals. The high-dose group had more time in stereotypical movements than controls, and less time resting than controls and the lowest exposure group. Maternal retrieval was not affected by NaW exposure. Tungsten analysis showed a systemic distribution of NaW in both parents and offspring, with preferential uptake within the immune organs, including the femur, spleen and thymus. Histopathological evidence suggested no severe chronic injury or loss of function in these organs. However, the heart showed histological lesions, histiocytic inflammation from minimal to mild with cardiomyocyte degeneration and necrosis in several P 0 animals of 125 mg NaW dose group. The result of this study suggests that pre and postnatal exposure to NaW may produce subtle neurobehavioral effects in offspring related to motor activity and emotionality.

  4. Inhalation toxicology of diesel fuel obscurant aerosol in Sprague-Dawley rats. Final report, Phase 3, subchronic exposures

    Energy Technology Data Exchange (ETDEWEB)

    Lock, S.; Dalbey, W.; Schmoyer, R.; Griesemer, R.

    1984-12-01

    Inhalation exposures were performed twice per week, for 13 weeks, to determine whether there was any potential toxicity to rats of comparatively low concentrations of a condensation aerosol from diesel fuel. Changes in breathing frequency and the response of animals to a loud sharp sound (startle response) were measured in selected animals prior to the start of the exposures, at various time points during the thirteen week exposure period, and at monthly intervals during the recovery period. Assays were performed on selected animals at the end of the exposure period, and again after the two month recovery period. Endpoints included pulmonary function tests, numbers of alveolar free cells, clinical chemistry, hematology, organ weights and histopathology. No mortalities were recorded during the exposure or recovery periods. Slight toxicity occurred at these low aerosol concentrations with the loss in body weight of all treated animals during the exposure period. During the exposure period there were also some slight changes in startle reflex, however, these were apparently acute effects, and there appeared to be no permanent CNS involvement as measured by this endpoint. Immediately post-exposure, the numbers of lavaged alveolar macrophages were slightly elevated in all aerosol exposed animals. Pulmonary function tests, pulmonary gas exchange and dynamic lung tests were all apparently unaffected by these low diesel fuel aerosol exposures. Changes in tissue weights in aerosol exposed animals were minor and the few histopathological lesions were randomly scattered amongst all groups included in this study and were more attributable to the age of the animals than any specific treatment group. No significant cumulative toxicity may be attributed to these diesel fuel aerosol exposures. 14 references, 1 figure, 42 tables.

  5. Ethanol-induced conditioned taste aversion in male sprague-dawley rats: impact of age and stress.

    Science.gov (United States)

    Anderson, Rachel I; Varlinskaya, Elena I; Spear, Linda P

    2010-12-01

    Age-specific characteristics may contribute to the elevation in ethanol intake commonly reported among adolescents compared to adults. This study was designed to examine age-related differences in sensitivity to ethanol's aversive properties using a conditioned taste aversion (CTA) procedure with sucrose serving as the conditioned stimulus (CS). Given that ontogenetic differences in responsiveness to stressors have been previously reported, the role of stressor exposure on the development of CTA was also assessed. Experiment 1 examined the influence of 5 days of prior restraint stress exposure on the expression of CTA in a 2-bottle test following 1 pairing of a sucrose solution with ethanol. In Experiment 2, the effects of 7 days of social isolation on the development of CTA were observed using a 1-bottle test following multiple sucrose-ethanol pairings. This study revealed age-related differences in the development of ethanol-induced CTA. In Experiment 1, adolescents required a higher dose of ethanol than adults to demonstrate an aversion. In Experiment 2, adolescents required not only a higher ethanol dose but also more pairings of ethanol with the sucrose CS. No effects of prior stressor exposure were observed in either experiment. Together, these experiments demonstrate an adolescent-specific insensitivity to the aversive properties of ethanol that elicit CTA, a pattern not influenced by repeated restraint stress or housing in social isolation. This age-related insensitivity to the dysphoric effects of ethanol is consistent with other work from our laboratory, adding further to the evidence that adolescent rats are less susceptible to negative consequences of ethanol that may serve as cues to curb consumption. Copyright © 2010 by the Research Society on Alcoholism.

  6. Chemotherapy-induced gastrointestinal toxicity is associated with changes in serum and urine metabolome and fecal microbiota in male Sprague-Dawley rats.

    Science.gov (United States)

    Forsgård, Richard A; Marrachelli, Vannina G; Korpela, Katri; Frias, Rafael; Collado, Maria Carmen; Korpela, Riitta; Monleon, Daniel; Spillmann, Thomas; Österlund, Pia

    2017-08-01

    Chemotherapy-induced gastrointestinal toxicity (CIGT) is a complex process that involves multiple pathophysiological mechanisms. We have previously shown that commonly used chemotherapeutics 5-fluorouracil, oxaliplatin, and irinotecan damage the intestinal mucosa and increase intestinal permeability to iohexol. We hypothesized that CIGT is associated with alterations in fecal microbiota and metabolome. Our aim was to characterize these changes and examine how they relate to the severity of CIGT. A total of 48 male Sprague-Dawley rats were injected intraperitoneally either with 5-fluorouracil (150 mg/kg), oxaliplatin (15 mg/kg), or irinotecan (200 mg/kg). Body weight change was measured daily after drug administration and the animals were euthanized after 72 h. Blood, urine, and fecal samples were collected at baseline and at the end of the experiment. The changes in the composition of fecal microbiota were analyzed with 16S rRNA gene sequencing. Metabolic changes in serum and urine metabolome were measured with 1 mm proton nuclear magnetic resonance ( 1 H-NMR). Irinotecan increased the relative abundance of Fusobacteria and Proteobacteria, while 5-FU and oxaliplatin caused only minor changes in the composition of fecal microbiota. All chemotherapeutics increased the levels of serum fatty acids and N(CH 3 ) 3 moieties and decreased the levels of Krebs cycle metabolites and free amino acids. Chemotherapeutic drugs, 5-fluorouracil, oxaliplatin, and irinotecan, induce several microbial and metabolic changes which may play a role in the pathophysiology of CIGT. The observed changes in intestinal permeability, fecal microbiota, and metabolome suggest the activation of inflammatory processes.

  7. Assessment of asbestos body formation by high resolution FEG-SEM after exposure of Sprague-Dawley rats to chrysotile, crocidolite, or erionite.

    Science.gov (United States)

    Gandolfi, Nicola Bursi; Gualtieri, Alessandro F; Pollastri, Simone; Tibaldi, Eva; Belpoggi, Fiorella

    2016-04-05

    This work presents a comparative FEG-SEM study of the morphological and chemical characteristics of both asbestos bodies and fibres found in the tissues of Sprague-Dawley rats subjected to intraperitoneal or intrapleural injection of UICC chrysotile, UICC crocidolite and erionite from Jersey, Nevada (USA), with monitoring up to 3 years after exposure. Due to unequal dosing based on number of fibres per mass for chrysotile with respect to crocidolite and erionite, excessive fibre burden and fibre aggregation during injection that especially for chrysotile would likely not represent what humans would be exposed to, caution must be taken in extrapolating our results based on instillation in experimental animals to human inhalation. Notwithstanding, the results of this study may help to better understand the mechanism of formation of asbestos bodies. For chrysotile and crocidolite, asbestos bodies are systematically formed on long asbestos fibres. The number of coated fibres is only 3.3% in chrysotile inoculated tissues. In UICC crocidolite, Mg, Si, and Fe are associated with the fibres whereas Fe, P and Ca are associated with the coating. Even for crocidolite, most of the observed fibres are uncoated as coated fibres are about 5.7%. Asbestos bodies do not form on erionite fibres. The crystal habit, crystallinity and chemistry of all fibre species do not change with contact time, with the exception of chrysotile which shows signs of leaching of Mg. A model for the formation of asbestos bodies from mineral fibres is postulated. Because the three fibre species show limited signs of dissolution in the tissue, they cannot act as source of elements (primarily Fe, P and Ca) promoting nucleation and growth of asbestos bodies. Hence, the limited number of coated fibres should be due to the lack of nutrients or organic nature. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. The Ramazzini Institute 13-week pilot study on glyphosate and Roundup administered at human-equivalent dose to Sprague Dawley rats: effects on the microbiome.

    Science.gov (United States)

    Mao, Qixing; Manservisi, Fabiana; Panzacchi, Simona; Mandrioli, Daniele; Menghetti, Ilaria; Vornoli, Andrea; Bua, Luciano; Falcioni, Laura; Lesseur, Corina; Chen, Jia; Belpoggi, Fiorella; Hu, Jianzhong

    2018-05-29

    Glyphosate-based herbicides (GBHs) are broad-spectrum herbicides that act on the shikimate pathway in bacteria, fungi, and plants. The possible effects of GBHs on human health are the subject of an intense public debate for both its potential carcinogenic and non-carcinogenic effects, including its effects on microbiome. The present pilot study examines whether exposure to GBHs at doses of glyphosate considered to be "safe" (the US Acceptable Daily Intake - ADI - of 1.75 mg/kg bw/day), starting from in utero, may modify the composition of gut microbiome in Sprague Dawley (SD) rats. Glyphosate alone and Roundup, a commercial brand of GBHs, were administered in drinking water at doses comparable to the US glyphosate ADI (1.75 mg/kg bw/day) to F0 dams starting from the gestational day (GD) 6 up to postnatal day (PND) 125. Animal feces were collected at multiple time points from both F0 dams and F1 pups. The gut microbiota of 433 fecal samples were profiled at V3-V4 region of 16S ribosomal RNA gene and further taxonomically assigned and assessed for diversity analysis. We tested the effect of exposure on overall microbiome diversity using PERMANOVA and on individual taxa by LEfSe analysis. Microbiome profiling revealed that low-dose exposure to Roundup and glyphosate resulted in significant and distinctive changes in overall bacterial composition in F1 pups only. Specifically, at PND31, corresponding to pre-pubertal age in humans, relative abundance for Bacteriodetes (Prevotella) was increased while the Firmicutes (Lactobacillus) was reduced in both Roundup and glyphosate exposed F1 pups compared to controls. This study provides initial evidence that exposures to commonly used GBHs, at doses considered safe, are capable of modifying the gut microbiota in early development, particularly before the onset of puberty. These findings warrant future studies on potential health effects of GBHs in early development such as childhood.

  9. Gestational hypoxia disrupts the neonatal leptin surge and programs hyperphagia and obesity in male offspring in the Sprague-Dawley rat.

    Science.gov (United States)

    Vargas, Vladimir E; Gurung, Sunam; Grant, Benjamin; Hyatt, Kimberly; Singleton, Krista; Myers, Sarah M; Saunders, Debra; Njoku, Charity; Towner, Rheal; Myers, Dean A

    2017-01-01

    The effect of gestational hypoxia on the neonatal leptin surge, development of hypothalamic arcuate nuclei (ARH) projections and appetite that could contribute to the programming of offspring obesity is lacking. We examined the effect of 12% O2 from gestational days 15-19 in the Sprague-Dawley rat on post-weaning appetite, fat deposition by MRI, adipose tissue cytokine expression, the neonatal leptin surge, ARH response to exogenous leptin, and αMSH projections to the paraventricular nucleus (PVN) in response to a high fat (HFD) or control diet (CD) in male offspring. Normoxia (NMX) and Hypoxia (HPX) offspring exhibited increased food intake when fed a HFD from 5-8 weeks post-birth; HPX offspring on the CD had increased food intake from weeks 5-7 vs. NMX offspring on a CD. HPX offspring on a HFD remained hyperphagic through 23 weeks. Body weight were the same between offspring from HPX vs. NMX dams from 4-12 weeks of age fed a CD or HFD. By 14-23 weeks of age, HPX offspring fed the CD or HFD as well as male NMX offspring fed the HFD were heavier vs. NMX offspring fed the CD. HPX offspring fed a CD exhibited increased abdominal adiposity (MRI) that was amplified by a HFD. HPX offspring fed a HFD exhibited the highest abdominal fat cytokine expression. HPX male offspring had higher plasma leptin from postnatal day (PN) 6 through 14 vs. NMX pups. HPX offspring exhibited increased basal c-Fos labeled cells in the ARH vs. NMX pups on PN16. Leptin increased c-Fos staining in the ARH in NMX but not HPX offspring at PN16. HPX offspring had fewer αMSH fibers in the PVN vs. NMX offspring on PN16. In conclusion, gestational hypoxia impacts the developing ARH resulting in hyperphagia contributing to adult obesity on a control diet and exacerbated by a HFD.

  10. Vasopressin V1a receptors are present in the carotid body and contribute to the control of breathing in male Sprague-Dawley rats.

    Science.gov (United States)

    Żera, Tymoteusz; Przybylski, Jacek; Grygorowicz, Tomasz; Kasarełło, Kaja; Podobińska, Martyna; Mirowska-Guzel, Dagmara; Cudnoch-Jędrzejewska, Agnieszka

    2018-04-01

    Vasopressin (AVP) maintains body homeostasis by regulating water balance, cardiovascular system and stress response. AVP inhibits breathing through central vasopressin 1a receptors (V1aRs). Chemoreceptors within carotid bodies (CBs) detect chemical and hormonal signals in the bloodstream and provide sensory input to respiratory and cardiovascular centers of the brainstem. In the study we investigated if CBs contain V1aRs and how the receptors are involved in the regulation of ventilation by AVP. We first immunostained CBs for V1aRs and tyrosine hydroxylase, a marker of chemoreceptor type I (glomus) cells. In urethane-anesthetized adult Sprague-Dawley male rats, we then measured hemodynamic and respiratory responses to systemic (intravenous) or local (carotid artery) administration of AVP prior and after systemic blockade of V1aRs. Immunostaining of CBs showed colocalization of V1aRs and tyrosine hydroxylase within glomus cells. Systemic administration of AVP increased mean arterial blood pressure (MABP) and decreased respiratory rate (RR) and minute ventilation (MV). Local administration of AVP increased MV and RR without significant changes in MABP or heart rate. Pretreatment with V1aR antagonist abolished responses to local and intravenous AVP administration. Our findings show that chemosensory cells within CBs express V1aRs and that local stimulation of the CB with AVP increases ventilation, which is contrary to systemic effects of AVP manifested by decreased ventilation. The responses are mediated by V1aRs, as blockade of the receptors prevents changes in ventilation. We hypothesize that excitatory effects of AVP within the CB provide a counterbalancing mechanism for the inhibitory effects of systemically acting AVP on the respiration. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Toxicity of the main electronic cigarette components, propylene glycol, glycerin, and nicotine, in Sprague-Dawley rats in a 90-day OECD inhalation study complemented by molecular endpoints.

    Science.gov (United States)

    Phillips, Blaine; Titz, Bjoern; Kogel, Ulrike; Sharma, Danilal; Leroy, Patrice; Xiang, Yang; Vuillaume, Grégory; Lebrun, Stefan; Sciuscio, Davide; Ho, Jenny; Nury, Catherine; Guedj, Emmanuel; Elamin, Ashraf; Esposito, Marco; Krishnan, Subash; Schlage, Walter K; Veljkovic, Emilija; Ivanov, Nikolai V; Martin, Florian; Peitsch, Manuel C; Hoeng, Julia; Vanscheeuwijck, Patrick

    2017-11-01

    While the toxicity of the main constituents of electronic cigarette (ECIG) liquids, nicotine, propylene glycol (PG), and vegetable glycerin (VG), has been assessed individually in separate studies, limited data on the inhalation toxicity of them is available when in mixtures. In this 90-day subchronic inhalation study, Sprague-Dawley rats were nose-only exposed to filtered air, nebulized vehicle (saline), or three concentrations of PG/VG mixtures, with and without nicotine. Standard toxicological endpoints were complemented by molecular analyses using transcriptomics, proteomics, and lipidomics. Compared with vehicle exposure, the PG/VG aerosols showed only very limited biological effects with no signs of toxicity. Addition of nicotine to the PG/VG aerosols resulted in effects in line with nicotine effects observed in previous studies, including up-regulation of xenobiotic enzymes (Cyp1a1/Fmo3) in the lung and metabolic effects, such as reduced serum lipid concentrations and expression changes of hepatic metabolic enzymes. No toxicologically relevant effects of PG/VG aerosols (up to 1.520  mg PG/L + 1.890 mg VG/L) were observed, and no adverse effects for PG/VG/nicotine were observed up to 438/544/6.6 mg/kg/day. This study demonstrates how complementary systems toxicology analyses can reveal, even in the absence of observable adverse effects, subtoxic and adaptive responses to pharmacologically active compounds such as nicotine. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    Science.gov (United States)

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

    2016-09-01

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

  13. Feeding and metabolic consequences of scheduled consumption of large, binge-type meals of high fat diet in the Sprague-Dawley rat.

    Science.gov (United States)

    Bake, T; Morgan, D G A; Mercer, J G

    2014-04-10

    Providing rats and mice with access to palatable high fat diets for a short period each day induces the consumption of substantial binge-like meals. Temporal food intake structure (assessed using the TSE PhenoMaster/LabMaster system) and metabolic outcomes (oral glucose tolerance tests [oGTTs], and dark phase glucose and insulin profiles) were examined in Sprague-Dawley rats given access to 60% high fat diet on one of 3 different feeding regimes: ad libitum access (HF), daily 2 h-scheduled access from 6 to 8 h into the dark phase (2 h-HF), and twice daily 1 h-scheduled access from both 1-2 h and 10-11 h into the dark phase (2×1 h-HF). Control diet remained available during the scheduled access period. HF rats had the highest caloric intake, body weight gain, body fat mass and plasma insulin. Both schedule-fed groups rapidly adapted their feeding behaviour to scheduled access, showing large meal/bingeing behaviour with 44% or 53% of daily calories consumed from high fat diet during the 2 h or 2×1 h scheduled feed(s), respectively. Both schedule-fed groups had an intermediate caloric intake and body fat mass compared to HF and control (CON) groups. Temporal analysis of food intake indicated that schedule-fed rats consumed large binge-type high fat meals without a habitual decrease in preceding intake on control diet, suggesting that a relative hypocaloric state was not responsible or required for driving the binge episode, and substantiating previous indications that binge eating may not be driven by hypothalamic energy balance neuropeptides. In an oGTT, both schedule-fed groups had impaired glucose tolerance with higher glucose and insulin area under the curve, similar to the response in ad libitum HF fed rats, suggesting that palatable feeding schedules represent a potential metabolic threat. Scheduled feeding on high fat diet produces similar metabolic phenotypes to mandatory (no choice) high fat feeding and may be a more realistic platform for mechanistic study

  14. The Haematological Profile Of The Sprague-Dawley Outbred Albino ...

    African Journals Online (AJOL)

    The results of the study were discussed in relation to climatic and geographical locational factors (especially temperature) as they affect the normal reference haematological values, and the relevance of haematology in model animal experimentation and biomedical research. Keywords: Haematology, Rat, Sprague-Dawley ...

  15. ENDOCANNABINOID 2-ARACHIDONOYLGLYCEROL SELF-ADMINISTRATION BY SPRAGUE-DAWLEY RATS AND STIMULATION OF IN VIVO DOPAMINE TRANSMISSION IN THE NUCLEUS ACCUMBENS SHELL

    Directory of Open Access Journals (Sweden)

    Maria Antonietta eDe Luca

    2014-10-01

    Full Text Available 2-Arachidonoylglycerol (2-AG is the most potent endogenous ligand of brain cannabinoid CB1 receptors and is synthesized on demand from 2-arachidonate-containing phosphoinositides by the action of diacyglycerol lipase in response to increased intracellular calcium. Several studies indicate that the endocannabinoid (eCB system is involved in the mechanism of reward and that diverse drugs of abuse increase brain eCB levels. In addition, eCB are self-administered (SA by squirrel monkeys, and anandamide increases nucleus accumbens (NAc shell dopamine (DA in rats. To date, there is no evidence on the reinforcing effects of 2-AG and its effects on DA transmission in rodents. In order to fill this gap, we studied intravenous 2-AG SA and monitored the effect of 2-AG on extracellular DA in the NAc shell and core via microdialysis in male Sprague-Dawley rats. Rats were implanted with jugular catheters and trained to self-administer 2-AG (25g/kg/inf iv in single daily 1h sessions for 5 weeks under initial Fixed Ratio (FR 1 schedule. The ratio was subsequently increased to FR2. Active nose-poking increased from the 6th SA session (acquisition phase but no significant increase of nose-pokes was observed after FR2. When 2-AG was substituted for vehicle (25th SA session, extinction phase, rate responding, as well as number of injections, slowly decreased. When vehicle was replaced with 2-AG, SA behavior immediately recovered (reacquisition phase. The reinforcing effects of 2-AG in SA behavior were fully blocked by the CB1 receptor inverse agonist/antagonist rimonabant (1 mg/kg ip, 30 min before SA session. In the microdialysis studies, we observed that 2-AG (0.1-1.0 mg/kg iv preferentially stimulates NAc shell as compared to the NAc core. NAc shell DA increased by about 25% over basal value at the highest doses tested (0.5 and 1.0 mg/kg iv. The results obtained suggest that the eCB system, via 2-AG, plays an important role in reward.

  16. Ethanol intake under social circumstances or alone in sprague-dawley rats: impact of age, sex, social activity, and social anxiety-like behavior.

    Science.gov (United States)

    Varlinskaya, Elena I; Truxell, Eric M; Spear, Linda P

    2015-01-01

    In human adolescents, heavy drinking is often predicted by high sociability in males and high social anxiety in females. This study assessed the impact of baseline levels of social activity and social anxiety-like behavior in group-housed adolescent and adult male and female Sprague-Dawley rats on ethanol (EtOH) intake when drinking alone or in a social group. Social activity and anxiety-like behavior initially were assessed in a modified social interaction test, followed by 6 drinking sessions that occurred every other day in animals given ad libitum food and water. Sessions consisted of 30-minute access to 10% EtOH in a "supersac" (3% sucrose + 0.1% saccharin) solution given alone as well as in groups of 5 same-sex littermates, with order of the alternating session types counterbalanced across animals. Adolescent males and adults of both sexes overall consumed more EtOH under social than alone circumstances, whereas adolescent females ingested more EtOH when alone. Highly socially active adolescent males demonstrated elevated levels of EtOH intake relative to their low and medium socially active counterparts when drinking in groups, but not when tested alone. Adolescent females with high levels of social anxiety-like behavior demonstrated the highest EtOH intake under social, but not alone circumstances. Among adults, baseline levels of social anxiety-like behavior did not contribute to individual differences in EtOH intake in either sex. The results clearly demonstrate that in adolescent rats, but not their adult counterparts, responsiveness to a social peer predicts EtOH intake in a social setting-circumstances under which drinking typically occurs in human adolescents. High levels of social activity in males and high levels of social anxiety-like behavior in females were associated with elevated social drinking, suggesting that males ingest EtOH for its socially enhancing properties, whereas females ingest EtOH for its socially anxiolytic effects. Copyright

  17. Combinatorial effects of quercetin and sex-steroids on fluid and electrolytes' (Na+, Cl-, HCO3- secretory mechanisms in the uterus of ovariectomised female Sprague-Dawley rats.

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    Huma Shahzad

    Full Text Available Dysregulation of uterine fluid environment could impair successful reproduction and this could be due to the effect of environmental estrogens. Therefore, in this study, effect of quercetin, an environmental estrogen on uterine fluid and electrolytes concentrations were investigated under sex-steroid influence. Ovariectomised adult female Sprague-Dawley rats were given 10, 50 or 100mg/kg/day quercetin subcutaneously with 17-β estradiol (E for seven days or three days E, then three days E plus progesterone (P (E+P treatment. Uterine fluid secretion rate, Na+, Cl- and HCO3- concentrations were determined by in-vivo perfusion. Following sacrifice, uteri were harvested and levels of the proteins of interest were identified by Western blotting and Realtime PCR. Distribution of these proteins in the uterus was observed by immunofluorescence. Levels of uterine cAMP were measured by enzyme-linked immunoassay (EIA. Administration of quercetin at increasing doses increased uterine fluid secretion rate, Na+, Cl- and HCO3- concentrations, but to the levels lesser than that of E. In concordant, levels of CFTR, SLC4A4, ENaC (α, β and γ, Na+/K+-ATPase, GPα/β, AC and cAMP in the uterus increased following increased in the doses of quercetin. Co-administration of quercetin with E caused uterine fluid secretion rate, Na+, Cl- and HCO3- concentrations to decrease. In concordant, uterine CFTR, SLC26A6, SLC4A4, ENaC (α, β and γ, Na+/K+-ATPase, GPα/β, AC and cAMP decreased. Greatest effects were observed following co-administration of 10mg/kg/day quercetin with E. Co-administration of quercetin with E+P caused uterine fluid Na+ and HCO3- concentrations to increase but no changes in fluid secretion rate and Cl- concentration were observed. Co-administration of high dose quercetin (100 mg/kg/day with E+P caused uterine CFTR, SLC26A6, AC, GPα/β and ENaC (α, β and γ to increase. Quercetin-induced changes in the uterine fluid secretion rate and

  18. Dose-dependent effects of cisplatin on the severity of testicular injury in Sprague Dawley rats: reactive oxygen species and endoplasmic reticulum stress

    Directory of Open Access Journals (Sweden)

    Soni KK

    2016-12-01

    Full Text Available Kiran Kumar Soni,1 Hye Kyung Kim,2 Bo Ram Choi,1 Keshab Kumar Karna,1 Jae Hyung You,1 Jai Seong Cha,1 Yu Seob Shin,1 Sung Won Lee,3 Chul Young Kim,4 Jong Kwan Park1 1Department of Urology, Institute for Medical Sciences, Chonbuk National University Medical School – Biomedical Research and Institute and Clinical Trial Center for Medical Devices, Chonbuk National University Hospital, Jeonju, 2College of Pharmacy, Kyungsung University, Busan, 3Department of Urology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University Medical School, Seoul, 4College of Pharmacy, Hanyang University, Ansan, Republic of Korea Abstract: Cisplatin (CIS is used in the treatment of cancer, but its nonspecific systemic actions lead to toxic effects on other parts of the body. This study investigated the severity of CIS toxicity by increasing its dose over a constant time period. Sprague Dawley rats were divided into five treatment groups and control group with CIS (2, 4, 6, 8, and 10 mg/kg administered intraperitoneally for 5 days. The body and organs were weighed, epididymal sperm was counted, and sperm motility and sperm apoptosis were evaluated. Blood samples were evaluated for complete blood count, reactive oxygen and nitrogen species, malondialdehyde levels, and total testosterone. The testicular tissue was examined for steroidogenic acute regulatory protein and endoplasmic reticulum stress protein. Epididymal sperm was collected for CatSper Western blot. The toxic effects of different doses of CIS on the testis and kidney were compared histologically. The weights of body, testis, epididymis, prostate, seminal vesicle, and kidney; sperm count; sperm motility; steroidogenic acute regulatory protein level; and epididymal sperm count were significantly lower in the CIS-treated groups than in the control group. In contrast, sperm apoptosis, plasma reactive oxygen and nitrogen species, and malondialdehyde, testosterone, red blood cell

  19. Effect of Exposure to 900 MHz GSM Mobile Phone Radiofrequency Radiation on Estrogen Receptor Methylation Status in Colon Cells of Male Sprague Dawley Rats

    Science.gov (United States)

    Mokarram, P.; Sheikhi, M.; Mortazavi, S.M.J.; Saeb, S.; Shokrpour, N.

    2017-01-01

    Background: Over the past several years, the rapidly increasing use of mobile phones has raised global concerns about the biological effects of exposure to radiofrequency (RF) radiation. Numerous studies have shown that exposure to electromagnetic fields (EMFs) can be associated with effects on the nervous, endocrine, immune, cardiovascular, hematopoietic and ocular systems. In spite of genetic diversity, the onset and progression of cancer can be controlled by epigenetic mechanisms such as gene promoter methylation. There are extensive studies on the epigenetic changes of the tumor suppressor genes as well as the identification of methylation biomarkers in colorectal cancer. Some studies have revealed that genetic changes can be induced by exposure to RF radiation. However, whether or not RF radiation is capable of inducing epigenetic alteration has not been clarified yet. To date, no study has been conducted on the effect of radiation on epigenetic alterations in colorectal cancer (CRC). Several studies have also shown that methylation of estrogen receptor α (ERα), MYOD, MGMT, SFRP2 and P16 play an important role in CRC. It can be hypothesized that RF exposure can be a reason for the high incidence of CRC in Iran. This study aimed to investigate whether epigenetic pattern of ERα is susceptible to RF radiation and if RF radiation can induce radioadaptive response as epigenetic changes after receiving the challenge dose (γ-ray). Material and Method: 40 male Sprague-Dawley rats were divided into 4 equal groups (Group I: exposure to RF radiation of a GSM cell phone for 4 hours and sacrificed after 24 hours; Group II: RF exposure for 4 hours, exposure to Co-60 gamma radiation (3 Gy) after 24 hours and sacrificed after 72 hrs; Group III: only 3Gy gamma radiation; Group 4: control group). DNA from colon tissues was extracted to evaluate the methylation status by methylation specific PCR. Results: Our finding showed that exposure to GSM cell phone RF radiation was

  20. Effect of Exposure to 900 MHz GSM Mobile Phone Radiofrequency Radiation on Estrogen Receptor Methylation Status in Colon Cells of Male Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Mokarram P.

    2017-03-01

    Full Text Available Background: Over the past several years, the rapidly increasing use of mobile phones has raised global concerns about the biological effects of exposure to radiofrequency (RF radiation. Numerous studies have shown that exposure to electromagnetic fields (EMFs can be associated with effects on the nervous, endocrine, immune, cardiovascular, hematopoietic and ocular systems. In spite of genetic diversity, the onset and progression of cancer can be controlled by epigenetic mechanisms such as gene promoter methylation. There are extensive studies on the epigenetic changes of the tumor suppressor genes as well as the identification of methylation biomarkers in colorectal cancer. Some studies have revealed that genetic changes can be induced by exposure to RF radiation. However, whether or not RF radiation is capable of inducing epigenetic alteration has not been clarified yet. To date, no study has been conducted on the effect of radiation on epigenetic alterations in colorectal cancer (CRC. Several studies have also shown that methylation of estrogen receptor α (ERα, MYOD, MGMT, SFRP2 and P16 play an important role in CRC. It can be hypothesized that RF exposure can be a reason for the high incidence of CRC in Iran. This study aimed to investigate whether epigenetic pattern of ERα is susceptible to RF radiation and if RF radiation can induce radioadaptive response as epigenetic changes after receiving the challenge dose (γ-ray. Material and Method: 40 male Sprague-Dawley rats were divided into 4 equal groups (Group I: exposure to RF radiation of a GSM cell phone for 4 hours and sacrificed after 24 hours; Group II: RF exposure for 4 hours, exposure to Co-60 gamma radiation (3 Gy after 24 hours and sacrificed after 72 hrs; Group III: only 3Gy gamma radiation; Group 4: control group. DNA from colon tissues was extracted to evaluate the methylation status by methylation specific PCR. Results: Our finding showed that exposure to GSM cell phone RF

  1. Conjugated Linoleic Acid Administration Induces Amnesia in Male Sprague Dawley Rats and Exacerbates Recovery from Functional Deficits Induced by a Controlled Cortical Impact Injury.

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    Rastafa I Geddes

    Full Text Available Long-chain polyunsaturated fatty acids like conjugated linoleic acids (CLA are required for normal neural development and cognitive function and have been ascribed various beneficial functions. Recently, oral CLA also has been shown to increase testosterone (T biosynthesis, which is known to diminish traumatic brain injury (TBI-induced neuropathology and reduce deficits induced by stroke in adult rats. To test the impact of CLA on cognitive recovery following a TBI, 5-6 month old male Sprague Dawley rats received a focal injury (craniectomy + controlled cortical impact (CCI; n = 17 or Sham injury (craniectomy alone; n = 12 and were injected with 25 mg/kg body weight of Clarinol® G-80 (80% CLA in safflower oil; n = 16 or saline (n = 13 every 48 h for 4 weeks. Sham surgery decreased baseline plasma progesterone (P4 by 64.2% (from 9.5 ± 3.4 ng/mL to 3.4 ± 0.5 ng/mL; p = 0.068, T by 74.6% (from 5.9 ± 1.2 ng/mL to 1.5 ± 0.3 ng/mL; p 0.05 animals by post-injury day 29, but rapidly reversed by post-injury day 1 the hypoadrenalism in Sham (11-DOC: 372.6 ± 36.6 ng/mL; corticosterone: 202.6 ± 15.6 ng/mL and CCI-injured (11-DOC: 384.2 ± 101.3 ng/mL; corticosterone: 234.6 ± 43.8 ng/mL animals. In Sham surgery animals, CLA did not alter body weight, but did markedly increase latency to find the hidden Morris Water Maze platform (40.3 ± 13.0 s compared to saline treated Sham animals (8.8 ± 1.7 s. In CCI injured animals, CLA did not alter CCI-induced body weight loss, CCI-induced cystic infarct size, or deficits in rotarod performance. However, like Sham animals, CLA injections exacerbated the latency of CCI-injured rats to find the hidden MWM platform (66.8 ± 10.6 s compared to CCI-injured rats treated with saline (30.7 ± 5.5 s, p < 0.05. These results indicate that chronic treatment of CLA at a dose of 25 mg/kg body weight in adult male rats over 1-month 1 does not reverse craniectomy- and craniectomy + CCI-induced hypogonadism, but does reverse

  2. A 90-day study of sub-chronic oral toxicity of 20 nm positively charged zinc oxide nanoparticles in Sprague Dawley rats

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    Park HS

    2014-12-01

    Full Text Available Hark-Soo Park,1 Seon-Ju Kim,1 Taek-Jin Lee,1 Geon-Yong Kim,1 EunHo Meang,1 Jeong-Sup Hong,1 Su-Hyon Kim,1 Sang-Bum Koh,1 Seung-Guk Hong,1 Yle-Shik Sun,1 Jin Seok Kang,2 Yu-Ri Kim,3 Meyoung-Kon Kim,3 Jayoung Jeong,4 Jong-Kwon Lee,4 Woo-Chan Son,5 Jae-Hak Park61General Toxicology Team, Korea Testing and Research Institute, Seoul, 2Department of Biomedical Laboratory Science, Namseoul University, Cheonan, 3Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, 4National Institute of Food and Drug Safety Evaluation, Seoul, 5Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 6Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, KoreaPurpose: The study reported here was conducted to determine the systemic oral toxicity and to find the no-observed-adverse-effect level of 20 nm positively charged zinc oxide (ZnOSM,20(+ nanoparticles in Sprague Dawley rats for 90 days.Methods: For the 90-day toxicity study, the high dose was set as 500 mg per kg of body weight (mg/kg and the middle and low dose were set to 250 mg/kg and 125 mg/kg, respectively. The rats were held for a 14-day recovery period after the last administration, to observe for the persistence or reduction of any toxic effects. A distributional study was also carried out for the systemic distribution of ZnOSM,20(+ NPs.Results: No rats died during the test period. There were no significant clinical changes due to the test article during the experimental period in functional assessment, body weight, food and water consumption, ophthalmological testing, urine analysis, necropsy findings, or organ weights, but salivation was observed immediately after administration in both sexes. The total red blood cell count was increased, and hematocrit, albumin, mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration were decreased significantly compared with

  3. Effects of Ginseng Fruit Saponins on Serotonin System in Sprague-Dawley Rats with Myocardial Infarction, Depression,and Myocardial Infarction Complicated with Depression

    Institute of Scientific and Technical Information of China (English)

    Dong-Fang He; Yan-Ping Ren; Mei-Yan Liu

    2016-01-01

    Background:Our previous studies have demonstrated that the levels of 5-hydroxytryptamine (5-HT) and 5-HT 2A receptor (5-HT2AR) in serum and platelet were associated with depression and myocardial infarction (MI),and pretreatment with ginseng fruit saponins (GFS) before MI and depression had an effect on the 5-HT system.In this study,the effects of GFS on the 5-HT system in the Sprague-Dawley (SD) rats with MI,depression,and MI + depression were evaluated.Methods:A total of eighty SD rats were allocated to four groups:MI,depression,MI + depression,and control groups (n =20 in each group).Each group included two subgroups (n =10 in each subgroup):Saline treatment subgroup and GFS treatment subgroup.The levels of5-HT,5-HT2AR,and serotonin transporter (SERT) were quantified in serum,platelet lysate,and brain tissue through the enzyme-linked immunosorbent assay method,respectively.Results:Compared with those in the saline treatment subgroups,the levels of 5-HT in serum and platelet lysate statistically significantly increased in the GFS treatment subgroups of MI,depression,and MI + depression groups (serum:all P =0.000;platelet lysate:P =0.002,0.000,0.000,respectively).However,the 5-HT levels in brain homogenate significantly decreased in the GFS treatment subgroups compared with those in the saline treatment subgroups in MI and depression groups (P =0.025 and 0.044 respectively),and no significant difference was observed between saline and GFS treatment subgroups in MI + depression group (P =0.663).Compared with that in GFS treatment subgroup of control group,the 5-HT2AR levels in the platelet lysate significantly decreased in GFS treatment subgroups of MI,depression,and MI + depression groups (all P=0.000).Compared to those in the saline treatment subgroups,the serum SERT levels significantly decreased in the GFS treatment subgroups in MI,depression,and MI + depression groups (P =0.009,0.038,and P=0.001,respectively),while the SERT levels ofplatelet lysate

  4. Differential susceptibilities of Holtzman and Sprague-Dawley rats to fetal death and placental dysfunction induced by 2,3,7,8-teterachlorodibenzo-p-dioxin (TCDD) despite the identical primary structure of the aryl hydrocarbon receptor

    International Nuclear Information System (INIS)

    Kawakami, Takashige; Ishimura, Ryuta; Nohara, Keiko; Takeda, Ken; Tohyama, Chiharu; Ohsako, Seiichiroh

    2006-01-01

    A single oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioin (TCDD) administered to pregnant Holtzman (HLZ) rats on gestational days 15 (GD15) caused placental dysfunction, resulting in fetal death (Ishimura, R., Ohsako, S., Miyabara, Y., Sakaue, M., Kawakami, T., Aoki, Y., Yonemoto, J., Tohyama, C., 2002a. Increased glycogen content and glucose transporter 3 mRNA level in the placenta of Holtzman rats after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol. Appl. Pharmacol. 178, 161-171; Ishimura, R., Ohsako, S., Kawakami, T., Sakaue, M., Aoki, Y., Tohyama, C., 2002b. Altered protein profile and possible hypoxia in the placenta of 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed rats. Toxicol. Appl. Pharmacol. 185, 197-206). In order to investigate the mechanism underlying the TCDD-induced fetal death, we compared two outbred strains of rats, namely, the HLZ and the Sprague-Dawley International Genetic Standard rats (SD-IGS), a strain with characteristics resembling those of the HLZ rats. Pregnant HLZ and SD-IGS rats were administered TCDD as a single dose by gavage on GD15, as described within the parentheses (HLZ, 0, 1.6 μg TCDD/kg; SD-IGS, 0, 2, 5, 10 μg TCDD/kg). Whereas a high incidence (14%) of fetal death was observed on GD20 in the HLZ rats, no fetal deaths occurred in the SD-IGS rats, even at the highest dose of TCDD. A histological marker of cellular abnormality at the placental junctional zone, i.e., delay in the disappearance of the glycogen cells and cysts filled with an eosinophilic material (GC-EM), which normally disappear by GD20, was observed in the HLZ rats after exposure to the lowest dose of TCDD (1.6 μg TCDD/kg), but not in the SD-IGS rats even after exposure to the highest dose of TCDD. Furthermore, maternal blood sinusoids in the labyrinth zone were constricted following exposure to TCDD in the HLZ, but not SD-IGS rats. These observations indicate that HLZ rats are more susceptible to the adverse effects of TCDD on fetal growth and

  5. Influence of a combination of two tetrachlorobiphenyl congeners (PCB 47; PCB 77) on thyroid status, choline acetyltransferase (ChAT) activity, and short- and long-term memory in 30-day-old Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Donahue, Douglas A.; Dougherty, Edward J.; Meserve, Lee A.

    2004-01-01

    The important role of thyroid hormones in growth and development, maintenance of body temperature, digestion, cardiac function, and normal brain development can be disrupted by environmental contaminants like polychlorinated biphenyls (PCB). Polychlorinated biphenyls are environmental contaminants that are widespread, persistent, lipophilic, and bioaccumulate through food webs, concentrating in adipose tissue. Placental and lactational PCB exposure of offspring causes metabolic and endocrine disruptions including hypothyroxinemia, spatial learning and memory deficits, neurochemical and neurobehavioral alterations, and reproductive problems. Previous studies in our lab using the individual congeners PCB 47 (2,2',4,4'-tetrachlorobiphenyl, ortho-substituted) and PCB 77 (3,3',4,4'-tetrachlorobiphenyl, non-ortho-substituted) have demonstrated alterations in thyroid hormone levels, alterations in brain choline acetyltransferase (ChAT) activity, and spatial learning deficits. In the present study, pregnant Sprague-Dawley rats were fed a diet with or without a mixture of PCB 47/77 at 1.25 ppm, 12.5 ppm or 25.0 ppm (w/w). Rat pups were swum in the Morris water maze four times a day on days 21-29 in order for the animals to learn the position of a submerged fixed platform. A probe test was run on day 24 (30 min after last swim) for short-term memory, and on day 29 (24 h after the last swim) for long-term memory after removal of the platform. Time spent in the quadrant previously containing the platform was recorded. Rats were decapitated on day 30, serum collected and frozen at -20 deg. ChAT activity was measured radiometrically in basal forebrain and hippocampus. All PCB-treated animals experienced a depression in both triiodothyronine (T 3 ) and thyroxine (T 4 ). The present study found that all doses of PCB depressed ChAT activity in hippocampus with no significant alteration in the basal forebrain. In PCB-treated animals, short-term memory showed a trend toward

  6. Report of final results regarding brain and heart tumors in Sprague-Dawley rats exposed from prenatal life until natural death to mobile phone radiofrequency field representative of a 1.8 GHz GSM base station environmental emission.

    Science.gov (United States)

    Falcioni, L; Bua, L; Tibaldi, E; Lauriola, M; De Angelis, L; Gnudi, F; Mandrioli, D; Manservigi, M; Manservisi, F; Manzoli, I; Menghetti, I; Montella, R; Panzacchi, S; Sgargi, D; Strollo, V; Vornoli, A; Belpoggi, F

    2018-08-01

    In 2011, IARC classified radiofrequency radiation (RFR) as possible human carcinogen (Group 2B). According to IARC, animals studies, as well as epidemiological ones, showed limited evidence of carcinogenicity. In 2016, the NTP published the first results of its long-term bioassays on near field RFR, reporting increased incidence of malignant glial tumors of the brain and heart Schwannoma in rats exposed to GSM - and CDMA - modulated cell phone RFR. The tumors observed in the NTP study are of the type similar to the ones observed in some epidemiological studies of cell phone users. The Ramazzini Institute (RI) performed a life-span carcinogenic study on Sprague-Dawley rats to evaluate the carcinogenic effects of RFR in the situation of far field, reproducing the environmental exposure to RFR generated by 1.8 GHz GSM antenna of the radio base stations of mobile phone. This is the largest long-term study ever performed in rats on the health effects of RFR, including 2448 animals. In this article, we reported the final results regarding brain and heart tumors. Male and female Sprague-Dawley rats were exposed from prenatal life until natural death to a 1.8 GHz GSM far field of 0, 5, 25, 50 V/m with a whole-body exposure for 19 h/day. A statistically significant increase in the incidence of heart Schwannomas was observed in treated male rats at the highest dose (50 V/m). Furthermore, an increase in the incidence of heart Schwann cells hyperplasia was observed in treated male and female rats at the highest dose (50 V/m), although this was not statistically significant. An increase in the incidence of malignant glial tumors was observed in treated female rats at the highest dose (50 V/m), although not statistically significant. The RI findings on far field exposure to RFR are consistent with and reinforce the results of the NTP study on near field exposure, as both reported an increase in the incidence of tumors of the brain and heart in RFR-exposed Sprague-Dawley

  7. Respiratory activity variations induced in groups of LD 12:12 synchronized Sprague-Dawley rats by a 100 dB white noise emitted at 12-h intervals.

    Science.gov (United States)

    Stupfel, M; Molin, D; Thierry, H; Busnel, M C

    1980-01-01

    A white noise is emitted during 2 h, either in the middle of the scotoperiod (activity period) or of the photoperiod (rest period), on grouped specific pathogen free (SPF) male Sprague-Dawley rats, LD 12:12 synchronized by light (L = 6 h = 150 lux). Continuous measurements of VCO2, taken as an index of respiratory activity shows: 1. a short increase both after the beginning and the end of the stimulus, with slight time length differences between young and older rats; 2. a slight (2-3%) continued increase during the photoperiod and a high decrease (13%) during the scotoperiod. These VCO2 variations obtained during and after the white noise emission correspond to measurements of activity displacement and observations of behavior performed on a small sample of rats.

  8. Differential Effect of the Dopamine D3 Agonist (±-7-Hydroxy-2-(N,N-di-n-propylamino Tetralin (7-OH-DPAT on Motor Activity between Adult Wistar and Sprague-Dawley Rats after a Neonatal Ventral Hippocampus Lesion

    Directory of Open Access Journals (Sweden)

    Sonia Guzmán-Velázquez

    2011-01-01

    Full Text Available The neonatal ventral hippocampal lesion (nVHL has been widely used as an animal model for schizophrenia. Rats with an nVHL show several delayed behavioral alterations that mimic some symptoms of schizophrenia. Sprague-Dawley (SD rats with an nVHL have a decrease in D3 receptors in limbic areas, but the expression of D3 receptors in Wistar (W rats with an nVHL is unknown. The 7-Hydroxy-2-(N,N-di-n-propylamino tetralin (7-OH-DPAT has been reported as a D3-preferring agonist. Thus, we investigated the effect of (±-7-OH-DPAT (0.25 mg/kg on the motor activity in male adult W and SD rats after an nVHL. The 7-OH-DPAT caused a decrease in locomotion of W rats with an nVHL, but it did not change the locomotion of SD rats with this lesion. Our results suggest that the differential effect of 7-OH-DPAT between W and SD rats with an nVHL could be caused by a different expression of the D3 receptors. These results may have implications for modeling interactions of genetic and environmental factors involved in schizophrenia.

  9. Erythrocyte osmotic fragility and general health status of adolescent Sprague Dawley rats supplemented with Hibiscus sabdariffa aqueous calyx extracts as neonates followed by a high-fructose diet post-weaning.

    Science.gov (United States)

    Ibrahim, K G; Lembede, B W; Chivandi, E; Erlwanger, K

    2018-02-01

    High-fructose diets (HFD) can cause oxidative damage to tissues including erythrocyte cell membranes. Hibiscus sabdariffa (HS) has protective antioxidant properties. Rats were used to investigate whether the consumption of HS by neonates would result in long-term effects on their erythrocyte osmotic fragility (EOF) and general health when later fed a high-fructose diet post-weaning through adolescence. Eighty of four-day-old Sprague Dawley rat pups were divided randomly into three treatment groups. The controls (n = 27) received distilled water at 10 ml/kg b. w, while the other groups received either 50 mg/kg (n = 28) or 500 mg/kg (n = 25) of an HS aqueous calyx extract orally till post-natal day 14. The rats in each group were weaned and divided into two subgroups; one continued on normal rat chow, and the other received fructose (20% w/v) in their drinking water for 30 days. Blood was collected in heparinised tubes and added to serially diluted (0.0-0.85%) phosphate-buffered saline to determine the EOF. Clinical markers of health status were determined with an automated chemical analyser. HS extracts did not programme metabolism in the growing rats to alter their general health and EOF in response to the HFD. © 2017 Blackwell Verlag GmbH.

  10. New insights into the toxicity of mineral fibres: A combined in situ synchrotron μ-XRD and HR-TEM study of chrysotile, crocidolite, and erionite fibres found in the tissues of Sprague-Dawley rats.

    Science.gov (United States)

    Gualtieri, Alessandro F; Bursi Gandolfi, Nicola; Pollastri, Simone; Burghammer, Manfred; Tibaldi, Eva; Belpoggi, Fiorella; Pollok, Kilian; Langenhorst, Falko; Vigliaturo, Ruggero; Dražić, Goran

    2017-05-15

    Along the line of the recent research topic aimed at understanding the in vivo activity of mineral fibres and their mechanisms of toxicity, this work describes the morpho-chemical characteristics of the mineral fibres found in the tissues of Sprague-Dawley rats subjected to intraperitoneal/intrapleural injection of UICC chrysotile, UICC crocidolite and erionite-Na from Nevada (USA). The fibres are studied with in situ synchrotron powder diffraction and high resolution transmission electron microscopy to improve our understanding of the mechanisms of toxicity of these mineral fibres. In contact with the tissues of the rats, chrysotile fibres are prone to dissolve, with leaching of Mg and production of a silica rich relict. On the other hand, crocidolite and erionite-Na fibres are stable even for very long contact times within the tissues of the rats, showing just a thin dissolution amorphous halo. These findings support the model of a lower biopersistence of chrysotile with respect to crocidolite and erionite-Na but the formation of a silica-rich fibrous residue after the pseudo-amorphization of chrysotile may justify a higher cytotoxic potential and intense inflammatory activity of chrysotile in the short term in contact with the lung tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. In vivo effects of diabetes, insulin and oleanolic acid on enzymes of glycogen metabolism in the skin of streptozotocin-induced diabetic male Sprague-Dawley rats.

    Science.gov (United States)

    Mukundwa, Andrew; Langa, Silvana O; Mukaratirwa, Samson; Masola, Bubuya

    2016-03-04

    The skin is the largest organ in the body and diabetes induces pathologic changes on the skin that affect glucose homeostasis. Changes in skin glycogen and glucose levels can mirror serum glucose levels and thus the skin might contribute to whole body glucose metabolism. This study investigated the in vivo effects of diabetes, insulin and oleanolic acid (OA) on enzymes of glycogen metabolism in skin of type 1 diabetic rats. Diabetic and non-diabetic adult male Sprague-Dawley rats were treated with a single daily dose of insulin (4 IU/kg body weight), OA (80 mg/kg body weight) and a combination of OA + insulin for 14 days. Glycogen phosphorylase (GP) expression; and GP, glycogen synthase (GS) and hexokinase activities as well glycogen levels were evaluated. The results suggest that diabetes lowers hexokinase activity, GP activity and GP expression with no change in GS activity whilst the treatments increased GP expression and the activities of hexokinase, GP and GS except for the GS activity in OA treated rats. Glycogen levels were increased slightly by diabetes as well as OA treatment. In conclusion diabetes, OA and insulin can lead to changes in GS and GP activities in skin without significantly altering the glycogen content. We suggest that the skin may contribute to whole body glucose homeostasis particularly in disease states. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Site-dependent modulating effects of conjugated fatty acids from safflower oil in a rat two-stage carcinogenesis model in female Sprague-Dawley rats.

    Science.gov (United States)

    Kimoto, N; Hirose, M; Futakuchi, M; Iwata, T; Kasai, M; Shirai, T

    2001-07-10

    Modifying effects of dietary administration of conjugated fatty acids from safflower oil (CFA-S), rich in conjugated linoleic acid, on major organs were examined in the post-initiation stage of a two-stage carcinogenesis model in female rats. Groups of 21 or 22 F344 female rats were treated sequentially with 2,2'-dihydroxy-di-n-propylnitosamine (intragastrically, i.g.), 7,12-dimethylbenz[a]anthracene (i.g.), 1,2-dimethylhydrazine (subcutaneously) and N-butyl-N-(4-hydroxybutyl)nitrosamine (in drinking water) during the first 3 weeks for initiation, and then administered diet containing 1 or 0.1% CFA-S for 33 weeks. Further groups of animals were treated with carcinogens or 1% CFA-S alone, or maintained as non-treated controls. All surviving animals were killed at week 36, and major organs were examined histopathologically for development of pre-neoplastic and neoplastic lesions. The 1 and 0.1% CFA-S treatment significantly decreased the incidence and multiplicity of mammary carcinomas, though a clear dose response was not observed. In the urinary bladder, the incidence of papillary or nodular hyperplasia but not tumors was significantly increased in the 1% CFA-S-treated group. The results indicate that low dose CFA-S may find application as a potent chemopreventor of mammary carcinogenesis.

  13. Dose response study of conjugated fatty acid derived from safflower oil on mammary and colon carcinogenesis pretreated with 7,12-dimethylbenz[a]anthracene (DMBA) and 1,2-dimethylhydrazine (DMH) in female Sprague-Dawley rats.

    Science.gov (United States)

    Cheng, Jing Lei; Futakuchi, Mitsuru; Ogawa, Kumiko; Iwata, Toshio; Kasai, Masaaki; Tokudome, Shinkan; Hirose, Masao; Shirai, Tomoyuki

    2003-07-10

    To clarify the chemopreventive effects of conjugated fatty acid derived from safflower oil (CFA-S), rich in conjugated linoleic acid (CLA), on mammary and colon carcinogenesis, 6 week old female Sprague-Dawley (SD) rats received diet containing 0.01, 0.05, 0.1, 1, or 2% CFA-S subsequent to five times subcutaneous injections of 1,2-dimethyl-hydrazine (DMH) at a dose of 40 mg/kg b.w. and a single 50 mg/kg b.w. intragastric application of 7,12-dimethylbenz[a]anthracene (DMBA) during the first 11 days. The experiment was terminated at week 36. Numbers of mammary tumors, colon aberrant crypt foci (ACF), and proliferative indices of mammary tumors, and colon epithelium were analyzed. The 1% dose was found to be optimal for suppression of carcinogenesis in both target organs, a good correlation being noted with between data for cell proliferation. These results suggest that a diet containing appropriate levels of CFA-S may be useful for prevention of mammary and colon cancer.

  14. Relevance of a Hypersaline Sodium-Rich Naturally Sparkling Mineral Water to the Protection against Metabolic Syndrome Induction in Fructose-Fed Sprague-Dawley Rats: A Biochemical, Metabolic, and Redox Approach

    Directory of Open Access Journals (Sweden)

    Cidália Dionísio Pereira

    2014-01-01

    Full Text Available The Metabolic Syndrome increases the risk for atherosclerotic cardiovascular disease and type 2 Diabetes Mellitus. Increased fructose consumption and/or mineral deficiency have been associated with Metabolic Syndrome development. This study aimed to investigate the effects of 8 weeks consumption of a hypersaline sodium-rich naturally sparkling mineral water on 10% fructose-fed Sprague-Dawley rats (Metabolic Syndrome animal model. The ingestion of the mineral water (rich in sodium bicarbonate and with higher potassium, calcium, and magnesium content than the tap water used as control reduced/prevented not only the fructose-induced increase of heart rate, plasma triacylglycerols, insulin and leptin levels, hepatic catalase activity, and organ weight to body weight ratios (for liver and both kidneys but also the decrease of hepatic glutathione peroxidase activity and oxidized glutathione content. This mineral-rich water seems to have potential to prevent Metabolic Syndrome induction by fructose. We hypothesize that its regular intake in the context of modern diets, which have a general acidic character interfering with mineral homeostasis and are poor in micronutrients, namely potassium, calcium, and magnesium, could add surplus value and attenuate imbalances, thus contributing to metabolic and redox health and, consequently, decreasing the risk for atherosclerotic cardiovascular disease.

  15. Non-acute effects of different doses of 3, 4-methylenedioxymethamphetamine on spatial memory in the Morris water maze in Sprague-Dawley male rats

    Institute of Scientific and Technical Information of China (English)

    Sara Soleimani Asl; Mohammad Hassan Farhadi; Nasser Naghdi; Samira Choopani; Alireza Samzadeh-Kermani; Mehdi Mehdizadeh

    2011-01-01

    3, 4-methylenedioxymethamphetamine (MDMA; also known as 'ecstasy') has been shown to impair learning and spatial memory in adult and neonatal rats.Many studies have focused on the acute effects of MDMA on memory.In the present study, we intraperitoneally administered MDMA (0, 5, 10, 20 mg/kg) to adult male rats to investigate the effects of different doses on rat spatial memory in the Morris water maze, body temperature, and mortality, twice a day, for 7 successive days.The results indicated that MDMA impaired spatial memory dose-dependently, with the highest dose (20 mg/kg) exerting the strongest effects.In addition, MDMA also caused hyperthermia and increased mortality in rats.

  16. General Toxicity/Reproductive Toxicity Screen of Modular Artillery Charge System (XM232) Administered in the Diet of Sprague-Dawley Rats

    National Research Council Canada - National Science Library

    Eggers, J

    1996-01-01

    .... No mortalities occurred and body weights were unaffected by treatment. Methemoglobin concentrations of high-dose rats measured after 28 days and at the conclusion of the study were significantly elevated (23-25...

  17. Role of UDP-Glucuronosyltransferase (UGT) 2B2 in Metabolism of Triiodothyronine: Effect of Microsomal Enzyme Inducers in Sprague Dawley and UGT2B2-Deficient Fischer 344 Rats

    Science.gov (United States)

    Richardson, Terrilyn A.; Klaassen, Curtis D.

    2010-01-01

    Microsomal enzyme inducers (MEI) that increase UDP-glucuronosyltransferases (UGTs) can impact thyroid hormone homeostasis in rodents. Increased glucuronidation can result in reduction of serum thyroid hormone and a concomitant increase in thyroid-stimulating hormone (TSH). UGT2B2 is thought to glucuronidate triiodothyronine (T3). The purposes of this study were to determine the role of UGT2B2 in T3 glucuronidation and whether increased T3 glucuronidation mediates the increased TSH observed after MEI treatment. Sprague Dawley (SD) and UGT2B2-deficient Fischer 344 (F344) rats were fed a control diet or diet containing pregnenolone-16α-carbonitrile (PCN; 800 ppm), 3-methylcholanthrene (3-MC; 200 ppm), or Aroclor 1254 (PCB; 100 ppm) for 7 days. Serum thyroxine (T4), T3, and TSH concentrations, hepatic androsterone/T4/T3 glucuronidation, and thyroid follicular cell proliferation were determined. In both SD and F344 rats, MEI treatments decreased serum T4, whereas serum T3 was maintained (except with PCB treatment). Hepatic T4 glucuronidation increased significantly after MEI in both rat strains. Compared with the other MEI, only PCN treatment significantly increased T3 glucuronidation (281 and 497%) in both SD and UGT2B2-deficient F344 rats, respectively, and increased both serum TSH and thyroid follicular cell proliferation. These data demonstrate an association among increases in T3 glucuronidation, TSH, and follicular cell proliferation after PCN treatment, suggesting that T3 is glucuronidated by other PCN-inducible UGTs in addition to UGT2B2. These data also suggest that PCN (rather than 3-MC or PCB) promotes thyroid tumors through excessive TSH stimulation of the thyroid gland. PMID:20421340

  18. Is a serotonergic mechanism involved in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced appetite suppression in the Sprague-Dawley rat

    Energy Technology Data Exchange (ETDEWEB)

    Rozman, K. (Kansas Univ., Kansas City, KS (USA). Dept. of Pharmacology, Toxicology and Therapeutics Gesellschaft fuer Strahlen- und Umweltforschung mbH Muenchen (GSF), Neuherberg (Germany, F.R.). Inst. fuer Toxikologie); Pfeifer, B.; Kerecsen, L.; Alper, R.H. (Kansas Univ., Kansas City, KS (USA). Dept. of Pharmacology, Toxicology and Therapeutics)

    1991-02-01

    The major cause of TCDD-induced death in rats is a progressive voluntary feed refusal which has been correlated with reduced gluconeogenesis. Since centrally administered TCDD does not cause death or decreased feed intake in rats, the ability of TCDD to suppress appetite via peripheral mechanisms acting on the central nervous system was examined in two experimental models. First, it was found that the feed intake of rats on scheduled feeding cycles was not decreased by blood transfused from rats with TCDD-induced appetite suppression (8 days after a lethal dose of TCDD, i.p.). In contrast, a similar transfusion from normal, satiated rats did reduce feed intake of recipient rats by approximately 40%, suggesting that TCDD-treated rats are not satiated but rather that they are not hunggy. In the second study tryptophan (the amino acid precursor of the neutrotransmitter serotonin) was measured in the plasma and tryptophan, serotonin, norepinephrine and dopamine in the hypothalamus as well as dopamine and its metabolites in the striatum 4, 8, and 16 days after TCDD dosage (125 {mu}g/kg, i.p.). Progressive time-dependent increases in tryptophan levels in plasma and brain were paralleled by increases in brain serotonin and 5-hydroxyindoleacetic acid (the primary metabolite of serotonin) in TCDD-treated rats. No changes were observed regarding the other biogenic amines. It is suggested based on these data and on substantial evidence from the published literature that a serotonergic mechanism may be involved in TCDD-induced feed intake reduction. (orig.).

  19. Chilean Strawberry Consumption Protects against LPS-Induced Liver Injury by Anti-Inflammatory and Antioxidant Capability in Sprague-Dawley Rats

    OpenAIRE

    Molinett, Sebastian; Nuñez, Francisca; Moya-León, María Alejandra; Zúñiga-Hernández, Jessica

    2015-01-01

    The Chilean strawberry fruit has high content of antioxidants and polyphenols. Previous studies evidenced antioxidant properties by in vitro methods. However, the antioxidant effect and its impact as functional food on animal health have not been evaluated. In this study, rats were fed with a Chilean strawberry aqueous extract (4 g/kg of animal per day) and then subjected to LPS-induced liver injury (5 mg/kg). Transaminases and histological studies revealed a reduction in liver injury in rats...

  20. Protective role of probiotic lactic acid bacteria against dietary fumonisin B1-induced toxicity and DNA-fragmentation in sprague-dawley rats.

    Science.gov (United States)

    Khalil, Ashraf A; Abou-Gabal, Ashgan E; Abdellatef, Amira A; Khalid, Ahmed E

    2015-08-18

    The genus Fusarium, especially F. verticillioides and F. proliferatum, has been found in several agricultural products worldwide, especially in maize. Regardless the occurrence of symptoms, the presence of Fusarium in maize constitutes an imminent risk due to its ability to produce fumonisins, mycotoxins with proven carcinogenic effect on rats, swine, and equines and already classified as possible carcinogens to humans. The toxicity of incremental levels of fumonisin B1 (FB1), that is, 50, 100, and 200 mg FB1/kg diet, and the role of Lactobacillus delbrueckii subsp. lactis DSM 20076 (LL) and Pediococcus acidilactici NNRL B-5627 (PA) supplementation in counteracting the FB1 effects in intoxicated rats were monitored over a period of 4 weeks. Effects on the feed intake and body weight gain were noticed. A significant (p ≤ 0.05) increase in the level of liver and kidney functions markers and DNA fragmentation was also noticed in rat groups T100 and T200. The lactic acid bacteria (LAB) supplementation could bring back the normal serum biochemical parameters in rats fed on fumonisin B1-contaminated diets (T50 and T100) compared to FB1-treated groups. In rats of high-dosage dietary groups supplemented with LAB (T200-LL and T200-PA), the supplementation reduced the serum activity levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and creatinine by 11.3, 11.9, 32, and 20%, respectively. DNA fragmentations were observed in the rat group treated with 200 mg FB1 after 3 weeks, while fragmentation was noticed in treated groups with 100 and 200 mg FB1 after 4 weeks. No DNA fragmentation was apparent in FB1-treated rats co-administered the LL or PA strain. These results suggest that in male rats consuming diets containing FB1, there is a time- and dose-dependent increase in serum enzyme activities and DNA lesions. Moreover, Lb. delbrueckii subsp. lactis (LL) and P. acidilactici (PA) strains have a protective effect

  1. Chilean Strawberry Consumption Protects against LPS-Induced Liver Injury by Anti-Inflammatory and Antioxidant Capability in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Sebastian Molinett

    2015-01-01

    Full Text Available The Chilean strawberry fruit has high content of antioxidants and polyphenols. Previous studies evidenced antioxidant properties by in vitro methods. However, the antioxidant effect and its impact as functional food on animal health have not been evaluated. In this study, rats were fed with a Chilean strawberry aqueous extract (4 g/kg of animal per day and then subjected to LPS-induced liver injury (5 mg/kg. Transaminases and histological studies revealed a reduction in liver injury in rats fed with strawberry aqueous extract compared with the control group. Additionally, white strawberry supplementation significantly reduced the serum levels and gene expression of TNF-α, IL-6, and IL-1β cytokines compared with nonsupplemented rats. The level of F2-isoprostanes and GSH/GSSG indicated a reduction in liver oxidative stress by the consumption of strawberry aqueous extract. Altogether, the evidence suggests that dietary supplementation of rats with a Chilean white strawberry aqueous extract favours the normalization of oxidative and inflammatory responses after a liver injury induced by LPS.

  2. Chilean Strawberry Consumption Protects against LPS-Induced Liver Injury by Anti-Inflammatory and Antioxidant Capability in Sprague-Dawley Rats.

    Science.gov (United States)

    Molinett, Sebastian; Nuñez, Francisca; Moya-León, María Alejandra; Zúñiga-Hernández, Jessica

    2015-01-01

    The Chilean strawberry fruit has high content of antioxidants and polyphenols. Previous studies evidenced antioxidant properties by in vitro methods. However, the antioxidant effect and its impact as functional food on animal health have not been evaluated. In this study, rats were fed with a Chilean strawberry aqueous extract (4 g/kg of animal per day) and then subjected to LPS-induced liver injury (5 mg/kg). Transaminases and histological studies revealed a reduction in liver injury in rats fed with strawberry aqueous extract compared with the control group. Additionally, white strawberry supplementation significantly reduced the serum levels and gene expression of TNF-α, IL-6, and IL-1β cytokines compared with nonsupplemented rats. The level of F2-isoprostanes and GSH/GSSG indicated a reduction in liver oxidative stress by the consumption of strawberry aqueous extract. Altogether, the evidence suggests that dietary supplementation of rats with a Chilean white strawberry aqueous extract favours the normalization of oxidative and inflammatory responses after a liver injury induced by LPS.

  3. EXPOSURE TO DIETHYL HEXYL PHTHALATE (DEHP) DELAYS PUBERTY AND REDUCES ANDROGEN-DEPENDENT TISSUE WEIGHTS IN LONG EVANS HOODED AND SPRAGUE DAWLEY MALE RATS

    Science.gov (United States)

    DEHP is a plasticizer that alters sexual differentiation in the male rat by reducing fetal Leydig cell testosterone synthesis and insl3 mRNA levels. When exposure includes the pubertal stage of life, DEHP and other phthalates delay puberty and reduce androgen-dependent tissue wei...

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

    Science.gov (United States)

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

  5. Novelty response and 50 kHz ultrasonic vocalizations: Differential prediction of locomotor and affective response to amphetamine in Sprague-Dawley rats.

    Science.gov (United States)

    Garcia, Erik J; Cain, Mary E

    2016-02-01

    Novelty and sensation seeking (NSS) predisposes humans and rats to experiment with psychostimulants. In animal models, different tests of NSS predict different phases of drug dependence. Ultrasonic vocalizations (USVs) are evoked by psychomotor stimulants and measure the affective/motivation response to stimuli, yet the role NSS has on USVs in response to amphetamine is not determined. The aim of the present study was to determine if individual differences in NSS and USVs can predict locomotor and USV response to amphetamine (0.0, 0.3, and 1.0 mg/kg) after acute and chronic exposure. Thirty male rats were tested for their response to novelty (IEN), choice to engage in novelty (NPP), and heterospecific play (H-USV). Rats were administered non-contingent amphetamine or saline for seven exposures, and USVs and locomotor activity were measured. After a 14-day rest, rats were administered a challenge dose of amphetamine. Regression analyses indicated that amphetamine dose-dependently increased locomotor activity and the NPP test negatively predicted treatment-induced locomotor activity. The H-USV test predicted treatment-induced frequency-modulated (FM) USVs, but the strength of prediction depended on IEN response. Results provide evidence that locomotor activity and FM USVs induced by amphetamine represent different behavioral responses. The prediction of amphetamine-induced FM USVs by the H-USV screen was changed by the novelty response, indicating that the affective value of amphetamine-measured by FM USVs-depends on novelty response. This provides evidence that higher novelty responders may develop a tolerance faster and may escalate intake faster.

  6. Insulin detemir attenuates food intake, body weight gain and fat mass gain in diet-induced obese Sprague-Dawley rats.

    Science.gov (United States)

    Rojas, J M; Printz, R L; Niswender, K D

    2011-07-04

    Initiation and intensification of insulin therapy commonly causes weight gain, a barrier to therapy. A contrasting body of evidence indicates that insulin functions as an adiposity negative feedback signal and reduces food intake, weight gain and adiposity via action in the central nervous system. Basal insulin analogs, detemir (Det) and glargine (Glar), have been associated with less hypoglycemia compared with neutral protamine hagedorn insulin, and Det with less weight gain, especially in patients with higher body mass index (BMI). We sought to determine whether insulin therapy per se causes body weight and fat mass gain when delivered via a clinically relevant subcutaneous (SC) route in the absence of hypoglycemia and glycosuria in non-diabetic lean and diet-induced obese rats. Rats were exposed to either a low-fat diet (LFD; 13.5% fat) or high-fat diet (HFD; 60% fat), and received Det (0.5 U kg(-1)), Glar (0.2 U kg(-1)) or vehicle (Veh) SC once daily for 4 weeks. These dosages of insulin were equipotent in rats with respect to blood-glucose concentration and did not induce hypoglycemia. As predicted by current models of energy homeostasis, neither insulin Det nor Glar therapy affected food intake and weight gain in LFD rats. Det treatment significantly attenuated food intake, body weight gain and fat mass gain relative to the Glar and Veh in high-fat fed animals, mirroring observations in humans. That neither insulin group gained excess weight, suggests weight gain with SC basal insulin therapy may not be inevitable. Our data further suggest that Det possesses a unique property to attenuate the development of obesity associated with a HFD.

  7. Absorption, distribution, metabolism, and excretion of 14C-MMB4 DMS administered intramuscularly to Sprague-Dawley rats and New Zealand White rabbits.

    Science.gov (United States)

    Lusiak, Bozena D; Kobs, Dean J; Hong, S Peter; Burback, Brian L; Johnson, Jerry D

    2013-01-01

    1,1'-Methylenebis[4-[(hydroxyimino)methyl]-pyridinium] dimethanesulfonate (MMB4 DMS) is currently under development for the treatment of chemical warfare organophosphorus nerve agent poisoning. The present study evaluates the absorption, distribution, metabolism, and excretion of (14)C-MMB4 DMS administered intramuscularly to rats and rabbits. The formulated mixture of radiolabeled and nonradiolabeled MMB4 DMS was administered as a single or 7-day repeated dose. Rat doses were 55 or 220 mg/kg (100 µCi/kg), and rabbit doses were 25 or 100 mg/kg (31.25 and 62.5 µCi/kg, respectively). Urine, bile (rats only), feces, blood, and tissues were collected for up to 72 hours. Metabolic profiling using high-performance liquid chromatography with radiodetection was performed on selected urine samples. For both animal species, the majority of the total radioactivity was excreted in the urine (74%-94%) by 72 hours after dosing with greater than 90% of the radioactivity measured in the urine within 8 to 12 hours after dosing. There were no apparent species or dose differences in the urine excretion pattern. The distribution of (14)C-MMB4 DMS-derived radioactivity was rapid and generally reached the highest concentration by the first collection time point (0.25 hours). The tissue-blood concentration ratios were highest at the injection sites and in the kidneys and gastrointestinal tract contents for both the species. Two metabolites of MMB4 DMS were detected in rat and rabbit urine; their structure was confirmed by liquid chromatography with tandem mass spectrometry as 4-pyridine aldoxime and isonicotinic acid (pyridine-4-carboxylic acid).

  8. A comprehensive approach to identify reliable reference gene candidates to investigate the link between alcoholism and endocrinology in Sprague-Dawley rats.

    Directory of Open Access Journals (Sweden)

    Faten A Taki

    Full Text Available Gender and hormonal differences are often correlated with alcohol dependence and related complications like addiction and breast cancer. Estrogen (E2 is an important sex hormone because it serves as a key protein involved in organism level signaling pathways. Alcoholism has been reported to affect estrogen receptor signaling; however, identifying the players involved in such multi-faceted syndrome is complex and requires an interdisciplinary approach. In many situations, preliminary investigations included a straight forward, yet informative biotechniques such as gene expression analyses using quantitative real time PCR (qRT-PCR. The validity of qRT-PCR-based conclusions is affected by the choice of reliable internal controls. With this in mind, we compiled a list of 15 commonly used housekeeping genes (HKGs as potential reference gene candidates in rat biological models. A comprehensive comparison among 5 statistical approaches (geNorm, dCt method, NormFinder, BestKeeper, and RefFinder was performed to identify the minimal number as well the most stable reference genes required for reliable normalization in experimental rat groups that comprised sham operated (SO, ovariectomized rats in the absence (OVX or presence of E2 (OVXE2. These rat groups were subdivided into subgroups that received alcohol in liquid diet or isocalroic control liquid diet for 12 weeks. Our results showed that U87, 5S rRNA, GAPDH, and U5a were the most reliable gene candidates for reference genes in heart and brain tissue. However, different gene stability ranking was specific for each tissue input combination. The present preliminary findings highlight the variability in reference gene rankings across different experimental conditions and analytic methods and constitute a fundamental step for gene expression assays.

  9. Safety evaluation of transgenic low-gliadin wheat in Sprague Dawley rats: An alternative to the gluten free diet with no subchronic adverse effects.

    Science.gov (United States)

    Ozuna, Carmen Victoria; Barro, Francisco

    2017-09-01

    Gluten-associated pathologies have increased in recent years and there is a greater demand for low or gluten-free products. Transgenic low-gliadin wheat lines showed low T-cell response, good bread-making properties, and excellent sensory assets. The aim of this study was to evaluate the safety of the whole-wheat flour from one transgenic low-gliadin line (named E82) in a 90-day feeding study. In this study males (n = 50) and females (n = 50) SD rats were used. They were fed with doses of 1.42, 2.83 and 5.67 g/kg/day of the transgenic E82 line, 5.67 g/kg/day of the WT and a blank group. We found that there were no significant differences in the development of animals. Biochemistry for liver and kidney function were similar for males and females of all groups. Other haematological and metabolic blood parameters, as well as organ weight did not show significant differences in the five groups of animals. In the histopathological study performed for the higher dose of transgenic E82 line, WT and blank group no abnormalities were observed. The whole-wheat flour of E82 line administered to rats at tested doses for 90 days did not have any adverse effects and there was no difference with the rats which ate WT wheat. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Hamish Alexander Fernando

    2014-11-01

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

  11. Perfluorooctanesulfonate (PFOS) Conversion from N-Ethyl-N-(2-hydroxyethyl)-perfluorooctanesulfonamide (EtFOSE) in male Sprague Dawley rats after inhalation exposure

    International Nuclear Information System (INIS)

    Chang, Sue; Mader, Brian T.; Lindstrom, Kent R.; Lange, Cleston C.; Hart, Jill A.; Kestner, Thomas A.; Schulz, Jay F.; Ehresman, David J.; Butenhoff, John L.

    2017-01-01

    Ethyl-N-(2-hydroxyethyl)-perfluorooctanesulfonamide (EtFOSE) was one of the key building blocks for many of the perfluorooctanesulfonyl-based chemistry and laboratory studies have shown that EtFOSE can metabolically degrade to perfluorooctanesulfonate (PFOS). Non-occupational contribution sources to PFOS are thought to occur in general population via diets, drinking water, air and dust. For workers, however, the exposure route was mostly airborne and the exposure source was predominantly to precursor compounds such as EtFOSE. We undertook this study to investigate how much EtFOSE was converted to PFOS in the serum for male rats after 6 h of exposure to EtFOSE vapor (whole body) at ambient temperature, which simulated a work place exposure scenario. There were no abnormal clinical observations and all rats gained weight during study. Interim tail-vein blood samples, collected up to 21 days after exposure, were analyzed for Et-FOSE and PFOS concentrations by LC-MS/MS. Upon inhalation exposure, the biotransformation of EtFOSE to PFOS in serum in the male rats was rapid and very little EtFOSE was detected in the serum within 24 h after EtFOSE exposure. The highest conversion to PFOS in serum after exposure to EtFOSE vapor appeared to occur between Day 8−14 post exposure. Considering the potential surface and fur adsorption of test compound in the whole-body exposure system, our data would support that at least 10% of the inhaled EtFOSE was biotransformed to PFOS in the serum based on the range of lower 95% CI (confidence interval) values. This information is valuable because it quantitatively translates EtFOSE exposure into serum PFOS concentration, which serves as a matrix for internal dosimetry (of PFOS exposure) that can be used as an anchor across species as well as between different exposure routes. - Highlights: • First inhalation study reported in rats that investigates the conversion of a major precursor compound (EtFOSE) to form PFOS. • Systemic

  12. Perfluorooctanesulfonate (PFOS) Conversion from N-Ethyl-N-(2-hydroxyethyl)-perfluorooctanesulfonamide (EtFOSE) in male Sprague Dawley rats after inhalation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Sue, E-mail: s.chang@mmm.com [Medical Department, 3M Company, St. Paul, MN 55144 (United States); Mader, Brian T., E-mail: bmader@mmm.com [Environmental Laboratory, 3M Company, St. Paul, MN 55144 (United States); Lindstrom, Kent R., E-mail: krlindstrom@mmm.com [Environmental Laboratory, 3M Company, St. Paul, MN 55144 (United States); Lange, Cleston C., E-mail: clange@mmm.com [Environmental Laboratory, 3M Company, St. Paul, MN 55144 (United States); Hart, Jill A., E-mail: jahart@mmm.com [Medical Department, 3M Company, St. Paul, MN 55144 (United States); Kestner, Thomas A., E-mail: takestner@mmm.com [Materials Resource Division, 3M Company, St. Paul, MN 55144 (United States); Schulz, Jay F., E-mail: jfschulz@mmm.com [Materials Resource Division, 3M Company, St. Paul, MN 55144 (United States); Ehresman, David J., E-mail: depqehr@gmail.com [Medical Department, 3M Company, St. Paul, MN 55144 (United States); Butenhoff, John L., E-mail: john.butenhoff@gmail.com [SaluTox, LLC, Lake Elmo, MN 55042 (United States)

    2017-05-15

    Ethyl-N-(2-hydroxyethyl)-perfluorooctanesulfonamide (EtFOSE) was one of the key building blocks for many of the perfluorooctanesulfonyl-based chemistry and laboratory studies have shown that EtFOSE can metabolically degrade to perfluorooctanesulfonate (PFOS). Non-occupational contribution sources to PFOS are thought to occur in general population via diets, drinking water, air and dust. For workers, however, the exposure route was mostly airborne and the exposure source was predominantly to precursor compounds such as EtFOSE. We undertook this study to investigate how much EtFOSE was converted to PFOS in the serum for male rats after 6 h of exposure to EtFOSE vapor (whole body) at ambient temperature, which simulated a work place exposure scenario. There were no abnormal clinical observations and all rats gained weight during study. Interim tail-vein blood samples, collected up to 21 days after exposure, were analyzed for Et-FOSE and PFOS concentrations by LC-MS/MS. Upon inhalation exposure, the biotransformation of EtFOSE to PFOS in serum in the male rats was rapid and very little EtFOSE was detected in the serum within 24 h after EtFOSE exposure. The highest conversion to PFOS in serum after exposure to EtFOSE vapor appeared to occur between Day 8−14 post exposure. Considering the potential surface and fur adsorption of test compound in the whole-body exposure system, our data would support that at least 10% of the inhaled EtFOSE was biotransformed to PFOS in the serum based on the range of lower 95% CI (confidence interval) values. This information is valuable because it quantitatively translates EtFOSE exposure into serum PFOS concentration, which serves as a matrix for internal dosimetry (of PFOS exposure) that can be used as an anchor across species as well as between different exposure routes. - Highlights: • First inhalation study reported in rats that investigates the conversion of a major precursor compound (EtFOSE) to form PFOS. • Systemic

  13. Sprague-Dawley rats display sex-linked differences in the pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA)

    International Nuclear Information System (INIS)

    Fonsart, Julien; Menet, Marie-Claude; Debray, Marcel; Hirt, Deborah; Noble, Florence; Scherrmann, Jean-Michel; Decleves, Xavier

    2009-01-01

    The use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has increased in recent years; it can lead to life-threatening hyperthermia and serotonin syndrome. Human and rodent males appear to be more sensitive to acute toxicity than are females. MDMA is metabolized to five main metabolites by the enzymes CYP1A2, CYP2D and COMT. Little is presently known about sex-dependent differences in the pharmacokinetics of MDMA and its metabolites. We therefore analyzed MDMA disposition in male and female rats by measuring the plasma and urine concentrations of MDMA and its metabolites using a validated LC-MS method. MDA AUC last and C max were 1.6- to 1.7-fold higher in males than in females given MDMA (5 mg/kg sc), while HMMA C max and AUC last were 3.2- and 3.5-fold higher, respectively. MDMA renal clearance was 1.26-fold higher in males, and that of MDA was 2.2-fold higher. MDMA AUC last and t 1/2 were 50% higher in females given MDMA (1 mg/kg iv). MDA C max and AUC last were 75-82% higher in males, with a 2.8-fold higher metabolic index. Finally, the AUC last of MDA was 0.73-fold lower in males given 1 mg/kg iv MDA. The volumes of distribution of MDMA and MDA at steady-state were similar in the two sexes. These data strongly suggest that differences in the N-demethylation of MDMA to MDA are major influences on the MDMA and MDA pharmacokinetics in male and female rats. Hence, males are exposed to significantly more toxic MDA, which could explain previously reported sexual dysmorphism in the acute effects and toxicity of MDMA in rats.

  14. A novel heterocyclic compound improves working memory in the radial arm maze and modulates the dopamine receptor D1R in frontal cortex of the Sprague-Dawley rat.

    Science.gov (United States)

    Hussein, Ahmed M; Aher, Yogesh D; Kalaba, Predrag; Aher, Nilima Y; Dragačević, Vladimir; Radoman, Bojana; Ilić, Marija; Leban, Johann; Beryozkina, Tetyana; Ahmed, Abdel Baset M A; Urban, Ernst; Langer, Thierry; Lubec, Gert

    2017-08-14

    A series of compounds have been shown to enhance cognitive function via the dopaminergic system and indeed the search for more active and less toxic compounds is continuing. It was therefore the aim of the study to synthetise and test a novel heterocyclic compound for cognitive enhancement in a paradigm for working memory. Specific and effective dopamine re-uptake inhibition DAT (IC50=4,1±0,8μM) made us test this compound in a radial arm maze (RAM) in the rat. CE-125 (4-((benzhydrylsulfinyl)methyl)-2-cyclopropylthiazole), was tested for dopamine (DAT), serotonin and norepinephrine re-uptake inhibition by a well-established system. The working memory index (WMI) was evaluated in male Sprague Dawley rats that were intraperitoneally injected with CE-125 (1 or 10mg/kg body weight). In order to evaluate basic neurotoxicity, the open field, elevated plus maze, rota rod studies and the forced swim test were carried out. Frontal cortex was taken at the last day of the RAM test and dopamine receptors D1R and D2R, DAT and phosphorylated DAT protein levels were determined. On the 10th day both doses were increasing the WMI as compared to the vehicle-treated group. In both, trained and treated groups, D1R levels were significantly reduced while D2R levels were unchanged. DAT levels were comparable between all groups while phosphorylated DAT levels were increased in the trained group treated with 1mg/kg body weight. CE-125 as a probably non-neurotoxic compound and specific reuptake inhibitor was shown to increase performance (WMI) and modulation of the dopaminergic system is proposed as a possible mechanism of action. Copyright © 2017. Published by Elsevier B.V.

  15. Differential effects of low-fat and high-fat diets on fed-state hepatic triacylglycerol secretion, hepatic fatty acid profiles, and DGAT-1 protein expression in obese-prone Sprague-Dawley rats.

    Science.gov (United States)

    Heden, Timothy D; Morris, E Matthew; Kearney, Monica L; Liu, Tzu-Wen; Park, Young-Min; Kanaley, Jill A; Thyfault, John P

    2014-04-01

    The purpose of this study was to compare the effects of short-term low-fat (LF) and high-fat (HF) diets on fed-state hepatic triacylglycerol (TAG) secretion, the content of proteins involved in TAG assembly and secretion, fatty acid oxidation (FAO), and the fatty acid profile of stored TAG. Using selectively bred obese-prone Sprague-Dawley rats, we directly measured fed-state hepatic TAG secretion, using Tyloxapol (a lipoprotein lipase inhibitor) and a standardized oral mixed meal (45% carbohydrate, 40% fat, 15% protein) bolus in animals fed a HF or LF diet for 2 weeks, after which the rats were maintained on their respective diet for 1 week (washout) prior to the liver being excised to measure protein content, FAO, and TAG fatty acid profiles. Hepatic DGAT-1 protein expression was ∼27% lower in HF- than in LF-fed animals (p < 0.05); the protein expression of all other molecules was similar in the 2 diets. The fed-state hepatic TAG secretion rate was ∼39% lower (p < 0.05) in HF- (4.62 ± 0.18 mmol·h(-1)) than in LF- (7.60 ± 0.57 mmol·h(-1)) fed animals. Hepatic TAG content was ∼2-fold higher (p < 0.05) in HF- (1.07 ± 0.15 nmol·g(-1) tissue) than in LF- (0.50 ± 0.16 nmol·g(-1) tissue) fed animals. In addition, the fatty acid profile of liver TAG in HF-fed animals closely resembled the diet, whereas in LF-fed animals, the fatty acid profile consisted of mostly de novo synthesized fatty acids. FAO was not altered by diet. LF and HF diets differentially alter fed-state hepatic TAG secretion, hepatic fatty acid profiles, and DGAT-1 protein expression.

  16. Disposition of 2,6-di-tert-butyl-4-nitrophenol (DBNP), a submarine atmosphere contaminant, in male Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Still, Kenneth R.; Jung, Anne E.; Ritchie, Glenn D.; Jederberg, Warren W.; Wilfong, Erin R.; Briggs, G. Bruce; Arfsten, Darryl P.

    2005-01-01

    The phenol 2,6-di-tert-butyl-4-nitrophenol (DBNP) is a contaminant found onboard submarines and is formed by the nitration of an antioxidant present in turbine lubricating oil TEP 2190. DBNP has been found on submarine interior surfaces, on eating utensils and dishes, and on the skin of submariners. DBNP exposure is a potential health concern because it is an uncoupler of mitochondrial oxidative phosphorylation. Adult male rats were dosed once by oral gavage with 15 or 40 mg/kg DBNP mixed with 14 C-DBNP in kanola oil and 0.8% v/v DMSO (n=16/group). The distribution of 14 C in major tissues was measured over time for up to 240 h post-dose. Unexpectedly, 6/16 (40%) of the rats gavaged with 40 mg/kg DBNP died within 24 h of dosing. Prostration, no auditory startle response, reduced locomotor activity, and muscular rigidity persisted in survivors for up to 8 days after dosing. For animals dosed with 15 mg/kg DBNP, radioactivity levels were significantly elevated in the following tissues 24 h after dosing: fat>>>liver>kidneys>heart>lungs>brain>striated muscle>spleen. Radioactivity levels were elevated for fat, liver, kidney, heart, and lungs of animals euthanized 144 h post-dosing and in the liver of animals euthanized 240 h post-dosing. These findings suggest that DBNP may accumulate in the body as a result of continuous or repeat exposures of short interval to DBNP

  17. Effects of early gestational all-trans retinoic acid treatment on motor skills: a longitudinal study in the offspring of Sprague-Dawley rats.

    Science.gov (United States)

    Coluccia, Addolorata; Borracci, Pietro; Belfiore, Domenico; Renna, Giuseppe; Giustino, Arcangela; Carratù, Maria Rosaria

    2008-11-01

    The purpose of the present study was to investigate the behavioral outcomes of all-trans retinoic acid (RA) treatment in the period spanning gestational day (GD) 8-10. A sublethal dose (2.5mg/kg b.w.) compatible with high neonatal survival, sufficient to supply male offspring for later behavioral testing, was used. Indeed, the mortality rate at birth was 7.8%. Reproduction parameters (body weight gain of dams during gestation, number of dams giving birth, pregnancy length, litter size at birth), offspring body weight gain and the development of their somatic characteristics (ear unfolding, auditory conduit opening, eyes opening, hair growth) were not altered by RA. Instead, the onset of righting reflex and negative geotaxis were delayed by 2 days, suggesting vestibular involvement and abnormal functioning of the cerebellum. Then, the performance of RA-treated rats on open field and rotarod/accelerod tasks was assessed from postnatal day (PND) 21 to 90. Similar to the previously investigated GD 11-13 RA treatment, the GD 8-10 RA treatment impaired the open field activity and rotarod/accelerod performance in young adult rats, thus suggesting a task-specific rather than a stage-specific effect of low-dose retinoids during brain development. The delayed appearance of these outcomes underlines the relevance of longitudinal studies to sort out specific RA-targeted neurochemical-behavioral pathways that could be labelled as having no phenotype based on standard examination at birth.

  18. A Preliminary Urinary Metabolomics Study of Sprague-Dawley Rats after Short-term Ketamine Administration by Proton Nuclear Magnetic Resonance Spectroscopy

    Directory of Open Access Journals (Sweden)

    Xiang Lu

    2016-01-01

    Full Text Available Drug abuse has become a global problem. The mass spectrometry-based metabolic consequences of ketamine administration in anesthesia and therapy have been well studied, but to the best of our knowledge, metabolomic studies of ketamine abuse based on nuclear magnetic resonance (NMR spectroscopy are still lacking. In this study, twenty Sprague–Dawley rats were randomly assigned into two groups: a control group (n = 10 and a ketamine group (n = 10. The animals in the ketamine group received intraperitoneal injections of ketamine twice daily at 12-h intervals at progressively increasing doses over a period of 9 days, while the control group received an equal volume of saline. The urine samples were collected for 24 h at days 0, 1, 3, 5, 7, and 9 for the metabolomics study. The metabolic changes in urine after short-term ketamine administration were analyzed by proton NMR coupled with multivariate statistical analysis. The results indicated that short-term ketamine exposure led to significant alterations of the metabolites in the urine of the rats. Specifically, 1,3,7-trimethyluric acid, 1,3-dimethyluric acid, acetoacetic acid, acetylglycine, creatine, sarcosine, dimethylglycine, glycine, and theobromine were significantly increased in the urine. Significant changes were also found in metabolites related to antioxidant and energy metabolism, including acetoacetic acid, succinate, 1,3,7-trimethyluric acid, 1,3-dimethyluric acid, creatine, and taurine. Our findings indicated that short-term ketamine administration leads to disorder of energy metabolism and oxidative stress. In addition, the modified metabolites identified could serve as the new biological markers and potential biological indices reflecting the underlying mechanism of ketamine abuse.

  19. Characterisation of Fecal Soap Fatty Acids, Calcium Contents, Bacterial Community and Short-Chain Fatty Acids in Sprague Dawley Rats Fed with Different sn-2 Palmitic Triacylglycerols Diets.

    Science.gov (United States)

    Wan, Jianchun; Hu, Songyou; Ni, Kefeng; Chang, Guifang; Sun, Xiangjun; Yu, Liangli

    2016-01-01

    The structure of dietary triacylglycerols is thought to influence fatty acid and calcium absorption, as well as intestinal microbiota population of the host. In the present study, we investigated the impact of palmitic acid (PA) esterified at the sn-2 position on absorption of fatty acid and calcium and composition of intestinal microorganisms in rats fed high-fat diets containing either low sn-2 PA (12.1%), medium sn-2 PA (40.4%) or high sn-2 PA (56.3%), respectively. Fecal fatty acid profiles in the soaps were measured by gas chromatography (GC), while fecal calcium concentration was detected by ICP-MS. The fecal microbial composition was assessed using a 16S rRNA high-throughput sequencing technology and fecal short-chain fatty acids were detected by ion chromatograph. Dietary supplementation with a high sn-2 PA fat significantly reduced total fecal contents of fatty acids soap and calcium compared with the medium or low sn-2 PA fat groups. Diet supplementation with sn-2 PA fat did not change the entire profile of the gut microbiota community at phylum level and the difference at genera level also were minimal in the three treatment groups. However, high sn-2 PA fat diet could potentially improve total short-chain fatty acids content in the feces, suggesting that high dietary sn-2 PA fat might have a beneficial effect on host intestinal health.

  20. A Diagnostic Approach for Rodent Progressive Cardiomyopathy and Like Lesions in Toxicology Studies up to 28 Days in the Sprague Dawley Rat (Part 2 of 2).

    Science.gov (United States)

    Hailey, James R; Maleeff, Beverly E; Thomas, Heath C; Pearse, Gail; Klapwijk, Jan C; Cristofori, Patrizia G; Berridge, Brian; Kimbrough, Carie L; Parker, George A; Morton, Daniel; Elmore, Susan; Hardisty, Jerry F; Dybdal, Noel O; Rehagen, David A; Fikes, James D; Lamb, Martin; Biddle, Kathleen; Buetow, Bernard S; Carreira, Vinicius; Nyska, Abraham; Tripathi, Niraj K; Workman, Heather C; Bienvenu, Jean-Guy; Brees, Ingrid; Turk, James R; Adler, Rick R

    2017-12-01

    To test the diagnostic approach described in part 1 of this article, 2 exercises were completed by pathologists from multiple companies/agencies. Pathologist's examination of whole slide image (WSI) heart sections from rats using personal diagnostic approaches (exercise #1) corroborated conclusions from study #1. Using the diagnostic approach described in part 1, these pathologists examined the same WSI heart sections (exercise #2) to determine whether that approach increased consistency of diagnosis of rodent progressive cardiomyopathy (PCM) lesions. In exercise #2, there was improved consistency of categorization of small borderline morphologies and mild lesions, but a decrement in consistency of categorizing minimal lesions. Exercises 1 and 2 suggest the described diagnostic approach is representative of that in use by the majority of toxicologic pathologists across companies/agencies and that application by all may improve diagnostic consistency of PCM/like lesions. Additionally, a criterion of approximately 5% heart section involvement is suggested for separating mild from moderate or greater severity. While evidence is not absolute, until further investigation shows otherwise, microscopic changes resembling PCM, but located in the epicardial and subepicardial region of the right ventricle, may be considered as part of the spectrum of PCM.

  1. Antiosteoporosis Effect of Radix Scutellariae Extract on Density and Microstructure of Long Bones in Tail-Suspended Sprague-Dawley Rats

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    Chen-Rui Li

    2013-01-01

    Full Text Available Radix Scutellariae (RS, a medicinal herb, is extensively employed in traditional Chinese medicines and modern herbal prescriptions. Two major flavonoids in RS were known to induce osteoblastic differentiation and inhibit osteoclast differentiation, respectively. This study aimed to investigate the effect of Radix Scutellariae extract (RSE against bone loss induced by mechanical inactivity or weightlessness. A hindlimb unloading tail-suspended rat model (TS was established to determine the effect of RSE on bone mineral density and bone microarchitecture. Treatment of RSE at 50 mg/kg/day and alendronate (ALE at 2 mg/kg/day as positive control for 42 days significantly increased the bone mineral density and mechanical strength compared with TS group. Enhanced bone turnover markers by TS treatment were attenuated by RSE and ALE administration. Deterioration of bone trabecula induced by TS was prevented. Moreover, both treatments counteracted the reduction of bone volume fraction, trabecular thickness and number, and connectivity density. In conclusion, RSE was demonstrated for the first time to prevent osteoporosis induced by TS treatment, which suggests the potential application of RSE in the treatment of disuse-induced osteoporosis.

  2. Gastroprotective Effect of Ethanolic Extract of Curcuma xanthorrhiza Leaf against Ethanol-Induced Gastric Mucosal Lesions in Sprague-Dawley Rats

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    Nurhidayah Ab. Rahim

    2014-01-01

    Full Text Available Herbal medicines appeared promising in prevention of many diseases. This study was conducted to investigate the gastroprotective effect of Curcuma xanthorrhiza leaf in the rats induced gastric ulcer by ethanol. Normal and ulcer control received carboxymethycellulose (5 mL/kg orally, positive control was administered with 20 mg/kg omeprazole (reference drug and 2 groups were received 250 mg/kg and 500 mg/kg of the leaf extract, respectively. To induce of gastric ulcers formation, ethanol (5 mL/kg was given orally to all groups except normal control. Gross ulcer areas, histology, and amount of prostaglandin E2, superoxide dismutase and malondialdehyde were assessed to determine the potentiality of extract in prevention against gastric ulcers. Oral administration of extract showed significant gastric protection effect as the ulcer areas was remarkably decreased. Histology observation showed less edema and leucocytes infiltration as compared with the ulcer control which exhibited severe gastric mucosa injury. Furthermore, the leaf extract elevated the mucus weight, level of prostaglandin E2 and superoxide dismutase. The extract also reduced malondialdehyde amount significantly. Results showed leaf extract of Curcuma xanthorrhiza can enhanced the gastric protection and sustained the integrity of gastric mucosa structure. Acute toxicity test did not showed any sign of toxicity (2 g/kg and 5 g/kg.

  3. Comparison of epoxide and free-radical mechanisms for activation of benzo[a]pyrene by Sprague-Dawley rat liver microsomes

    International Nuclear Information System (INIS)

    Selkirk, J.K.

    1980-01-01

    Coincubation of [6- 3 H]benzo[a]pyrene ([6- 3 H]BP) and [ 14 C]BP with SD rat liver microsomes produced metabolic profiles that showed that the C-6 of BP was not affected by formation of 4,5-dihydro-4,5-dihydroxy-BP, 7,8-dihydro-7,8-dihydroxy-BP, and 9,10-dihydro-9,10-dihydroxy-BP nor the 3- and 9-phenols of BP. Complete retention of tritium at C-6, except in the three quinones, confirmed the radical-cation model for formation of the 6-oxo-radical followed by oxidation to quinone. Epoxide formation at the carcinogenically active regions of BP appeared to biochemically isolate from 6-position activation and suggested that the microsomal epoxide pathway is unrelated to the radicalcation scheme. These molar ratios derived from double-label experiments reinforced the current literature that indicates the epoxide mechanism as the major pathway toward carcinogenic forms of BP

  4. The Effect of Propiconazole and Protective Effects of Selenium Gene Expression Profile of Caspase 9 in the Testicular Tissue of Male Sprague Dawley (SD Rats

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    S Rashidi pouya

    2016-08-01

    Full Text Available Background & aim: Conazoles including imidazoles or triazoles are anti- fungal agents widely used to prevent fungal growth and their infections. Propiconazole placed in this group is a systemic fungicide used widely for detoxification of cereal seeds especially rice in Iran and other countries. This fungicide were designed to inhibit a specific cytochrome P450, CYP51 (lanosterol-14-α- demethylase, a critical step in the biosynthesis of ergosterol, a steroid required for the formation of the fungal cell wall. In the present experimental study, the effect of propiconazole on Caspase 9 gene expression profile as an initiator of apoptotic process and protective effect of selenium were investigated. Methods: Forty SD rats were divided into 10 groups of 4,  including : control , sham1 (solvent of propiconazole, distilled water, sham 2 (solvent of selenium, normal saline and 1 group received 0.5 mg/kg selenium ,3 groups received propiconazole in doses of 10,50,75  mg/kg and 3 groups received propiconazole in doses of 10,50,75 mg/kg propiconazole with 0.5 mg/kg of selenium. Injections were intrapritoneal for two weeks in alternate days. Then, using RT-PCR and Total Lab program gene expression of caspase-9 testicular of all groups were studied. Data were analyzed using descriptive statistics. Results:  A significant increase of caspase 9 expression were observed among all experimental groups compared to control and sham groups. These findings indicated that 0.5 mg/kg selenium is not a suitable dose to create protection in this experimental study.  Conclusion: The significant increase in Caspase 9 gene expression profile observed in all experimental groups as compared to control suggests activation of apoptosis and inefficacy of selenium to protect the testis against induced damages.

  5. Study of damages induced by fungicide propiconazole on testicular tissue and process of spermatogenesis and protective effects of selenium in male Sprague Dawley rat

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    H Mohsenikouchesfehani

    2015-04-01

    Full Text Available Background & aim: Propiconazole is an herbal fungicide which is used as a tropical and systematic drug for fungal infection and also as an agricultural chemical for protection and preservation of fruits, vegetables and grains. The aim of this study was to assess the efficacy of fungicides propiconazol and possible protective effects of selenium on testes tissue. Methods: The present expremental trail study was conducted on forty rats which were divided into ten groups of four including control , sham (solvent of propiconazole, distilled water, solvent of selenium (normal saline and seven experimental groups : group 1 received 0.5 mg/kg/day of selenium, groups 2,3,4 received three doses of 10,50,75 mg/kg/day of Propiconazole, and groups 5,6,7 received three doses of 10, 50, 75 mg/kg/day of propiconazole with 0.5 mg/kg/day of selenium toevaluate. The administration was done intrapritoneal for two weeks in an alternatively fashion. After determining the level of LH, FSH, Testosterone, sperm was counted by hemocitometer. Data were analyzed by the SPSS software using ANOVA test. Results: No significant differences was observed in the level of hormones in the experimental groups2-7 compared with the control group, but the number of sertoli cells, spermatogonia , primary spermatocyte , spermatid and sperm decreased significantly in comparison with the control group (p<0.05. Conclusion: The decrease in numbers of counted sperm indicates that propiconazole has disrupted the production process of these cells and selenium was unable to improve that.

  6. Effects of prenatal low protein and postnatal high fat diets on visceral adipose tissue macrophage phenotypes and IL-6 expression in Sprague Dawley rat offspring.

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    Linglin Xie

    Full Text Available Adipose tissue macrophages (ATM are implicated in adipose tissue inflammation and obesity-related insulin resistance. Maternal low protein models result in fetal programming of obesity. The study aims to answer whether maternal undernutrition by protein restriction affects the ATM M1 or M2 phenotype under postnatal high fat diet in F1 offspring. Using a rat model of prenatal low protein (LP, 8% protein diet followed by a postnatal high fat energy diet (HE, 45% fat or low fat normal energy diet (NE, 10% fat for 12 weeks, we investigated the effects of these diets on adiposity, programming of the offspring ATM phenotype, and the associated inflammatory response in adipose tissue. Fat mass in newborn and 12-week old LP fed offspring was lower than that of normal protein (20%; NP fed offspring; however, the adipose tissue growth rate was higher compared to the NP fed offspring. While LP did not affect the number of CD68+ or CD206+ cells in adipose tissue of NE offspring, it attenuated the number of these cells in offspring fed HE. In offspring fed HE, LP offspring had a lower percentage of CD11c+CD206+ ATMs, whose abundancy was correlated with the size of the adipocytes. Noteworthy, similar to HE treatment, LP increased gene expression of IL-6 within ATMs. Two-way ANOVA showed an interaction of prenatal LP and postnatal HE on IL-6 and IL-1β transcription. Overall, both LP and HE diets impact ATM phenotype by affecting the ratio of CD11c+CD206+ ATMs and the expression of IL-6.

  7. Disposition of Lead (Pb) in Saliva and Blood of Sprague-Dawley Rats Following a Single or Repeated Oral Exposure to Pb-Acetate

    Energy Technology Data Exchange (ETDEWEB)

    Timchalk, Chuck; Lin, Yuehe; Weitz, Karl K.; Wu, Hong; Gies, Richard A.; Moore, Dean A.; Yantasee, Wassana

    2006-05-01

    Biological monitoring for lead (Pb) is usually based upon a determination of blood Pb concentration; however, saliva has been suggested as a non-invasive biological matrix for assessing exposure. To further evaluate the potential utility of saliva for biomonitoring, the disposition of Pb was evaluated in whole blood (WB), red blood cells (RBC), plasma, parotid gland, bone, and saliva following either a single oral dose of 100 mg Pb-acetate/kg body weight in rats or {approx}1-week after 5 sequential daily oral gavage doses of 1, 10, or 100 mg Pb-acetate/kg/day. Saliva volume, pH, total saliva protein, and ?-amylase activity were also determined. At specified times post-dosing groups of animals were anethetized and administered pilocarpine to induce salivation. Saliva was collected, the animals were humanely sacrificed, and tissue samples were likewise collected, weighed, and processed for Pb analysis. Following a single dose exposure to PB-acetate, Pb was detectable in all samples by 30 min post-dosing. For both the single and repeated dose treatments the concentration of Pb was highest in WB and RBC relative to plasma and saliva. However, the Pb rapidly redistributed (within 5-days post-treatment) from the blood into the bone compartment based on the substantial decrease in WB and RBC Pb concentration, and the concurrent increase in bone Pb following repeated exposure at all dose levels. Although there is clear variability in the observed Pb concentrations in plasma and saliva, there was a reasonable correlation (r2=0.922) between the average Pb concentrations in these biological matrices which was consistent with previous observations. The single oral dose of Pb-acetate resulted in a decrease in salivary pH which recovered by 24 hr post-dosing and a decrease in ?-amylase enzyme activity which did recover within 5-days of ceasing exposure. It is currently unclear what impact these slight functional changes may or may not have on Pb salivary clearance rates. These

  8. Assessment of immunotoxicity in female Fischer 344/N and Sprague Dawley rats and female B6C3F1 mice exposed to hexavalent chromium via the drinking water.

    Science.gov (United States)

    Shipkowski, Kelly A; Sheth, Christopher M; Smith, Matthew J; Hooth, Michelle J; White, Kimber L; Germolec, Dori R

    2017-12-01

    Sodium dichromate dihydrate (SDD), an inorganic compound containing hexavalent chromium (Cr(VI)), is a common environmental contaminant of groundwater sources due to widespread industrial use. There are indications in the literature that Cr(VI) may induce immunotoxic effects following dermal exposure, including acting as both an irritant and a sensitizer; however, the potential immunomodulatory effects of Cr(VI) following oral exposure are relatively unknown. Following the detection of Cr(VI) in drinking water sources, the National Toxicology Program (NTP) conducted extensive evaluations of the toxicity and carcinogenicity of SDD following drinking water exposure, including studies to assess the potential for Cr(VI) to modulate immune function. For the immunotoxicity assessments, female Fischer 344/N (F344/N) and Sprague Dawley (SD) rats and female B 6 C 3 F 1 mice were exposed to SDD in drinking water for 28 consecutive days and evaluated for alterations in cellular and humoral immune function as well as innate immunity. Rats were exposed to concentrations of 0, 14.3, 57.3, 172, or 516 ppm SDD while mice were exposed to concentrations of 0, 15.6, 31.3, 62.5, 125, or 250 ppm SDD. Final mean body weight and body weight gain were decreased relative to controls in 250 ppm B 6 C 3 F 1 mice and 516 ppm SD rats. Water consumption was significantly decreased in F344/N and SD rats exposed to 172 and 516 ppm SDD; this was attributed to poor palatability of the SDD drinking water solutions. Several red blood cell-specific parameters were significantly (5-7%) decreased in 250 ppm mice; however, these parameters were unaffected in rats. Sporadic increases in the spleen IgM antibody response to sheep red blood cells (SRBC) were observed, however, these increases were not dose-dependent and were not reproducible. No significant effects were observed in the other immunological parameters evaluated. Overall, exposure to Cr(VI) in drinking water had limited effects on

  9. Evaluation of the role of oxidative stress, inflammation and apoptosis in the pulmonary and the hepatic toxicity induced by cerium oxide nanoparticles following intratracheal instillation in male Sprague-Dawley rats

    Science.gov (United States)

    Nalabotu, Siva Krishna

    The field of nanotechnology is rapidly progressing with potential applications in the automobile, healthcare, electronics, cosmetics, textiles, information technology, and environmental sectors. Nanomaterials are engineered structures with at least one dimension of 100 nanometers or less. With increased applications of nanotechnology, there are increased chances of exposure to manufactured nanomaterials. Recent reports on the toxicity of engineered nanomaterials have given scientific and regulatory agencies concerns over the safety of nanomaterials. Specifically, the Organization for Economic Co-operation and Development (OECD) has identified fourteen high priority nanomaterials for study. Cerium oxide (CeO2) nanoparticles are one among the high priority group. Recent data suggest that CeO2 nanoparticles may be toxic to lung cell lines in vitro and lung tissues in vivo. Other work has proposed that oxidative stress may play an important role in the toxicity; however, the exact mechanism of the toxicity, has to our knowledge, not been investigated. Similarly, it is not clear whether CeO2 nanoparticles exhibit systemic toxicity. Here, we investigate whether pulmonary exposure to CeO2 nanoparticles is associated with oxidative stress, inflammation and apoptosis in the lungs and liver of adult male Sprague-Dawley rats. Our data suggest that the intratracheal instillation of CeO2 nanoparticles can cause an increased lung weight to body weight ratio. Changes in lung weights were associated with the accumulation of cerium in the lungs, elevations in serum inflammatory markers, an increased Bax to Bcl-2 ratio, elevated caspase-3 protein levels, increased phosphorylation of p38-MAPK and diminished phosphorylation of ERK1/2-MAPK. Our findings from the study evaluating the possible translocation of CeO2 nanoparticles from the lungs to the liver suggest that CeO 2 nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase

  10. The pyrethroid metabolites 3-phenoxybenzoic acid and 3-phenoxybenzyl alcohol do not exhibit estrogenic activity in the MCF-7 human breast carcinoma cell line or Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Laffin, Brian; Chavez, Marco; Pine, Michelle

    2010-01-01

    induced an estrogen receptor α/ERE-controlled luciferase reporter in the MCF-7 cells. Following the in vitro screenings, the metabolites were then evaluated for estrogenic activity in vivo using the uterotrophic assay in Sprague-Dawley rats. Animals were orally gavaged (10.0, 5.0, and 1.0 mg/kg) once daily for 3 days. Neither metabolite had any effect on uterine wet weight, body weight, or organ weight. Lastly, in order to determine if either metabolite was able to alter the onset of puberty, immature female rats were orally gavaged (10.0, 5.0, and 1.0 mg/kg) once a day with the metabolites beginning 1 day post-weaning until the onset of puberty as evidenced by vaginal opening (VO). Again, neither metabolite had any effect on the onset of VO.

  11. Changes of Serotonin (5-HT), 5-HT2A Receptor, and 5-HT Transporter in the Sprague-Dawley Rats of Depression,Myocardial Infarction and Myocardial Infarction Co-exist with Depression

    Institute of Scientific and Technical Information of China (English)

    Mei-Yan Liu; Yah-Ping Ren; Wan-Lin Wei; Guo-Xiang Tian; Guo Li

    2015-01-01

    Background:To evaluate whether serotonin (5-HT),5-HT2A receptor (5-HT2AR),and 5-HT transporter (serotonin transporter [SERT]) are associated with different disease states of depression,myocardial infarction (MI) and MI co-exist with depression in Sprague-Dawley rats.Methods:After established the animal model of four groups include control,depression,MI and MI with depression,we measured 5-HT,5-HT2AR and SERT from serum and platelet lysate.Results:The serum concentration of 5-HT in depression rats decreased significantly compared with the control group (303.25 ± 9.99 vs.352.98 ± 13.73;P =0.000),while that in MI group increased (381.78 ± 14.17 vs.352.98 ± 13.73;P =0.000).However,the depression + MI group had no change compared with control group (360.62 ± 11.40 vs.352.98 ± 13.73;P =0.036).The changes of the platelet concentration of 5-HT in the depression,MI,and depression + MI group were different from that of serum.The levels of 5-HT in above three groups were lower than that in the control group (380.40 ± 17.90,387.75 ± 22.28,246.40 ± 18.99 vs.500.29 ± 20.91;P =0.000).The platelet lysate concentration of 5-HT2AR increased in depression group,MI group,and depression + MI group compared with the control group (370.75 ± 14.75,393.47 ± 15.73,446.66 ± 18.86 vs.273.66 ± 16.90;P =0.000).The serum and platelet concentration of SERT in the depression group,MI group and depression + MI group were all increased compared with the control group (527.51 ± 28.32,602.02 ± 23.32,734.76 ± 29.59 vs.490.56 ± 16.90;P =0.047,P =0.000,P =0.000 in each and 906.38 ± 51.84,897.33 ± 60.34,1030.17 ± 58.73 vs.708.62 ± 51.15;P =0.000 in each).Conclusions:The concentration of 5-HT2AR in platelet lysate and SERT in serum and platelet may be involved in the pathway of MI with depression.Further studies should examine whether elevated 5-HT2AR and SERT may contribute to the biomarker in MI patients with depression.

  12. Relationship Between Circulating Fatty Acids and Fatty Acid Ethanolamide Levels After a Single 2-h Dietary Fat Feeding in Male Sprague-Dawley Rats : Elevated levels of oleoylethanolamide, palmitoylethanolamide, linoleoylethanolamide, arachidonoylethanolamide and docosahexanoylethanolamide after a single 2 h dietary fat feeding in male Sprague Dawley rats.

    Science.gov (United States)

    Olatinsu, Anthonia O; Sihag, Jyoti; Jones, Peter J H

    2017-11-01

    Previous studies show that long term variations in dietary fat consumption impact circulating fatty acid ethanolamide (FAE) concentrations, however, few studies have investigated short term effects of dietary fat feeding on FAE levels. The trial's objective was to explore the effect of acute feeding of varying amounts of dietary n-9 and n-3 fatty acids on plasma and organ levels of FAE. Sixty-four rats were assigned to four groups fed meals containing 40% of energy as either safflower oil (control), canola oil (CO), or DHA rich oil (DRO), each consumed as a bolus within a 2-h window. Plasma and tissue FAE levels were measured at 3, 6, 12 and 24 h following the bolus. FAE profiles over time exhibited patterns that were specific both to FAE and to dietary fat type provided. At 3 h, plasma and liver OEA levels were higher (p < 0.05) in the 95% CO:5% DRO compared with other groups. At 12 h, plasma PEA levels were lower (p < 0.05) in the 50% CO:50% DRO group compared to the 95% CO group. Plasma DEA levels showed an increase (p < 0.05) only after 24 h of feeding. All four dietary groups manifested increased DEA levels in a dose-dependent manner. Data demonstrate that a single meal feeding of diets with different ratios of fat types impacts tissue levels of FAE within a short time frame, which could further influence the physiological roles of FAE on appetite regulation and energy expenditure.

  13. Efek eugenol terhadap jumlah sel inflamasi pada pulpa gigi molar tikus Sprague Dawley

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    Raras Ajeng Enggardipta

    2016-08-01

    Full Text Available Inflammatory cells infiltration after eugenol administration in Sprague Dawley rat’s molars. The purpose of this study was to determine effect of eugenol on inflammatory cells infiltration (neutrophils, macrophages and lymphocytes in the inflamed dental pulp. Thirty male Sprague Dawley rats aged 3-4 months and weighed 300-350 g were randomly divided into 2 groups: treated and control groups. Rats were injected with ketamine HCl i.m. (0.1 ml/100 grams BW before cavity preparation at occlusal surface of the upper molars. Cavity preparation was made using a round bur No.010 to pulp perforation. At the cavity base of treated group, 15 rats were given eugenol and of control group 15 rats were given aquadest, before filled with temporary filling. Three rats from each group were sacrificed at 1, 3, 5, 7 and 14 days after the cavity preparation. Rats were injected with ketamine HCl im (0.1 ml / 100 g BW on the thigh then tissues were collected for histological process and stained using haematoxylin eosin. The number of inflammatory cells (neutrophils, macrophages and lymphocytes was analysed by Two-Way Anova. The result of the study showed number of inflammatory cells infiltration of treated group was lower than control and showed significant differences between groups (p <0.05. The conclusion from this study is eugenol administration in Sprague Dawley rats’s inflamed dental pulp can reduce the number of inflammatory cells (neutrophils, macrophages and lymphocytes. ABSTRAK Penelitian ini bertujuan untuk mengetahui pengaruh eugenol terhadap jumlah sel inflamasi (netrofil, makrofag dan limfosit pada pulpa gigi terinflamasi. Tiga puluh ekor tikus Sprague Dawley jantan berumur  3-4 bulan dengan berat badan 300-350 g dibagi secara acak dalam 2 kelompok yaitu perlakuan dan kontrol. Tikus diinjeksi ketamine HCl i.m. (0,1 ml/100 gram BB sebelum dilakukan preparasi kavitas pada permukaan oklusal gigi molar satu rahang atas. Preparasi kavitas dibuat dengan

  14. Disposition and metabolism of the bisphenol analogue, bisphenol S, in Harlan Sprague Dawley rats and B6C3F1/N mice and in vitro in hepatocytes from rats, mice, and humans.

    Science.gov (United States)

    Waidyanatha, Suramya; Black, Sherry R; Snyder, Rodney W; Yueh, Yun Lan; Sutherland, Vicki; Patel, Purvi R; Watson, Scott L; Fennell, Timothy R

    2018-05-10

    With the removal of bisphenol A (BPA) from many consumer products, the potential use of alternatives such as bisphenol S (BPS) and its derivatives is causing some concerns. These studies investigated the comparative in vitro hepatic clearance and metabolism of BPS and derivatives and the disposition and metabolism of BPS in rats and mice following gavage and intravenous administration. The clearance of BPS and its derivatives was slower in human hepatocytes than in rodents. In male rats following gavage administration of 50, 150, and 500 mg/kg [ 14 C]BPS the main route of excretion was via urine; the urinary excretion decreased (72 to 48%) and the fecal excretion increased (16 to 30%) with increasing dose. The disposition was similar in female rats and male and female mice following gavage administration. Radioactivity remaining in tissues at 72 h in both species and sexes was ≤2.4%. In bile duct cannulated rats 53% of a gavage dose was secreted in bile suggesting extensive enterohepatic recirculation of [ 14 C]BPS. Following an intravenous dose in rats and mice, the pattern of excretion was similar to gavage. These data suggest that the dose excreted in feces folowing gavage administration is likely the absorbed dose. Urinary metabolites included the glucuronide and sulfate conjugates with a moderate amount of parent. The pattern of in vitro hepatic metabolsim was similar to in vivo with some difference among derivatives. These data suggest that similar to other bisphenol analogues, BPS was well absorbed following oral expsosure and extensively excreted with minimal tissue retention. Copyright © 2017. Published by Elsevier Inc.

  15. Reaksi Radang pada Lidah dengan Tongue Piercing (Kajian in vivo pada Lidah Tikus Jantan Sprague dawley

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    Feby Aryani

    2015-10-01

    Full Text Available Today tongue piercing has become increasingly popular in the society. Several case reports associated with tongue piercing have presented various complications, such as tooth fracture, viral infection (HIV, Hepatitis B and C, herpes simplex, Epstein Barr, fungal infection (Candida spp, pain altered taste, edema, paresthesis, gingival recession, prolonged bleeding, contact dermatitis. However, there is no scientific evidence to reveal hispathological change in tongue piercing. The aim of this study is to investigate the inflammation response to tongue piercing in Spraque Dawley rats. Eighteen Sprague Dawley rats were divided into one control group of 3 untreated rats and three experimental groups of 5 rats each, according to the duration of tongue piercing until the end of 1st week (A, 6th week (B and 12th week (C. At the end of treatments, the rats were anesthetized and sacrifices. Paraffin embedded tongue specimens were prepared for histological examination with H&E stainig. The number of inflammatory cells (PMN leukocytes, lymphocytes, macrophages was counted under light microscope. All experimental procedures were carried out under approval of study protocol by the Health and Medical Research Ethics Committee, Faculty of Medicine, Gadjah Mada University, Yogyakarta. The results of this study indicated that the number of PMN leukocytes, lymphocytes, and macrophages was increasing to the 1st week after tongue piercing. The number of lymphocytes and macrohpages was still increasing after 6th and 12th weeks of piercing, but the bumber of PMN leukocytes, lymphocytes, and macrophages between the groups of 1st, 6th, and 12th weeks after piercing. It was concluded that tongue piercing induce inflammatory response for 12 weeks in Sprague Dawley rats.

  16. Metabolism and disposition of 2-ethylhexyl-p-methoxycinnamate following oral gavage and dermal exposure in Harlan Sprague Dawley rats and B6C3F1/N mice and in hepatocytes in vitro.

    Science.gov (United States)

    Fennell, Timothy R; Mathews, James M; Snyder, Rodney W; Hong, Yan; Watson, Scott L; Black, Sherry R; McIntyre, Barry S; Waidyanatha, Suramya

    2017-11-23

    1. 2-Ethylhexyl-p-methoxycinnamate (EHMC) is commonly used as an ingredient in sunscreens, resulting in potential oral and dermal exposure in humans. 2. Clearance and metabolism of EHMC in hepatocytes and disposition and metabolism of EHMC in rodents following oral (8-800 mg/kg) intravenous (IV) (8 mg/kg) or dermal (0.8-80 mg/kg representing 0.1-10% formulation concentration) exposure to [ 14 C]EHMC were investigated in rats and mice. 3. EHMC was rapidly cleared from rat and mouse hepatocytes (half-life ≤3.16 min) and less rapidly (half-life ≤48 min) from human hepatocytes. 4. [ 14 C]EHMC was extensively absorbed and excreted primarily in urine by 72 h after oral administration to rats (65-80%) and mice (63-72%). Oral doses to rats were excreted to a lesser extent (3-8%) in feces and as CO 2 (1-4%). Radioactive residues in tissues were <1% of the dose. There were no sex or species differences in disposition in rats. 5. Following dermal application, 34-42% of an 8-mg/kg dose was absorbed in rats, and 54-62% in mice in 72-h. 6. Among numerous urinary metabolites associated with hydrolysis of the ester, two potential reproductive and developmental toxicants, 2-ethylhexanol and 2-ethylhexanoic acid were produced by metabolism of EHMC.

  17. Sex ratio of the offspring of Sprague-Dawley rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in utero and lactationally in a three-generation study

    International Nuclear Information System (INIS)

    Rowlands, J.C.; Budinsky, R.A.; Aylward, L.L.; Faqi, A.S.; Carney, E.W.

    2006-01-01

    Reports of a decreased male/female sex ratio in children born to males exposed to TCDD in Seveso, Italy, at a young age have sparked examinations of this endpoint in other populations exposed to TCDD or related compounds. Overall, the male/female sex ratio results reported in these studies, with slightly different age-exposed male populations, have shown mixed results. Experimental studies of the effects of in utero exposure to TCDD in laboratory animals have reported no effect on the f 1 sex ratio and mixed results for the sex ratio of the f 2 generation. In order to better understand the potential effects of TCDD on second generation sex ratio, we retrieved archived data from a comprehensive three-generation feeding study of TCDD in rats that was conducted and published in the 1970s, but which did not publish data on sex ratio of the offspring [Murray, F.J., Smith, F.A., Nitschke, K.D., Humiston, C.G., Kociba, R.J., Schwetz, B.A., 1979. Three-generation reproduction study of rats given 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the diet. Toxicol. Appl. Pharmacol. 50, 241-252]. A re-examination of the original Murray et al. data found no statistically significant treatment-related changes in postnatal day 1 sex ratio in any generation of treated animals, consistent with one other relatively large study reporting on this endpoint. We discuss mechanistic data underlying a potential effect of TCDD on this endpoint. We conclude that the inconsistency in findings on sex ratio of the offspring of male rats exposed to TCDD in utero is likely due to random variation associated with a relatively small sample size, although differences between studies in strain of rat, dose regimen, and day of ascertainment of sex ratio cannot be ruled out

  18. Hair Follicle Bulb as a Biodosimeter for Low-Level VX Vapor Exposure: Initial Studies Validating the Presence of Potential Protein Biomarkers of Exposure in the Sprague-Dawley Rat Whisker Follicle

    Science.gov (United States)

    2006-10-01

    amphetamine, methamphetamine, heroin , marijuana, and steroids), therapeutic drugs (e.g. ephedrine, benzodiazepines, and barbiturates), and inorganic heavy...Urine, Hair, Sweat and Saliva to Detect Drug Use. Drug and Alcohol Review 2004, 23, 213-217. 13. Kidwell, D.A.; Lee, E.H.; DeLauder, S.F. Evidence...Tomic, M. Effect of Soman Intoxication on the Organization of Rat Brain Ribosomes and the Translational Activity of mRNA in a Cell-free System

  19. Comparison of grain from corn rootworm resistant transgenic DAS-59122-7 maize with non-transgenic maize grain in a 90-day feeding study in Sprague-Dawley rats.

    Science.gov (United States)

    He, X Y; Huang, K L; Li, X; Qin, W; Delaney, B; Luo, Y B

    2008-06-01

    DAS-59122-7 (59122) is a transgenic maize (Zea mays L.) that contains genes encoding Cry34Ab1 and Cry35Ab1 proteins from Bacillus thuringiensis Berliner strain 149B1 and phosphinothricin acetyltransferase (PAT) protein from Streptomyces viridochromogenes. Expression of these proteins in planta confers resistance to corn rootworms and other Coleopteran parasites and tolerance to herbicides containing glufosinate ammonium, respectively. In the current study, processed flours from 59122 maize grain or its near isogenic control line (091) were used at two concentrations (50% and 70% wt/wt) to produce diets that were fed to rats for 90 days in accordance with Chinese toxicology guidelines (GB15193.13-2003). A commercial AIN93G diet was used as an additional negative control. No significant differences in body weight and feed utilization were observed between rats consuming diets formulated with 59122 and 091 Control corn. Statistical differences (p<0.05) were observed in certain hematology and serum chemistry response variables between rats consuming diets formulated with 59122 or 091 Control flour compared to AIN93G diet. However, the mean value of these response variables in the 59122 groups were not statistically different from those observed in diets formulated with corresponding high and low concentrations of the flour from the 091 Control maize grain. Therefore, the statistical differences were considered to be related to consumption of diets containing high concentrations of maize flour (compared to AIN93G diets) regardless of source rather than to consumption of flour from 59122 maize grain. The results from this study demonstrated that 59122 maize grain is as safe as non-transgenic maize grain.

  20. Neonatal tactile stimulation reverses the effect of neonatal isolation on open-field and anxiety-like behavior, and pain sensitivity in male and female adult Sprague-Dawley rats.

    Science.gov (United States)

    Imanaka, A; Morinobu, S; Toki, S; Yamamoto, S; Matsuki, A; Kozuru, T; Yamawaki, S

    2008-01-10

    It is well known that early life events induce long-lasting psychophysiological and psychobiological influences in later life. In rodent studies, environmental enrichment after weaning prevents the adulthood behavioral and emotional disturbances in response to early adversities. We compared the behavioral effect of neonatal isolation (NI) with the effect of NI accompanied by tactile stimulation (NTS) to determine whether NTS could reverse or prevent the effects of NI on the adulthood behavioral and emotional responses to environmental stimuli. In addition, we also examined the sex difference of the NTS effect. Measurements of body weights, an open-field locomotor test, an elevated plus maze test, a hot-plate test, and a contextual fear-conditioning test were performed on postnatal day 60. As compared with rats subjected to NI, rats subjected to NTS showed significantly higher activity and exploration in the open-field locomotor test, lower anxiety-like behavior in the elevated plus maze test, and significantly prolonged latencies in the hot-plate test, and this effect was equal among males and females. In the contextual fear-conditioning test, whereas NTS significantly reduced the enhanced freezing time due to NI in females, no significant difference in the freezing time between NI and NTS was found in males. These findings indicate that adequate tactile stimulation in early life plays an important role in the prevention of disturbances in the behavioral and emotional responses to environmental stimuli in adulthood induced by early adverse experiences.

  1. Chronic treatment of (R)-α-lipoic acid reduces blood glucose and lipid levels in high-fat diet and low-dose streptozotocin-induced metabolic syndrome and type 2 diabetes in Sprague-Dawley rats.

    Science.gov (United States)

    Ghelani, Hardik; Razmovski-Naumovski, Valentina; Nammi, Srinivas

    2017-06-01

    (R)- α -lipoic acid ( ALA ), an essential cofactor in mitochondrial respiration and a potential antioxidant, possesses a wide array of metabolic benefits including anti-obesity, glucose lowering, insulin-sensitizing, and lipid-lowering effects. In this study, the curative effects of ALA (100 mg/kg) on a spectrum of conditions related to metabolic syndrome and type 2 diabetes ( T2D ) were investigated in a high-fat diet (HFD)-fed and low-dose streptozotocin (STZ)-induced rat model of metabolic syndrome and T2D . The marked rise in the levels of glucose, triglycerides, total-cholesterol, LDL-cholesterol, and VLDL-cholesterol in the blood of HFD-fed and low-dose STZ-injected rats were significantly reduced by ALA treatment. Furthermore, ALA treatment significantly increased the serum HDL-cholesterol levels and tended to inhibit diabetes-induced weight reduction. Mathematical computational analysis revealed that ALA also significantly improved insulin sensitivity and reduced the risk of atherosclerotic lesions and coronary atherogenesis. This study provides scientific evidence to substantiate the use of ALA to mitigate the glucose and lipid abnormality in metabolic syndrome and T2D .

  2. New Modified UPLC/Tandem Mass Spectrometry Method for Determination of Risperidone and Its Active Metabolite 9-Hydroxyrisperidone in Plasma: Application to Dose-Dependent Pharmacokinetic Study in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Essam Ezzeldin

    2017-01-01

    Full Text Available Sensitive and specific liquid-chromatography tandem mass spectrometry (UPLC-MS/MS assay has been developed and validated for simultaneous quantification of risperidone (RIS and its active metabolite 9-hydroxyrisperidone (9-OH-RIS in rat plasma using olanzapine (OLA as internal standard (IS. Pharmacokinetics of risperidone and its active metabolite 9-hydroxyrisperidone was compared across different doses (0.3, 1.0, and 6.0 mg/kg. Serial blood sample was collected over a time of 48 hours and analyzed for risperidone and its active metabolite 9-hydroxyrisperidone. The pharmacokinetics parameters including Cmax, tmax, and AUC were determined for risperidone and its active ingredient. The method was linear in the concentration range of 0.2–500 ng/mL for risperidone and 9-OH-risperidone, with coefficients of determination greater than 0.998 and lower limit of quantitation of 0.2 ng/mL. Blood levels of risperidone and its active metabolite were roughly dose-proportional. The method developed herein is simple and rapid and was successfully applied for dose-dependent pharmacokinetic study.

  3. Neuronal Function in Male Sprague Dawley Rats During Normal ...

    African Journals Online (AJOL)

    olayemitoyin

    Summary: During normal ageing, there are physiological changes especially in high energy ... science and technology (U.S. Bureau of the Census ... strategies that can be applied to preserve function with ..... Intelligent Technology for an.

  4. Induction of mammary gland tumor in female Sprague- Dawley rats ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-07-12

    Jul 12, 2010 ... The current methods for tumor induction in breast cancer research animal models are time-consuming, hazardous ... issue in animal has been a controversial and much disputed ..... to therapy and early detection of cancer.

  5. Study on the Potential Toxicity of a Thymoquinone-Rich Fraction Nanoemulsion in Sprague Dawley Tats

    Directory of Open Access Journals (Sweden)

    Maznah Ismail

    2013-06-01

    Full Text Available Toxicological studies constitute an essential part of the effort in developing an herbal medicine into a drug product. A newly developed thymoquinone-rich fraction nanoemulsion (TQRFNE has been prepared using a high pressure homogenizer. The purpose of this study was to investigate the potential acute toxicity of this nanoemulsion in Sprague Dawley rats. The acute toxicity studies were conducted as per the OECD guidelines 425, allowing for the use of test dose limit of 20 mL TQRFNE (containing 44.5 mg TQ/kg. TQRFNE and distilled water (DW as a control were administered orally to both sexes of rats on Day 0 and observed for 14 days. All the animals appeared normal, and healthy throughout the study. There was no observed mortality or any signs of toxicity during the experimental period. The effects of the TQRFNE and DW groups on general behavior, body weight, food and water consumption, relative organ weight, hematology, histopathology, and clinical biochemistry were measured. All the parameters measured were unaffected as compared to the control (DW group. The administration of 20 mL TQRFNE /kg was not toxic after an acute exposure.

  6. Pencegahan hipertensi dan penebalan dinding aorta dengan pemberian kecambah kacang hijau (Phaseolus radiatus (L pada tikus putih Sprague Dawley

    Directory of Open Access Journals (Sweden)

    Novian Swasono Hadi

    2016-01-01

    Full Text Available Background: Lifestyle changes with high-fat food consumption is one of the factors the risks of cardiovascular diseases like of coronary heart disease and atherosclerosis. A healthy diet and a balanced diet and consume foods that contain lots of antioxidants is one of the effective ways to prevent hyperlipidemia. Mung bean sprouts have properties that neutralize free radicals cause Hyperlipidemia and cardiovascular diseases because it is an antioxidant compound. Objective: The aim of this study was to determinate the effect of mung bean sprouts (Phaseolus radiatus (L to blood pressure and histopathology aorta of Sprague-Dawley male rats. Method: The type of study was experimental research using pre-post test controlled group design for blood pressure variable and post test only controlled group design histopathology aorta. The thirty-five of Sprague-Dawley male rats was eight weeks divided into 5 groups. The first group was given standard diet, group 2 was given a hight fat diet, the third group was given a high-fat diet and mung bean sprout 0,67 gram, group 4 was given a high-fat diet and mung bean 1,34 gram, and group 5 was given a high-fat diet and vitamin E doses of 23 IU. Results: Result of this study showed that after 4 weeks of treatment, increased in blood pressure systole in the given of  high fat diet higher than group who were given a high fat diet and mung bean sprout and also on group who were given high fat diet and vitamin E, but there is no difference effect a decrease in blood pressure between the provision of mung bean sprouts and vitamin E (p>0,05. Statistical analysis to thick the wall the aorta show the similarity meaningful in all the treatment group, it can be said that overall thick the wall the aorta in this research is not different. Conclusion: A dose of mung bean sprout 0,67 g is optimal doses in preventing a rise in blood pressure and prevent alterations histopathology Sprague-Dawley male rats.

  7. Efek antigenotoksik ekstrak etanolik daun sirsak (Annona muricata Linn terhadap frekuensi mikronukleus mukosa bukal tikus Sprague Dawley

    Directory of Open Access Journals (Sweden)

    Tyas Prihatiningsih

    2017-10-01

    Full Text Available The effect of soursop leaves (Annona uricata linn ethanolic extract on micronucleus frequency  of buccal mucosa epithelium of Sprague dawley rats. Polycyclic aromatic hydrocarbons is one of the largest  groups of carcinogen in environment. 7,12-Dimetillbez (α antransena is a compound of PAH class that has genotoxic carcinogen potency. One of the most frequently applied genotoxicity tests is micronucleus test. Soursop is a plant that can grow well in Indonesia. Its leaves contain avonoid and acetogenin assumed to have potential chemopreventive and anticancer activities. The aim of this study was to assess the antigenotoxic effect soursop leaves ethanolic extraction the micronucleus frequency of DMBA-induced buccal mucosa of rat. This research was conducted on 24 male Sprague Dawley rats aged 5 weeks and divided into six groups. Carcinogenesis on the lingual dorsum of group I-III were induced by DMBA topically 3 times a week for 16 weeks, group II and III were not only induced by carcinogenesis, but also were given soursop leaves ethanolic extract of 100 and 200 mg/kg body weight for 18 weeks, group IV was given soursop leaves ethanolic extract 200 mg/kg body weight, group V was given DMSO 1% and group VI was given no treatment. After 18th week, buccal mucosa swab for micronucleus test was conducted and stained with Feulgen-Rossenbeck method. The number of micronucleus is calculated under a light microscope, data were analized using using one-way ANOVA followed by Tukey HSD. The result showed that the average of buccal micronucleus frequency of group II (13 ± 0.82 and group III (12 ± 0.96 were decrease signicantly (p<0,05 than group I (24 ± 1.71. From the experiment,   it is concluded that the soursop leaves ethanolic extract has antigenotoxic effect shown by decreasing of the buccal micronucleus frequency of rat. ABSTRAK Polycyclic aromatic hydrocarbon atau PAH merupakan salah satu kelompok karsinogen terbesar di lingkungan. 7

  8. TOXICIDAD AGUDA DE Aleurites moluccana POR VIA ORAL EN RATAS SPRAGUE-DAWLEY

    Directory of Open Access Journals (Sweden)

    Laura Rocío Orellana-Cuéllar

    2014-12-01

    Full Text Available Objetivo: Determinar la toxicidad aguda por Aleurites moluccana por administración oral en ratas Sprague-Dawley. Metodología: Estudio experimental realizado en el Instituto de Patología de la Facultad de Medicina-UNMSM. Se usaron treinta ratas Sprague-Dawley, hembras y machos, de 6 semanas de edad. Se formaron aleatoriamente tres grupos de diez ratas: grupo A1, recibió 8,2 mg/Kg de peso de A. moluccana; grupo  A2, recibió 2000 mg/Kg de peso de A. moluccana; grupo control, recibió agua ad libitum. Se evaluaron los signos clínicos de toxicidad, los pesos, variables bioquímicas y las características histopatológicas de hígado, riñón, corazón, intestino, bazo y gónadas. Se consideró significativo un p0,05. Los grupos  A1 y A2 presentaron signos clínicos de toxicidad y la muerte de tres ratas; células hepáticas binucleadas y regenerativas en el hígado; y hemorragia glomerular en el riñón. Conclusiones: Las variables clínicas e histopatológicas en hígado y riñón demostraron que la Aleurites moluccana produce toxicidad aguda, las variables bioquímicas no demostraron este efecto. Palabras Claves: Aleurites moluccana, Toxicidad aguda, Ratas Sprague-Dawley.

  9. Effectiveness of anchovy substrate application on decreasing acid solubility of Sprague Dawley rats’ tooth enamel (in vivo)

    Science.gov (United States)

    Triputra, F.; Puspitawati, R.; Gunawan, H. A.

    2017-08-01

    Anchovies (Stolephorus insularis), a natural resource of Indonesia, contain fluoride in the form of CaF2 and can function as a fluoridation material to prevent dental caries. The aim of this study is to study the effectiveness of anchovy substrate, through food or topical application, in decreasing the acid solubility of tooth enamel. This research used 14 Sprague Dawley rats as subjects divided into the following 5 groups: baseline, experimental feeding, experimental smearing, and their negative controls. After 15 days of anchovy substrate application, lower incisors were extracted and the acid solubility of enamel was analyzed qualitatively and quantitatively using a stereo microscope and a Micro-Vickers Hardness Tester. Analysis of enamel surface destruction and enamel surface microscopic hardness shifting after a 60 sec application of H2PO4 (50% concentration) resulted in a decrease in acid solubility of enamel treated with anchovy substrate. This result can be seen with both the chewing and smearing method. S. insularis can be used as an alternative material for fluoridation.

  10. The elimination, distribution, and metabolism of 14C-toxaphene in the pregnant rat

    International Nuclear Information System (INIS)

    Pollock, G.A.; Hillstrand, R.

    1982-01-01

    Pregnant Sprague-Dawley rats were orally administered 14 C-toxaphene in olive oil on day 15 of pregnancy and housed in glass metabolism cages. Urine, feces, and tissues were collected and assayed for radioactivity. The elimination was similar to that in virgin females with the majority of activity excreted in the feces (38.4%; five days) and less in the urine (23.7%; five days). The fetuses contained the lowest levels of radioactivity of all tissues tested (28 ppb; five days) and fat contained the highest levels (7476 ppb; five days). A comparison of the activity in the fetuses with that in the dam's fat showed slight differences, indicating the presence of more polar compounds (perhaps metabolites)

  11. Global gene expression and morphological alterations in the mammary gland after gestational exposure to bisphenol A, genistein and indole-3-carbinol in female Sprague-Dawley offspring

    International Nuclear Information System (INIS)

    Grassi, Tony F.; Silva, Glenda N. da; Bidinotto, Lucas T.; Rossi, Bruna F.; Quinalha, Marília M.; Kass, Laura; Muñoz-de-Toro, Mónica; Barbisan, Luís F.

    2016-01-01

    This study aimed to evaluate the modifying effects of dietary genistein (GEN) and indole-3-carbinol (I3C) on early mammary gland development in female Sprague-Dawley offspring born to mothers exposed to BPA during gestation. Pregnant rats were treated with BPA25 or 250 μg/kg bw/day from gestational days 10 to 21 with or without dietary intake of GEN (250 mg/kg chow) or I3C (2000 mg/kg chow). At post-natal day (PND) 21, female offspring from different litters were euthanized for mammary gland development and gene expression analyses. Our results indicated that prenatal exposure to BPA25 and 250 did not modify the ductal elongation of the mammary gland tree or the estrogen receptor alpha (ER-α) expression in terminal end buds (TEBs). However, BPA25-exposed offspring had a higher number of terminal structures (TEBs + TDs) and an increased mammary branching and cell proliferation index in TEBs. Besides that, BPA25 and 250 modulated the expression of several genes in the immature mammary gland that were not changed in a dose dependent manner and involved different clusters of up- and down-regulated genes. Furthermore, BPA25 and BPA250 + I3C-treated groups also had a higher number of enriched functional gene categories. In addition, maternal dietary GEN and I3C in association with BPA exposure produced specific gene expression alterations in the mammary gland and overcome the adverse effect of BPA25, decreasing the branching of the mammary gland. In conclusion, prenatal BPA exposure induced both morphological and gene expression modifications on the mammary gland that dietary intake of GEN and I3C reverted on BPA25-exposed animals. - Highlights: • Gestational BPA and its association with GEN and I3C modify gene expression on the early mammary gland development. • GEN and I3C induced a different gene expression signature than lower BPA dose. • Dietary GEN and I3C countered the adverse effect of lower BPA dose on the cell proliferation and mammary gland development.

  12. Global gene expression and morphological alterations in the mammary gland after gestational exposure to bisphenol A, genistein and indole-3-carbinol in female Sprague-Dawley offspring

    Energy Technology Data Exchange (ETDEWEB)

    Grassi, Tony F. [UNESP – Univ. Estadual Paulista, Botucatu Medical School, Department of Pathology, Botucatu, SP (Brazil); Silva, Glenda N. da [UFOP – Federal University of Ouro Preto, Analysis Clinical Department, Ouro Preto, MG (Brazil); Bidinotto, Lucas T. [Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP (Brazil); Barretos School of Health Sciences, Dr. Paulo Prata - FACISB, Barretos, SP (Brazil); Rossi, Bruna F.; Quinalha, Marília M. [UNESP – Univ. Estadual Paulista, Botucatu Biosciences Institute, Department of Morphology, Botucatu, SP (Brazil); Kass, Laura; Muñoz-de-Toro, Mónica [UNL – Universidad Nacional del Litoral, School of Biochemistry and Biological Sciences, Human Pathology Department, Instituto de Salud y Ambiente del Litoral (ISAL, CONICET-UNL), Santa Fe (Argentina); Barbisan, Luís F., E-mail: barbisan@ibb.unesp.br [UNESP – Univ. Estadual Paulista, Botucatu Biosciences Institute, Department of Morphology, Botucatu, SP (Brazil)

    2016-07-15

    This study aimed to evaluate the modifying effects of dietary genistein (GEN) and indole-3-carbinol (I3C) on early mammary gland development in female Sprague-Dawley offspring born to mothers exposed to BPA during gestation. Pregnant rats were treated with BPA25 or 250 μg/kg bw/day from gestational days 10 to 21 with or without dietary intake of GEN (250 mg/kg chow) or I3C (2000 mg/kg chow). At post-natal day (PND) 21, female offspring from different litters were euthanized for mammary gland development and gene expression analyses. Our results indicated that prenatal exposure to BPA25 and 250 did not modify the ductal elongation of the mammary gland tree or the estrogen receptor alpha (ER-α) expression in terminal end buds (TEBs). However, BPA25-exposed offspring had a higher number of terminal structures (TEBs + TDs) and an increased mammary branching and cell proliferation index in TEBs. Besides that, BPA25 and 250 modulated the expression of several genes in the immature mammary gland that were not changed in a dose dependent manner and involved different clusters of up- and down-regulated genes. Furthermore, BPA25 and BPA250 + I3C-treated groups also had a higher number of enriched functional gene categories. In addition, maternal dietary GEN and I3C in association with BPA exposure produced specific gene expression alterations in the mammary gland and overcome the adverse effect of BPA25, decreasing the branching of the mammary gland. In conclusion, prenatal BPA exposure induced both morphological and gene expression modifications on the mammary gland that dietary intake of GEN and I3C reverted on BPA25-exposed animals. - Highlights: • Gestational BPA and its association with GEN and I3C modify gene expression on the early mammary gland development. • GEN and I3C induced a different gene expression signature than lower BPA dose. • Dietary GEN and I3C countered the adverse effect of lower BPA dose on the cell proliferation and mammary gland development.

  13. Peri-OVLT E-series prostaglandins and core temperature do not increase after intravenous IL-1beta in pregnant rats.

    Science.gov (United States)

    Fewell, James E; Eliason, Heather L; Auer, Roland N

    2002-08-01

    Rats have an attenuated febrile response to endogenous pyrogen near the term of pregnancy. Given the fundamental role of E-series prostaglandins (PGEs) in mediating the febrile response to blood-borne endogenous pyrogen, the present experiments were carried out to determine whether PGEs increase in the area surrounding the organum vasculosum laminae terminalis (peri-OVLT) of near-term pregnant (P) rats as in nonpregnant (NP) rats after intravenous (iv) administration of recombinant rat interleukin-1beta (rrIL-1beta). Core temperature was measured by telemetry and peri-OVLT interstitial fluid was sampled in 12 NP and 12 P chronically instrumented, Sprague-Dawley rats by microdialysis for determination of total PGEs by radioimmunoassay. Basal core temperatures were higher in NP compared with P rats (NP 37.9 degrees C +/- 0.5, P 36.9 degrees C +/- 0.4; P endogenous pyrogen near the term of pregnancy, warrants further investigation.

  14. Impact of tamsulosin and nifedipine on contractility of pregnant rat ureters in vitro.

    Science.gov (United States)

    Haddad, Lisette; Corriveau, Stéphanie; Rousseau, Eric; Blouin, Simon; Pasquier, Jean-Charles; Ponsot, Yves; Roy-Lacroix, Marie-Ève

    2018-01-01

    To evaluate the in vitro effect of tamsulosin and nifedipine on the contractility of pregnant rat ureters and to perform quantitative analysis of the pharmacological effects. Medical expulsive therapy (MET) is commonly used to treat urolithiasis. However, this treatment is seldom used in pregnant women since no studies support this practice. This was an in vitro study on animal tissue derived from pregnant Sprague-Dawley rats. A total of 124 ureteral segments were mounted in an organ bath system and contractile response to methacholine (MCh) was assessed. Tamsulosin or nifedipine were added at cumulative concentrations (0.001-1 μM). The area under the curve (AUC) from isometric tension measurements was calculated. The effect of pharmacological agents and the respective controls were assessed by calculating the AUC for each 5-min interval. Statistical analyses were performed using the Mann-Whitney-Wilcoxon nonparametric test. Both drugs displayed statistically significant inhibitory activity at concentrations of 0.1 and 1 μM for tamsulosin and 1 μM for nifedipine when calculated as the AUC as compared to DMSO controls. Tamsulosin and nifedipine directly inhibit MCh-induced contractility of pregnant rat ureters. Further work is needed to determine the clinical efficacy of these medications for MET in pregnancy.

  15. Efektivitas ekstrak umbi sarang semut (myrmecodia pendens merr.& perry sebagai penurun kadar glukosa darah tikus sprague dawley yang diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Maxianus Kopong Raya

    2016-06-01

    Full Text Available Background : Diabetes Mellitus (DM is a disease associated with pancreatic β cell damage and causes hyperglycemia Antioxidants were effective in reducing the state of hyperglycemia that was triggered by free radicals. Sarang semut contains flavonoids and tannins that act as antioxidants. Objective : The purpose to analyze the effectiveness of sarang semut stem extract as lowering blood glucose on diabetic white male Sprague Dawley rats. Method : True experimental with 30 rats which divided into five groups : negative control (DM+ water, positive control (DM+glibenklamid and 3 treatment groups of DM + water extract of  sarang semut stem powder 90 mg/200gBW, 180 mg/200g BW and 360/200g BW respectively. DM was induced by 65mg/kgBW Streptozotocin and 230 mg/kgBW Nicotinamide intraperitonealy. Extract was given by sonde. The data was analyzed by Kruskall-Wallis and Mann-Whitney. Results : IC50 value of  sarang semut stem extract were 6,56-10,07 mg/ml in powder and 9,12-15,62 mg/ml whole. The average rats weight alteration on groups of negative control, positive control,  and 3 treatment groups of DM + water extract of  sarang semut stem powder 90 mg/200gBW, 180 mg/200g BW and 360/200g BW before and after treatment were -7,60± -0,40; 25,80±0,51; 16,40±0,44; 17,20±1,28 dan 19,20±0,06 gram respectively (ρ=0,001. The average fasting blood glucose level on groups of negative control, positive control,  and 3 treatment groups of DM + water extract of  sarang semut stem powder 90 mg/200gBW, 180 mg/200g BW and 360/200g BW before and after treatment were 3,33±2,42; -122,44±-0,51; -79,42±-11,38; -94,08±-11,97 and -134,66±-2,59 mg/dL respectively (ρ=0,001. Conclusion : The IC50­ value in sarang semut stem powder was higher than a whole form. Dose of 360 mg/200g BW lowered blood glucose better than 90 and 180 /200g BW dosage.

  16. Cummulative effects of a 9 phthalate mixture using DEHP, DiHP, DiBP, DBP, BBP, DCHP, D(hexyl)P,D(heptyl)P and DPeP on Charles River-Sprague Dawley (CR-SD) fetal rat testis testosterone(T) production and gene expression

    Science.gov (United States)

    In utero exposure to mixtures of 2 to 5 phthalate esters (PE) with similar modes of action have been shown to inhibit male reproductive development in a dose-additive fashion. Further when PE were administered to pregnant dams during the period of sexual differentiation, when rep...

  17. Ensayo de inmunogenicidad y toxicidad local del cocleato de Neisseriameningitidis en ratas Sprague Dawley

    Directory of Open Access Journals (Sweden)

    Juan F. Infante

    2009-04-01

    Full Text Available Los estudios de tolerancia local para productos vacunales resultan fundamentales como requisitos regulatorios para los estudios preclínicos. En este ensayo se utilizaron 48 ratas Sprague Dawley, de ambos sexos, con un peso corporal de 180-220 g, suministradas por el Centro Nacional para la Producción de Animales de Laboratorio, y una duración de 17 días. Las ratas fueron distribuidas en 5 grupos: 3 con diferentes concentraciones de cocleatos, uno sin inocular y otro que recibió el diluente del producto en prueba. A estas se les realizaron las observaciones clínicas necesarias, tales como: mediciones de incremento de peso, consumo de alimentos y agua, así como la evaluación anatomopatológica en los dos tiempos de sacrificio, uno a los 12 y otro a los 17 días; se enfatizó en el estudio histopatológico de encéfalo y las fosas nasales en tres niveles de su extensión. Se hicieron investigaciones inmunológicas consistentes en la determinación de IgG en suero, saliva y líquido cefalorraquídeo. Los resultados arrojaron un incremento del peso. En el consumo de agua y alimento no se observaron alteraciones clínicas, la anatomopatología evidenció discretos cambios inflamatorios que guardaron una relación directa con el aumento de las concentraciones del producto, los títulos de IgG en la saliva y suero de las ratas inoculadas con los cocleatos difirieron de forma significativa (P < 0,05 respecto a los grupos controles, el líquido cefalorraquídeo resultó negativo a la presencia de anticuerpos específicos IgG. Se concluye que los cocleatos aplicados por esta vía en ratas resultaron inmunogénicos e inocuos para el referido producto.

  18. Caracterización del apego materno en ratas wistar y sprague dawley

    Directory of Open Access Journals (Sweden)

    Norma A. Moy-López

    2008-01-01

    Full Text Available Después del parto, las señales sensoriales que emiten las crías contribuyen al establecimiento de la conducta maternal (CM y la formación del apego materno (AM, entendido éste último como "la capacidad conductual y emocional de formar un vínculo selectivo, único y duradero de la cría hacia la madre y viceversa" [1]. El objetivo del presente trabajo fue sistematizar y caracterizar el AM en dos cepas de ratas (Rattus novergicus: Wistar (W y Sprague Dawley (SD. Se registró la frecuencia en las conductas de transporte, búsqueda, olfateo, limpieza de las madres antes, durante y después de la gestación (n= 5/cepa, encontrando diferencias significativas entre cepas sólo en la fase de gestación (Z = 2.19, P<0.05. El AM fue clasificado como alto y bajo con base a la frecuencia de conductas de madre hacia las crías y viceversa (promedio ± 1 DE. No se encontraron diferencias significativas entre el sexo y tipo de AM; sin embargo, la cepa SD mostró una tendencia de preferencia hacia los machos para el apego alto y hacia las hembras para el apego bajo. Al analizar el vínculo madre-cría, en la cepa W se encontró una correlación positiva entre CM y conducta de búsqueda de las crías hacia la madre (r = 0.91, mientras que en la SD la correlación es baja (r = -0.42. Estos datos muestran que en la cepa W el vínculo madre-crías se puede identificar con mayor claridad y que el protocolo diseñado para la evaluación del AM es sensible a las variaciones naturales de la CM por camada y por cepa.

  19. Estereología Comparativa entre el Bazo del Cuye (Cavia porcellus) y la Rata (Rattus novergicus, Sprague Dawley)

    OpenAIRE

    Furrianca, María Cristina; Vásquez, Bélgica; del Sol, Mariano

    2008-01-01

    El bazo es el órgano linfático periférico más grande del organismo y conocer sus aspectos morfológicos cuantitativos es importante para determinar posibles patologías. El objetivo del estudio fue determinar en dos especies: cuye (Cavia porcellus) y rata (Rattus novergicus Sprague Dawley), las características estereológicas del bazo, para obtener patrones de normalidad cuantitativos, los que servirán de base para futuros estudios morfofuncionales. Se utilizaron 5 bazos de cada especie, clínica...

  20. Teratogenicity and metabolism of water-soluble forms of vitamin A in the pregnant rat

    International Nuclear Information System (INIS)

    Gunning, D.B.; Barua, A.B.; Olson, J.A.

    1990-01-01

    Retinoyl β-glucuronide, unlike retinoic acid, has been shown to be non-teratogenic when administered orally, even in large doses, to pregnant rats. The degree to which water-solubility is associated with low teratogenicity is not known. Other water-soluble forms of vitamin A have now been synthesized in our laboratory and are being evaluated for teratogenicity. New water-soluble forms of vitamin A were administered orally to pregnant Sprague-Dawley rats in a single dose of 0.35 mmole/kg bw on day 8 of gestation. On day 19, the dams were sacrificed and the litters were examined. Control animals received either vehicle only or an equivalent dose of all-trans retinoic acid. Maternal and fetal tissues were taken and analyzed by HPLC for vitamin A metabolites. In another experiment, a large single oral dose of the radiolabelled water-soluble compound was administered on day 10. At either 30 minutes or 1 hour after the dose, dams were sacrificed and the embryos analyzed both for radioactivity and for specific metabolites. In contrast to retinoyl β-glucuronide, retinoyl β-glucose is highly teratogenic under identical conditions. Thus, water-solubility does not seem to be the determining factor in the teratogenicity of retinoic acid conjugates

  1. Bioavailability of HBCD/TBB/TBPH from dust and oil vehicles in Sprague-Dawley rats

    Science.gov (United States)

    Recent data have revealed that homes, offices and cars are often more polluted with environmental contaminants than the outdoors due to high use of textiles, electronics, and insulation that are treated with brominated flame retardants (BFRs). BFRs volatilize and/or weather from consumer products a...

  2. Reproductive Toxicity Screen of Trifluoroiodomethane (CF31) in Sprague-Dawley Rats

    National Research Council Canada - National Science Library

    Dodd, Darol

    1998-01-01

    .... The purpose of this study was to determine and evaluate the potential for CF3I to produce reproductive toxicity and to provide additional information on the effect of CF3I exposure on the thyroid...

  3. Acute Oral Toxicity of DIGL-RP Solid Propellant in Sprague-Dawley Rats

    Science.gov (United States)

    1989-11-30

    protein droplet and cast formation, glomeruli and cortical tubules Liver--diffuse vacuolation Stomach--multifocal, acute, necrotizing gastritis ...The choice of tissues examined histologically was biased by gross evaluation. Indications of renal protein loss were noted in five animals (casts and

  4. Subacute Oral Toxicity Study of Korean Red Ginseng Extract in Sprague-Dawley Rats

    OpenAIRE

    Park, Sang-Jin; Lim, Kwang-Hyun; Noh, Jeong-Ho; Jeong, Eun Ju; Kim, Yong-Soon; Han, Byung-Cheol; Lee, Seung-Ho; Moon, Kyoung-Sik

    2013-01-01

    Ginseng is a well-known traditional medicine used in Asian countries for several thousand years, and it is currently applied to medicine, cosmetics, and nutritional supplements due to its many healing and energygiving properties. It is well demonstrated that ginsenosides, the main ingredient of ginseng, produce a variety of pharmacological and therapeutic effects on central nerve system (CNS) disorders, cardiovascular disease, endocrine secretions, aging, and immune function. Korean red ginse...

  5. Heterotopic Ossification Following Extremity Blast Amputation: An Animal Model in the Sprague Dawley Rat

    Science.gov (United States)

    2016-03-01

    extremity injuries and our animal model. We hope to identify various surgical and medical techniques to reduce heterotopic bone formation, potentially...analyses. J Bone Joint Surg 1976; 58: 453–458. 4. Barr JE. Principles of wound cleansing. Ostomy Wound Manage 1995; 41(7A Suppl.):15S–21S; Discussion 22S 5

  6. Accretion of visceral fat and hepatic insulin resistance in pregnant rats.

    Science.gov (United States)

    Einstein, Francine H; Fishman, Sigal; Muzumdar, Radhika H; Yang, Xiao Man; Atzmon, Gil; Barzilai, Nir

    2008-02-01

    Insulin resistance (IR) is a hallmark of pregnancy. Because increased visceral fat (VF) is associated with IR in nonpregnant states, we reasoned that fat accretion might be important in the development of IR during pregnancy. To determine whether VF depots increase in pregnancy and whether VF contributes to IR, we studied three groups of 6-mo-old female Sprague-Dawley rats: 1) nonpregnant sham-operated rats (Nonpreg; n = 6), 2) pregnant sham-operated rats (Preg; n = 6), and 3) pregnant rats in which VF was surgically removed 1 mo before mating (PVF-; n = 6). VF doubled by day 19 of pregnancy (Nonpreg 5.1 +/- 0.3, Preg 10.0 +/- 1.0 g, P Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp in late gestation in chronically catheterized unstressed rats. Glucose IR (mg.kg(-1).min(-1)) was highest in Nonpreg (19.4 +/- 2.0), lowest in Preg (11.1 +/- 1.4), and intermediate in PVF- (14.7 +/- 0.6; P insulin sensitivity than Preg [hepatic glucose production (HGP): Nonpreg 4.5 +/- 1.3, Preg 9.3 +/- 0.5 mg.kg(-1).min(-1); P insulin sensitivity was similar to nonpregnant levels in PVF- (HGP 4.9 +/- 0.8 mg.kg(-1).min(-1)). Both pregnant groups had lower peripheral glucose uptake compared with Nonpreg. In parallel with hepatic insulin sensitivity, hepatic triglyceride content was increased in pregnancy (Nonpreg 1.9 +/- 0.4 vs. Preg 3.2 +/- 0.3 mg/g) and decreased with removal of VF (PVF- 1.3 +/- 0.4 mg/g; P insulin action in pregnancy.

  7. Effects of maternal acrolein exposure during pregnancy on testicular testosterone production in fetal rats

    OpenAIRE

    Yang, Yuzhuo; Zhang, Zhe; Zhang, Hongliang; Hong, Kai; Tang, Wenhao; Zhao, Lianming; Lin, Haocheng; Liu, Defeng; Mao, Jiaming; Wu, Han; Jiang, Hui

    2017-01-01

    Acrolein has been reported to have diverse toxic effects on various organs, including the reproductive system. However, little is known regarding the effects of maternal acrolein exposure on testicular steroidogenesis in male offspring. The present study investigated the effects of acrolein on fetal testosterone production and associated genes. Pregnant Sprague-Dawley rats were intraperitoneally injected with vehicle (normal saline) or 1, 2 or 5 mg/kg acrolein from gestational day (GD) 14?20,...

  8. Maternal Melatonin Therapy Rescues Prenatal Dexamethasone and Postnatal High-Fat Diet Induced Programmed Hypertension in Male Rat Offspring

    OpenAIRE

    Tain, You-Lin; Sheen, Jiunn-Ming; Yu, Hong-Ren; Chen, Chih-Cheng; Tiao, Mao-Meng; Hsu, Chien-Ning; Lin, Yu-Ju; Kuo, Kuang-Che; Huang, Li-Tung

    2015-01-01

    Prenatal dexamethasone (DEX) exposure and high-fat (HF) intake are linked to hypertension. We examined whether maternal melatonin therapy prevents programmed hypertension synergistically induced by prenatal DEX plus postnatal HF in adult offspring. We also examined whether DEX and melatonin causes renal programming using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received intraperitoneal dexamethasone (0.1 mg/kg) or vehicle from gestational day 16 to 22. In ...

  9. PENURUNAN KADAR GULA DARAH AKIBAT PEMBERIAN EXTRA VIRGIN OLIVE OIL (Studi pada Tikus Galur Sprague Dawley yang Diinduksi Pakan Tinggi Lemak

    Directory of Open Access Journals (Sweden)

    SH Bintari

    2013-07-01

    Full Text Available Prevalensi penyakit diabetes mengalami peningkatan dari tahun ke tahun. Salah satu penyebabnya adalah hiperglikemia yang dipicu oleh pola makan tinggi lemak. Alternatif cara pengobatan dan pencegahannya adalah mengkonsumsi minyak zaitun. Diperlukan bukti ilmiah bahwa minyak zaitun dapat menurunkan kadar gula darah. Tujuan penelitian ini adalah mengetahui pengaruh pemberian minyak zaitun ekstra virgin terhadap kadar glukosa darah tikus putih yang diinduksi pakan tinggi lemak. Desain penelitian pre experimental dengan rancangan post test only randomized controlled group design. Subjek penelitian adalah 28 ekor tikus putih jantan galur Sprague Dawley usia 8 minggu, berat badan 180-220 gram, dan kondisi sehat. Tikus dibagi menjadi empat kelompok secara simple random sampling. Kelompok kontrol diberi akuades, kelompok perlakuan P1, P2, dan P3 berturut-turut diberi minyak zaitun ekstra virgin sebanyak 0,5 g/hari; 0,7 g/hari; dan 0,9 g/hari. Penelitian dilakukan selama 6 minggu. Pengukuran kadar glukosa darah menggunakan metode glukosa oksidase (GOD PAP. Data dianalisis dengan uji Kruskal Wallis dengan derajat kemaknaan 95%. Pemberian minyak zaitun ekstra virgin pada dosis 0,5 g/hari; 0,7 g/hari; dan 0,9 g/hari dapat menurunkan kadar glukosa darah tikus putih. Penurunan ini terbukti bermakna pada semua kelompok perlakuan. Persentase penurunan kadar glukosa darah paling tinggi ditemukan pada dosis pemberian 0,9 gram/hari yaitu sebesar 62,23%. Minyak zaitun ekstra virgin terbukti dapat menurunkan kadar gula darah akibat dislipidemia. The prevalence of diabetes has increased from year to year. It is caused by hyperglycemia induced by high-fat diet. Several alternative methods of treatment and prevention widely used is consuming olive oil. Therefore we need scientific evidence that olive oil can lowered blood sugar levels. The purpose of research to determine the effects of extra virgin olive oil on blood glucose levels of white rats induced by high

  10. Disposition of diiosononyl phthalate and its effects on sexual development of the male fetus following repeated dosing in pregnant rats.

    Science.gov (United States)

    Clewell, Rebecca A; Sochaski, Mark; Edwards, Kendra; Creasy, Dianne M; Willson, Gabrielle; Andersen, Melvin E

    2013-01-01

    Pregnant Sprague-Dawley rats received 50, 250, and 500 mg/kg/day diisononyl phthalate (DiNP) from GD 12 to 19 via corn oil gavage to study the dose response for effects on fetal male rat sexual development as well as metabolite disposition in the dam and fetus. Monoisononyl phthalate (MiNP), mono(carboxy-isooctyl) phthalate (MCiOP), mono(hydroxyl-isononyl) phthalate (MHiNP), mono(oxo-isononyl) phthalate (MOiNP), and monoisononyl phthalate glucuronide (MiNP-G) were found in all measured tissues. MCiOP was the major metabolite, followed in decreasing order by MiNP, MHiNP, MOiNP, and MiNP-G. Percentage of dose absorbed decreased at 750 mg/kg/day. Testosterone concentration in the fetal testes was reduced at 250 and 750 mg/kg/day. Multinucleated germ cells were increased in the testes of rats at 250 and 750 mg/kg/day. The no observed effect level (NOEL) for this study was 50 mg/kg/day based on increased MNGs and reduced testes testosterone concentration in the fetal rat. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Effect of Light and Darkness on Packed Cell Volume in the Rat ...

    African Journals Online (AJOL)

    The aim of the study is to identify and characterize the circadian oscillation of Packed Cell Volume (PCV) within a 24-hour time frame in adult Sprague-Dawley rats. 56 adult Sprague-Dawley rats consists of 28 male and 28 female rats were used. Male animals weighed 150-170g while the females weighed 130140g.

  12. Comparación entre dos biomodelos murinos (ratones Balb/c y ratas Sprague Dawley en el ensayo de micronúcleos transplacentarios

    Directory of Open Access Journals (Sweden)

    Daniel Francisco Arencibia Arrebola

    2012-03-01

    Full Text Available Objetivo: comparar fetos de ratones Balb/c y ratas Sprague Dawley como biomodelos en el ensayo de micronúcleos transplacentarios, determinando la frecuencia espontánea e inducida, y vincular el efecto genotóxico y reproductivo. Métodos: se formaron tres grupos experimentales/especie: control negativo (simulacro, control solvente NaCl (0,9 % y ciclofosfamida 50 mg/kg. Todos los grupos se administraron por vía intraperitoneal los días 14, 15 y 16 de la gestación, y 24 h después de la última inoculación en ratones y 48 h en ratas se procedió a realizar la eutanasia de las gestantes, para obtener las muestras de hígado fetal. Resultados: los fetos de ratas Sprague Dawley demostraron tener menores índices de citotoxicidad y de genotoxicidad, y se obtuvieron los resultados más bajos de micronúcleos endógenos. Los mejores resultados de inducción de citotoxicidad y genotoxicidad por la alta formación de micronúcleos con ciclofosfamida fueron en fetos de ratas Sprague Dawley, los que resultaron más susceptibles al daño genotóxico de este mutágeno. Se corroboró el poder clastogénico transplacentario de la ciclofosfamida, vinculando este ensayo de genotoxicidad a toxicología de la reproducción. Conclusiones: los resultados sugieren el mejor uso de fetos de ratas Sprague Dawley como biomodelo en este ensayo cuando es utilizada la ciclofosfamida como control positivo por la vía y dosis estudiada; además, se pudieran utilizar en la evaluación de nuevas drogas con carácter antigenotóxico por vía transplacentaria.

  13. Maternal adipose tissue becomes a source of fatty acids for the fetus in fasted pregnant rats given diets with different fatty acid compositions.

    Science.gov (United States)

    López-Soldado, Iliana; Ortega-Senovilla, Henar; Herrera, Emilio

    2017-11-10

    The utilization of long-chain polyunsaturated fatty acids (LCPUFA) by the fetus may exceed its capacity to synthesize them from essential fatty acids, so they have to come from the mother. Since adipose tissue lipolytic activity is greatly accelerated under fasting conditions during late pregnancy, the aim was to determine how 24 h fasting in late pregnant rats given diets with different fatty acid compositions affects maternal and fetal tissue fatty acid profiles. Pregnant Sprague-Dawley rats were given isoenergetic diets containing 10% palm-, sunflower-, olive- or fish-oil. Half the rats were fasted from day 19 of pregnancy and all were studied on day 20. Triacylglycerols (TAG), glycerol and non-esterified fatty acids (NEFA) were analyzed by enzymatic methods and fatty acid profiles were analyzed by gas chromatography. Fasting caused increments in maternal plasma NEFA, glycerol and TAG, indicating increased adipose tissue lipolytic activity. Maternal adipose fatty acid profiles paralleled the respective diets and, with the exception of animals on the olive oil diet, maternal fasting increased the plasma concentration of most fatty acids. This maintains the availability of LCPUFA to the fetus during brain development. The results show the major role played by maternal adipose tissue in the storage of dietary fatty acids during pregnancy, thus ensuring adequate availability of LCPUFA to the fetus during late pregnancy, even when food supply is restricted.

  14. Effects of High Intensity Interval Training on Pregnant Rats, and the Placenta, Heart and Liver of Their Fetuses.

    Science.gov (United States)

    Songstad, Nils Thomas; Kaspersen, Knut-Helge Frostmo; Hafstad, Anne Dragøy; Basnet, Purusotam; Ytrehus, Kirsti; Acharya, Ganesh

    2015-01-01

    To investigate the effects of high intensity interval training (HIIT) on the maternal heart, fetuses and placentas of pregnant rats. Female Sprague-Dawley rats were randomly assigned to HIIT or sedentary control groups. The HIIT group was trained for 6 weeks with 10 bouts of high intensity uphill running on a treadmill for four minutes (at 85-90% of maximal oxygen consumption) for five days/week. After three weeks of HIIT, rats were mated. After six weeks (gestational day 20 in pregnant rats), echocardiography was performed to evaluate maternal cardiac function. Real-time PCR was performed for the quantification of gene expression, and oxidative stress and total antioxidant capacity was assessed in the tissue samples. Maternal heart weight and systolic function were not affected by HIIT or pregnancy. In the maternal heart, expression of 11 of 22 genes related to cardiac remodeling was influenced by pregnancy but none by HIIT. Litter size, fetal weight and placental weight were not affected by HIIT. Total antioxidant capacity, malondialdehyde content, peroxidase and superoxide dismutase activity measured in the placenta, fetal heart and liver were not influenced by HIIT. HIIT reduced the expression of eNOS (p = 0.03), hypoxia-inducible factor 1α (p = 0.04) and glutathione peroxidase 4.2 (p = 0.02) in the fetal liver and increased the expression of vascular endothelial growth factor-β (p = 0.014), superoxide dismutase 1 (p = 0.001) and tissue inhibitor of metallopeptidase 3 (p = 0.049) in the fetal heart. Maternal cardiac function and gene expression was not affected by HIIT. Although HIIT did not affect fetal growth, level of oxidative stress and total antioxidant capacity in the fetal tissues, some genes related to oxidative stress were altered in the fetal heart and liver indicating that protective mechanisms may be activated.

  15. Effects of High Intensity Interval Training on Pregnant Rats, and the Placenta, Heart and Liver of Their Fetuses

    Science.gov (United States)

    Hafstad, Anne Dragøy; Basnet, Purusotam; Ytrehus, Kirsti; Acharya, Ganesh

    2015-01-01

    Objective To investigate the effects of high intensity interval training (HIIT) on the maternal heart, fetuses and placentas of pregnant rats. Methods Female Sprague-Dawley rats were randomly assigned to HIIT or sedentary control groups. The HIIT group was trained for 6 weeks with 10 bouts of high intensity uphill running on a treadmill for four minutes (at 85–90% of maximal oxygen consumption) for five days/week. After three weeks of HIIT, rats were mated. After six weeks (gestational day 20 in pregnant rats), echocardiography was performed to evaluate maternal cardiac function. Real-time PCR was performed for the quantification of gene expression, and oxidative stress and total antioxidant capacity was assessed in the tissue samples. Results Maternal heart weight and systolic function were not affected by HIIT or pregnancy. In the maternal heart, expression of 11 of 22 genes related to cardiac remodeling was influenced by pregnancy but none by HIIT. Litter size, fetal weight and placental weight were not affected by HIIT. Total antioxidant capacity, malondialdehyde content, peroxidase and superoxide dismutase activity measured in the placenta, fetal heart and liver were not influenced by HIIT. HIIT reduced the expression of eNOS (p = 0.03), hypoxia-inducible factor 1α (p = 0.04) and glutathione peroxidase 4.2 (p = 0.02) in the fetal liver and increased the expression of vascular endothelial growth factor-β (p = 0.014), superoxide dismutase 1 (p = 0.001) and tissue inhibitor of metallopeptidase 3 (p = 0.049) in the fetal heart. Conclusions Maternal cardiac function and gene expression was not affected by HIIT. Although HIIT did not affect fetal growth, level of oxidative stress and total antioxidant capacity in the fetal tissues, some genes related to oxidative stress were altered in the fetal heart and liver indicating that protective mechanisms may be activated. PMID:26566220

  16. Effects of High Intensity Interval Training on Pregnant Rats, and the Placenta, Heart and Liver of Their Fetuses.

    Directory of Open Access Journals (Sweden)

    Nils Thomas Songstad

    Full Text Available To investigate the effects of high intensity interval training (HIIT on the maternal heart, fetuses and placentas of pregnant rats.Female Sprague-Dawley rats were randomly assigned to HIIT or sedentary control groups. The HIIT group was trained for 6 weeks with 10 bouts of high intensity uphill running on a treadmill for four minutes (at 85-90% of maximal oxygen consumption for five days/week. After three weeks of HIIT, rats were mated. After six weeks (gestational day 20 in pregnant rats, echocardiography was performed to evaluate maternal cardiac function. Real-time PCR was performed for the quantification of gene expression, and oxidative stress and total antioxidant capacity was assessed in the tissue samples.Maternal heart weight and systolic function were not affected by HIIT or pregnancy. In the maternal heart, expression of 11 of 22 genes related to cardiac remodeling was influenced by pregnancy but none by HIIT. Litter size, fetal weight and placental weight were not affected by HIIT. Total antioxidant capacity, malondialdehyde content, peroxidase and superoxide dismutase activity measured in the placenta, fetal heart and liver were not influenced by HIIT. HIIT reduced the expression of eNOS (p = 0.03, hypoxia-inducible factor 1α (p = 0.04 and glutathione peroxidase 4.2 (p = 0.02 in the fetal liver and increased the expression of vascular endothelial growth factor-β (p = 0.014, superoxide dismutase 1 (p = 0.001 and tissue inhibitor of metallopeptidase 3 (p = 0.049 in the fetal heart.Maternal cardiac function and gene expression was not affected by HIIT. Although HIIT did not affect fetal growth, level of oxidative stress and total antioxidant capacity in the fetal tissues, some genes related to oxidative stress were altered in the fetal heart and liver indicating that protective mechanisms may be activated.

  17. Blood burden of di(2-ethylhexyl) phthalate and its primary metabolite mono(2-ethylhexyl) phthalate in pregnant and nonpregnant rats and marmosets

    International Nuclear Information System (INIS)

    Kessler, Winfried; Numtip, Wanwiwa; Grote, Konstanze; Csanady, Gyoergy A.; Chahoud, Ibrahim; Filser, Johannes G.

    2004-01-01

    A comparison of the dose-dependent blood burden of di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate (MEHP) in pregnant and nonpregnant rats and marmosets is presented. Sprague-Dawley rats and marmosets were treated orally with 30 or 500 mg DEHP/kg per day, nonpregnant animals on 7 (rats) and 29 (marmosets) consecutive days, pregnant animals on gestation days 14-19 (rats) and 96-124 (marmosets). In addition, rats received a single dose of 1000 mg DEHP/kg. Blood was collected up to 48 h after dosing. Concentrations of DEHP and MEHP in blood were determined by GC/MS. In rats, normalized areas under the concentration-time curves (AUCs) of DEHP were two orders of magnitude smaller than the normalized AUCs of the first metabolite MEHP. Metabolism of MEHP was saturable. Repeated DEHP treatment and pregnancy had only little influence on the normalized AUC of MEHP. In marmosets, most of MEHP concentration-time courses oscillated. Normalized AUCs of DEHP were at least one order of magnitude smaller than those of MEHP. In pregnant marmosets, normalized AUCs of MEHP were similar to those in nonpregnant animals with the exception that at 500 mg DEHP/kg per day, the normalized AUCs determined on gestation days 103, 117, and 124 were distinctly smaller. The maximum concentrations of MEHP in blood of marmosets were up to 7.5 times and the normalized AUCs up to 16 times lower than in rats receiving the same daily oral DEHP dose per kilogram of body weight. From this toxicokinetic comparison, DEHP can be expected to be several times less effective in the offspring of marmosets than in that of rats if the blood burden by MEHP in dams can be regarded as a dose surrogate for the MEHP burden in their fetuses

  18. Role of Nitric Oxide Synthase on Blood Pressure Regulation and Vascular Function in Pregnant Rats on a High-Fat Diet.

    Science.gov (United States)

    Palei, Ana C; Spradley, Frank T; Granger, Joey P

    2017-03-01

    While obesity is a leading risk factor for preeclampsia, the mechanisms whereby obese women are more susceptible to pregnancy-induced hypertension are unclear. As high-fat diet (HFD) is an important contributor to the development of obesity, we tested the hypothesis that pregnant rats on HFD have hypertension and endothelial dysfunction due to reduced nitric oxide synthase (NOS). Twelve-week-old Sprague-Dawley female rats were fed normal diet (ND, 13% fat kcal) or HFD (40% fat kcal) for 9 weeks. Timed-pregnant rats were then generated and the effect of HFD on mean arterial blood pressure (MAP) and vascular function was assessed on gestational day (GD) 19. MAP was not different between HFD and ND pregnant rats. Intriguingly, sensitivity to acetylcholine-induced endothelium-dependent vasorelaxation was enhanced in small mesenteric arteries of HFD dams compared to ND controls (logEC50 -7.9 ± 0.3 vs. -6.7 ± 0.3 M; P hydrochloride (100 mg/l, drinking water) from GD 14 to 19. It was found that NOS inhibition increased MAP equally in HFD and ND groups. Contrary to our initial hypothesis, HFD dams were normotensive and presented increased endothelial function and NO/NOS3 levels. This enhanced NOS-mediated vascular function does not appear to have a major impact on blood pressure regulation of HFD-fed pregnant rats. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  19. Potential of Anti Breast Cancer Black Ethanol Rice Extract (Oryza sativa L. indica In Decreasing Levels of CA 15-3 Serum in the White Mice Sprague dawley in Induction 7.12-Dimethylbenz (α Antracene (DMBA and Estrogen

    Directory of Open Access Journals (Sweden)

    Zanuar Abidin

    2017-01-01

    Full Text Available Breast cancer is cancer that has the high incidence in Indonesia. Black rice (Oryza sativa L. indica is a plant that has an anticancer potency. This research aim is to prove black rice as a potential anticancer by using experimental animals, 20 Sprague Dawley female rats aged 7-8 weeks induced breast cancer by using the combination of 7,12-dimethylbenz (α anthracene (DMBA and estrogen. Rats were divided into two groups, namely the K-induced breast cancer and a group of P-induced cancer and treated with black rice. Black rice is given in the form of ethanol extract at a dose of 75 mg / kg / day for six weeks. Levels of CA 15-3 serum are used as a parameter. The result showed that the differences in levels of serum CA 15-3 are significant (p <0.05. Serum CA 15-3 level in P group is lower than in K group. This study proved that the ethanol extract of black rice (Oryza sativa L. indica has potential as an anticancer breast as indicated by decreased level of serum CA 15-3

  20. Distribution of 14C-morphine and macromolecules in the brain and liver and their nuclei in pregnant rats and their foetuses after infusion of morphine into pregnant rats at near-term

    International Nuclear Information System (INIS)

    Steele, W.J.; Johannesson, T.

    1975-01-01

    Timed-pregnant (day 21 or 22) Sprague-Dawley rats were administered 14 C-morphine (2.85 mci/mmol) 5 mg/kg/hr, or saline in equivalent volumes, by continuous intravenous infusion for periods of up to 4hrs. The brains and livers of the maternal rats and of their foetuses were collected and their nuclei were isolated. The tissues and nuclei isolated from them were analyzed for DNA, RNA, protein content and radioactivity. Morphine infused maternal rats exhibited no significant difference in the total amount of DNA, RNA and protein in the brain or in the concentration of these constituents in brain nuclei. The concentration of nuclear RNA in foetal brain of morphine infused mothers was significantly lower at 4 hrs than that of saline infused controls. It was concluded that RNA synthesis in the foetal brain must be much more sensitive to the inhibitory effect of morphine on macromolecular synthesis than that in maternal brain. The change in nuclear RNA concentration in foetal brain became significantly different when morphine reached its highest level in foetal brain nuclei. The morphine concentration (pmol 14 C-morphine equivalents per mg DNA) in the brain of foetal and maternal rats was the same at each time period, whereas the maternal liver levels were at least eight times greater than those in foetal liver. The concentrations in foetal brain nuclei were 2-14 times greater than those in maternal brain nuclei, whereas levels in the latter were found to be low and virtually constant at all time periods tested. It was concluded that foetal brain nuclei have a greater capacity to bind or retain morphine than maternal brain nuclei. (author)

  1. Distribution of /sup 14/C-morphine and macromolecules in the brain and liver and their nuclei in pregnant rats and their foetuses after infusion of morphine into pregnant rats at near-term

    Energy Technology Data Exchange (ETDEWEB)

    Steele, W J; Johannesson, T [Iowa Univ., Iowa City (USA)

    1975-01-01

    Timed-pregnant (day 21 or 22) Sprague-Dawley rats were administered /sup 14/C-morphine (2.85 mci/mmol) 5 mg/kg/hr, or saline in equivalent volumes, by continuous intravenous infusion for periods of up to 4hrs. The brains and livers of the maternal rats and of their foetuses were collected and their nuclei were isolated. The tissues and nuclei isolated from them were analyzed for DNA, RNA, protein content and radioactivity. Morphine infused maternal rats exhibited no significant difference in the total amount of DNA, RNA and protein in the brain or in the concentration of these constituents in brain nuclei. The concentration of nuclear RNA in foetal brain of morphine infused mothers was significantly lower at 4 hrs than that of saline infused controls. It was concluded that RNA synthesis in the foetal brain must be much more sensitive to the inhibitory effect of morphine on macromolecular synthesis than that in maternal brain. The change in nuclear RNA concentration in foetal brain became significantly different when morphine reached its highest level in foetal brain nuclei. The morphine concentration (pmol /sup 14/C-morphine equivalents per mg DNA) in the brain of foetal and maternal rats was the same at each time period, whereas the maternal liver levels were at least eight times greater than those in foetal liver. The concentrations in foetal brain nuclei were 2-14 times greater than those in maternal brain nuclei, whereas levels in the latter were found to be low and virtually constant at all time periods tested. It was concluded that foetal brain nuclei have a greater capacity to bind or retain morphine than maternal brain nuclei.

  2. Establishment and optimization of NMR-based cell metabonomics study protocols for neonatal Sprague-Dawley rat cardiomyocytes.

    Science.gov (United States)

    Zhang, Ming; Sun, Bo; Zhang, Qi; Gao, Rong; Liu, Qiao; Dong, Fangting; Fang, Haiqin; Peng, Shuangqing; Li, Famei; Yan, Xianzhong

    2017-01-15

    A quenching, harvesting, and extraction protocol was optimized for cardiomyocytes NMR metabonomics analysis in this study. Trypsin treatment and direct scraping cells in acetonitrile were compared for sample harvesting. The results showed trypsin treatment cause normalized concentration increasing of phosphocholine and metabolites leakage, since the trypsin-induced membrane broken and long term harvesting procedures. Then the intracellular metabolite extraction efficiency of methanol and acetonitrile were compared. As a result, washing twice with phosphate buffer, direct scraping cells and extracting with acetonitrile were chosen to prepare cardiomyocytes extracts samples for metabonomics studies. This optimized protocol is rapid, effective, and exhibits greater metabolite retention. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. High fructose feeding induces copper deficiency in Sprague-Dawley rats: A novel mechanism for obesity related fatty liver

    Science.gov (United States)

    Dietary copper deficiency is associated with a variety of manifestations of the metabolic syndrome, including hyperlipidemia and fatty liver. Fructose feeding has been reported to exacerbate complications of copper deficiency. In this study, we investigated whether copper deficiency plays a role in ...

  4. DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR DELTAMETHRIN IN THE ADULT MALE SPRAGUE-DAWLEY RAT

    Science.gov (United States)

    Deltamethrin (DLT) is a Type II pyrethroid insecticide widely used in agriculture and public health. DLT is a potent neurotoxin that is primarily cleared from the body by metabolism. To better understand the dosimetry of DLT in the central nervous system, a physiologically based ...

  5. Increasing pro-survival factors within whole brain tissue of Sprague Dawley rats via intracerebral administration of modified valproic acid

    Directory of Open Access Journals (Sweden)

    Ryan C. Bates

    2015-08-01

    Full Text Available Neural tissue exposure to valproic acid (VPA increases several pro-survival phospho-proteins that can be used as biomarkers for indicating a beneficial drug response (pAktSer473, pGSK3βSer9, pErk1/2Thr202/Tyr204. Unfortunately, targeting VPA to neural tissue is a problem due to severe asymmetrical distribution, wherein the drug tends to remain in peripheral blood rather than localizing within the brain. Intracerebral delivery of an amide-linked VPA–PEG conjugate could address these issues by enhancing retention and promoting cerebro-global increases in pro-survival phospho-proteins. It is necessary to assay for the retained bioactivity of a PEGylated valproic acid molecule, along with locating an intracranial cannula placement that optimizes the increase of a known downstream biomarker for chronic VPA exposure. Here we show an acute injection of VPA–PEG conjugate within brain tissue increased virtually all of the assayed phospho-proteins, including well-known pro-survival factors. In contrast, an acute injection of VPA expectedly decreased signaling throughout the hour. Needle penetration into whole brain tissue is the intentional cause of trauma in this procedure. The trauma to brain tissue was observed to overcome known phospho-protein increases for unmodified VPA in the injected solution, while VPA–PEG conjugate appeared to induce significant increases in pro-survival phospho-proteins, despite the procedural trauma.

  6. Effects of anti-obesity drugs, phentermine and mahuang, on the behavioral patterns in Sprague-Dawley rat model

    OpenAIRE

    Go, Ryeo-Eun; Hwang, Kyung-A; Kim, Seung-Hee; Lee, Min-Young; Kim, Cho-Won; Jeon, So-Ye; Kim, Yun-Bae; Choi, Kyung-Chul

    2014-01-01

    According to WHO global estimates from 2008, more than 1.4 billion adults were overweight and among them, over 200 million men and 300 million women were obese. Although the main treatment modalities for overweight and obese individuals remain dieting and physical exercise, the synthetic anti-obesity medications have been increasingly used due to their perceived convenience. Generally, anti-obesity medications are classified as appetite suppressants or fat absorption blockers. In the present ...

  7. Black ginseng extract ameliorates hypercholesterolemia in rats

    Directory of Open Access Journals (Sweden)

    Evelyn Saba

    2016-04-01

    Conclusion: Administration of BG extracts to Sprague Dawley rats fed with high-cholesterol diet ameliorated hypercholesterolemia, which was mediated via modulation of cholesterol-metabolizing marker genes. This data throw a light on BG's cardioprotective effects.

  8. Reactive Protein Synthesis in Pregnant Rats

    African Journals Online (AJOL)

    olayemitoyin

    Department of Physiology, College of Medicine, University of Lagos, Nigeria. Summary: Genistein ... Oral exposure of pregnant rats to genistein precipitated hypothyroidism, altered some metabolic hormones with a ... consumption. Exposure to ...

  9. Extracellular ATP induces albuminuria in pregnant rats

    NARCIS (Netherlands)

    Faas, M.M.; van der Schaaf, G.; Borghuis, T.; Jongman, R.M.; van Pampus, Maria; de Vos, P.; van Goor, Harry; Bakker, W.W.

    BACKGROUND: As circulating plasma ATP concentrations are increased in pre-eclampsia, we tested whether increased plasma ATP is able to induce albuminuria during pregnancy. METHODS: Pregnant (day 14) and non-pregnant rats were infused with ATP (3000 microg/kg bw) via a permanent jugular vein cannula.

  10. Induced hypothermia is protective in a rat model of pneumococcal pneumonia associated with increased adenosine triphosphate availability and turnover

    NARCIS (Netherlands)

    Beurskens, Charlotte J. P.; Aslami, Hamid; Kuipers, Maria T.; Horn, Janneke; Vroom, Margreeth B.; van Kuilenburg, André B. P.; Roelofs, Joris J. T. H.; Schultz, Marcus J.; Juffermans, Nicole P.

    2012-01-01

    Objective: To determine the effect of induced hypothermia on bacterial growth, lung injury, and mitochondrial function in a rat model of pneumococcal pneumosepsis. Design: Animal study. Setting: University research laboratory. Subjects: Male Sprague-Dawley rats. Interventions: Subjects were

  11. Neurodevelopmental malformations of the cerebellar vermis in genetically engineered rats

    Science.gov (United States)

    The cerebellar vermis is particularly vulnerable to neurodevelopmental malformations in humans and rodents. Sprague-Dawley, and Long-Evans rats exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the vermis. Malformati...

  12. Differential strain vulnerability to binge eating behaviors in rats.

    Science.gov (United States)

    Hildebrandt, Britny A; Klump, Kelly L; Racine, Sarah E; Sisk, Cheryl L

    2014-03-29

    Binge eating is a significantly heritable phenotype, but efforts to detect specific risk genes have fallen short. Identification of animal strain differences in risk for binge eating could highlight genetic differences across individuals of the same species that can be exploited in future animal and molecular genetic research. The current study aimed to explore strain differences in risk for binge eating in Sprague-Dawley versus Wistar female rats using the Binge Eating Resistant/Binge Eating Prone model. A sample of male Sprague-Dawley rats, a known low-risk group for binge eating, was included as a comparison group. A total of 83 rats (23 Wistar females, 30 Sprague-Dawley females, 30 Sprague-Dawley males) completed a protocol of intermittently administered, palatable food. Binge eating prone (BEP) and binge eating resistant (BER) rats were identified using a tertile approach. Sprague-Dawley female rats consumed the highest amount of palatable food and were more likely to be classified as BEP compared to Wistar female and Sprague-Dawley male rats. Wistar female rats were not significantly different from Sprague-Dawley male rats in their palatable food intake and tendency to be classified as BER rather than BEP. Sprague-Dawley female rats appear to be a particularly vulnerable genotype for binge eating. Comparisons between this group and others could help identify specific genetic/biological factors that differentiate it from lower risk groups. The reward system, linked to binge eating in humans, is a possible candidate to explore. Strain differences in the reward system could help increase understanding of individual differences in risk for binge eating in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Hsp70 Expression Profile in Preeclampsia Model of Pregnant Rat (Rattus norvegicus) after Giving the EVOO

    Science.gov (United States)

    Irianti, E.; ilyas, S.; Rosidah; Hutahaean, S.

    2017-03-01

    Heat shock protein (Hsp) has long been known to protect cells from oxidative stress. In this case an increased expression is found on several cases of preeclampsia. One of the efforts to prevent preeclampsia is by giving antioxidants such as Extra Virgin Olive Oil (EVOO) or it’s better known as olive oil (Oleoa europaea), in the form of extra virgin known for its rich antioxidant content of tocopherols (vitamin E). The purpose of this study is to determine the expression levels of Hsp70 serum on pregnant white rat model of preeclampsia after being given EVOO. This type of research is true experiment; the subjects were female white rats and male virgin with Sprague Dawley, ± 8-11 weeks old, 180g BB s / d 200g, healthy and didn’t show any physical defects. Samples were 25 animals, divided into 5 groups, which consisted of different control and treatment given to T2 (rat model of preeclampsia), T3 (rat model of preeclampsia + EVOO 0.45g/bw/day), T4 (rat model of preeclampsia + EVOO 0.9g/bw/day) and T5 (rat model of preeclampsia + EVOO 1.8g/bw/day). The determination of each group was done by simple random sampling. Result on serum levels of Hsp70 that were tested by Elisa test in rats showed the average control was 14.64 mg / ml, group T2: 22:51 mg/ml, T3: 13.62 mg/ml, T4: 15.92 mg/ml, T5: 16:09 mg/ml. ANOVA test showed the P value was 0.001 <0.005, which meant there were significant differences on serum Hsp70 levels in the control and treatment pregnant rats group. It was known that there was a significant difference level of Hsp70 serum in group of control rats with T2 (P value <0.001) after LSD test was conducted, but not so with the group T3, T4, and T5, where the difference was not significant. There was a significant difference in the levels of Hsp70 serum on group T2 and T3 (P value 0.000), T4 (0004), T5 (0000). The gift of EVOO in the treatment group which was given EVOO with even low doses was able to control the induction of Hsp70 serum levels, which

  14. Estudio de toxicidad por dosis única y tolerancia local de una vacuna antimeningocócica tipo B en ratas Sprague Dawley

    Directory of Open Access Journals (Sweden)

    Juan F. Núñez

    2006-08-01

    Full Text Available La vacuna antimeningocócica tipo B, objetivo de este estudio, contiene vesículas purificadas de la membrana externa del meningococo del serogrupo B de la cepa (Cu- 385 - 83 B:4:P1.19,15. El esquema de vacunación propuesto en humanos consiste en tres dosis de 0,5 mL, separadas por un intervalo óptimo de ocho semanas. El objetivo de este estudio de toxicidad en ratas Sprague Dawley (SD fue determinar la toxicidad potencial, letalidad, órganos, sistemas susceptibles y otros eventos adversos, así como la toxicidad en el sitio de inoculación después de la administración de una dosis de la vacuna en estudio. Los resultados indicaron que, bajo las condiciones del estudio y según los criterios establecidos para evaluar los resultados, la vacuna antimeningocócica tipo B, no produce efectos tóxicos en el modelo animal usado. Todo lo que se observó fueron formaciones granulomatosas a nivel del punto de inoculación. Estas formaciones han sido reportadas como pertenecientes a los adyuvantes de depósito, como el hidróxido de aluminio, usado en otras vacunas parenterales. Se concluye que la vacuna antimeningocócica tipo B resultó satisfactoria en las pruebas de toxicidad por dosisúnica y tolerancia local realizadas en la especie rata.

  15. Valoración de una dieta hipercalórica en el desarrollo de osteoporosis en ratas Sprague-Dawley gonadectomizadas

    Directory of Open Access Journals (Sweden)

    Mónica A. Gutiérrez

    1995-09-01

    Full Text Available El trabajo se inició con 34 ratas Sprague-Dawley de siete semanas de edad, de las cuales 26 se sometieron a gonadectomía bilateral para inducirles la menopausia. El grupo control quedó constituido por las restantes 8 ratas no gonadectomizadas. Para evaluar la influencia de la dieta hipercalórica en el desarrollo de osteoporosis, a 13 ratas gonadectomizadas se les suministró una dieta rica en grasa (grupo A, mientras que las otras 13 ratas (grupo B y el grupo control recibieron una dieta regular. Cinco meses después de la ovariectomía, la dieta hipercalórica causó la disminución del contenido de calcio en vértebras lumbares (L3, L4 y L5, mostrándose el efecto de la dieta en cuanto a que, bajo la ingesta de los demás nutrientes, se modificó su utilización, causando una desnutrición generalizada y cooperando así con el proceso de génesis de la osteoporosis. La ovariectomía indujo cambios hormonales que favorecieron el proceso de desmineralización condicionante de osteoporosis, validándose así el modelo experimental.

  16. Toluene depresses plasma corticosterone in pregnant rats

    DEFF Research Database (Denmark)

    Hougaard, K. S.; Hansen, A. M.; Hass, Ulla

    2003-01-01

    of corticosteroids from the maternal to the foetal compartment. Pregnant rats were subjected to either 1500 ppm toluene 6 hr/day and/or a schedule of "Chronic mild stress" during the last two weeks of gestation. Exposure to toluene was associated with reduced birth weight and lower maternal weight gain, the latter...

  17. Effect of valproic acid on 65Zn distribution in the pregnant rat

    International Nuclear Information System (INIS)

    Keen, C.L.; Peters, J.M.; Hurley, L.S.

    1989-01-01

    The effect of valproic acid on the distribution of gavaged 65 Zn in maternal and embryonic tissue of Sprague-Dawley rats was examined 24 h after gavaging of the drug on d 13 of pregnancy. Valproic acid treatment resulted in a significantly higher retention of 65 Zn in maternal liver and lower amounts in uterus, placenta and embryos than in controls. Compared to controls, gel chromatography of maternal liver from valproic acid-treated dams showed higher 65 Zn counts associated with a protein peak of molecular weight of 6,500, the approximate molecular weight of the Zn-binding protein metallothionein. These results support the idea that the teratogenicity of valproic acid is in part due to an induction of embryonic Zn deficiency secondary to a drug-induced sequestering of Zn into maternal liver that results in a decrease in maternal plasma Zn and subsequent reduction in embryonic Zn uptake

  18. Effects of diuron on male rat reproductive organs: a developmental and postnatal study.

    Science.gov (United States)

    Fernandes, Glaura S A; Favareto, Ana Paula A; Fernandez, Carla D B; Bellentani, Fernanda F; Arena, Arielle C; Grassi, Tony F; Kempinas, Wilma G; Barbisan, Luís F

    2012-01-01

    This study was performed to determine whether developmental exposure (perinatal and juvenile) to the herbicide diuron exerted adverse effects on adult rat male reproductive system. Pregnant Sprague-Dawley rats received basal diet or diet containing diuron at 500 or 750 ppm from gestational day 12 (GD 12) until the end of lactation period (postnatal day 21, PND 21). After weaning male offspring received basal diet or diet containing diuron until PND 42 (peripubertal age). At PND 90, adult male rats from each experimental group were anesthetized and euthanized for evaluation of body and reproductive organ weights, sperm parameters, plasma testosterone levels, and testicular and epididymal histopathology. Male offspring exposed to diuron at 750 ppm displayed reduced body weight at PND 10, 21, 42, and 90 compared to controls. At PND 90, diuron treatment did not induce significant change in daily sperm production, sperm morphology and motility, and testosterone levels compared to controls. In conclusion, diuron at 750 ppm induced male offspring toxicity but these alterations were not permanent, as evidenced by absence of reproductive-system alterations in adult Sprague Dawley rats.

  19. Evaluación de la toxicidad por dosis única de la vacuna antitetánica vax-TET en ratas Sprague Dawley

    Directory of Open Access Journals (Sweden)

    Yulieé López.

    2007-12-01

    Full Text Available La vacuna vax-TET® está indicada en la prevención del tétanos y es efectiva si se logra un completo y apropiado esquema de inmunización. Para investigar el potencial tóxico de este producto se realizó una prueba toxicológica con una dosis única, por vía intramuscular, en un volumen de 0,2 mL en ratas Sprague Dawley. La composición de la vacuna de ensayo probada fue la misma de la vacuna comercial. Los animales fueron observados diariamente en busca de síntomas locales y sistémicos de toxicidad. Se realizaron mediciones del consumo de agua y alimento, así como del peso corporal. Dos semanas después de la inoculación las ratas fueron sacrificadas por métodos de eutanasia sin dolor y sometidas a necropsia. No se observaron muertes ni síntomas de toxicidad en los animales estudiados. Tampoco se encontraron diferencias de interés toxicológico entre los grupos experimentales en cuanto a las variables medidas. El estudio anatomopatológico reveló la presencia de formaciones granulomatosas de tipo macrofágico asociadas, fundamentalmente, al hidróxido de aluminio. Estos resultados permitieron concluir que, bajo las condiciones del estudio y según los criterios establecidos, esta vacuna no produce efectos adversos en el modelo animal usado, por lo que se considera potencialmente no tóxica para humanos.

  20. Evaluación de la toxicidad por dosis única y tolerancia local de la vacuna vax-SPIRAL® en ratas Sprague Dawley

    Directory of Open Access Journals (Sweden)

    Juan F. Infante

    2004-04-01

    Full Text Available Las pruebas preclínicas de toxicidad en dosis única y en dosis repetidas brindan una valiosa información sobre la seguridad del producto, al incluir el estudio macroscópico e histopatológico de órganos importantes, así como evaluaciones de las vías de administración y el régimen de dosificación. Cuba desarrolló una vacuna polivalente de células inactivadas químicamente adyuvadas con hidróxido de aluminio, vax-SPIRAL®. Esta vacuna presenta ventajas en relación con otras vacunas como la procedente de la antigua URSS. El esquema de vacunación para humanos consiste en dos dosis de 0,5 mL, separadas por un intervalo óptimo de seis semanas. El objetivo de este estudio de toxicidad en ratas Sprague Dawley fue determinar la toxicidad potencial, letalidad, órganos y sistemas susceptibles y otros eventos adversos, así como la toxicidad en el sitio de inoculación después de la administración de una dosis de la vacuna en estudio. Los resultados indicaron que, bajo las condiciones en estudio y según los criterios establecidos para evaluar los datos obtenidos, la vacuna antileptospirósica trivalente no produce efectos tóxicos en el modelo animal usado. Las únicas alteraciones encontradas fueron formaciones granulomatosas a nivel del sitio de inoculación. Estas formaciones han sido reportadas como pertenecientes al adyuvante de depósito (hidróxido de aluminio, también usado en otras vacunas de aplicación parenteral.

  1. Toxicidad por dosis repetidas de la solución CM-95 tratada magnéticamente en ratas Sprague Dawley

    Directory of Open Access Journals (Sweden)

    Clara E. Martínez

    2008-08-01

    Full Text Available En este trabajo se realizó la evaluación toxicológica a dosis repetidas por el método de test límite del candidato a inmunopotenciador, la solución CM-95 tratada magnéticamente, acorde con las regulaciones de la Organización para la Colaboración Económica y el Desarrollo, incluida en la Guía 407. El objetivo fue establecer las posibles lesiones orgánicas y funcionales ocasionadas por la solución CM-95, tratada magnéticamente con la máxima inducción magnética permisible (0,16 T, para la obtención del candidato a inmunopotenciador. Se emplearon tres grupos: Experimental, Control y Satélite. Como Biomodelo experimental se utilizaron ratas Sprague Dawley machos y hembras con pesos de 150 a 200 g. Durante el estudio no se registraron signos clínicos de toxicidad ni muertes en ninguno de los animales de los grupos tratados, ni en los controles. No hubo afectación del peso corporal durante el ensayo. Aunque hubo variaciones en los valores de algunos parámetros hematológicos y bioquímicos, estos no tuvieron significación biológica. No se encontraron lesiones macroscópicas, ni microscópicas; solo se observaron efectos proliferativos en el tejido linfoide de timo y bazo, relacionados con la respuesta del sistema inmune. La solución CM-95 tratada magnéticamente, no mostró toxicidad en el modelo animal y nivel de dosis utilizado, y bajo las condiciones experimentales ensayadas.

  2. The similitude of some negative outcomes of Omega-3 to those of gamma radiation in pregnant albino rats and their fetuses

    International Nuclear Information System (INIS)

    Ibrahim, M.F.; Yacoub, S.F.; Abdel Aziz, N.

    2011-01-01

    Even though it is established that manipulation of Omega-3, the essential long-chain polyunsaturated fatty acid, is beneficial during pregnancy for its well known antioxidant capacity, yet the present work aims at underscoring the adverse maternal biochemical and fetal teratological traits arising in consequence of excessive Omega-3 peri conceptional supplementation, some of which resemble various oxidative stress induced harmful effects of the prenatal maternal whole body gamma irradiation during the sensitive period of organogenesis. In the present study, adult Sprague Dawley female rats were randomized into 3 groups, one of which served as pregnant control (Group 1) whereas another one was orally administered with Omega-3 (0.5 g / kg /day) for 45 consecutive days (25 days preconception + 20 days of pregnancy) (Group 2) while the third group was subjected to 4 Gy whole body gamma irradiation on the 15th gestational day (Group 3). Five rats of each group were sacrificed after 20 days of gestation. The results revealed that both Omega-3 administration for 45 consecutive days or gamma radiation exposure resulted in a remarkable decrease in maternal blood Glutathione (GSH) content and Catalase accompanied by a significant elevation in maternal plasma Malonaldehyde (MDA), Total Cholesterol, Triglycerides and LDL-Cholesterol levels when compared to the control group. Accordingly, the fetuses of the Omega-3 treated mothers, despite their lively active appearance, showed the occurrence of unexpected abnormal malformed extremities, sharing this phenomenon with the fetuses of the irradiated mother group who showed an exceptional high mortality rate together with higher incidence of recorded growth defects. Thus it can be speculated that Omega-3 over supplementation, may be inadvisable in pregnancy time in a manner relative to some extent to the maternal gamma irradiation prohibition.

  3. Evaluación de la toxicidad a dosis repetidas (90 días) por vía oral del concentrado de proteína de pota (Dosidicus gigas), en ratas Sprague dawley

    OpenAIRE

    Rojas Hurtado, Daniel Percy

    2009-01-01

    Universidad Nacional Agraria La Molina. Escuela de Posgrado. Maestría en Tecnología de Alimentos El potencial tóxico de un concentrado de proteína de calamar gigante (Dosidicus gigas) fue evaluado mediante el estudio de toxicidad de dosis repetidas a 90 días en ratas Sprague Dawley de ambos sexos. Los métodos empleados fueron los descritos por las normas OECD (1998). Se administró por vía oral la dosis de 500, 1000 y 2000 mg/kg/día durante 13 semanas. Se evaluaron los signos tóxicos y peso...

  4. INHIBITION OF GAP JUNCTIONAL INTERCELLULAR COMMUNICATION BY PERFLUORINATED COMPOUNDS IN RAT LIVER AND DOLPHIN KIDNEY EPITHELIAL CELL LINES IN VITRO AND SPRAGUE-DAWLEY RATS IN VIVO

    Science.gov (United States)

    Abstract Gap Junctional Intercellular Communication (GJIC) is the major pathway of intercellular signal transduction, and is, thus, important for normal cell growth and function. Recent studies have revealed a global distribution of some perfluorinated organic compounds e...

  5. Inhalative cadmium effects in pregnant and fetal rats

    Energy Technology Data Exchange (ETDEWEB)

    Prigge, E.

    1978-01-01

    Pregnant and non-pregnant rats were continuously exposed for 21 days to an aerosol containing 0.2, 0.4, and 0.6 mg cadmium/m/sup 3/ air. Pregnant and non-pregnant rats exposed to clean air served as controls. The aerosol was generated by an ultrasonic nebulizer and was carried into inhalation chambers. The median aerodynamic diameters were on the order of 0.6 ..mu..m. After inhalation of cadmium aerosols, serum iron levels were not lowered significantly in adult rats. A polycythaemic response of non-pregnant rats was observed due to a direct stimulatory effect of cadmium on erythropoiesis. Polycythaemia was less marked in pregnancy, presumably due to iron loss to placenta and fetus. Disturbances of pulmonary gas exchange or decreased plasma volumes were excluded as causative mechanisms of polycythaemia. In pregnant rats there was a marked dose dependent decrease of the activity of the alkaline phosphatase after cadmium inhalation, while there was no effect in exposed non-pregnant rats. This decreased enzyme activity, together with slowed growth rates and hemolytic effect indicate a higher sensitivity to cadmium in pregnancy. Proteinuria was not found in neither pregnant nor non-pregnant rats. Therefore, it is concluded that in this respect cadmium intoxication by inhalation does not resemble human toxemia of pregnancy, as discussed in the literature.

  6. Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth-restricted rats

    Science.gov (United States)

    Goodspeed, Danielle; Seferovic, Maxim D.; Holland, William; Mcknight, Robert A.; Summers, Scott A.; Branch, D. Ware; Lane, Robert H.; Aagaard, Kjersti M.

    2015-01-01

    Intrauterine growth restriction (IUGR) confers heritable alterations in DNA methylation, rendering risk of adult metabolic syndrome (MetS). Because CpG methylation is coupled to intake of essential nutrients along the one-carbon pathway, we reasoned that essential nutrient supplementation (ENS) may abrogate IUGR-conferred multigenerational MetS. Pregnant Sprague-Dawley rats underwent bilateral uterine artery ligation causing IUGR in F1. Among the F2 generation, IUGR lineage rats were underweight at birth (6.7 vs. 8.0 g, P 30% elevated, P 5-fold less central fat mass, normal hepatic glucose efflux, and >70% reduced circulating triglycerides and very-LDLs compared with IUGR control-fed F2 offspring (P intrauterine growth-restricted rats. PMID:25395450

  7. Prenatal exposure to nanosized zinc oxide in rats: neurotoxicity and postnatal impaired learning and memory ability.

    Science.gov (United States)

    Xiaoli, Feng; Junrong, Wu; Xuan, Lai; Yanli, Zhang; Limin, Wei; Jia, Liu; Longquan, Shao

    2017-04-01

    To examine the neurotoxicity of prenatal exposure to ZnO nanoparticles on rat offspring. Pregnant Sprague-Dawley rats were exposed to ZnO nanoparticles (NPs) by gavage. Toxicity was assessed including zinc biodistribution, cerebral histopathology, antioxidant status and learning and memory capability. A significantly elevated concentration of zinc was detected in offspring brains. Transmission electron microscope observations showed abnormal neuron ultrastructures. Histopathologic changes such as decreased proliferation and higher apoptotic death were observed. An obvious imbalanced antioxidant status occurred in brains. Adult experimental offspring exhibited impaired learning and memory behavior in the Morris water maze test compared with control groups. These adverse effects on offspring brain may cause impaired learning and memory capabilities in adulthood, particularly in female rats.

  8. Release of Zn from maternal tissues in pregnant rats deficient in Zn or Zn and Ca

    International Nuclear Information System (INIS)

    Hurley, L.S.; Masters, D.G.; Lonnerdal, B.; Keen, C.L.

    1986-01-01

    Earlier studies have shown that diets that increase tissue catabolism reduce the teratogenic effects of Zn deficiency. The hypothesis that Zn may be released from body tissues when the metabolic state is altered was further tested. Nonpregnant Sprague Dawley females were injected with Zn-65; after equilibration, the two major pools of Zn, bone and muscle, had different specific activities (SA), muscle being much higher. Females were mated and fed diets adequate in Zn and Ca (C) or deficient in Zn (ZnD) or deficient in both Zn and Ca (ZnCaD). Calculations using weight loss in ZnD and ZnCaD rats, Zn content of maternal bone and muscle, and total fetal Zn at term indicated that in ZnCaD rats a relatively small amount of Zn from bone early in pregnancy was sufficient to prevent abnormal organogenesis, but most fetal Zn came from breakdown of maternal muscle in the last 3 days of pregnancy. Isotope data supported this conclusion. SA of Zn in ZnD fetuses was equal and high, indicating that most Zn came from the same maternal tissue. High muscle SA prior to mating, and increased SA in tibia and liver during pregnancy suggest that muscle provided Zn for other maternal tissues as well as fetuses. In contrast, SA in C fetuses was less than 30% of that of the D groups, consistent with the earlier hypothesis that most fetal Zn in C rats is accrued directly from the diet

  9. Iron supplementation during pregnancy and its effects on epiphyseal growth plate of newborn rat: a histological study

    International Nuclear Information System (INIS)

    Umbreen, F.; Qamar, K.; Rehman, S.

    2017-01-01

    To study the effect of iron supplementation during pregnancy on epiphyseal growth plate of Sprague dawley rat pups. Study Design: Laboratory based randomized control trial. Place and Duration of Study: This study was conducted at Department of Anatomy, Army Medical College Rawalpindi in collaboration with National Institute of Health (NIH) Islamabad, from Mar 2016 to Nov 2016. Material and Methods: Eight female and two male Sprague Dawley rats, 3-4 months old were selected and divided into two groups and kept for breeding. Pregnant rats were divided into two groups. Four pregnant rats in each group. Group A1was control group and group B1 was experimental group. Iron supplementation was given once daily throughout pregnancy till the time of delivery. Iron was given to the experimental group in syrup form (Sytron syrup containing iron as sodium feredetate). Each 5ml of sytron syrup contains 27.5mg of elemental iron content1. The dose was mixed in water given to the animal. Maternal body weight (wt.) was recorded at the start and the end of experiment. As the rat pups were born, they were weighed and euthanized. Right femur of each rat pup was removed for the epiphyseal plate analysis. It was processed, embedded and stained with Hematoxylin and Eosin, Perl's stain for histological study. Hypertrophy and proliferative zone length were histologically and statistically analyzed. Results: Height of hypertrophy and proliferative zone was measured. Mean values of the heights of two zones were taken. Heights of hypertrophy and proliferative zones were considerably decreased in group B1 as compared to groups A1. Conclusion: Indiscriminate iron supplementation to the rats throughout pregnancy without checking serum iron levels can disturb the longitudinal growth of epiphyseal plate of femur. The height of the hypertrophy zone and proliferative zone was significantly reduced in iron supplementation group as compared to the control group. (author)

  10. Differential Effects of Intrauterine Growth Restriction on the Regional Neurochemical Profile of the Developing Rat Brain.

    Science.gov (United States)

    Maliszewski-Hall, Anne M; Alexander, Michelle; Tkáč, Ivan; Öz, Gülin; Rao, Raghavendra

    2017-01-01

    Intrauterine growth restricted (IUGR) infants are at increased risk for neurodevelopmental deficits that suggest the hippocampus and cerebral cortex may be particularly vulnerable. Evaluate regional neurochemical profiles in IUGR and normally grown (NG) 7-day old rat pups using in vivo 1 H magnetic resonance (MR) spectroscopy at 9.4 T. IUGR was induced via bilateral uterine artery ligation at gestational day 19 in pregnant Sprague-Dawley dams. MR spectra were obtained from the cerebral cortex, hippocampus and striatum at P7 in IUGR (N = 12) and NG (N = 13) rats. In the cortex, IUGR resulted in lower concentrations of phosphocreatine, glutathione, taurine, total choline, total creatine (P regions. Persistent neurochemical changes may lead to cortex-based long-term neurodevelopmental deficits in human IUGR infants.

  11. Effect of combined doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea using rat (Sprague- Dawley) models of conditioned gaping.

    Science.gov (United States)

    Rock, Erin M; Limebeer, Cheryl L; Parker, Linda A

    2015-12-01

    Δ(9)-Tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) found in cannabis both reduce the distressing symptom of nausea, but their combined effects are not understood. The potential of combined doses of THC and CBDA to reduce acute nausea and anticipatory nausea in rodent models was assessed. For acute nausea, the potential of cannabinoid pretreatment(s) to reduce LiCl-induced nausea paired with saccharin was evaluated in a subsequent drug free taste reactivity test, followed by a taste avoidance test. For anticipatory nausea, the potential of the cannabinoid pretreatment(s) to reduce the expression of LiCl-induced contextually elicited conditioned gaping was evaluated. Combined subthreshold doses of THC (0.01 and 0.1 mg/kg) and CBDA (0.01 and 0.1 μg/kg) reduced acute nausea. Higher doses of THC (1.0, 10 mg/kg) or CBDA (1.0, 10 μg/kg) alone, as well as these combined doses also reduced acute nausea. THC (10 mg/kg) interfered with conditioned taste avoidance, an effect attenuated by CBDA (10 μg/kg). On the other hand, combined subthreshold doses of THC (0.01 and 0.1 mg/kg) and CBDA (0.01 and 0.1 μg/kg) did not suppress contextually elicited conditioned gaping in a test for anticipatory nausea. However, higher doses of THC (1.0, 10 mg/kg) or CBDA (1.0, 10 μg/kg) alone, as well as these combined doses, also reduced anticipatory nausea. Only at the highest dose (10 mg/kg) did THC impair locomotor activity, but CBDA did not at any dose. Combined subthreshold doses of THC:CBDA are particularly effective as a treatment for acute nausea. At higher doses, CBDA may attenuate THC-induced interference with learning.

  12. Decreased beige adipocyte number and mitochondrial respiration coincide with reduced FGF21 gene expression in Sprague Dawley rats fed prenatal low protein and postnatal high fat diets

    Science.gov (United States)

    We have shown that protein malnutrition during fetal growth followed by postnatal high-fat diets results in a rapid increase in subcutaneous adipose tissue mass in the offspring contributing to development of obesity and insulin resistance. Recent studies have shown that the absence of a key transcr...

  13. Effects of Ginseng Fruit Saponins on Serotonin System in Sprague-Dawley Rats with Myocardial Infarction, Depression, and Myocardial Infarction Complicated with Depression

    Directory of Open Access Journals (Sweden)

    Dong-Fang He

    2016-01-01

    Conclusions: This study indicated that GFS might inhibit the reuptake of 5-HT from serum to platelet according to decreased 5-HT2AR in platelet and SERT in serum and platelet. The change of 5-HT in serum after GFS treatment was inconsistent with that in the brain. It seemed that GFS could not pass through the blood-brain barrier to affect the central serotonergic system.

  14. Milk transfer, distribution, and metabolism of a single oral dose of [14CH3S]methamidophos in Sprague Dawley rats

    International Nuclear Information System (INIS)

    Bakry, N.M.; Salama, A.K.; Aly, H.A.; Abou-Donia, M.B.

    1990-01-01

    A single oral dose of 8 mg/kg (8 μci/kg) of [ 14 CH 3 S]methamidophos was administered to the dams right after delivery. Suckling groups were collected at intervals of 1, 3, 6, 12, 24, 36, and 48 hr after dosing. Radiolabeled material was rapidly absorbed and subsequently distributed throughout the body. Generally, the highest concentration of radioactivity were associated with kidneys, liver, lung, small intestine, spleen, stomach, and uterus; the lowest were found in the heart, muscles, skin, diaphragm, brain, spinal cord, and adipose tissues. Total radioactivity in the sucklings reached a maximum value of 1,067 ng methamidophos equivalent (1.89% of applied dose). Methamidophos and its metabolites were analyzed by gas-liquid chromatography/mass spectrometry, thin-layer chromatography and liquid scintillation counting. Methamidophos disappeared biexponentially from the suckling pups. The terminal half-life of methamidophos was 43.5 hr corresponding to a constant rate value of 0.02 hr -1 . The major metabolites in the sucklings were monomethyl phosphoroamidate and monomethyl phosphate

  15. Simvastatin and Dipentyl Phthalate Display Different Mechanisms of Action but Exhibit Dose Additive Effects on Fetal Testicular Testosterone Production in Sprague Dawley Rats

    Science.gov (United States)

    Sex differentiation of the male reproductive tract in mammals is driven, in part, by fetal androgen production. In utero exposure to some phthalate esters (PEs) alters fetal Leydig cell differentiation, reducing the expression of several genes associated with steroid synthesis/tr...

  16. Comparison of fetal testosterone production in various tissues of the male sprague dawley rat dosed in utero with dipentyl phthalate during the critical window of sexual differentiation

    Science.gov (United States)

    Phthalate esters are high-production volume chemicals used in the manufacture of numerous plastics and consumer products, which generates major concern for potential human exposure and environmental contamination. Several studies have demonstrated adverse effects associated with ...

  17. Comparison of Fetal Testosterone Production in Various Tissues of the Male Sprague Dawley Rat dosed In Utero with Dipentyl Phthalate during the Critical Window of Sexual Differentiation###

    Science.gov (United States)

    Phthalate esters are high-production volume chemicals used in the manufacture of numerci plastics and consumer products, which generates major concern for potential human exposure and environmental contamination. Several studies have demonstrated adverse effects associated with p...