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Sample records for pregnant long-evans rats

  1. Teratogenic effects of trichloroacetonitrile in the Long-Evans rat

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    Smith, M.K.; Randall, J.L.; Tocco, D.R.; York, R.G.; Stober, J.A.; Read, E.J.

    1988-08-01

    Trichloroacetonitrile (TCAN) is among a number of contaminants found in drinking water produced by reactions of chlorine with background organic material. Long-Evans rats were intubated with TCAN (0, 1, 7.5, 15, 35, 55 mg/kg) in a tricaprylin vehicle on gestation days 6-18. The highest dose tested (55 mg/kg) was lethal in 21% of the dams and produced 100% resorptions in two-thirds of the survivors. Only one maternal death was seen at the next-lower dose; however, fetal weight and viability were decreased in a dose-related manner. The percentage of embryolethality was 13.9% at the lowest dose and 78.4% at the high dose, with resorption of entire litters seen at 7.5 mg/kg and above. At all doses, cardiovascular (interventricular septal defect, levocardia, common carotid, and right-sided aortic arch and ductus arteriosus) and urogenital (hypoplastic, missing, misplaced and fused kidneys, and hypoplastic uterine horns) malformations were seen in the offspring. Frequency of these malformations was dose related, ranging from 8% to 35% at the 1.0- and 35-mg/kg doses, respectively. The incidence of total soft tissue malformations was statistically significant at 15 and 35 mg/kg. There were no significant treatment-related changes in the incidence of skeletal malformations. The no-effect dose was established by statistical analysis to be 1.0 mg/kg/day.

  2. EVALUATION OF SENSORY EVOKED POTENTIALS IN LONG EVANS RATS GESTATIONALLY EXPOSED TO MERCURY (HGO) VAPOR.

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    Human exposure to mercury vapor (Hg0) has been reported to result in sensory disturbances. Developmental exposure to toxicants may result in long-lasting changes in neural function. This manuscript describes the lack of effect of gestational exposure of Long Evans rats to Hg0 on ...

  3. BROMATE-INDUCED TRANSCRIPTIONAL CHANGES IN LONG-EVANS RAT KIDNEYS

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    Bromate-Induced Transcriptional Changes in Long-Evans Rat Kidneys.Ozone disinfection of surface waters containing bromide ion (Br-) results in the oxidation of bromide to bromate, which can be found in finished drinking water as a by-product. Potassium bromate (KBrO3)...

  4. Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis. A model of Wilson's disease.

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    Li, Y; Togashi, Y; S. Sato; Emoto, T; J. H. Kang; TAKEICHI N.; Kobayashi, H; Y. Kojima; Une, Y.; Uchino, J

    1991-01-01

    Long-Evans Cinnamon (LEC) rats, an inbred strain of a mutant rat isolated from Long-Evans rats, develop hereditary hepatitis. To elucidate the role of copper metabolism in the development of the hepatitis in LEC rats, we examined the copper concentration in the tissues and serum levels of copper and ceruloplasmin. Copper concentration in the liver of LEC rats was over 40 times that of normal Long-Evans Agouti (LEA) rats, while the serum ceruloplasmin and copper concentrations in LEC rats decr...

  5. Vascular aldosterone production at the pre-diabetic stage of young Otsuka Long-Evans Tokushima Fatty (OLETF) rats, compared with Long-Evans Tokushima Otsuka (LETO) rats.

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    Matsuzawa, Yoko; Suematsu, Sachiko; Saito, Jun; Omura, Masao; Nishikawa, Tetsuo

    2013-12-13

    We examined the ability of aortic smooth muscle cells (AoSMC) prepared from spontaneously diabetic rats to produce aldosterone (Aldo) and the regulatory mechanism that controls their Aldo production. AoSMC of 6 week-old Long-Evans Tokushima Otsuka (LETO: the control group) and 6 week-old Otsuka Long-Evans Tokushima Fatty (OLETF: the type 2 diabetes group) rats were used in the present experiments. CYP11B2 (Aldo synthetase) mRNA expression was detected in both the LETO and OLETF AoSMC. Basal Aldo production was significantly greater (4-5 fold higher) in the OLETF AoSMC culture medium than in the LETO AoSMC culture medium. When AoSMC were co-incubated with high-density lipoproteins (HDL), supplying cholesterol as a substrate for steroidogenesis in rats, angiotensin II (AII) significantly increased greater Aldo production in the OLETF AoSMC than in the LETO AoSMC. The present data suggested that future onset of diabetic vascular dysfunction is partly caused by excess Aldo production by AoSMC in young OLETF rats. Concomitant stimulation by HDL and AII resulted in elevated Aldo production in the OLETF and the LETO AoSMC, and also demonstrated that AII-induced Aldo production is greatly enhanced by HDL in OLETF, rather than in LETO. In conclusion, our data clearly demonstrated that Aldo production in the OLETF AoSMC was significantly higher than in the LETO AoSMC, suggesting possible future onset of vascular dysfunction in diabetes, induced by local Aldo production in the AoSMC.

  6. [Overgrowth and DNA synthesis of neuroepithelium in embryonic stages of induced Long-Evans rat myeloschisis].

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    Chono, Y

    1993-01-01

    Overgrowth of the myeloschisis, namely the excessive amount of the neural plate tissue, has been reported in the human myeloschisis. However, it is still debatable how the overgrowth develops and whether the overgrowth is the cause, or the secondary effect of spinal dysraphism. The author induced myeloschisis in the fetuses of Long-Evans rats by the administration of ethylenethiourea (ETU) to pregnant rats on day 10 of gestation. The fetuses were removed 1 hour after the treatment with bromodeoxyuridine (BrdU) to the dams on day 14 and 21. The fetuses were fixed in alcohol and embedded in paraffin. H-E staining and the immunohistologic examination were performed on the staining patterns to anti-neurofilament (NFP), anti-glial fibrillary acidic protein (GFAP) and anti-BrdU antibody by ABC method. On day 14, the lateral portion of everted neural plate showed a loose arrangement of cells and there was rosette formation in the mesoderm. On day 21, cell necrosis was observed at the dorsolateral portion of myeloschisis, although the ventral portion showed almost normal cytoarchitecture and was positive to NFP and GFAP. The cause of myeloschisis in this model is supposed to be the local and direct cytotoxic effect of ETU to neuro-ectodermal junction. On day 14, control animals contained few BrdU-incorporated cells at the basal plate of neural tube. In contrast, everted neural plate showed an active uptake of BrdU diffusely in the subependymal matrix layer cells. Overgrowth was not yet identified. On day 21, overgrowth of myeloschisis was found in spite of a few positive cells to BrdU which was identical to the control animals. These findings seem to suggest that cells in the myeloschisis retain their ability of DNA synthesis for longer periods of development and overgrowth found on day 21 is possibly a secondary effect of spinal dysraphism in this model.

  7. Alpha-lipoic acid attenuates cardiac fibrosis in Otsuka Long-Evans Tokushima Fatty rats

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    Lee Jung Eun

    2012-09-01

    Full Text Available Abstract Background Hyperglycemia leads to cardiac oxidative stress and an imbalance in glucose homeostasis. Diabetic cardiomyopathy is characterised by cardiac hypertrophy and fibrosis. However, the underlying mechanisms of diabetic cardiomyopathy are not fully understood. This study aimed to investigate the effects of alpha-lipoic acid (ALA on cardiac energy metabolism, antioxidant effect, and fibrosis in the hearts of Otsuka Long-Evans Tokushima fatty (OLETF rats. Methods Animals were separated into non-diabetic Long-Evans Tokushima Otsuka (LETO rats and diabetes-prone OLETF rats with or without ALA (200 mg/kg/day administration for 16 weeks. Diabetic cardiomyopathy was assessed by staining with Sirius Red. The effect of ALA on AMPK signalling, antioxidant enzymes, and fibrosis-related genes in the heart of OLETF rats were performed by Western blot analysis or immunohistochemistry. Results Western blot analysis showed that cardiac adenosine monophosphate-activated kinase (AMPK signalling was lower in OLETF rats than in LETO rats, and that ALA treatment increased the signalling in OLETF rats. Furthermore, the low antioxidant activity in OLETF rats was increased by ALA treatment. In addition to increased Sirius red staining of collagen deposits, transforming growth factor-β1 (TGF-β1 and connective tissue growth factor (CTGF were expressed at higher levels in OLETF rat hearts than in LETO rat hearts, and the levels of these factors were decreased by ALA. Conclusions ALA enhances AMPK signalling, antioxidant, and antifibrogenic effect. Theses findings suggest that ALA may have beneficial effects in the treatment of diabetic cardiomyopathy.

  8. Mammary gland development and response to prenatal atrazine exposure in the Sprague Dawley and Long-Evans rats.

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    Mammary gland (MG) tumor development in Sprague Dawley (SD) rats is increased by longterm dietary exposure to the chlorotriazine herbicide atrazine (ATR). ATR is proposed to cause these changes in the adult SD rat by altering hormonally-regulated estrous cyclicity. In Long-Evans...

  9. Tempol protects sleep-deprivation induced behavioral deficits in aggressive male Long-Evans rats.

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    Solanki, Naimesh; Atrooz, Fatin; Asghar, Saman; Salim, Samina

    2016-01-26

    Earlier, we reported that elevated anxiety-like behavior and high aggression in aged retired breeder Long-Evans (L-E) rats was associated with increased plasma corticosterone and elevated oxidative stress levels. In the present study, we examined how this aged aggressive and anxious rat strain responds to acute sleep deprivation (24h) and whether their behaviors can be modulated via antioxidant tempol treatment. Four groups of L-E rats were utilized: naïve control (NC), tempol treated control (T+NC), sleep deprived (SD), tempol treated and sleep deprived (T+SD). Thus, two groups were treated with tempol (1mM in drinking water for 2 weeks) while the other two were not. Two groups were subjected to acute sleep deprivation (24h) using the columns-in-water model while the other two were not. Sleep deprivation induced anxiety-like behavior, led to significant depression-like behavior and short-term memory impairment in SD rats. And, decision-making behavior also was compromised in SD rats. These behavioral and cognitive impairments were prevented with tempol treatment in T+SD rats. Tempol treatment also reduced SD-induced increase in corticosterone and oxidative stress levels in T+SD rats. These results suggest potential involvement of oxidative stress mechanisms in regulation of sleep deprivation induced behavioral and cognitive deficits in male aged-aggressive rats.

  10. Ovariectomized Sprague-Dawley and Long-Evans rats release prolactin differently in response to estrogen

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    Lawson, D.M.; Sensui, N.; Gala, R.R.

    1984-01-30

    Mature female Sprague-Dawley (SD) and Long-Evans (LE) rats were ovariectomized (OVX), and given a single sc injection of either 25 or 100 ..mu..g polyestradiol phosphate (PEP); seven days later blood samples were withdrawn at two hour intervals from 1100 to 2100 hours to detect the presence of an afternoon surge of prolactin (PRL). Other groups of OVX rats of both strains also treated with PEP were sampled before and at 2, 5, 10 and 30 min after iv administration of 1 ..mu..g synthetic thyrotropin releasing hormone (TRH). Pituitary (AP) and uterine weights were determined following sacrifice one day after TRH treatment. The AP homogenates and plasma samples were assayed for PRL by radioimmunoassay. Rats of both strains had afternoon PRL surges and in both strains the magnitude and/or duration of the surges were enhanced by the higher dose of PEP. However, within each PEP dose LE rats released significantly more PRL during the surge than did SD drats. Rats of both strains also rleased PRL in response to TRH and this response was enhanced in both strains by the higher of the two doses of PEP. These data not only show that strain differences exist in estrogen-induced or mediated PRL release in the rat but also indicate that the differences are not uniform.

  11. Obesity in the Otsuka Long Evans Tokushima Fatty Rat: Mechanisms and Discoveries

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    Sheng Bi

    2016-07-01

    Full Text Available Understanding the neural systems underlying the controls of energy balance has been greatly advanced by identifying the deficits and underlying mechanisms in rodent obesity models. The current review focuses on the Otsuka Long Evans Tokushima Fatty (OLETF rat obesity model. Since its recognition in the 1990’s significant progress has been made in identifying the causes and consequences of obesity in this model. Fundamental is a deficit in the cholecystokinin (CCK 1 receptor gene resulting in the absence of CCK 1 receptors in both the gastrointestinal track and the brain. OLETF rats have a deficit in their ability to limit the size of meals and in contrast to CCK1 receptor knock-out mice, do not compensate for this increase in the size of their spontaneous meals, resulting in hyperphagia. Prior to becoming obese and in response to pair feeding, OLETF rats have increased expression of neuropeptide Y (NPY in the compact region of the dorsomedial hypothalamus (DMH and this over-expression contributes to their overall hyperphaigia. Study of the OLETF rats has revealed important differences in the organization of the DMH in rats and mice and elucidated previously unappreciated roles for DMH NPY in energy balance and glucose homeostasis.

  12. Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis. A model of Wilson's disease.

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    Li, Y; Togashi, Y; Sato, S; Emoto, T; Kang, J H; Takeichi, N; Kobayashi, H; Kojima, Y; Une, Y; Uchino, J

    1991-05-01

    Long-Evans Cinnamon (LEC) rats, an inbred strain of a mutant rat isolated from Long-Evans rats, develop hereditary hepatitis. To elucidate the role of copper metabolism in the development of the hepatitis in LEC rats, we examined the copper concentration in the tissues and serum levels of copper and ceruloplasmin. Copper concentration in the liver of LEC rats was over 40 times that of normal Long-Evans Agouti (LEA) rats, while the serum ceruloplasmin and copper concentrations in LEC rats decreased significantly. The hepatocytes of LEC rats show steatosis in cytoplasm and pleomorphism of mitochondria, resembling the histologic features of the liver in Wilson's disease. These findings suggest that the hereditary hepatitis in LEC rats is closely associated with copper toxicity, and may be dealing with a rat form of Wilson's disease. Thus the LEC rats will provide a unique and useful animal model for clarifying the mechanism and for developing treatment strategies for Wilson's disease and other abnormal copper metabolism in humans.

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

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

    2012-02-01

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

  14. Metallothionein and antioxidant enzymes in Long-Evans Cinnamon rats treated with zinc.

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    Medici, Valentina; Santon, Alessandro; Sturniolo, Giacomo Carlo; D'Incà, Renata; Giannetto, Sabrina; Albergoni, Vincenzo; Irato, Paola

    2002-09-01

    The Long-Evans Cinnamon (LEC) rat is a mutant animal model for Wilson's disease. It is known that an abnormal accumulation of Cu and Fe in the liver and low concentrations of both ceruloplasmin and Cu in the serum occur in these rats. The accumulation of Cu is explained by the defective expression of the Cu-transporting P-type ATPase gene, homologous to the gene for Wilson's disease (ATP7B). The aim of this work was to clarify the action mechanism of Zn, and to verify the role that this metal plays in LEC rats in short-term treatment experiments (1 and 2 weeks) on concentrations of Cu, Zn, Fe, metallothionein (MT), 8-hydroxy-2'-deoxyguanosine (oh(8)dG) and on the activity of antioxidant enzymes. It is well known that Zn induces MT and has the ability to prevent redox-active metals, Cu and Fe, binding to and causing oxidative damage at active sites of Zn metalloenzymes and nonspecific binding sites on proteins. Zn administration reduces Cu and Fe transport from mucosal to serosal intestinal sides through competitive mechanisms. Our findings show that treatment with zinc acetate increases tissue Zn and MT contents and decreases Cu and Fe concentrations in the liver and kidneys, even if hepatic Zn and MT concentrations decrease with treatment period. Induction of MT synthesis by Zn contributes to the reduction in free radicals produced by Cu and Fe. We also observed that the superoxide dismutase (SOD)activity in liver decreases with treatment duration in association with the Cu and Fe liver decrease. However, the SOD activity in kidney increases in untreated rats at 2 weeks relative to those untreated for 1 week.

  15. Mechanisms contributing to the regional haemodynamic effects of neurotensin in conscious, unrestrained Long Evans rats.

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    Bachelard, H; Gardiner, S M; Kemp, P A; Bennett, T

    1992-01-01

    1. The regional haemodynamic effects of i.v. bolus doses of neurotensin (10-1000 ng) were assessed in conscious, unrestrained Long Evans rats chronically instrumented with miniaturized, pulsed Doppler probes. 2. Neurotensin caused increases in blood pressure, together with dose-related tachycardias and constrictions in the renal, superior mesenteric and hindquarters vascular beds. The tachycardia elicited by the 1000 ng dose of neurotensin was preceded by a transient bradycardia. 3. In the presence of phentolamine, the pressor effect of neurotensin (1000 ng) was converted into a hypotensive effect, accompanied by reduced tachycardic and constrictor responses in the renal, superior mesenteric and hindquarters vascular beds. The tachycardia was not preceded by a bradycardia. 4. In the presence of phentolamine and propranolol, the pressor and bradycardic responses to neurotensin were unaffected, whereas the tachycardia was abolished. The renal vasconstrictor effect was smaller, while the constrictions in the superior mesenteric and hindquarters vascular beds were not different from those in untreated rats. 5. In rats neonatally treated with capsaicin (50 mg kg-1, s.c.), the pressor effects elicited by neurotensin (300 and 1000 ng) were reduced as were the constrictor responses in the renal (at the dose of 300 ng), superior mesenteric (at the dose of 300 ng) and hindquarters (at both doses) vascular beds. The bradycardia elicited by neurotensin (1000 ng) was absent, whereas the tachycardia was potentiated. 6. The results indicate that in conscious, intact rats neurotensin appears to exert cardiovascular influences through activation of sympathoadrenal mechanisms and also through non-adrenergic effects on the heart, renal, superior mesenteric and hindquarters vascular beds. The latter effects appear to involve capsaicin-sensitive nerves.

  16. Dietary copper triggers onset of fulminant hepatitis in the Long-Evans cinnamon rat model

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    Ramsi Siaj; Vanessa Sauer; Sandra St(o)ppeler; Hans-Ullrich Spiegel; Gabriele K(o)hler; Andree Zibert

    2012-01-01

    To investigate the impact of dietary copper given at different time paints on the onset of fulminant hepatitis.METHODS:The Long-Evans cinnamon (LEC) rat model of Wilson's disease (WD) was used to study the impact of high dietary copper (hCu) on the induction of fulminant hepatitis at early or late time points of life.High Cu diet was started in rat pups or in adults (month5) for three months.Animals that received reduced dietary copper (rCu) throughout their lifetime served as a control.Hepatitis-associated serum markers (alanine aminotransferase,aspartate transaminase,bilirubin)were analyzed in animal groups receiving hCu or rCu.Liver copper content and liver histology were revealed at sacrifice.A set of 5 marker genes previously found to be affected in injured liver and which are related to angiogenesis (Vegfa),fat metabolism (Srebf1),extracellular matrix (Timp1),oxidative stress (Hmox1),and the cell cycle (Cdkn1a) were analyzed by real-time polymerase chain reaction.RESULTS:Regardless of the time point when hCu wasstarted,LEC rats (35/36) developed fulminant hepatitis and died.Animals receiving rCu (36/36) remained healthy,did not develop hepatitis,and survived long term without symptoms of overt disease,although liver copper accumulated in adult animals (477 ± 75 lg/g).With regard to start of hCu,onset of fulminant hepatitis was significantly (P < 0.001) earlier in adults (35 ± 9d)that showed pre-accumulation of liver copper as compared to the pup group (77 ± 15 d).Hepatitis-associated serum markers,liver copper and liver histology,as well as gene expression,were affected in LEC rats receiving hCu.However,except for early and rapid onset of hepatitis,biochemical and molecular markers were similar at the early and late time points of disease.CONCLUSION:Rapid onset of fulminant hepatitis in asymptomatic LEC rats with elevated liver copper suggests that there is a critical threshold of liver copper which is important to trigger the course of WD.

  17. Mechanism of enhanced lipid peroxidation in the liver of Long-Evans cinnamon (LEC) rats.

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    Yamamoto, H; Hirose, K; Hayasaki, Y; Masuda, M; Kazusaka, A; Fujita, S

    1999-11-01

    The Long-Evans Cinnamon (LEC) rat is a mutant strain of rats that accumulate copper (Cu) in the liver in much the same way as individuals who suffer from Wilson's disease (WD) and has been suggested as a model for this disease. Lipid peroxidation (LPO) is considered to be involved in the toxic action of Cu in the livers of LEC rats. We investigated the mechanism of LPO in the livers of LEC rats showing apparent signs of hepatitis. Several-fold higher LPO levels were observed in post-mitochondrial supernatant (S-9) fraction of livers from hepatitic LEC rats than in those from Wistar rats. To mimic living cells, we introduced NADPH-generating system (NADPH-gs) into the S-9 incubation system. Thus was ensured a constant supply of NADPH to vital enzymes that may be directly or indirectly involved in the generation and/or elimination of reactive oxygen species (ROSs), such as glutathione reductase (GSSG-R), which require NADPH for their reactions. The levels of LPO in liver S-9 from hepatitic LEC rats were further increased by incubating liver S-9 at 37 degrees C in the presence of NADPH-gs. This increase was inhibited by EDTA, butylated hydroxytoluene (BHT), and catalase (CAT), suggesting that some metal, most likely the accumulated Cu, and ROSs derived from hydrogen peroxide (H2O2) are involved in the increased levels of LPO in the livers of hepatitic LEC rats. The requirement of NADPH-gs for enhanced LPO in the livers of hepatitic LEC rats indicates the consumption of NADPH during reactions leading to LPO. It is known that H2O2, and consequently hydroxyl radical are generated during Cu-catalyzed glutathione (GSH) oxidation. The cyclic regeneration of GSH from GSSG by NADPH-dependent GSSG-R in the presence of NADPH-gs may cause sustained generation of hydroxyl radical in the presence of excess free Cu. The generation of H2O2 in S-9 fraction of livers from hepatitic LEC rats was observed to be significantly higher than that in S-9 fraction of livers from non

  18. Methylphenidate alters flash-evoked potentials, body temperature, and behavior in Long-Evans rats.

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    Hetzler, Bruce E; Meckel, Katherine R; Stickle, Bruce A

    2014-01-01

    This experiment examined the effects of methylphenidate hydrochloride on flash-evoked potentials (FEPs) recorded from the visual cortex (VC) and superior colliculus (SC) of chronically implanted male Long-Evans rats, as well as on body temperature and open field behavior. FEPs were recorded at 10, 20 and 40 min following intraperitoneal injections of saline, and of doses of 0.7, 2.9, and 11.6 mg/kg methylphenidate on separate days. The 0.7 mg/kg dose did not produce significant effects. In the VC, following administration of the 11.6 mg/kg dose of methylphenidate the amplitude of components P83, N146, and P232 decreased, the amplitude of component N64 briefly increased and components P23, N30, N40, and P48 were unchanged in amplitude. In the SC, component P29 was unaffected, while components P38 and N51 were reduced in amplitude by the 11.6 mg/kg dose of methylphenidate. Peak latencies of components N40, P48, P83, and N146 in the VC and component P38 in the SC were increased by the 11.6 mg/kg dose of methylphenidate. When body temperature was recorded 45 min after drug administration, a mild dose-dependent hypothermia was found with the 2.9 and 11.6 mg/kg methylphenidate doses, suggesting that this may have contributed to the increased latencies. In subsequent open field observations, both line crossings and rearings were significantly increased by the 11.6 mg/kg dose. Increased movement into the center of the testing area was also observed, which could be a sign of increased exploration and reduced anxiety following methylphenidate.

  19. Dietary isoflavones alter regulatory behaviors, metabolic hormones and neuroendocrine function in Long-Evans male rats

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    Bu Lihong

    2004-12-01

    Full Text Available Abstract Background Phytoestrogens derived from soy foods (or isoflavones have received prevalent usage due to their 'health benefits' of decreasing: a age-related diseases, b hormone-dependent cancers and c postmenopausal symptoms. However, little is known about the influence of dietary phytoestrogens on regulatory behaviors, such as food and water intake, metabolic hormones and neuroendocrine parameters. This study examined important hormonal and metabolic health issues by testing the hypotheses that dietary soy-derived isoflavones influence: 1 body weight and adipose deposition, 2 food and water intake, 3 metabolic hormones (i.e., leptin, insulin, T3 and glucose levels, 4 brain neuropeptide Y (NPY levels, 5 heat production [in brown adipose tissue (BAT quantifying uncoupling protein (UCP-1 mRNA levels] and 6 core body temperature. Methods This was accomplished by conducting longitudinal studies where male Long-Evans rats were exposed (from conception to time of testing or tissue collection to a diet rich in isoflavones (at 600 micrograms/gram of diet or 600 ppm vs. a diet low in isoflavones (at approximately 10–15 micrograms/gram of diet or 10–15 ppm. Body, white adipose tissue and food intake were measured in grams and water intake in milliliters. The hormones (leptin, insulin, T3, glucose and NPY were quantified by radioimmunoassays (RIA. BAT UCP-1 mRNA levels were quantified by PCR and polyacrylamide gel electrophoresis while core body temperatures were recorded by radio telemetry. The data were tested by analysis of variance (ANOVA (or where appropriate by repeated measures. Results Body and adipose tissue weights were decreased in Phyto-600 vs. Phyto-free fed rats. Food and water intake was greater in Phyto-600 animals, that displayed higher hypothalamic (NPY concentrations, but lower plasma leptin and insulin levels, vs. Phyto-free fed males. Higher thyroid levels (and a tendency for higher glucose levels and increased uncoupling

  20. Vitamin B12 and ketorolac on pain in Long Evans rats

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    Mizanur Rahman

    2016-12-01

    Full Text Available Background: Effects of vitamin B12 on pain have been demonstrated in different animal and humanstudies. But comparison of these effects with similar effects of ketorolac tromethamine (KT and theircombination have not been established. Objective: To assess the effects of vitamin B12 on pain andalso to compare them with those of the combinations of vitamin B12 with KT in rat models. Methods:This experimental study was conducted in the Department of Physiology, Bangabandhu Sheikh MujibMedical University (BSMMU, Dhaka, from March 2015 to February 2016. For this, 20 (twentyLong Evans rats (215±35 gm of both sexes were divided into control (A, with 5 ml/kg normal salineand experimental (B1, with 15 mg/kg B12; B2, with 10 mg/kg KT; B3, with B12+KT groups with 5rats in each group. All the drugs and vitamin were administered intraperitoneally in a single dose justone hour before formalin test. To evaluate the treatments’ effect on nociceptive pain, early phase (1st-5th minutes; on central analgesic system, interphase (6th-15th minutes; and on inflammatory pain,late phase (16th-60th minutes of the formalin test, were observed. In all phases, total frequency ofjerking and total duration of flexing and licking of the right hind paw were counted after administrationof subcutaneous formalin (50 μl, 2.5% injection. Statistical analysis was done by ANOVA, followedby Bonferroni post hoc test. In the interpretation of results, p≤0.05 was considered as significant.Results: B12 lowered only the jerking frequency and KT lowered both jerking frequency and flexinglicking duration significantly (p≤0.001 in the late phase of formalin test. On the other hand, combinationof B12 and KT significantly (p≤0.001 lowered both the study variables in all 3 phases of formalintest. Conclusion: From this study it may be concluded that, vitamin B12 possess analgesic effects andcombination of B12 with KT is more effective than those of their individual administration.

  1. Changes in plasma glucose in Otsuka Long-Evans Tokushima Fatty rats after oral administration of maple syrup.

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    Nagai, Noriaki; Yamamoto, Tetsushi; Tanabe, Wataru; Ito, Yoshimasa; Kurabuchi, Satoshi; Mitamura, Kuniko; Taga, Atsushi

    2015-01-01

    We investigate whether maple syrup is a suitable sweetener in the management of type 2 diabetes using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The enhancement in plasma glucose (PG) and glucose absorption in the small intestine were lower after the oral administration of maple syrup than after sucrose administration in OLETF rats, and no significant differences were observed in insulin levels. These data suggested that maple syrup might inhibit the absorption of glucose from the small intestine and preventing the enhancement of PG in OLETF rats. Therefore, maple syrup might help in the prevention of type 2 diabetes.

  2. Ethanol seeking by Long Evans rats is not always a goal-directed behavior.

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    Regina A Mangieri

    Full Text Available BACKGROUND: Two parallel and interacting processes are said to underlie animal behavior, whereby learning and performance of a behavior is at first via conscious and deliberate (goal-directed processes, but after initial acquisition, the behavior can become automatic and stimulus-elicited (habitual. With respect to instrumental behaviors, animal learning studies suggest that the duration of training and the action-outcome contingency are two factors involved in the emergence of habitual seeking of "natural" reinforcers (e.g., sweet solutions, food or sucrose pellets. To rigorously test whether behaviors reinforced by abused substances such as ethanol, in particular, similarly become habitual was the primary aim of this study. METHODOLOGY/PRINCIPAL FINDINGS: Male Long Evans rats underwent extended or limited operant lever press training with 10% sucrose/10% ethanol (10S10E reinforcement (variable interval (VI or (VR ratio schedule of reinforcement, or with 10% sucrose (10S reinforcement (VI schedule only. Once training and pretesting were complete, the impact of outcome devaluation on operant behavior was evaluated after lithium chloride injections were paired with the reinforcer, or unpaired 24 hours later. After limited, but not extended instrumental training, lever pressing by groups trained under VR with 10S10E and under VI with 10S was sensitive to outcome devaluation. In contrast, responding by both the extended and limited training 10S10E VI groups was not sensitive to ethanol devaluation during the test for habitual behavior. CONCLUSIONS/SIGNIFICANCE: Operant behavior by rats trained to self-administer an ethanol-sucrose solution showed variable sensitivity to a change in the value of ethanol, with relative insensitivity developing sooner in animals that received time-variable ethanol reinforcement during training sessions. One important implication, with respect to substance abuse in humans, is that initial learning about the

  3. Quantitative assessment of mammary gland development in female Long Evans rats following in utero exposure to atrazine.

    Science.gov (United States)

    Hovey, Russell C; Coder, Pragati Sawhney; Wolf, Jeffrey C; Sielken, Robert L; Tisdel, Merrill O; Breckenridge, Charles B

    2011-02-01

    In this study, we quantified the effects of in utero exposure to the herbicide atrazine on subsequent mammary gland development. Atrazine was administered to pregnant female Long Evans rats from gestation days 13-19 at doses of 0, 6.5, 50, or 100 mg/kg/day. A pair-fed control group was yoked to the high-dose atrazine-treated group. Litter size was standardized to 10 pups on postnatal day (PND) 4. Whole mounts of the left fourth mammary gland and histologic sections of the right fourth gland were obtained from a subgroup of offspring on PND1, 21, 33, on day of vaginal opening (VO), or around PND65 at diestrus. A blinded, quantitative analysis of key morphological features in mammary gland whole mounts (ductal elongation, ductal network area, epithelial area, terminal end bud [TEB] incidence, and epithelial density) as well as epithelial proliferation within different parenchymal structures was conducted. There was no effect of atrazine exposure on any of the measures of mammary gland development at the maternal dose of 6.5 mg/kg/day. On PND1, ductal elongation was increased by approximately 20% (p < 0.05) in the female offspring born to dams exposed to 50 and 100 mg/kg/day atrazine, coincident with decreased epithelial proliferation in the 100 mg/kg/day group at this age. These differences were not present on PND21, or thereafter. An increased incidence of TEB in the mammary glands from females that were born to both the pair-fed and 50 mg/kg/day-treated dams at the time of VO indicated that this response was a specific result of maternal caloric restriction. Collectively, these data indicate that maternal atrazine exposure has no long-term effects on mammary gland development in female offspring beyond a transitory response to high doses at PND1.

  4. Absence of diurnal variation in visceromotor response to colorectal distention in normal Long Evans rats [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Sara Botschuijver

    2016-01-01

    Full Text Available Background: Enhanced colorectal sensitivity (i.e. visceral hypersensitivity is thought to be a pathophysiological mechanism in irritable bowel syndrome (IBS. In healthy men a circadian variation in rectal perception to colonic distention was described. Disturbed day and night rhythms, which occur in shift work and trans meridian flights, are associated with the prevalence of IBS. This raises the question whether disruptions of circadian control are responsible for the observed pathology in IBS. Prior to investigating altered rhythmicity in relation to visceral hypersensitivity in a rat model for IBS, it is relevant to establish whether normal rats display circadian variation similar to healthy men.  Methodology and findings: In rodents colorectal distension leads to reproducible contractions of abdominal musculature. We used quantification of this so called visceromotor response (VMR by electromyography (EMG to assess visceral sensitivity in rats. We assessed the VMR in normal male Long Evans rats at different time points of the light/dark cycle. Although a control experiment with male maternal separated rats confirmed that intentionally inflicted (i.e. stress induced changes in VMR can be detected, normal male Long Evans rats showed no variation in VMR along the light/dark cycle in response to colorectal distension. Conclusions: In the absence of a daily rhythm of colorectal sensitivity in normal control rats it is not possible to investigate possible aberrancies in our rat model for IBS.

  5. Effects of Moderate Alcohol Intake in the Bladder of the Otsuka Long Evans Tokushima Fatty Diabetic Rats.

    Science.gov (United States)

    Bae, Woong Jin; Choi, Yong Sun; Kim, Su Jin; Cho, Hyuk Jin; Hong, Sung Hoo; Kim, Sae Woong; Hwang, Tae-Kon; Kim, Dai Jin; Lee, Ji Youl

    2015-09-01

    Diabetes is related with a number of cystopathic complications. However, there have been no studies about the influence of alcohol consumption in the bladder of type 2 diabetes. Thus, we investigated the effect of moderate alcohol intake in the bladder of the Otsuka Long Evans Tokushima Fatty (OLETF) diabetic rat. The non-diabetic Long-Evans Tokushima Otsuka (LETO, n=14) and the OLETF control group (n=14) were fed an isocaloric diet; the LETO (n=14) and the OLETF ethanol group (n=14) were fed 36% ethanol 7 g/kg/day. After ten weeks, muscarinic receptors, RhoGEFs, myogenic change, and the level of oxidative stress were evaluated. Moderate alcohol intake significantly decreased excessive muscarinic receptor and Rho kinase expressions in the OLETF rats compared with the LETO rats. In addition, iNOS and collagen expression were not changed in the OLETF rats in spite of alcohol consumption. Superoxide dismutase levels, which is involved in antioxidant defense, in the LETO rats were significantly decreased after alcohol consumption, however those in the OLETF rats were similar. Moderate alcohol consumption reduces the oxidative stress, and may prevent molecular and pathologic changes of the bladder of rats with type 2 diabetes.

  6. Troglitazone prevented the development of fatty liver under obese and diabetic condition in Otsuka Long-Evans Tokushima fatty rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    We aimed to clarify the effects of troglitazone to prevent the development of fatty liver in Otsuka Long-Evans Tokushima fatty (OLETF) rats, an obese type2 diabetes model. Treatment of 0.2% troglitazone for 16 weeks significantly decreased blood glucose, serum insulin and free fatty acid (FFA) concentration (P<0.05 for each) in the OLETF rats leaving their food intake, body weight and general fat pad weight unaffected compared with those of their lean littermates, Long-Evans Tokushima Otsuka (LETO) rats. Troglitazone restored increase in liver weight and hepatic triglyceride(TG) content of the OLETF rats (P<0.05 for each). These findings were accertained by histological examination which showed that fat deposition, necrosis and vacuolization of hepatocyte, markers for fatty liver, were diminished by troglitazone treatment. Messenger RNA expression of microsomal triglyceride transfer protein in the liver, a marker for hepatic TG output, was not significantly different between OLETF and LETO rats with or without troglitazone treatment. Fatty acid composition such as C18∶1(oleic acid) showed no remarkable change after troglitazone treatment in OLETF rats, indicating no dietary influence to hepatic lipogenesis. These indicate that reduction in circulating FFA level may be one of the main mechanisms for troglitazone to prevent the development of insulin resistance and fatty liver.

  7. S-Allyl cysteine improves nonalcoholic fatty liver disease in type 2 diabetes Otsuka Long-Evans Tokushima Fatty rats via regulation of hepatic lipogenesis and glucose metabolism.

    Science.gov (United States)

    Takemura, Shigekazu; Minamiyama, Yukiko; Kodai, Shintaro; Shinkawa, Hiroji; Tsukioka, Takuma; Okada, Shigeru; Azuma, Hideki; Kubo, Shoji

    2013-09-01

    It is important to prevent and improve diabetes mellitus and its complications in a safe and low-cost manner. S-Allyl cysteine, an aged garlic extract with antioxidant activity, was investigated to determine whether S-allyl cysteine can improve type 2 diabetes in Otsuka Long-Evans Tokushima Fatty rats with nonalcoholic fatty liver disease. Male Otsuka Long-Evans Tokushima Fatty rats and age-matched Long-Evans Tokushima Otsuka rats were used and were divided into two groups at 29 weeks of age. S-Allyl cysteine (0.45% diet) was administered to rats for 13 weeks. Rats were killed at 43 weeks of age, and detailed analyses were performed. S-Allyl cysteine improved hemoglobinA1c, blood glucose, triglyceride, and low-density lipoprotein cholesterol levels. Furthermore, S-allyl cysteine normalized plasma insulin levels. S-Allyl cysteine activated the mRNA and protein expression of both peroxisome proliferator-activated receptor α and γ, as well as inhibiting pyruvate dehydrogenase kinase 4 in Otsuka Long-Evans Tokushima Fatty rat liver. Sterol regulatory element-binding protein 1c and forkhead box O1 proteins were normalized by S-allyl cysteine in Otsuka Long-Evans Tokushima Fatty rat liver. In conclusions, these findings support the hypothesis that S-allyl cysteine has diabetic and nonalcoholic fatty liver disease therapeutic potential as a potent regulating agent against lipogenesis and glucose metabolism.

  8. Evolution of exchangeable copper and relative exchangeable copper through the course of Wilson's disease in the Long Evans Cinnamon rat.

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    Françoise Schmitt

    Full Text Available BACKGROUND: Wilson's disease (WD is an inherited disorder of copper metabolism leading to liver failure and/or neurological impairment. Its diagnosis often remains difficult even with genetic testing. Relative exchangeable copper (REC has recently been described as a reliable serum diagnostic marker for WD. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this study was to validate the use of REC in the Long Evans Cinnamon (LEC rat, an animal model for WD, and to study its relevance under different conditions in comparison with conventional markers. Two groups of LEC rats and one group of Long-Evans (LE rats were clinically and biologically monitored from 6 to 28 weeks of age. One group of LEC rats was given copper-free food. The other groups had normal food. Blood samples were collected each month and different serum markers for WD (namely ceruloplasmin oxidase activity, exchangeable copper (CuEXC, total serum copper and REC and acute liver failure (serum transaminases and bilirubinemia were tested. Every LEC rat under normal food developed acute liver failure (ALF, with 40% global mortality. Serum transaminases and bilirubinemia along with total serum copper and exchangeable copper levels increased with the onset of acute liver failure. A correlation was observed between CuEXC values and the severity of ALF. Cut-off values were different between young and adult rats and evolved because of age and/or liver failure. Only REC, with values >19%, was able to discriminate LEC groups from the LE control group at every time point in the study. REC sensitivity and specificity reached 100% in adults rats. CONCLUSIONS/SIGNIFICANCE: REC appears to be independent of demographic or clinical data in LEC rats. It is a very simple and reliable blood test for the diagnosis of copper toxicosis owing to a lack of ATP7B function. CuEXC can be used as an accurate biomarker of copper overload.

  9. Mozart K.448 attenuates spontaneous absence seizure and related high-voltage rhythmic spike discharges in Long Evans rats.

    Science.gov (United States)

    Lin, Lung-Chang; Juan, Chun-Ting; Chang, Hsueh-Wen; Chiang, Ching-Tai; Wei, Ruey-Chang; Lee, Mei-Wen; Mok, Hin-Kiu; Yang, Rei-Cheng

    2013-05-01

    Recent research has revealed more evidence supporting the positive effects of music on humans and animals. However, evidence of music's effects on improving epilepsy in animals is sparse. This study aimed to clarify the influence of Mozart's music in Long Evans rats, which are characterized by spontaneous absence epilepsy (SAE) and high-voltage rhythmic spike (HVRS) discharges. Continuous electroencephalograms comprised of HVRS discharges, and behavioral performance were recorded in Long Evans rats (n=5) before, during, and after exposure to the Mozart's Sonata for Two Pianos in D Major, K.448 (Mozart K.448). The same evaluation was repeated after they had been subjected to daily exposure of the music for 20 days. Seizure frequencies and spontaneous HVRS discharges were reduced in all of the SAE rats during and after music exposure compared with the pre-music stage. The average seizure frequencies were 79.8±24.6, 48±15.2, and 33±12.1/h before, during, and after music exposure, respectively. The average run of spike episodes were 84.6±18.4, 52±17.8, and 36.8±16.9/h before, during, and after music exposure, respectively. The seizure frequencies and related run of spike episodes decreased by 39.8% and 38.5% during, and 58.6% and 56.6% post music exposure, respectively. The average run of spike durations and spike numbers also showed significant decreases (reduction by 47.1%, 47.8% during music and 60.8%, 61.3% post music). After daily music exposure for 20 days, the number of HVRS discharges and seizure frequencies during and after music exposure, however, showed no further accumulative reduction or adaptation effect. These results suggest that Mozart K.448 had a positive short-term effect in attenuating the spontaneous HVRS discharges in Long Evans rats. However, the mechanism needs further investigation. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Redox regulation of apurinic/apyrimidinic endonuclease 1 activity in Long-Evans Cinnamon rats during spontaneous hepatitis.

    Science.gov (United States)

    Karmahapatra, Soumendra Krishna; Saha, Tapas; Adhikari, Sanjay; Woodrick, Jordan; Roy, Rabindra

    2014-03-01

    The Long-Evans Cinnamon (LEC) rat is an animal model for Wilson's disease. This animal is genetically predisposed to copper accumulation in the liver, increased oxidative stress, accumulation of DNA damage, and the spontaneous development of hepatocellular carcinoma. Thus, this animal model is useful for studying the relationship of endogenous DNA damage to spontaneous carcinogenesis. In this study, we have investigated the apurinic/apyrimidinic endonuclease 1 (APE1)-mediated excision repair of endogenous DNA damage, apurinic/apyrimidinic (AP)-sites, which is highly mutagenic and implicated in human cancer. We found that the activity was reduced in the liver extracts from the acute hepatitis period of LEC rats as compared with extracts from the age-matched Long-Evans Agouti rats. The acute hepatitis period had also a heightened oxidative stress condition as assessed by an increase in oxidized glutathione level and loss of enzyme activity of glyceraldehyde 3-phosphate dehydrogenase, a key redox-sensitive protein in cells. Interestingly, the activity reduction was not due to changes in protein expression but apparently by reversible protein oxidation as the addition of reducing agents to extracts of the liver from acute hepatitis period reactivated APE1 activity and thus, confirmed the oxidation-mediated loss of APE1 activity under increased oxidative stress. These findings show for the first time in an animal model that the repair mechanism of AP-sites is impaired by increased oxidative stress in acute hepatitis via redox regulation which contributed to the increased accumulation of mutagenic AP-sites in liver DNA.

  11. Hepatic iron deprivation prevents spontaneous development of fulminant hepatitis and liver cancer in Long-Evans Cinnamon rats.

    Science.gov (United States)

    Kato, J; Kobune, M; Kohgo, Y; Sugawara, N; Hisai, H; Nakamura, T; Sakamaki, S; Sawada, N; Niitsu, Y

    1996-08-15

    Several clinical studies have suggested that excess hepatic iron accumulation is a progressive factor in some liver diseases including chronic viral hepatitis and hemochromatosis. However, it is not known whether iron-induced hepatotoxicity may be directly involved in hepatitis, cirrhosis, and liver cancer. The Long-Evans Cinnamon (LEC) rat, which accumulates excess copper in the liver as in patients with Wilson's disease, is of a mutant strain displaying spontaneous hemolysis, hepatitis, and liver cancer. We found previously that LEC rats harbored an additional abnormality: accumulation of as much iron as copper in the liver. In the present study, we compared the occurrence of hepatitis and liver cancer in LEC rats fed an iron-deficient diet (ID) with those in rats fed a regular diet (RD). The RD group showed rapid increments of hepatic iron concentrations as the result of hemolysis, characteristics of fulminant hepatitis showing apoptosis, and a 53% mortality rate. However, no rats in the ID group died of fulminant hepatitis. Hepatic iron, especially "free" iron concentration and the extent of hepatic fibrosis in the ID group were far less than those of the RD group. At week 65, all rats in the RD group developed liver cancer, whereas none did in the ID group. These results suggest that the accumulation of iron, possibly by virtue of synergistic radical formation with copper, plays an essential role in the development of fulminant hepatitis, hepatic fibrosis, and subsequent hepatocarcinogenesis in LEC rats.

  12. Effects of prenatal exposure to a low dose atrazine metabolite mixture on pubertal timing and prostate development of male Long-Evans rats

    Energy Technology Data Exchange (ETDEWEB)

    Stanko, Jason [National Institute of Environmental Health Sciences (NIEHS); Enoch, Rolondo [North Carolina Central University, Durham; Rayner, Jennifer L [ORNL; Davis, Christine [U.S. Environmental Protection Agency; Wolf, Douglas [U.S. Environmental Protection Agency; Malarkey, David [University of North Carolina, Chapel Hill; Fenton, Suzanne [National Institute of Environmental Health Sciences (NIEHS)

    2010-12-01

    The present study examines the postnatal reproductive development of male rats following prenatal exposure to an atrazine metabolite mixture (AMM) consisting of the herbicide atrazine and its environmental metabolites diaminochlorotriazine, hydroxyatrazine, deethylatrazine, and deisopropylatrazine. Pregnant Long-Evans rats were treated by gavage with 0.09, 0.87, or 8.73 mg AMM/kg body weight (BW), vehicle, or 100 mg ATR/kg BW positive control, on gestation days 15 19. Preputial separation was significantly delayed in 0.87 mg and 8.73 mg AMM-exposed males. AMM-exposed males demonstrated a significant treatment-related increase in incidence and severity of inflammation in the prostate on postnatal day (PND) 120. A dose-dependent increase in epididymal fat masses and prostate foci were grossly visible in AMM-exposed offspring. These results indicate that a short, late prenatal exposure to mixture of chlorotriazine metabolites can cause chronic prostatitis in male LE rats. The mode of action for these effects is presently unclear.

  13. Effects of prenatal exposure to a low dose atrazine metabolite mixture onpubertal timing and prostate development of male Long-Evans rats

    Science.gov (United States)

    Atrazine (ATR) is a chlorotriazine herbicide extensively used in the US and other countries. Studies examining the effects of adult or developmental ATR exposure on the mammary gland (MG) have used either the Sprague Dawley (SD) or Long-Evans (LE) rat, but no strain comparisons h...

  14. Strain Differences in Dimethylbenz[a]anthracene-Induced Mammary Tumor Incidence in Long Evans and Sprague Dawley Rat Offspring Following Prenatal Atrazine Exposure

    Science.gov (United States)

    It has been shown that prenatal exposure to the chlorotriazine herbicide atrazine (ATR) during mammary bud outgrowth (late gestation) delays postnatal mammary epithelial progression in Long Evans (LE) rats. Our laboratory has recently found that prenatal exposure to ATR also effe...

  15. THE EFFECT OF TARGETED KNOCKOUT MUTATION ON THE TRANSCRIPTIONAL PROFILE OF THE KIDNEY IN TSC2 MUTANT LONG-EVANS (EKER) RATS.

    Science.gov (United States)

    The effect of a targeted knockout mutation on the transcriptional profile of the kidney inTsc2 mutant Long-Evans (Eker) rats. Renal cell carcinoma (RCC) is the most common tumor of the adult kidney, accounting for up to 80% of malignant renal neoplasms. Hereditary...

  16. Effects of prenatal exposure to a low dose atrazine metabolite mixture onpubertal timing and prostate development of male Long-Evans rats

    Science.gov (United States)

    Atrazine (ATR) is a chlorotriazine herbicide extensively used in the US and other countries. Studies examining the effects of adult or developmental ATR exposure on the mammary gland (MG) have used either the Sprague Dawley (SD) or Long-Evans (LE) rat, but no strain comparisons h...

  17. Consumption of pork-liver protein hydrolysate reduces body fat in Otsuka Long-Evans Tokushima Fatty rats by suppressing hepatic lipogenesis.

    Science.gov (United States)

    Shimizu, Muneshige; Tanabe, Soichi; Morimatsu, Fumiki; Nagao, Koji; Yanagita, Teruyoshi; Kato, Norihisa; Nishimura, Toshihide

    2006-01-01

    This study was performed to examine the effect of consumption of pork-liver protein hydrolysate (PLH) on body fat accumulation in Otsuka Long-Evans Tokushima Fatty (OLETF) rats as a non-insulin-dependent diabetes mellitus model and in Long-Evans Tokushima Otsuka (LETO) rats as a control. Male 20-week-old OLETF and LETO rats were pair-fed either PLH or casein containing diet for 14 weeks. In the OLETF rats, dietary PLH significantly reduced the growth and weight of fat pad including perirenal and epididymal adipose tissues. Consumption of PLH markedly suppressed hepatic activities of lipogenesis enzymes such as glucose-6-phosphate dehydrogenase and fatty acid synthase and slightly elevated fecal excretion of total fat. In the LETO rats, growth and adipose tissue weight were unaffected by dietary treatment. The results suggest that PLH is a novel ingredient suppressing body fat in genetically obese rats by reducing lipogenesis.

  18. Mechanism of hepatorenal syndrome in rats of Long-Evans Cinnamon strain, an animal model of fulminant Wilson's disease.

    Science.gov (United States)

    Nomiyama, K; Nomiyama, H; Kameda, N; Tsuji, A; Sakurai, H

    1999-02-15

    Rats of Long-Evans Cinnamon (LEC) strain were used as a hepatorenal syndrome model of fulminant Wilson's disease. Copper levels in the kidneys increased markedly from 16 to 126 microg Cu/g from 12 to 16 weeks, and remained at the same level at 16 and 19 weeks when the rats suffered from severe renal dysfunction and also at 20 weeks in some other normal rats. The above findings imply that the renal dysfunction may have been induced independently of the copper level in the kidneys. The present study suggested the following mechanism: immediately after copper-induced hepatic dysfunction, plasma copper-metallothionein (CuMT), which was released from the liver, became elevated. The elevation was closely related to the increases in alkaline phosphatase, glucose and amino acids, all in the urine. The above findings suggest that plasma CuMT, which was released from the liver into the blood upon copper-induced hepatic dysfunction, was subsequently filtered at the glomeruli due to its smaller molecular weight, and then caused dysfunction of the brush border membrane of the renal proximal tubules probably after splitting into radical copper and amino acids in acidic vesicles close to the membrane. The critical concentration of plasma CuMT required to induce renal dysfunction was estimated as 1 microg Cu/l.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Ku, Katherine M.; Weir, Ruth K.; Silverman, Jill L.; Berman, Robert F.; Bauman, Melissa D.

    2016-01-01

    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. PMID:27351457

  1. Anti-obesity effects of granulocyte-colony stimulating factor in Otsuka-Long-Evans-Tokushima fatty rats.

    Directory of Open Access Journals (Sweden)

    Yonggu Lee

    Full Text Available Granulocyte-colony stimulating factor (G-CSF has molecular structures and intracellular signaling pathways that are similar to those of leptin and ciliary neurotropic factor (CNTF. It also has immune-modulatory properties. Given that leptin and CNTF play important roles in energy homeostasis and that obesity is an inflammatory condition in adipose tissue, we hypothesized that G-CSF could also play a role in energy homeostasis. We treated 12 38-week-old male Otsuka-Long-Evans-Tokushima fatty rats (OLETF, diabetic and 12 age-matched male Long-Evans-Tokushima rats (LETO, healthy with 200 µg/day G-CSF or saline for 5 consecutive days. Body weight reduction was greater in G-CSF-treated OLETF (G-CSF/OLETF than saline-treated OLETF (saline/OLETF following 8 weeks of treatment (-6.9±1.6% vs. -3.1±2.2%, p<0.05. G-CSF treatment had no effect on body weight in LETO or on food intake in either OLETF or LETO. Body fat in G-CSF/OLETF was more reduced than in saline/OLETF (-32.2±3.1% vs. -20.8±6.2%, p<0.05. Energy expenditure was higher in G-CSF/OLETF from 4 weeks after the treatments than in saline/OLETF. Serum levels of cholesterol, triglyceride, interleukin-6 and tumor necrosis factor-α were lower in G-CSF/OLETF than in saline/OLETF. Uncoupling protein-1 (UCP-1 expression in brown adipose tissue (BAT was higher in G-CSF/OLETF than in saline/OLETF, but was unaffected in LETO. Immunofluorescence staining and PCR results revealed that G-CSF receptors were expressed in BAT. In vitro experiments using brown adipocyte primary culture revealed that G-CSF enhanced UCP-1 expression from mature brown adipocytes via p38 mitogen-activated protein kinase pathway. In conclusion, G-CSF treatment reduced body weight and increased energy expenditure in a diabetic model, and enhanced UCP-1 expression and decreased inflammatory cytokine levels may be associated with the effects of G-CSF treatment.

  2. Proteins Associated with the Termination of Ocular Dominance Column Plasticity in Long Evans Rats

    Institute of Scientific and Technical Information of China (English)

    Junping Yao; Zhengqin Yin; Shijun Wang

    2007-01-01

    Purpose: To investigate the mechanism of the termination of ocular dominance column plasticity by electrophysiologic analysis and 2-dimensional electrophoresis-mass spectrography (2-DE/MS).Methods: The changes in ocular dominance columns following monocular deprivation were electrophysiologically detected in 22-day-old, 100-day-old and chondroitinaseperfused 100-day-old rats. Total protein of grey matter of the primary visual cortex was extracted and studied by 2-DE/MS from the three groups of rats.Results: Monocular deprivation may lead to shifts in ocular dominance columns in 22-day-old and chondroitinase-perfused 100-day-old rats, but not in 100-day-old rats. Four protein spots present in grey matter of the primary visual cortex in 100-day-old, but not in that of 22-day-old and chondroitinase-perfused rats, and mass spectrography identified two of these proteins.Conclusions: The electrophysiologic results show that ocular dominance column plasticity presents in 22-day-old rats, ends up in 100-day-old rats and restored in chondroitinaseperfused 100-day-old rats. 2-DE/MS results show that phosphatidylethanolamine binding protein and glial fibrillary acidic protein delta may be associated with the termination of ocular dominance column plasticity in the rat, but need more evidence to confirm it.

  3. Stress facilitates late reversal learning using a touchscreen-based visual discrimination procedure in male Long Evans rats.

    Science.gov (United States)

    Bryce, Courtney A; Howland, John G

    2015-02-01

    The stress response is essential to the survival of all species as it maintains internal equilibrium and allows organisms to respond to threats in the environment. Most stress research has focused on the detrimental impacts of stress on cognition and behavior. Reversal learning, which requires a change in response strategy based on one dimension of the stimuli, is one type of behavioral flexibility that is facilitated following some brief stress procedures. The current study investigated a potential mechanism underlying this facilitation by blocking glucocorticoid receptors (GRs) during stress. Thirty-seven male Long Evans rats learned to discriminate between two images on a touchscreen, one of which was rewarded. Once a criterion was reached, rats received stress (30 min of restraint stress or no stress) and drug (GR antagonist RU38486 or vehicle) administration prior to each of the first 3 days of reversal learning. We expected that stress would facilitate reversal learning and RU38486 (10 mg/kg) would prevent this facilitation in both early (50% correct in one session) stages of reversal learning. Results showed that stressed rats performed better than unstressed rats (fewer days for late reversal, fewer correction trials, and fewer errors) in the late but not early stage of reversal learning. RU38486 did not block the facilitation of RL by stress, although it dramatically increased response, but not reward, latencies. These results confirm the facilitation of late reversal by stress in a touchscreen-based operant task in rats and further our understanding of how stress affects higher level cognitive functioning and behavior.

  4. Increase in osteoclastogenesis in an obese Otsuka Long-Evans Tokushima fatty rat model.

    Science.gov (United States)

    Ootsuka, Tomoyo; Nakanishi, Atsuko; Tsukamoto, Ikuyo

    2015-09-01

    In the present study, the effects of obesity on bone metabolism were investigated using a hyperphagic and obese rat model, the Otsuka Long‑Evans Tokushima fatty (OLETF) rat, which exhibits normal glycemic control at 8 weeks of age. Body weight, food intake, fat mass, markers of bone resorption, the activities of tartrate‑resistant acid phosphatase (TRAP) and cathepsin K, the number of osteoclasts in the proximal tibia, and the serum C‑terminal crosslinking telopeptide level were higher in OLETF rats than those in control rats (Long‑Evans Tokushima Otsuka; LETO). However, no differences in markers of bone formation, alkaline phosphatase activity, the number of osteoblasts in the proximal tibia or the serum osteocalcin level were observed. mRNA and protein levels of c‑fms, receptor for activation of nuclear factor‑κB (RANK), RANK ligand (RANKL), TRAP and cathepsin K were significantly increased in OLETF rats, although those levels of macrophage colony‑stimulating factor (M‑CSF) and osteoprotegerin (OPG) were similar to those in LETO rats. The level of serum tumor necrosis factor α (TNFα), and that of TNFα mRNA in bone, increased in association with the activation of NFκB. Furthermore, a frequency analysis and a colony formation assay respectively showed that the number of osteoclast precursors and the number of colony‑forming cells induced by M‑CSF each increased in OLETF rats compared with the control group. These results suggested that hyperphagia‑induced obesity with normal glycemic control induces the upregulation of osteoclastogenesis that is associated with an increase in the expression of c‑fms, RANK and RANKL, which is induced by TNFα, via the activation of NFκB.

  5. Chronic ethanol exposure increases voluntary home cage intake in adult male, but not female, Long-Evans rats.

    Science.gov (United States)

    Morales, Melissa; McGinnis, Molly M; McCool, Brian A

    2015-12-01

    The current experiment examined the effects of 10 days of chronic intermittent ethanol (CIE) exposure on anxiety-like behavior and home cage ethanol intake using a 20% intermittent access (M, W, F) paradigm in male and female Long-Evans rats. Withdrawal from alcohol dependence contributes to relapse in humans and increases in anxiety-like behavior and voluntary ethanol consumption in preclinical models. Our laboratory has shown that 10 days of CIE exposure produces both behavioral and neurophysiological alterations associated with withdrawal in male rats; however, we have yet to examine the effects of this exposure regime on ethanol intake in females. During baseline, females consumed more ethanol than males but, unlike males, did not show escalations in intake. Rats were then exposed to CIE and were again given intermittent access to 20% ethanol. CIE males increased their intake compared to baseline, whereas air-exposed males did not. Ethanol intake in females was unaffected by CIE exposure. Notably, both sexes expressed significantly elevated withdrawal-associated anxiety-like behavior in the plus maze. Finally, rats were injected with the cannabinoid CB1 receptor antagonist, SR141716A (0, 1, 3, 10mg/kg, i.p.) which reduced ethanol intake in both sexes. However, females appear to be more sensitive to lower doses of this CB1 receptor antagonist. Our results show that females consume more ethanol than males; however, they did not escalate their intake using the intermittent access paradigm. Unlike males, CIE exposure had no effect on drinking in females. It is possible that females may be less sensitive than males to ethanol-induced increases in drinking after a short CIE exposure. Lastly, our results demonstrate that males and females may have different pharmacological sensitivities to CB1 receptor blockade on ethanol intake, at least under the current conditions.

  6. Strain-dependent effects of acute caffeine on anxiety-related behavior in PVG/c, Long-Evans and Wistar rats.

    Science.gov (United States)

    Hughes, Robert N; Hancock, Nicola J

    2016-01-01

    To assess the possibility that acute caffeine's behavioral action might depend on rats' strain, effects of 50mg/kg of the drug were observed on activity, anxiety-related behavior and habituation learning in male and female rats from three different strains, namely PVG/c, Long-Evans and Wistar. All subjects were tested in an open field, an elevated plus maze and a light-dark box. For the three strains combined, increased occupancy of the center of the open field and entries of the open plus-maze arms with caffeine suggested caffeine-induced anxiolysis, whereas increased grooming in the open field, decreased rearing in the plus maze and increased risk assessment in the light-dark box were consistent with anxiogenesis. Caffeine also reduced open-field rearing only for PVG/c rats, and entries into and occupation of the light side of the light-dark box only for Long-Evans rats, and increased total defecation in the three types of apparatus for all three strains combined. Overall, caffeine appeared to be mainly anxiogenic. The drug also increased open-field ambulation for PVG/c rats and walking for all rats, but decreased open-field ambulation and entries into the plus maze closed arms for Wistar rats alone. In general, Wistar rats appeared to be the least and Long-Evans the most anxious of the three strains investigated. Caffeine also decreased within-session habituation of open-field ambulation for PVG/c rats alone, thereby suggesting strain-dependent interference with non-associative learning and short-term memory. Several overall sex differences were also observed that supported female rats being more active and less anxious than males.

  7. Protection from spontaneous hepatocellular damage by N-benzyl-D-glucamine dithiocarbamate in Long-Evans Cinnamon rats, an animal model of Wilson's disease

    OpenAIRE

    Shimada, Hideaki; Takahashi, Makiko; SHIMADA, Akinori; Okawara, Tadashi; Yasutake, Akira; Imamura, Yorishige; Kiyozumi, Morio; シマダ, ヒデアキ; タカハシ, マキコ; シマダ, アキノリ; オオカワラ, タダシ; ヤスタケ, アキラ; イマムラ, ヨリシゲ; キヨズミ, モリオ; 島田, 秀昭

    2005-01-01

    The Long-Evans Cinnamon (LEC) rat is a mutant strain that accumulates excessive tissue copper (Cu) and models the clinical symptoms and biological features of Wilson’s disease in humans. We compared the effects of three metal chelating agents, N-benzyl-D-glucamine dithiocarbamate (BGD), D-penicillamine (D-PEN), and triethylenetetramine (TETA) on the biliary and urinary excretions of Cu using LEC rats. The animals were treated ip with each chelating agent (1 mmol/kg body weight) and then the...

  8. Competition between copper and silver in Fischer rats with a normal copper metabolism and in Long-Evans Cinnamon rats with an abnormal copper metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Sugawara, N.; Sugawara, C. [Sapporo Medical Univ. (Japan). Dept. of Public Health

    2000-07-01

    Long-Evans Cinnamon (LEC) rats inherently lacking in serum ceruloplasmin (CP) activity and biliary Cu excretion were established from a closed colony of Long-Evans rats. These deficiencies, linked to a dysfunction of P-type ATPase, stimulate deposition of Cu and then of Cu metallothionein (MT) in the liver. Male LEC and Fischer rats were injected subcutaneously with Ag (AgNO{sub 3}), which is an antagonist to Cu. They were operated on 24 h after the injection while under anesthesia. Total uptake of Ag into the liver was not stimulated, but its uptake into the MT fraction increased significantly in the LEC rats. Ag injection notably decreased the activity of serum CP in the Fischer rats, but not in the LEC rats. The decrease was accompanied by a reduction of serum Cu. In Fischer rat serum treated with Ag, Ag was detected mainly in the albumin region and partly in the CP fraction. In LEC rat serum, however, the Ag concentration was about 1/20 of that in the Fischer rats, and Ag was not detected in the CP fraction. Ag injection decreased the biliary excretion of Cu in the Fischer rats (0.183-0.052 {mu}g Cu/20 min sampling), but not in the LEC rats (0.014-0.014 {mu}g Cu/20 min sampling). On the other hand, biliary excretion of Ag was much greater in the Fischer rats (1.25 {mu}g Ag/20 min) than in the LEC rats (0.04 {mu}g Ag/20 min). Our results suggest that uptake of Ag into the liver is not dependent on the hepatic Cu content and status, but that biliary excretion of Ag from the liver is affected by these. Hepatic MT is not a transporter of hepatobiliary excretion of Cu and Ag. It seems likely that, unlike Cu excretion, Ag is excreted by not only the CP route but also by another route into the serum. Ag may compete with Cu in the uptake into CP (conversion of apo-CP to holo-CP). (orig.)

  9. Maternal behavior priming in virgin and caesarean-delivered Long-Evans rats: effects of brief contact or continuous exteroceptive pup stimulation.

    Science.gov (United States)

    Stern, J M

    1983-12-01

    The effects of 8 days of prior exposure to pups (Priming) in the form of continuous exteroceptive (smell, sight and sound), or 15 min/day physical access (taste and touch possible) stimulation on the subsequent latency to become maternal during cohabitation with pups (concaveation) was studied in Long-Evans female rats. Brief daily access was effective in hastening the onset of maternal behavior only in those virgins which engaged in pup licking during Priming and in maintaining short-latency maternal responsiveness only in those day 21 pregnancy-terminated, thelectomized rats which initiated maternal behavior during Priming. Exteroceptive stimulation was ineffective in both virgins and caesarean-sectioned rats. These findings stress the importance of physical interactions with pups (unrelated to nipple stimulation) for the development of nurturance.

  10. Role of p38 Mapk in development of acute hepatic injury in Long-Evans Cinnamon (LEC) rats, an animal model of human Wilson's disease.

    Science.gov (United States)

    Kadowaki, Shingo; Meguro, Saori; Imaizumi, Yoshitaka; Sakai, Hiroshi; Endoh, Daiji; Hayashi, Masanobu

    2013-12-30

    The Long-Evans Cinnamon (LEC) rat, an animal model of human Wilson's disease, spontaneously develops fulminant hepatitis associated with severe jaundice at about 4 months of age. In this study, we examined the changes in gene expression during progression of acute hepatic injury. When levels of gene expression in the liver of LEC rats at 13 weeks of age were compared to those in rats at 4 weeks of age using oligonucleotide arrays, 1,620 genes out of 7,700 genes analyzed showed more than 2-fold differences. Expression levels of 11 of 29 genes related to stress-activating protein kinase (SAPK) changed by more than 2-fold in the liver of LEC rats, but none of the SAPK-related genes showed changes in expression levels in the liver of control rats. Activity of p38 mapk in the liver of LEC rats at 13 weeks of age was about 8.1-fold higher than that in rats at 4 weeks of age. When LEC rats were administered SB203580, a p38 mapk-specific inhibitor, by s.c. injection twice a week from 10 to 13 weeks of age, activities of p38 mapk in the liver, activities of AST and ALT and concentrations of bilirubin in sera of rats administered SB203580 significantly decreased compared to those in rats not administered. These results showed that the increase in activities of p38 mapk was related to the occurrence of acute hepatic injury in LEC rats.

  11. Multiple (/sup 3/H)imipramine binding sites in brains of male and female Fawn-Hooded and Long-Evans rats

    Energy Technology Data Exchange (ETDEWEB)

    Ieni, J.R.; Zukin, S.R.; Praag, H.M. van; Tobach, E.; Barr, G.A.

    1985-06-07

    Comparisons of high- and low-affinity (/sup 3/H)imipramine binding to whole brain homogenates from adult male and female rats of the Fawn-Hooded and Long-Evans strains were performed. Most strikingly, no significant differences were observed between the two strains in any of the binding parameters, indicating that brain (/sup 3/H)imipramine binding sites, which may be related to the serotonergic uptake process, appear normal in a strain of rats with serotonin platelet storage pool disease. However, a significant sex difference in high- but not low-affinity whole brain (/sup 3/H)imipramine Bsub(max) values was observed, with females of both strains having higher densities than males.

  12. Disturbance of response to acute thermal pain in naturally occurring cholecystokinin-a receptor gene knockout Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

    Science.gov (United States)

    Miyasaka, Kyoko; Nomoto, Shigeki; Ohta, Minoru; Kanai, Setsuko; Kaneko, Takao; Tahara, Shoichi; Funakoshi, Akihiro

    2006-08-01

    Otsuka Long-Evans Tokushima Fatty (OLETF) rats lack cholecystokinin-A receptor (CCK-AR) because of a genetic abnormality. We observed that body temperature homeostasis in response to changes in ambient temperature was deteriorated in OLETF rats, while the functions of the signal outputs from the hypothalamus to effectors were not impaired. Deteriorated homeostasis was also seen in CCK-AR deficient (-/-) mice. In the present study, we examined whether the sensory pathway involved in transmitting signals about temperature from the skin to the brain was impaired in OLETF rats. To elucidate the involvement of CCK-AR function, we conducted the same experiment in CCK-AR(-/-) mice. Responses to thermal pain were assessed using the Hargreaves' plantar test apparatus. Shortening of withdrawal latency was observed in OLETF rats compared to control rats, indicating thermal hyperalgesia. Behavioral responses following paw withdrawal were disturbed in OLETF rats. The 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid contents in the hippocampus and frontal cortex of OLETF rats were significantly higher than in those of the controls. CCK-AR(-/-) mice did not show any differences from wild-type mice. In conclusion, OLETF rats showed thermal hyperalgesia and disturbed responses to thermal pain, and an alteration of 5-HT function might have a role in this disturbance.

  13. Comparison of the enhancement of plasma glucose levels in type 2 diabetes Otsuka Long-Evans Tokushima Fatty rats by oral administration of sucrose or maple syrup.

    Science.gov (United States)

    Nagai, Noriaki; Ito, Yoshimasa; Taga, Atsushi

    2013-01-01

    Maple syrup is used as a premium natural sweeter, and is known for being good for human health. In the present study, we investigate whether maple syrup is suitable as a sweetener in the management of type 2 diabetes using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. OLETF rats develop type 2 diabetes mellitus by 30 weeks of age, and 60-week-old OLETF rats show hyperglycemia and hypoinsulinemia via pancreatic β-cell dysfunction. The administration of sucrose or maple syrup following an OGT test increased plasma glucose (PG) levels in OLETF rats, but the enhancement in PG following the oral administration of maple syrup was lower than in the case of sucrose administration in both 30- and 60-week-old OLETF rats. Although, the insulin levels in 30-week-old OLETF rats also increased following the oral administration of sucrose or maple syrup, no increase in insulin levels was seen in 60-week-old OLETF rats following the oral administration of either sucrose or maple syrup. No significant differences were observed in insulin levels between sucrose- and maple syrup-administered OLETF rats at either 30 or 60 weeks of age. The present study strongly suggests that the maple syrup may have a lower glycemic index than sucrose, which may help in the prevention of type 2 diabetes.

  14. OTSUKA-LONG-EVANS-TOKUSHIMA FATTY 糖尿病大鼠周围神经的结构蛋白改变%STRUCTURAL PROTEIN ALTERATIONS IN PERIPHERAL NERVE OF OTSUKA-LONG-EVANS-TOKUSHIMA FATTY DIABETIC RATS

    Institute of Scientific and Technical Information of China (English)

    李建萍; 吕传真

    2004-01-01

    为了解Otsuka-Long Evans-Tokushima Fatty(OLETF)糖尿病大鼠周围神经的结构蛋白改变,使用OLETF大鼠10只/Long Evans-Tokushima Otsuka(LETO对照大鼠6只,于糖尿病发病后6个月取坐骨神经,制成冰冻切片和单纤维贴片,进行神经结构蛋白的免疫组织化学染色.在光镜下观察到OLETF大鼠周围神经部分区域有结构异常.轴索结构中,Ranvier结区的钠离子通道蛋白密度降低并向结旁区移位,近结旁段的钾离子通道蛋白(Kv1.1)向Ranvier结区和节间段弥散,神经丝着色浅淡且不均匀.髓鞘结构中,结旁段的髓鞘相关糖蛋白着色不均匀并向节间段弥散,致密髓鞘层的髓鞘碱性蛋白和Schwann细胞表面的半乳糖脑苷脂基本正常.上述结果提示Ranvier结区的轴膜和结旁段的髓鞘是OLETF糖尿病大鼠周围神经的起始损害位点.

  15. Four weeks' inhalation exposure of Long Evans rats to 4-tert-butyltoluene: Effect on evoked potentials, behaviour and brain neurochemistry

    DEFF Research Database (Denmark)

    Lam, Henrik Rye; Ladefoged, Ole; Østergaard, Grete

    2000-01-01

    Long-lasting central nervous system (CNS) neurotoxicity of 4-tert-butyltoluene (TBT) has been investigated using electrophysiology, behaviour, and neurochemistry in Long Evans rats exposed by inhalation to 0, 20, or 40 p.p.m. TBT 6 hr/day, 7 days/week for 4 weeks. Flash evoked potentials...... and somatosensory evoked potentials were not affected by TBT In Auditory Brain Stem Response there was no shift in hearing threshold, but the amplitude of the first wave was increased in both exposed groups at high stimulus levels. Three to four months after the end of exposure, behavioural studies in Morris water...... maze and eight-arm maze failed to demonstrate any TBT induced effects. Exposure was followed by a 5 months exposure-free period prior to gross regional and subcellular (synaptosomal) neurochemical investigations of the brain. TBT reduced the NA concentration in whole brain minus cerebellum...

  16. Attenuation of Diabetic Nephropathy in Otsuka Long-Evans Tokushima Fatty (OLETF Rats with a Combination of Chinese Herbs (Tangshen Formula

    Directory of Open Access Journals (Sweden)

    Haojun Zhang

    2011-01-01

    Full Text Available Diabetic nephropathy is one of the most significant microvascular complications in patients with type 2 diabetics. The concise mechanism of diabetic nephropathy is unknown and there is no successful treatment. The objective of study was to investigate effects of Chinese herbs (Tangshen Formula on diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty (OLETF rats. OLETF rats and LETO rats were divided into four groups: LETO control, OLETF diabetics, OLETF diabetics treated with Tangshen Formula, and OLETF diabetics treated with Monopril. Body weight, blood glucose, and 24 h urinary proteins were measured once every four weeks. Blood samples and kidney tissues were obtained for analyses of total cholesterol, triglyceride, whole blood viscosity, plasma viscosity, and pathohistological examination at 36 and 56 weeksrespectively. Untreated OLETF rats displayed diabetic nephropathy over the study period. Treatment of OLETF rats with Tangshen Formula attenuated the increases in blood glucose, body weight, 24 h urinary protein content, serum total cholesterol, whole blood viscosity and plasma viscosity at certain time. Treatment with Tangshen Formula also reduced glomerulosclerotic index and interstitial fibrotic index seen in OLETF rats. In conclusion, Tangshen Formula could attenuate the development of diabetic nephropathy in OLETF rat diabetic model.

  17. Reduced hippocampal dendritic spine density and BDNF expression following acute postnatal exposure to di(2-ethylhexyl phthalate in male Long Evans rats.

    Directory of Open Access Journals (Sweden)

    Catherine A Smith

    Full Text Available Early developmental exposure to di(2-ethylhexyl phthalate (DEHP has been linked to a variety of neurodevelopmental changes, particularly in rodents. The primary goal of this work was to establish whether acute postnatal exposure to a low dose of DEHP would alter hippocampal dendritic morphology and BDNF and caspase-3 mRNA expression in male and female Long Evans rats. Treatment with DEHP in male rats led to a reduction in spine density on basal and apical dendrites of neurons in the CA3 dorsal hippocampal region compared to vehicle-treated male controls. Dorsal hippocampal BDNF mRNA expression was also down-regulated in male rats exposed to DEHP. No differences in hippocampal spine density or BDNF mRNA expression were observed in female rats treated with DEHP compared to controls. DEHP treatment did not affect hippocampal caspase-3 mRNA expression in male or female rats. These results suggest a gender-specific vulnerability to early developmental DEHP exposure in male rats whereby postnatal DEHP exposure may interfere with normal synaptogenesis and connectivity in the hippocampus. Decreased expression of BDNF mRNA may represent a molecular mechanism underlying the reduction in dendritic spine density observed in hippocampal CA3 neurons. These findings provide initial evidence for a link between developmental exposure to DEHP, reduced levels of BDNF and hippocampal atrophy in male rats.

  18. Reduced hippocampal dendritic spine density and BDNF expression following acute postnatal exposure to di(2-ethylhexyl) phthalate in male Long Evans rats.

    Science.gov (United States)

    Smith, Catherine A; Holahan, Matthew R

    2014-01-01

    Early developmental exposure to di(2-ethylhexyl) phthalate (DEHP) has been linked to a variety of neurodevelopmental changes, particularly in rodents. The primary goal of this work was to establish whether acute postnatal exposure to a low dose of DEHP would alter hippocampal dendritic morphology and BDNF and caspase-3 mRNA expression in male and female Long Evans rats. Treatment with DEHP in male rats led to a reduction in spine density on basal and apical dendrites of neurons in the CA3 dorsal hippocampal region compared to vehicle-treated male controls. Dorsal hippocampal BDNF mRNA expression was also down-regulated in male rats exposed to DEHP. No differences in hippocampal spine density or BDNF mRNA expression were observed in female rats treated with DEHP compared to controls. DEHP treatment did not affect hippocampal caspase-3 mRNA expression in male or female rats. These results suggest a gender-specific vulnerability to early developmental DEHP exposure in male rats whereby postnatal DEHP exposure may interfere with normal synaptogenesis and connectivity in the hippocampus. Decreased expression of BDNF mRNA may represent a molecular mechanism underlying the reduction in dendritic spine density observed in hippocampal CA3 neurons. These findings provide initial evidence for a link between developmental exposure to DEHP, reduced levels of BDNF and hippocampal atrophy in male rats.

  19. Protection from spontaneous hepatocellular damage by N-benzyl-d-glucamine dithiocarbamate in Long-Evans Cinnamon rats, an animal model of Wilson's disease.

    Science.gov (United States)

    Shimada, Hideaki; Takahashi, Makiko; Shimada, Akinori; Okawara, Tadashi; Yasutake, Akira; Imamura, Yorishige; Kiyozumi, Morio

    2005-01-01

    The Long-Evans Cinnamon (LEC) rat is a mutant strain that accumulates excessive tissue copper (Cu) and models the clinical symptoms and biological features of Wilson's disease in humans. We compared the effects of three metal chelating agents, N-benzyl-d-glucamine dithiocarbamate (BGD), d-penicillamine (D-PEN), and triethylenetetramine (TETA), on the biliary and urinary excretions of Cu using LEC rats. The animals were treated ip with each chelating agent (1 mmol/kg body weight) and then the bile and urine samples were collected for 3 h. Because single treatment with BGD markedly stimulated biliary excretion of Cu, the protective effect of repeated BGD injection on spontaneous hepatocellular damage was further examined. Separate groups received two weekly injections of BGD starting at 11 weeks of age and were compared to saline-injected controls. Serum alanine aminotransferase (ALT) activity and bilirubin level were significantly increased in control LEC rats by 19 weeks of age and histopathological analysis demonstrated extensive hepatic damage in these rats. However, repeated BGD injections prevented the increases in serum ALT and bilirubin and blocked the histopathological changes in the liver. Furthermore, although Cu rapidly accumulated in the liver, kidney, spleen, and serum of control LEC rats during the test period, repeated BGD injection largely prevented these increases. These results indicate that BGD treatment is effective in blocking excessive Cu accumulation in LEC rats that, in turn, provides protection from spontaneous liver damage.

  20. Effects of granulocyte-colony stimulating factor (G-CSF on diabetic cardiomyopathy in Otsuka Long-Evans Tokushima Fatty rats

    Directory of Open Access Journals (Sweden)

    Kim Jung-Hyun

    2011-10-01

    Full Text Available Abstract Background Diabetic cardiomyopathy (CMP is a common and disabling disease in diabetic patients, however no effective treatments have been developed. Although granulocyte-colony stimulating factor (G-CSF improves heart function in myocardial infarction, its effect on non-ischemic CMP such as diabetic CMP is unknown. In the present study, we investigated the effects of G-CSF on diabetic CMP in a rat model of type II diabetes. Methods Twenty 7-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF: a rat model of diabetes rats and 10 male Long-Evans Tokushima Otsuka (LETO: normal controls rats were used. All of the LETO and 8 OLETF rats were fed on tap water while the rest were fed on sucrose-containing water. After 10 weeks, saline or recombinant human G-CSF (100 μg/kg/day was injected intraperitoneally for 5 days. Blood levels of glucose, total cholesterol and triglyceride, and Doppler echocardiograms for diastolic dysfunction were obtained just before and 4 weeks after the saline or G-CSF treatment. Light microscopy, electron microscopy (EM and immunohistochemistry for transforming growth factor-β were employed to examine myocardial histology 4 weeks after the saline or G-CSF treatment. Results Diastolic dysfunction developed at 17 weeks (before the saline or G-CSF treatment in the OLETF rats whether or not they were fed sucrose water, but were more severe in those fed sucrose water. Four weeks after saline or G-CSF treatment, diastolic function had recovered in the G-CSF-treated group regardless of sucrose water feeding, and perivascular and/or interstitial fibrosis in the G-CSF-treated group had decreased significantly. TGF-β immunoreactivity in the interstitial and perivascular tissue was also reduced in the G-CSF-treated group, and EM studies revealed less severe disruption of myofilaments and mitochondrial cristae, and decreased collagen deposition. Conclusions G-CSF can ameliorate cardiac diastolic dysfunction and morphological

  1. The effect of subcutaneous tetrathiomolybdate administration on copper and iron metabolism, including their regional redistribution in the brain, in the Long-Evans Cinnamon rat, a bona fide animal model for Wilson's disease.

    Science.gov (United States)

    Sugawara, N; Ikeda, T; Lai, Y R; Sugawara, C

    1999-05-01

    The present work was performed to examine the effect of tetrathiomolybdate on Cu and Fe metabolism, especially redistribution of Cu and Fe in the brains of Long-Evans Cinnamon rats, with inherently abnormal Cu deposition in the liver. The drug was injected subcutaneously at 5 mg/kg of body weight twice a week for 65 days (total dose of 20 mg) into 40-day-old Long-Evans Cinnamon rats. In Long-Evans Cinnamon rats treated with tetrathiomolybdate, the hepatic Cu concentration was 60 microg/g wet weight, compared to 170 microg/g in untreated rats. In seven brain regions (cerebellum, medulla oblongata, hypothalamus, striatum, midbrain, hippocampus and cortex) of the Long-Evans Cinnamon rats treated with tetrathiomolybdate. the Cu concentration (1.5 to 2.3 microg/g) was slightly lower (1.6 to 2.7 microg/g) than in untreated rats. A significant difference between the two groups was found only in the midbrain. Brain Fe concentrations in regions other than the striatum were not changed significantly by the tetrathiomolybdate injections. The hepatic Fe concentration was about 120 microg/g in Long-Evans Cinnamon rats without tetrathiomolybdate. Tetrathiomolybdate injection further increased the concentration to about 250 microg/g. Our results indicated that subcutaneous tetrathiomolybdate injection did not have an effect that stimulated redistribution of Cu and Fe in the seven brain regions examined, although hepatic Cu was markedly decreased and the removed Cu was deposited in kidneys, spleen and testes. The increased hepatic Fe level should be taken into account when considering side effects of the compound.

  2. Effect of magnesium ion supplementation on obesity and diabetes mellitus in Otsuka Long-Evans Tokushima Fatty (OLETF) rats under excessive food intake.

    Science.gov (United States)

    Nagai, Noriaki; Ito, Yoshimasa

    2013-01-01

    Several epidemiologic studies have found that magnesium ion (Mg²⁺) is related to obesity and type 2 diabetes mellitus. However, there have been almost no reports on the effects of a combination of excessive food intake and Mg²⁺ supplementation on metabolic syndrome and various blood tests values for diabetes mellitus. In this study, we investigated changes in body weight and blood test values for diabetes mellitus of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model for human type 2 diabetes mellitus via metabolic syndrome, under conditions of combined excessive food intake and Mg²⁺ supplementation. The rats received Mg²⁺ supplementation by drinking magnesium water (Mg²⁺; 200 mg/l). No significant differences were observed in the levels of food or water intake between OLETF rats drinking purified water (PW) or magnesium water (MW). Type 2 diabetes mellitus with metabolic syndrome developed at 30 weeks of age, and the body weights and plasma insulin levels of OLETF rats at 60 weeks of age were lower than those of normal rats. The plasma glucose (PG) levels in 38-week-old OLETF rats drinking MW were significantly lower than in those of rats drinking PW, while the body weights and the levels of triglycerides (TG) and insulin of 38-week-old MW-drinking OLETF rats were significantly higher than those of their PW-drinking counterparts. On the other hand, the decreases in body weight and insulin levels in 60-week-old OLETF rats were suppressed by MW supplementation. The present study demonstrates that Mg²⁺ supplementation delays the development of diabetes mellitus in OLETF rats under conditions of excessive food intake. In addition, obesity and high blood TG levels were observed in OLETF rats receiving Mg²⁺ supplementation in conjunction with excessive food intake.

  3. Taurine ameliorates hyperglycemia and dyslipidemia by reducing insulin resistance and leptin level in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term diabetes

    Science.gov (United States)

    Oh, Da Hee; Kim, Jung Yeon; Lee, Bong Gn; You, Jeong Soon; Chang, Kyung Ja; Chung, Hyunju; Yoo, Myung Chul; Yang, Hyung-In; Kang, Ja-Heon; Hwang, Yoo Chul; Ahn, Kue Jeong; Chung, Ho-Yeon

    2012-01-01

    This study aimed to determine whether taurine supplementation improves metabolic disturbances and diabetic complications in an animal model for type 2 diabetes. We investigated whether taurine has therapeutic effects on glucose metabolism, lipid metabolism, and diabetic complications in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term duration of diabetes. Fourteen 50-week-old OLETF rats with chronic diabetes were fed a diet supplemented with taurine (2%) or a non-supplemented control diet for 12 weeks. Taurine reduced blood glucose levels over 12 weeks, and improved OGTT outcomes at 6 weeks after taurine supplementation, in OLETF rats. Taurine significantly reduced insulin resistance but did not improve β-cell function or islet mass. After 12 weeks, taurine significantly decreased serum levels of lipids such as triglyceride, cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol. Taurine significantly reduced serum leptin, but not adiponectin levels. However, taurine had no therapeutic effect on damaged tissues. Taurine ameliorated hyperglycemia and dyslipidemia, at least in part, by improving insulin sensitivity and leptin modulation in OLETF rats with long-term diabetes. Additional study is needed to investigate whether taurine has the same beneficial effects in human diabetic patients. PMID:23114424

  4. Investigation of DNA synthesis in experimentally induced Long-Evans rat myeloschisis by the BrdU/antiBrdU technique.

    Science.gov (United States)

    Chono, Y; Abe, H; Iwasaki, Y; Nagashima, K

    1994-04-01

    The volume and DNA synthesis of the neuroepithelium in induced myeloschisis in Long-Evans rats as shown by hematoxylin-eosin and BrdU/antiBrdU immunohistochemical staining patterns were examined at different stages of embryonal development. On day 14 of gestation, control animals contained BrdU-incorporating cells mainly at the alar plate of the closed neural tube. On the same day, the everted neural plate of rats with myeloschisis showed active, diffuse uptake of BrdU in the cells of the matrix layer, although an increase in the volume of the everted neural plate was not yet identifiable. On day 21 of gestation, rats with myeloschisis showed a marked increase in the volume of the neuroepithelium compared with controls. Our investigations suggest that, in myeloschisis, more neuroepithelial cells than normal retain their capability for DNA synthesis on day 14 of gestation, and the overgrowth of the neuroepithelium found on day 21 is possibly a secondary effect of failure of neural tube closure.

  5. Breeder and batch-dependent variability in the acquisition and performance of a motor skill in adult Long-Evans rats.

    Science.gov (United States)

    O'Bryant, Amber J; Allred, Rachel P; Maldonado, Monica A; Cormack, Lawrence K; Jones, Theresa A

    2011-10-10

    Reaching tasks are popular tools for investigating the neural mechanisms of motor skill learning and recovery from brain damage in rodents, but there is considerable unexplained variability across studies using these tasks. We investigated whether breeder, batch effects, experimenter, time of year, weight and other factors contribute to differences in the acquisition and performance of a skilled reaching task, the single pellet retrieval task, in adult male Long-Evans hooded rats. First, we retrospectively analyzed task acquisition and performance in rats from different breeding colonies that were used in several studies spanning a 3 year period in our laboratory. Second, we compared reaching variables in age-matched rats from different breeders that were trained together as a batch by the same experimenters. All rats had received daily training on the reaching task until they reached a criterion of successful reaches per attempt. We found significant breeder-dependent differences in learning rate and final performance level. This was found even when age-matched rats from different breeders were trained together by the same experimenters. There was also significant batch-to-batch variability within rats from the same breeder trained by the same experimenter. Other factors, including weight, paw preference and the experimenter, were not as strong or consistent in their contributions to differences across studies. The breeder and batch effects found within the same rat strain may reflect genetic and environmental influences on the neural substrates of motor skill learning. This is an important consideration when comparing baseline performance across studies and for controlling variability within studies.

  6. An iron-deficient diet stimulates the onset of the hepatitis due to hepatic copper deposition in the Long-Evans Cinnamon (LEC) rat

    Energy Technology Data Exchange (ETDEWEB)

    Sugawara, Naoki; Sugawara, Chieko [Sapporo Medical Univ. (Japan). Dept. of Public Health

    1999-09-01

    To study effects of dietary Cu and Fe levels on the onset of hepatitis in Long-Evans Cinnamon (LEC) rats, female rats (40 days old) were fed a semipurified diet containing 0.1 or 10 mg Cu/kg and 1.5 or 150 mg Fe/kg in a 2 x 2 factorial arrangement for 35 days. At 75 days after birth, LEC rats (+Cu-Fe) fed a Cu-sufficient but Fe-deficient diet (Cu, 10 mg/kg; Fe, 1.5 mg/kg) showed jaundice, with lethargy, anorexia, and malaise. The biochemical variables relating to liver function were significantly increased compared to three other groups, a Cu- and Fe-deficient (-Cu-Fe) group, a Cu-deficient but Fe-sufficient (-Cu+Fe) group, and a Cu and Fe sufficient (+Cu+Fe) group. Furthermore, the +Cu-Fe rat liver showed massive necrosis with huge nuclei. The other three groups presented no biochemical and histological findings of hepatitis. Hepatic Cu and metallothionein concentrations were 289 {+-} 87 (mean {+-} SD) {mu}g/g liver and 8.7 {+-} 1.8 mg/g liver, respectively, in the +Cu-Fe rats. However, in the +Cu+Fe group the values were 196 {+-} 28 {mu}g Cu/g liver and 10.8 {+-} 1.0 mg/g liver. Hepatic Fe deposition was not influenced significantly by the dietary Cu level. The +Cu-Fe group with jaundice showed the highest free Cu concentration in the liver among the four groups, but the hepatic free Fe concentration was similar to those in the -Cu+Fe and +Cu+Fe groups. Our results indicate that an Fe-deficient diet enhances the deposition of hepatic Cu due to increased absorption of Cu from the gastrointestinal tract. This deposition stimulated the onset of hepatitis. (orig.)

  7. The antioxidant effect of DL-alpha-lipoic acid on copper-induced acute hepatitis in Long-Evans Cinnamon (LEC) rats.

    Science.gov (United States)

    Yamamoto, H; Watanabe, T; Mizuno, H; Endo, K; Fukushige, J; Hosokawa, T; Kazusaka, A; Fujita, S

    2001-01-01

    The Long-Evans Cinnamon (LEC) rats, due to a genetic defect, accumulate excess copper (Cu) in the liver in a manner similar to patients with Wilson's disease and spontaneously develop acute hepatitis with severe jaundice. In this study we examined the protective effect of DL-alpha-Lipoic acid (LA) against acute hepatitis in LEC rats. LA was administered to LEC rats by gavage in doses of 10, 30 and 100 mg/kg five times per week, starting at 8-weeks-old and continuing till 12-weeks-old. Although LA had little effect against the increases in serum transaminase activities, it suppressed the loss of body weight and prevented severe jaundice in a dose-dependent manner. Antioxidant system analyses in liver showed that LA treatment significantly suppressed the inactivations of catalase and glutathione peroxidase, and the induction of heme oxygenase-1, an enzyme which is inducible under oxidative stress. Furthermore, LA showed dose-dependent suppressive effect against increase in nonheme iron contents of both cytosolic and crude mitochondrial fractions in a dose-dependent manner. Although at the highest dose, LA slightly suppressed the accumulation of Cu in crude mitochondrial fraction, it had no effect on the accumulation of Cu in cytosolic fraction. While LA completely suppressed the increase in lipid peroxidation (LPO) in the microsomal fraction at the highest dose, the suppressive effect against LPO in crude mitochondrial fractions was slight. From these results, it is concluded that LA has antioxidant effects at the molecular level against the development of Cu-induced hepatitis in LEC rats. Moreover, mitochondrial oxidative damage might be involved in the development of acute hepatitis in LEC rats.

  8. THE TRANSCRIPTIONAL PROFILE OF THE KIDNEY IN TSC2 HETEROZYGOUS MUTANT LONG EVANS (EKER) RATS COMPARED TO WILD-TYPE

    Science.gov (United States)

    Hereditary renal cell carcinoma (RCC) in Eker rats results from an inherited insertional mutation in the Tsc2 tumor suppressor gene and provides a valuable experimental model to characterize the function of the Tsc2 gene product, tuberin in vivo. The Tsc2 mutation predisposes the...

  9. In vitro autoradiography of ionotropic glutamate receptors in hippocampus and striatum of aged Long-Evans rats: relationship to spatial learning

    Energy Technology Data Exchange (ETDEWEB)

    Gallagher, M. [Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Bizon, J.L. [Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Nicolle, M.M. [Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, NC (United States)

    1996-08-02

    Using in vitro autoradiography, we investigated [{sup 3}H]{alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, [{sup 3}H]kainate and [{sup 3}H]N-methyl-d-aspartate binding in two forebrain regions, the hippocampus and striatum, of young (four months of age) and aged (24-25 months of age) Long-Evans rats that had previously been tested for spatial learning ability in the Morris water maze. Although there was substantial preservation of binding in the aged rats, reductions in binding were present in the aged rats that were specific to ligand and anatomical region. In the hippocampus of aged rats, [{sup 3}H]{alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionate binding in CA1 and [{sup 3}H]kainate binding in CA3 were reduced. In contrast, N-methyl-d-aspartate binding was not significantly different between age groups. There was evidence of sprouting in the dentate gyrus molecular layer of aged rats, indicated by changes in the topography of [{sup 3}H]kainate binding. Binding density was analysed with respect to patch/matrix compartmentalization in the striatum. The most striking result was a large decrease in N-methyl-d-aspartate binding in aged rats that was not limited to any dorsal/ventral or patch/matrix area of the striatum. Additionally, [{sup 3}H]kainate binding in striatal matrix was modestly reduced in aged rats. Of these age effects, only N-methyl-d-aspartate binding in the striatum and [{sup 3}H]kainate binding in the CA3 region of the hippocampus were correlated with spatial learning, with lower binding in the aged rats associated with better spatial learning ability.Age-related alterations in ionotropic glutamate receptors differ with respect to the receptor subtype and anatomical region examined. The age effects were not neccessarily indicative of cognitive decline, as only two age-related binding changes were correlated with spatial learning. Interestingly, in these instances, lower binding in the aged rats was associated with preserved spatial

  10. Adolescent social instability stress increases aggression in a food competition task in adult male Long-Evans rats.

    Science.gov (United States)

    Cumming, Mark J; Thompson, Madison A; McCormick, Cheryl M

    2014-11-01

    Adolescent social instability stress (SS; daily 1 hr isolation + new cage partners postnatal days 30-45; thereafter with original cage partner, also in the SS condition) and control (CTL) rats competed for access to a preferred food in five sessions against their cage partner. In the first session, SS pairs displayed more aggression (face whacks, p = .02; rear attacks, p = .03), were less likely to relinquish access to the food voluntarily (p = .03), spent more time at the feeder than CTL pairs (p = .06), but did not differ in latency to access the feeder (p = .41). Pairs were considered in dominant-submissive relationships (DSR) if one rat spent significantly more time at the feeder than the other; 8 of 12 SS and 8 of 12 CTL pairs displayed DSRs (remaining: no-DSR). Aggression increased from the 1st to 5th session (p aggression in groups), and was higher in SS than CTL pairs (p = .05). Because the increased aggression of SS compared with CTL pairs did not result in a significant increase in their time at the feeder, the increased aggression may be considered maladaptive, and may reflect an increased motivation for food reward. These results add to evidence that SS in adolescence modifies the adult social repertoire of rats and highlight the importance of adolescent social experiences for adult behavior.

  11. Exposure to methylphenidate during peri-adolescence affects endocrine functioning and sexual behavior in female Long-Evans rats.

    Science.gov (United States)

    Guarraci, Fay A; Holifield, Caroline; Morales-Valenzuela, Jessica; Greene, Kasera; Brown, Jeanette; Lopez, Rebecca; Crandall, Christina; Gibbs, Nicole; Vela, Rebekah; Delgado, Melissa Y; Frohardt, Russell J

    2016-03-01

    The present study was designed to test the effects of methylphenidate (MPH) exposure on the maturation of endocrine functioning and sexual behavior. Female rat pups received either MPH (2.0mg/kg, i.p.) or saline twice daily between postnatal days 20-35. This period of exposure represents the time just prior to puberty as well as puberty onset. Approximately five weeks after the last injection of MPH or saline, female subjects were hormone-primed and tested during their first sexual experience. Subjects were given the choice to interact with a sexually active male or a sexually receptive female rat (i.e., the partner-preference test). The partner-preference paradigm allows us to assess multiple aspects of female sexual behavior. MPH exposure during peri-adolescence delayed puberty and, when mated for the first time, affected sexual behavior (e.g., increased time spent with the male stimulus and decreased the likelihood of leaving after mounts) during the test of partner preference. When monitoring estrous cyclicity, female subjects treated with MPH during peri-adolescence frequently experienced irregular estrous cycles. The results of the present study suggest that chronic exposure to a therapeutic dose of MPH around the onset of puberty alters long-term endocrine functioning, but with hormone priming, increases sensitivity to sexual stimuli. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Dorsal lateral geniculate substructure in the Long-Evans rat: A cholera toxin B-subunit study

    Directory of Open Access Journals (Sweden)

    Claire B. Discenza

    2012-09-01

    Full Text Available The pigmented rat is an increasingly important model in visual neuroscience research, yet the lamination of retinal projections in the dLGN has not been examined in sufficient detail. From previous studies it was known that most of the rat dLGN receives monocular input from the contralateral eye, with a small island receiving predominantly ipsilateral projections. Here we revisit the question using cholera toxin B subunit (CTB, a tracer that efficiently fills retinal terminals after intra-ocular injection. We imaged retinal termini throughout the dLGN at 0.5 um resolution and traced areas of ipsilateral and contralateral terminals to obtain a high resolution 3D reconstruction of the projection pattern. Retinal termini in the dLGN are well segregated by eye of origin, as expected. We find, however, that the ipsilateral projections form multiple discrete projection zones in three dimensions, not the single island previously described. It remains to be determined whether these subdomains represent distinct functional sublaminae, as is the case in other mammals.

  13. Decreased sexual motivation and heightened anxiety in male Long-Evans rats are correlated with the memory for a traumatic event.

    Science.gov (United States)

    Hawley, Wayne R; Grissom, Elin M; Belkin, Mark N; James, Thomas F; Dohanich, Gary P

    2013-05-01

    Individuals suffering from posttraumatic stress disorder (PTSD) frequently report disturbances in sexual functioning in addition to alterations in their affective behaviors. Notably, maladaptive cognitions and dysfunctional behaviors are perpetuated by the emergence of the intrusive thoughts that characterize the disorder. In rats, reminders of a traumatic event designed to simulate intrusive thoughts are associated with impairments in affective, social, and sexual behaviors. The current study examined the relationship between the memory for a traumatic event and changes in sexual and affective behaviors in male Long-Evans rats (N = 36). The trauma featured a combination stressor consisting of simultaneous exposure to a footshock and the odor of soiled cat litter. Memory for the trauma was reactivated by re-exposures to the context of the trauma in the absence of stressors and confirmed by assessing the percentage of time spent freezing. Following the second and final reminder, traumatized males exhibited reduced sexual motivation and increased anxiety, signified by longer latencies to achieve their first mount on a post-stress test of sexual behavior, and longer latencies to begin feeding in a novel environment, respectively. Correlational analyses revealed that decreased sexual motivation and heightened anxiety were predicted by the memory for the trauma as indicated by the time spent freezing during the re-exposures. The findings from the current study have implications for understanding the relationship between stress and sexual functioning and indicate that the impairments in sexual behavior that often occur in individuals with PTSD may be impacted by their memory for the trauma.

  14. Operant self-administration of sweetened ethanol and time course of blood ethanol levels in adolescent and adult male Long-Evans rats.

    Science.gov (United States)

    Doherty, James M; Gonzales, Rueben A

    2015-03-01

    Little is known regarding mechanisms regulating ethanol (EtOH) self-administration during adolescence or if the mechanisms differ from adults. One of the best models of abuse liability is operant self-administration. Therefore, we characterized operant sweetened EtOH self-administration behavior in adolescent and adult rats. Adolescent (36 days old at first EtOH exposure) and adult male Long-Evans rats were first trained to self-administer 10% sucrose (10S) in an appetitive/consummatory operant model for 1 week, and then the drinking solution was switched to 10% sucrose plus 10% EtOH (10S10E) for 2 weeks. Next, rats were switched to a fixed ratio 2 schedule, and this was followed by 1 session using a progressive ratio schedule of reinforcement. Last, rats were tested for cue-induced reinstatement of lever-pressing behavior under extinction conditions after 13 days of abstinence. Blood EtOH concentration (BEC) of sweetened EtOH (self-administered or intragastric [IG] administration of 1 g/kg) was determined via gas chromatography. Control rats drank only 10S. Consumption of sweetened EtOH was not different between adolescents and adults under any schedule tested, reaching 1 g/kg in 20 minutes in the appetitive/consummatory model. Appetitive behavior directed at sweetened EtOH was less focused in adolescents versus adults. No age differences were found in motivation for sweetened EtOH. Cue-induced reinstatement of EtOH-seeking behavior after abstinence also did not differ by age. In control groups, no age difference was found in appetitive behavior or the amount of sucrose consumed, although adults exhibited greater cue-induced reinstatement. BEC after self-administration or IG administration of sweetened EtOH was higher in adults than adolescents. Consumption and motivation for sweetened EtOH are similar in adolescents and adults, although adolescents are more vulnerable to the effects of EtOH consumption on appetitive behavior. The IG results suggest larger volume

  15. Sex differences in diazepam effects and parvalbumin-positive GABA neurons in trait anxiety Long Evans rats.

    Science.gov (United States)

    Ravenelle, Rebecca; Neugebauer, Nichole M; Niedzielak, Timothy; Donaldson, S Tiffany

    2014-08-15

    In clinical populations, prevalence rates for a number of anxiety disorders differ between males and females and gonadal hormones are thought to contribute to these differences. While these hormones have been shown to modulate the anxiolytic effects of the benzodiazepine agonist diazepam in some models, findings are inconsistent. Here, we tested for sex differences in response to anxiogenic stimuli following a 30-min diazepam (1.0mg/kg) pre-treatment in male and female rats showing high (HAn) and low (LAn) anxiety-like behavior on the elevated plus maze. Acute diazepam administration resulted in decreased anxiety-like behavior only in HAn males as demonstrated by a significant increase in percent open arm time in the elevated plus maze (EPM). Immunohistochemical analysis for parvalbumin (PV; a calcium-binding protein that selectively stains GABAergic neurons) in central amygdala (CeA), caudate putamen (CPu) and the hippocampus indicated the number of GABAergic interneurons in these areas differed across sex and anxiety trait. In the CPu, females had significantly more PV-immunoreactive (IR) cells than males, and LAn females had greater PV-IR neurons than HAn females. In the CeA, males displayed an increased number of PV-IR neurons compared to females, with no differences found between LAn and HAn. Further, trait differences were evident in the CA2 region of the hippocampus, regardless of sex. Taken together, these data suggest that gonadal hormones and trait anxiety may influence the sensitivity to the anti-anxiety effects of diazepam and these differences may be due in part to the distribution of GABA-containing interneurons.

  16. Paper or Plastic? Exploring the Effects of Natural Enrichment on Behavioural and Neuroendocrine Responses in Long-Evans Rats.

    Science.gov (United States)

    Bardi, M; Kaufman, C; Franssen, C; Hyer, M M; Rzucidlo, A; Brown, M; Tschirhart, M; Lambert, K G

    2016-05-01

    Enriched environments are beneficial to neurobiological development; specifically, rodents exposed to complex, rather than standard laboratory, environments exhibit evidence of neuroplasticity and enhanced cognitive performance. In the present study, the nature of elements placed in the complex environment was investigated. Accordingly, rats (n = 8 per group) were housed either in a natural environment characterised by stimuli such as dirt and rocks, an artificial environment characterised by plastic toys and synthetic nesting materials, a natural/artificial environment characterised by a combination of artificial and natural stimuli or a laboratory standard environment characterised by no enrichment stimuli. Following exposure to emotional and cognitive behavioural tasks, including a cricket hunting task, a novel object preference task and a forced swim task, brains were processed for glial fibrillary acidic protein (GFAP)-, neuronal nuclei (NeuN)- and brain-derived neurotrophic factor (BDNF) immunoreactivity. Baseline and stress foecal samples were collected to assess corticosterone (CORT) and dehydroepiandrosterone (DHEA). Natural environment animals exhibited shorter diving latencies and increased diving frequencies in the second forced swimming task, along with higher DHEA/CORT ratios, and higher GFAP immunoreactivity in the hippocampus. The type of environmental enrichment did not influence levels of BDNF immunoreactivity in the CA1, CA3 and dentate gyrus of the hippocampus; however, natural environment animals exhibited higher levels of NeuN immunoreactivity in the retrosplenial cortex, an area involved in spatial memory and other cognitive functions. These results suggest that, in addition to enhancing behavioural and endocrinological variables associated with resilience, exposure to natural stimuli might alter plasticity in brain areas associated with cortical processing and learning. © 2016 British Society for Neuroendocrinology.

  17. Inactivating the infralimbic but not prelimbic medial prefrontal cortex facilitates the extinction of appetitive Pavlovian conditioning in Long-Evans rats.

    Science.gov (United States)

    Mendoza, J; Sanio, C; Chaudhri, N

    2015-02-01

    The infralimbic medial prefrontal cortex (IL) has been posited as a common node in distinct neural circuits that mediate the extinction of appetitive and aversive conditioning. However, appetitive extinction is typically assessed using instrumental conditioning procedures, whereas the extinction of aversive conditioning is customarily studied using Pavlovian assays. The role of the IL in the extinction of appetitive Pavlovian conditioning remains underexplored. We investigated the involvement of the IL and prelimbic medial prefrontal cortex (PrL) in appetitive extinction in Pavlovian and instrumental conditioning assays in male, Long-Evans rats. Following acquisition, a gamma-aminobutyric acid agonist solution (0.03 nmol muscimol; 0.3 nmol baclofen; 0.3 μl/side) was bilaterally microinfused into the IL or PrL to pharmacologically inactivate each region before the first extinction session. Compared to saline, PrL inactivation did not affect the acquisition of extinction or the recall of extinction memory 24-h later. IL inactivation caused a more rapid extinction of Pavlovian conditioning, but had no effect on the extinction of instrumental conditioning or extinction recall. IL inactivation during a Pavlovian conditioning session in which conditioned stimulus (CS) trials were paired with sucrose did not affect CS-elicited behaviour, but increased responding during intervals that did not contain the CS. The same manipulation did not impact lever pressing for sucrose. These findings suggest that the IL may normally maintain Pavlovian conditioned responding when an anticipated appetitive CS is unexpectedly withheld, and that this region has distinct roles in the expression of Pavlovian conditioning when an appetitive unconditioned stimulus is either presented or omitted.

  18. Antihyperglycemic, insulin-sensitivity and anti-hyperlipidemic potential of Ganoderma lucidum, a dietary mushroom, on alloxan- and glucocorticoid-induced diabetic Long-Evans rats

    Directory of Open Access Journals (Sweden)

    Md. Moklesur Rahman Sarker

    2015-12-01

    Full Text Available Background: Reishi (Ganoderma lucidum is a well-known and popular edible mushroom eaten as vegetables all over the world. It has been used as alternative medicine for long years in China, Korea, Japan, Malaysia, and in eastern Russia. It is reported to exhibit a number of medicinal properties including antitumor, antioxidant, immunomodulating, anti-inflammatory, hepatoprotective, and hypoglycemic activities due to the presence of bioactive polysaccharide. Glucocorticoids, prescribed for the treatment of arthritis to protect inflammation and reduce pain, can induce hyperglycemia or aggravate the hyperglycemic condition reaching to very high glucose levels in diabetic patients. However, no report has been published for its activity on glucocorticoid-induced diabetes. Objective: To investigate the effect of Ganoderma lucidum on alloxan- and glucocorticoid- induced diabetes in Long-Evans rats. Methods: Alloxan monohydrate (150 mg/kg was intraperitoneally administered to Long-Evans rats as a single dose. The same volume of normal saline was injected to control rats. Three days after alloxan injection, rats with plasma glucose levels higher than 12 mmoL /L were considered as diabetic and they were included in the study. Reishi mushroom was collected from the Mushroom Development Institute, Ministry of Agriculture, Savar, Dhaka, Bangladesh, where it was identified by a Taxonomist. Petroleum ether extract (PEE Methanol extract (ME were prepared by maceration and distillation techniques. The extracts were orally administered once in a day at doses of 200, 400, 600 and 800 mg/kg, respectively for 7 days. Metformin (150 mg/kg was orally administered as a standard antidiabetic drug. Glucose levels were measured at 0 and 7th days of treatment. The rats were allowed to rest for 1 week without treatment. The animals were again injected with dexamethasone (2 mg/kg through intra-muscular route for 3 days and glucose levels were monitored regularly. Rats were

  19. Effect of oral intake of dibutyl phthalate on reproductive parameters of Long Evans rats and pre-pubertal development of their offspring.

    Science.gov (United States)

    Salazar, Veronica; Castillo, Carmen; Ariznavarreta, Carmen; Campón, Rocío; Tresguerres, Jesús A F

    2004-12-01

    To investigate the influence of dibutyl phtalate (DBP) given in a soy-free rat chow on pre-pubertal development, 46 Long Evans female rats 2-month-old were divided into three experimental groups and fed three different chows: (1) control; (2) DP 0.61 g/kg chow (12 mg/kgrat/day); (3) DP 2.5 g/kg chow (50 mg/kg rat/day) for 2 months. While under this treatment, they were mated and their offspring studied. Litter size and female:male ratio were recorded. At 14 days of age 6, male pups of each group were sacrificed and testis and thymus were excised and weighed. Pups were weaned at 22 days of age and continued into three experimental groups according to diet. From day 22 onwards, vaginal opening, occurrence of first estrous, and pre-putial separation were recorded. The percent of pregnancies showed a marked decrease in group 3, while no difference was observed between groups 1 and 2. Sex prevalence and litter size were not affected by the different diets. Pup survival showed a decrease when mothers were fed diet 2, but it was similar in diets 1 and 3. Pup weights on day 2 showed an evident (P < 0.05) reduction in groups 2 and 3, the decrease being more marked (P < 0.001) in group 3. On day 6, pups of group 2 showed lower weights (P < 0.01) as compared with the other groups. Weight gain was significantly higher in pups of group 3. Eye opening was not affected by the different diets. Fourteen-day-old male pups' relative weight of thymus and testis showed a decrease in animals whose mothers had been fed diets 2 and 3. Vaginal opening and occurrence of first estrous showed an evident delay (P < 0.05; P < 0.01) in females fed diets 2 and 3. Significant differences (P < 0.001) in pre-putial separation were observed between treated and untreated groups. Offspring pre-pubertal development seems to be affected by oral intake of DBP by their mothers during pregnancy, the effects being more evident in the reproductive development of male pups.

  20. Oral buspirone causes a shift in the dose-response curve between the elevated-plus maze and Vogel conflict tests in Long-Evans rats: relation of brain levels of buspirone and 1-PP to anxiolytic action.

    Science.gov (United States)

    Vaidya, A H; Rosenthal, D I; Lang, W; Crooke, J J; Benjamin, D; Ilyin, S E; Reitz, A B

    2005-05-01

    Most studies concerning the effects of oral buspirone in the rat elevated plus-maze (EPM) test, spontaneous motor activity (SMA) test, and Vogel conflict (VC) test have used Sprague-Dawley or Wistar rats. Although it has been documented that the behavior of Long-Evans rats is more sensitive to detection of anxiolytics when compared to the aforementioned strains, the effects of oral buspirone have not been fully characterized in the Long-Evans strain in the EPM and VC tests. Thus, we studied the effects of orally administered buspirone (0.03-10.0 mg/kg) in the EPM, SMA, and VC (0.3-60.0 mg/kg) tests in Long-Evans rats. In a separate experiment, brain and plasma concentrations of buspirone and 1-(2-pyrimidinyl)-piperazine (1-PP) were determined after oral administration of buspirone (0.3 and 10 mg/kg) to relate the behavioral effects of buspirone with brain and plasma concentrations of buspirone and 1-PP. Our results showed that buspirone exhibited an inverted-U-shaped dose-response curve in both the EPM and the VC tests. In the EPM, buspirone produced anxiolytic activity in a low, narrow dose-range (0.03, 0.1, 0.3 mg/kg, p.o.) with maximum efficacy at 0.3 mg/kg, whereas in the VC test, significant anxiolytic activity was observed in a high, narrow dose-range (10, 30 mg/kg, p.o.) with maximum efficacy occurring at 10 mg/kg. In the SMA test, buspirone (10 mg/kg, p.o.) significantly decreased horizontal activity and vertical movements suggestive of sedation. Also, one hour following oral doses of buspirone (0.3 and 10 mg/kg), both buspirone and 1-PP concentrations were higher in brain when compared with those in plasma. Additionally, the concentrations of 1-PP were always higher in brain and in plasma compared with the concentrations of buspirone. Of particular interest is our finding of the shift in the dose-response curve between the EPM and VC tests. This shift in the dose-response curve is discussed in relation to brain levels of buspirone and 1-PP levels and their

  1. Investigation of Metabolism of Exogenous Glucose at the Early Stage and Onset of Diabetes Mellitus in Otsuka Long-Evans Tokushima Fatty Rats Using [1, 2, 3-13C]Glucose Breath Tests.

    Science.gov (United States)

    Kawagoe, Naoyuki; Kano, Osamu; Kijima, Sho; Tanaka, Hideki; Takayanagi, Masaaki; Urita, Yoshihisa

    2016-01-01

    This study aimed to evaluate changes in glucose metabolism at the early stage and onset of diabetes in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Specifically, after the oral administration of [1, 2, 3-13C]glucose, the levels of exhaled 13CO2, which most likely originated from pyruvate decarboxylation and tricarboxylic acid, were measured. Eight OLETF rats and eight control rats (Long-Evans Tokushima Otsuka [LETO]) were administered 13C-glucose. Three types of 13C-glucose breath tests were performed thrice in each period at 2-week intervals. [3-13C]glucose results in a 13C isotope at position 1 in the pyruvate molecule, which provides 13CO2. The 13C at carbons 1 and 2 of glucose is converted to 13C at carbons 2 and 1 of acetate, respectively, which produce 13CO2. Based on metabolic differences of the labeled sites, glucose metabolism was evaluated using the results of three breath tests. The increase in 13CO2 excretion in OLETF rats was delayed in all three breath tests compared to that in control rats, suggesting that OLETF rats had a lower glucose metabolism than control rats. In addition, overall glucose metabolism increased with age in both groups. The utilization of [2-13C]glucose was suppressed in OLETF rats at 6-12 weeks of age, but they showed higher [3-13C]glucose oxidation than control rats at 22-25 weeks of age. In the [1-13C]glucose breath test, no significant differences in the area under the curve until 180 minutes (AUC180) were observed between OLETF and LETO rats of any age. Glucose metabolism kinetics were different between the age groups and two groups of rats; however, these differences were not significant based on the overall AUC180 of [1-13C]glucose. We conclude that breath 13CO2 excretion is reduced in OLETF rats at the primary stage of prediabetes, indicating differences in glucose oxidation kinetics between OLETF and LETO rats.

  2. 新生Long Evans大鼠初级视皮层神经元的培养和鉴定%Identification and culture of visual cortex neurons in newborn Long Evans rats

    Institute of Scientific and Technical Information of China (English)

    姚军平; 侯文生; 刘慧; 陈丽峰; 阴正勤

    2012-01-01

    目的 建立新生Long Evans大鼠视皮层神经元原代培养方法.方法 采用钝性分离1d龄Long Evans大鼠双侧视皮层,2.5 g· L-1胰蛋白酶消化法获得细胞悬液,在无血清培养基中进行培养,7~14d后行免疫组织化学及膜片钳鉴定.结果 用该方法培养的视皮层神经细胞存活率高,生长状态良好,存活可达1个月左右,β-Ⅲ tubulin免疫组织化学染色阳性神经元占培养细胞中的80%以上,膜片钳成功记录了180个细胞,静息膜电位在- 50 ~ - 70 mV,存在内向、外向电流,脉冲恒流刺激可诱发多个动作电位.结论 本研究所采用的分离及原代培养方法是一种简单、高效的视皮层神经元培养方法.%Objective To establish the protocol for culturing visual cortex neurons derived from newborn Long Evans rats in vitro. Methods Tissues from visual cortex of one day aged Long Evans rats were harvested and digested into cell suspension by 2. 5 g · L-1 trypsogen. Those cells were then cultured with serum free medium, the cultured cells were identified by immunochemical staining and patch clamp recording after cultured from 7 days to 14 days. Results The neurons from visual cortex had high survival rate and good conditions during growth, some cells could survive one month. The positive cells staining of β-III tubulin were more than 80% ,180 cultured visual cortex neurons were successful recorded by patch clamp, the resting membrane potentials were between -50 mV and -70 mV, inward current and outward current were existed, several action potentials could be elicited by constant current stimulation. Conclusion This method is simple and effective for the culture of visual cortex neurons.

  3. Effects of Prenatal Exposure to a Low Dose Atrazine Metabolite Mixture on pubertal timing and prostrate Development of Male Long Evans Rats.

    Science.gov (United States)

    The present study examines the postnatal reproductive development of male rats following prenatal exposure to an atrazine metabolite mixture (AMM) consisting of the herbicide atrazine and its environmental metabolites diaminochlorotriazine, hydroxyatrazine, deethylatrazine, and d...

  4. Effects of Prenatal Exposure to a Low Dose Atrazine Metabolite Mixture on pubertal timing and prostrate Development of Male Long Evans Rats.

    Science.gov (United States)

    The present study examines the postnatal reproductive development of male rats following prenatal exposure to an atrazine metabolite mixture (AMM) consisting of the herbicide atrazine and its environmental metabolites diaminochlorotriazine, hydroxyatrazine, deethylatrazine, and d...

  5. Long-term treatment of aged Long Evans rats with a dietary supplement containing neuroprotective peptides (N-PEP-12) to prevent brain aging: effects of three months daily treatment by oral gavage.

    Science.gov (United States)

    Hutter-Paier, B; Reininger-Gutmann, B; Wronski, R; Doppler, E; Moessler, H

    2015-01-01

    Aging is associated with morphological and functional changes in the brain, resulting in the deterioration of cognitive performance. Growth factors like BDNF are suggested to be involved in the regulation of age-related processes in the brain. A novel dietary supplement produced from purified nerve cell proteins, N-PEP-12, has shown to share properties with naturally occurring peptide growth factors by stimulating neurite outgrowth and beneficial effects on neuronal survival and protection against metabolic stress in cell cultures. The current study investigates the effects of long-term intake on age-dependent memory decline by assessing cognitive performance and synaptic density. All the experiments were performed in aged Long Evans rats randomly assigned to saline or N-PEP-12 once daily by gavage over a period of three months. Behavioral tests were performed in the Morris Water Maze after one, two and three months of treatment. Histological examinations were performed in the hippocampal formation and in the entorhinal cortex by measuring the synaptic density. This study shows that the oral intake of N-PEP-12 has beneficial effects on the cognitive performance of aged animals and that these effects go along with an increase in the synaptic density. Thus, N-PEP-12 may help maintain memory and learning performance during the aging process.

  6. Herbal composition Gambigyeongsinhwan (4) from Curcuma longa, Alnus japonica, and Massa Medicata Fermentata inhibits lipid accumulation in 3T3-L1 cells and regulates obesity in Otsuka Long-Evans Tokushima Fatty rats.

    Science.gov (United States)

    Roh, Jong Sung; Lee, Hyunghee; Woo, Sangee; Yoon, Miso; Kim, Jeongjun; Park, Sun Dong; Shin, Soon Shik; Yoon, Michung

    2015-08-02

    Adipocyte lipid accumulation due to impaired fatty acid oxidation causes adipocyte hypertrophy and adipose tissue increment, leading to obesity. The aim of this study was to determine the antiobesity effects of the herbal composition Gambigyeongsinhwan (4) (GGH(4)) composed of Curcuma longa L. (Zingiberaceae), Alnus japonica (Thunb.) Steud. (Betulaceae), and the fermented traditional Korean medicine Massa Medicata Fermentata. The effects of GGH(4) and the individual components on lipid accumulation in 3T3-L1 adipocytes and body weight gain in Otsuka Long-Evans Tokushima Fatty (OLETF) rats were examined using Oil red O staining, hematoxylin and eosin staining, quantitative real-time PCR, and peroxisome proliferator-activated receptor α (PPARα) transactivation assay. GGH(4), individual components, and an active principle of Curcuma longa curcumin inhibited lipid accumulation and mRNA levels of adipocyte-specific genes (PPARγ, aP2, and C/EBPα) in 3T3-L1 adipocytes compared with control cells. Treatment with GGH(4), the individual components or curcmumin increased mRNA levels of mitochondrial (CPT-1, MCAD, and VLCAD) and peroxisomal (ACOX and thiolase) PPARα target genes. GGH(4) and the individual components also increased PPARα reporter gene expression compared with control cells. These effects were most prominent in GGH(4)-treated cells. However, the PPARα antagonist GW6471 reversed the inhibitory effects of GGH(4) on adipogenesis. An in vivo study showed that GGH(4) decreased body weight gain, adipose tissue mass, and visceral adipocyte size with increasing mRNA levels of adipose tissue PPARα target genes in OLETF rats. These results demonstrate that GGH(4) has an antiobesity effects through the inhibition of adipocyte lipid accumulation, and this process may be mediated in part through adipose PPARα activation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Additive effects of cilnidipine, an L-/N-type calcium channel blocker, and an angiotensin II receptor blocker on reducing cardiorenal damage in Otsuka Long-Evans Tokushima Fatty rats with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Mori Y

    2014-06-01

    Full Text Available Yutaka Mori,1,2 Shizuka Aritomi,3 Kazumi Niinuma,3 Tarou Nakamura,3 Kenichi Matsuura,1 Junichi Yokoyama,1 Kazunori Utsunomiya1 1Division of Diabetes and Endocrinology, Department of Internal Medicine, The Jikei University School of Medicine, Minato-ku, Japan; 2Department of Clinical Research, National Hospital Organization, Utsunomiya National Hospital, Utsunomiya, Japan; 3Research Center, Ajinomoto Pharmaceuticals Co, Ltd, Kanagawa, Japan Abstract: Cilnidipine (Cil, which is an L-/N-type calcium channel blocker (CCB, has been known to provide renal protection by decreasing the activity of the sympathetic nervous system (SNS and the renin–angiotensin system. In this study, we compared the effects of the combination of Cil and amlodipine (Aml, which is an L-type CCB, with an angiotensin (Ang II receptor blocker on diabetic cardiorenal damage in spontaneously type 2 diabetic rats. Seventeen-week-old Otsuka Long-Evans Tokushima Fatty rats were randomly assigned to receive Cil, Aml, valsartan (Val, Cil + Val, Aml + Val, or a vehicle (eight rats per group for 22 weeks. Antihypertensive potencies were nearly equal among the CCB monotherapy groups and the combination therapy groups. The lowering of blood pressure by either treatment did not significantly affect the glycemic variables. However, exacerbations of renal and heart failure were significantly suppressed in rats administered Cil or Val, and additional suppression was observed in those administered Cil + Val. Although Val increased the renin–Ang system, Aml + Val treatment resulted in additional increases in these parameters, while Cil + Val did not show such effects. Furthermore, Cil increased the ratio of Ang-(1–7 to Ang-I, despite the fact that Val and Aml + Val decreased the Ang-(1–7 levels. These actions of Cil + Val might be due to their synergistic inhibitory effect on the activity of the SNS, and on aldosterone secretion through N-type calcium channel antagonism and Ang II

  8. Effects of Rosiglitazone on Transforming Growth Factor-β1 and its Signaling Pathway Genes Expressions in Pulmonary Tissue of Otsuka Long-Evans Tokushima Fattv Rats%罗格列酮对OLETF大鼠肺组织转化生长因子β1及其信号转导分子的影响

    Institute of Scientific and Technical Information of China (English)

    刘佳; 赵伟; 宋旭臣; 郝久营; 张雅静; 张宏

    2012-01-01

    目的 探讨罗格列酮对自发性糖尿病OLETF( Otsuka Long-Evans Tokushima Fatty)大鼠肺组织纤维化的影响及其机制.方法 30周龄雄性OLETF大鼠16只,随机分为糖尿病组(DM组)和罗格列酮组(RGT组,予罗格列酮3 mg· kg-1·d-1灌胃12周),对照组为LETO (Long Evans Tokushima Otsuka)大鼠8只.HE、Masson染色观察各组大鼠肺组织结构及其胶原沉积变化,免疫印迹( Western blotting)方法检测肺组织Smad3 、Smad7和Ⅲ型胶原表达,ELISA检测肺组织转化生长因子β1(transforming growth factor-β1,TGF-β1)的表达.结果 与对照组大鼠相比,DM组大鼠肺组织TGF-β1、Smad3和Ⅲ型胶原表达增加,Smad7表达减少,差异均有统计学意义(P<0.05),肺组织胶原沉积增加,呈纤维化趋势;罗格列酮治疗可使RGT组大鼠上述指标逆转.结论 罗格列酮对OLETF大鼠肺组织有抗纤维化作用,可能通过下调TGF-β1/Smad信号转导通路发挥作用.%Objective To explore effects and its mechanism of Rosiglitazone treatment on transforming growth factor-β1/ SmadCTGF-β1Smad) signaling pathways in Otsuka Long-Evans Tokushima Fatty(OLETF) rats. Methods Sixteen OLETF rats were divided into two groups: DM group and rosiglitazone-treated group (RGT group) , and 8 of Long Evans Tokushima Otsuka (LETO) rats as control (N group). RGT group rats were treated with rosiglitazone (3 mg/kg/day, in drinking water) for 12 weeks, starting at the age of 30 weeks. The structural and collagen deposition changes of pulmonary tissue in three groups rats were observed by HE and Masson staining; the expression of Smad7 and collagen type III in lung tissues were examined by western blotting; the expression of TGF-β1 of lung tissues were examined by ELISA. Results The expression of TGF-pi, Smad3 and collagen type III increased in pulmonary tissues of OLETF rats, which higher than those of LETO rats (P<0.05). The expression of Smad7 decreased in OLETF group(P<0.05). Pulmonary interstitial

  9. Effects of rosiglitazone treatment on TGF-β1/Smad signaling pathways in Otsuka Long-Evans Tokushima Fatty rat lungs%罗格列酮对OLETF大鼠肺组织TGF-β1/Smad信号转导途径的影响

    Institute of Scientific and Technical Information of China (English)

    赵伟; 姜丽娟; 朱梦瑜; 刘佳; 张雅静; 陈晓琴; 张宏

    2011-01-01

    目的 探讨罗格列酮对自发性2型糖尿病Otsuka Long-Evans Tokushima Fatty(OLETF)大鼠肺组织转化生长因子(TGF)-β1 /Smad信号转导途径的影响.方法 OLETF大鼠16只,分为未治疗的OLETF组和接受罗格列酮治疗组(OLETF/L组)各8只,设Long Evans Tokushima Otsuka(LETO)大鼠8只为对照组.免疫组织化学分析各组大鼠肺组织TGF-β1、Smad2、Smad3、Smad7、纤维连接蛋白(FN)和Ⅲ型胶原表达.结果与LETO组大鼠相比,OLETF组大鼠肺组织TGF-β1、Smad2、Smad3、FN和Ⅲ型胶原表达均显著增加 (P<0.01),Smad7表达显著减少(P<0.01);OLETF/L组比OLETF组大鼠肺组织TGF-β1、Smad2、Smad3、FN和Ⅲ型胶原表达均显著减少(P<0.01),Smad7表达显著增加(P<0.01).结论罗格列酮可能通过调控TGF-β1/Smad信号转导途径抗糖尿病肺纤维化.%Objective To approach the effects of rosiglitazone treatment on transforming growth factor-β1/Smad (TGF-β1/Smad) signaling pathways in Otsuka Long-Evans Tokushima Fatty(OLETF) rats.Methods Experimental rats were divided into three groups: OLETF group, rosiglitazone-treated group( OLETF/L group) and Long Evans Tokushima Otsuka rats (LETO group) as control, 8 rats in each group.The expression of TGF-β1, Smad2, Smad3, Smad7,fibronectin(FN), and collagen type Ⅲ in rat lungs were examined by immunohistochemistry.Results The expressions of TGF-β1, Smad2, Smad3, FN and collagen type Ⅲ increased in OLETF rat lungs than those of LETO rats(P < 0.O1 ),while the expression of Smad7 decreased in OLETF group( P < 0.01 ).The expressions of TGF-β1, Smad2, Smad3, FN and collagen type Ⅲ decreased in OLETF/L group than those of the OLETF group ( P < 0.01 ), and the expression of Smad7 increased in OLETF/L group ( P < O.01 ).Conclusion Rosiglitazone may improve diabetic pulmonary fibrosis probably by regulating TGF-β1/ Smad signaling pathways.

  10. Effects of GLP-1 treatment on protection of B cells in Otsuka Long-Evans Tokushima fatty rats%胰升糖素样多肽-1对OLETF大鼠胰腺的保护作用

    Institute of Scientific and Technical Information of China (English)

    王昱; 郭晓蕙

    2006-01-01

    目的:观察胰升糖素样多肽-1(glucagon like peptide-1, GLP-1)对OLETF(Otsuka Long-Evans Tokushima fatty)大鼠血糖和糖耐量的影响,及其对胰腺B细胞的保护作用.方法:将12周雄性OLETF大鼠分为GLP-1治疗和未治疗组,并以同种系非糖尿病LETO(Long-Evans Tokushima Otsuka)大鼠为正常对照.于12,14及20周时,对所有大鼠进行口服葡萄糖耐量试验(OGTT)试验,饲养至20周时处死.对胰腺病理切片分别进行HE染色、胰岛素染色、增殖细胞核抗原染色(proliferation cell nuclear antigen, PCNA)及凋亡细胞染色,测量胰岛B细胞的增殖率和凋亡率.用电镜观察胰岛内细胞超微结构.结果:(1)14及20周OLETF大鼠GLP-1治疗组血糖曲线下面积低于OLETF未治疗组,分别为(29.93±3.15 vs. 34.99±4.30, P<0.01)和(38.37±3.18 vs. 42.38±2.37,P<0.01).(2)14及20周OLETF大鼠 GLP-1治疗组胰岛素曲线下面积高于OLETF未治疗组,分别为(10.86±1.56 vs. 9.07±1.28,P<0.01)和(13.00±1.50 vs. 10.35±0.86,P<0.01).(3)20周龄GLP-1治疗组OLETF大鼠胰岛内胰岛素含量以及胰岛中B细胞数量增加,B细胞超微结构改善.胰岛B细胞的增殖率增加(48.9±39.6 vs. 39.6±9.3,P<0.05),凋亡率下降(24.8±4.2 vs. 30.8±5.8,P<0.01).结论:GLP-1能够通过促进胰岛B细胞增殖抑制其凋亡,增加胰岛B细胞数目,改善B细胞内分泌颗粒的形态,从而改善2型糖尿病大鼠的糖耐量.

  11. EXPERIMENTAL PARACOCCIDIOIDOMYCOSIS IN PREGNANT RATS

    Science.gov (United States)

    LOTH, Eduardo Alexandre; CECATTO, Vanessa; BIAZIM, Samia Khalil; FERREIRA, José Henrique Fermino; DANIELLI, Caroline; GENSKE, Rodrigo Daniel; GANDRA, Rinaldo Ferreira; de FRANCO, Marcello Fabiano

    2015-01-01

    Paracoccidioidomycosis (PCM), caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb), is the most prevalent systemic mycosis in Latin America. There are few reports in the literature about the disease damages during pregnancy and the consequences to the fetuses and breeding. This study evaluated the implications of PCM during pregnancy on offspring and mothers in Wistar rats. Groups of rats were submitted to systemic Pb infection, by intraperitoneal infusion, and mated 30 days after the infection date. Immediately after birth, rats and neonates were sacrificed to obtain organs for standard histological examination, morphometric analysis, fungi recovery by plating (CFU) and dosing of anti-Pb antibodies by ELISA. There were no stillbirths or miscarriages, however, the fetuses from infected pregnant rats had lower body and organ weight but the fertility rate was 100%. The largest number of CFU was recovered from the organ of pregnant rats, the pathological examination revealed more severe infection in the same group, further on the largest number of granulomas and fungal field. It can be concluded that the PCM was more severe in the group of pregnant rats, with implications to the weight of offspring. PMID:27049707

  12. EXPERIMENTAL PARACOCCIDIOIDOMYCOSIS IN PREGNANT RATS.

    Science.gov (United States)

    Loth, Eduardo Alexandre; Cecatto, Vanessa; Biazim, Samia Khalil; Ferreira, José Henrique Fermino; Danielli, Caroline; Genske, Rodrigo Daniel; Gandra, Rinaldo Ferreira; Franco, Marcello Fabiano de

    2015-12-01

    Paracoccidioidomycosis (PCM), caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb), is the most prevalent systemic mycosis in Latin America. There are few reports in the literature about the disease damages during pregnancy and the consequences to the fetuses and breeding. This study evaluated the implications of PCM during pregnancy on offspring and mothers in Wistar rats. Groups of rats were submitted to systemic Pb infection, by intraperitoneal infusion, and mated 30 days after the infection date. Immediately after birth, rats and neonates were sacrificed to obtain organs for standard histological examination, morphometric analysis, fungi recovery by plating (CFU) and dosing of anti-Pb antibodies by ELISA. There were no stillbirths or miscarriages, however, the fetuses from infected pregnant rats had lower body and organ weight but the fertility rate was 100%. The largest number of CFU was recovered from the organ of pregnant rats, the pathological examination revealed more severe infection in the same group, further on the largest number of granulomas and fungal field. It can be concluded that the PCM was more severe in the group of pregnant rats, with implications to the weight of offspring.

  13. EXPERIMENTAL PARACOCCIDIOIDOMYCOSIS IN PREGNANT RATS

    Directory of Open Access Journals (Sweden)

    Eduardo Alexandre LOTH

    2015-12-01

    Full Text Available Paracoccidioidomycosis (PCM, caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb, is the most prevalent systemic mycosis in Latin America. There are few reports in the literature about the disease damages during pregnancy and the consequences to the fetuses and breeding. This study evaluated the implications of PCM during pregnancy on offspring and mothers in Wistar rats. Groups of rats were submitted to systemic Pb infection, by intraperitoneal infusion, and mated 30 days after the infection date. Immediately after birth, rats and neonates were sacrificed to obtain organs for standard histological examination, morphometric analysis, fungi recovery by plating (CFU and dosing of anti-Pb antibodies by ELISA. There were no stillbirths or miscarriages, however, the fetuses from infected pregnant rats had lower body and organ weight but the fertility rate was 100%. The largest number of CFU was recovered from the organ of pregnant rats, the pathological examination revealed more severe infection in the same group, further on the largest number of granulomas and fungal field. It can be concluded that the PCM was more severe in the group of pregnant rats, with implications to the weight of offspring.

  14. Mercury 203 distribution in pregnant and nonpregnant rats following systemic infusions with thiol-containing amino acids

    Energy Technology Data Exchange (ETDEWEB)

    Aschner, M.; Clarkson, T.W.

    1987-12-01

    Near-term pregnant (gestational day 17) and nonpregnant Long-Evans female rats were continuously infused into the external jugular vein with 0.1 mmole/hour L-cysteine, 0.1 mmole/hour L-leucine, or saline. At 24, 48, and 72 hours, 50 mumole/hour (/sup 203/Hg)-MeHgCl was administered over 1 hour. Total /sup 203/Hg body burden, brain, kidney, liver, and blood /sup 203/Hg concentrations were determined at 96 hours by gamma scintillation spectrometry. Despite significantly greater /sup 203/Hg whole body retention in the pregnant animals /sup 203/Hg concentrations in blood, brain, kidney, and liver were higher in nonpregnant rats. In addition, brain /sup 203/Hg concentrations in both pregnant and virgin rats were significantly higher in L-cysteine-treated rats compared with controls. These results suggest that the fetus may act as a sink for MeHg, thus decreasing /sup 203/Hg concentrations in maternal blood, brain, kidney, and liver. Furthermore, the data indicate that brain uptake of methylmercury in both pregnant and nonpregnant rats is enhanced by chronic L-cysteine infusion, lending support to the hypothesis that methylmercury in the rat may be translocated across the blood-brain barrier by the neutral amino acid carrier transport system.

  15. Effects of Fipronil on the EEG of Long Evans Rats

    Science.gov (United States)

    We have reported that the non-stimulus driven EEG is differentially altered by deltamethrin or permethrin (Lyke and Herr, Toxicologist, 114(S-1):265, 2010). In the current study, we examined the ability to detect changes in EEG activity produced by fipronil, a phenylpyrazole pest...

  16. Effects of Fipronil on the EEG of Long Evans Rats

    Science.gov (United States)

    We have reported that the non-stimulus driven EEG is differentially altered by deltamethrin or permethrin (Lyke and Herr, Toxicologist, 114(S-1):265, 2010). In the current study, we examined the ability to detect changes in EEG activity produced by fipronil, a phenylpyrazole pest...

  17. 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.

    2010-01-01

    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.

  18. Expression of aquaporin 7 in perirenal adipose tissue of Otsuka Long-Evans Tokushima Fatty diabetic rats%自发2型糖尿病模型OLETF大鼠肾周脂肪组织水通道蛋白7的表达

    Institute of Scientific and Technical Information of China (English)

    段玉敏; 袁振芳; 姚军; 张婷婷; 陈程; 郭晓蕙

    2011-01-01

    龄大鼠分别上调了21.9%和8.9%;18及28周OLETF/M组AQP7 mRNA表达较同组8周龄大鼠分别上调了25%及8.3%,AQP7蛋白表达较同组8周龄大鼠分别上调了14.6%及1.6%.OLETF及OLETF/M组均呈先增高而后下降的趋势,于18周时增高,28周下降,与血清丙三醇变化趋势一致.OLETF/M组AQP7 mRNA及蛋白表达水平低于同周龄OLETF组,但两组差异无统计学意义.OLETF/M组的体重、胰岛素与OLETF组差异无统计学意义.OLETF/M组AQP7 mRNA及蛋白表达水平低于同周龄OLETF组,但两组差异无统计学意义.结论:内脏脂肪AQP7参与了糖脂代谢,与2型糖尿病和肥胖发病相关.二甲双胍可改善OLETF大鼠的脂代谢和糖代谢紊乱,但对AQP7 mRNA及蛋白表达未见明显影响.%Objective : To observe perirenal adipose tissue aquaporin 7 ( AQP7 ) mRNA and protein expression in the spontaneous type 2 diabetes animal model Otsuka Long-Evans Toku-shima Fatty ( OLETF ) rats in different stages of diabetes and explore the role of AQP7 in obesity development and diabetes. Methods: OLETF rats ( n =30) were studied, with the same strains of non-diabetic Long-Evans Tokushima Otsuka ( LETO) rats ( n = 18) used as age-matched normal controls. After 8 weeks ( baseline) , 6 rats in each of the two groups were sacrificed. Then the rest of the OLETF rats were divided into untreated group ( OLETF group, n = 12) and metformin hydrochloride treated group ( OLETF/M group, n = 12). At the age of 8 , 18 and 28 weeks, their body weights were obtained, and biochemical items were measured including serum triglyceride, cholesterol, glycerol, glucose and insulin levels with oral glucose tolerance test ( OGTT) , and the perirenal adipose tissue ( PAT) was obtained to measure the AQP7 mRNA expression (by Real-time PCR) and AQP7 protein relative expression ( by Western blotting). Results : ( 1 ) OLETF group rats developed diabetes at week 18 [60 min glucose : ( 25. 67 ±6. 78 ) mmol/ 1. 120 min glucose : (16. 19 ±2.98) mmol/L] . The body

  19. OLETF大鼠肺泡上皮细胞基板的超微结构改变与定量检测%Ultrastrucural characteristics and morphometry of the alveolar epithelial basal lamina in Otsuka Long-Evans Tokushima fatty rats

    Institute of Scientific and Technical Information of China (English)

    汤秀英; 王书合; 柴立军

    2009-01-01

    目的 观察自发性2型糖尿病OLETF(Otsuka Long-Evans Tokushima Fatty)大鼠肺泡上皮细胞基板的超微结构改变.方法 用透射电镜观察、图像分析仪及形态计量学方法计算OLETF及对照的LETO(Long-Evans Tokushima Otsuka)大鼠肺泡上皮细胞基板的超微结构及厚度.结果 与LETO组大鼠相比,OLETF组大鼠肺泡毛细血管内皮细胞基板与Ⅰ型肺泡上皮细胞基板融合部及Ⅱ型肺泡上皮细胞基板均增厚(分别为110.6±14.14 vs.57.3±11.08和116.4±10.22 vs.71.89±7.68,P<0.01).结论 OLETF大鼠肺泡上皮细胞基板增厚,提示可能与糖尿病高血糖环境引起毛细血管基板成分发生改变有关.

  20. Toluene depresses plasma corticosterone in pregnant rats

    DEFF Research Database (Denmark)

    Hougaard, Karin S; Hansen, Åse Marie; 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...

  1. 自发性肝癌的LEC大鼠的GST-P异常表达和p53基因突变%p53 gene mutations and unusual expression of GST-P in spontaneous hepatocellular carcinoma of Long Evans Cinnamon rats

    Institute of Scientific and Technical Information of China (English)

    李兴华; 徐云虹; 许爱芳; 龚燕芳; 屠振兴; 李兆申

    2005-01-01

    原发性肝癌的发病原因及机制尚未完全清楚,可能与多种因素的综合作用有关,一般采用肝癌的手术标本或化学致癌的动物进行研究,但标本成分复杂,同质性差,影响因素多,从遗传学角度看,人体基因的高度杂合性,个体暴露于致癌物质的种类和量也不同,结果缺乏客观的评价。本实验采用自发性发生癌的实验动物LEC(Long Evans Cinnamon)鼠。

  2. Effects of glucagon like peptide-1 treatment on the alveolar capillary basal lamina in Otsuka Long-Evans Tokushima Fatty rats%胰高血糖素样多肽-1对OLETF大鼠肺泡毛细血管基板的影响

    Institute of Scientific and Technical Information of China (English)

    汤秀英; 王昱; 郭晓蕙; 王书合; 柴立军; 张烨

    2008-01-01

    目的:电镜观察并定量分析胰高血糖素样多肽-1(glucagon like peptide-1, GLP-1)对自发性2型糖尿病OLETF(Otsuka Long-Evans Tokushima Fatty)大鼠肺泡毛细血管基板的影响.方法:将OLETF大鼠分为未治疗的OLETF组及GLP-1治疗组(OLETF/G组),对照为LETO(Long-Evans Tokushima Otsuka)组大鼠.用透射电镜观察及形态计量学方法测量肺泡毛细血管基板的超微结构及厚度.结果:与LETO组大鼠相比,OLETF大鼠肺泡毛细血管内皮细胞基板与Ⅰ型肺泡上皮细胞基板融合部(F-BL)及肺泡毛细血管内皮细胞基板(Cap-BL)均增厚,分别为 (110.60±14.14) nm vs (57.30±11.08) nm和 (118.40±19.12) nm vs (66.80±8.63) nm (P<0.01).OLETF/G组大鼠肺F-BL及Cap-BL均比OLETF组大鼠明显变薄,分别为 (79.70±5.44) nm vs (110.60±14.14) nm和 (69.80±3.32) nm vs (118.40±19.12) nm (P<0.01).结论:OLETF大鼠肺泡毛细血管基板发生明显的超微结构变化;GLP-1治疗能减轻OLETF大鼠肺泡毛细血管基板损伤.

  3. Glomerular immunoglobulin deposits induce glomerular inflammation in pregnant but not in non-pregnant rats

    NARCIS (Netherlands)

    Faas, MM; Van Der Schaaf, G; Schipper, M; Moes, H

    2003-01-01

    PROBLEM: Does an inflammatory stimulus evoke a more intense inflammatory response in pregnant rats as compared with nonpregnant rats? METHOD OF STUDY: Non-pregnant rats were injected with antibodies against the glomerular basement membrane (GBM), 14 days before pregnancy, to induce a subclinical glo

  4. Potentiation of the hypotensive effect of adrenomedullin in pregnant rats.

    Science.gov (United States)

    Makino, I; Shibata, K; Makino, Y; Kangawa, K; Kawarabayashi, T

    1999-12-03

    The hypotensive effect of adrenomedullin, a potent vasodilator peptide, was examined in conscious pregnant (6, 13 and 20 days of pregnancy) and non-pregnant rats. The intravenous administration of adrenomedullin (0.01-3.0 nmol/kg) produced a dose-dependent depressor response in pregnant and non-pregnant rats. At low doses (0.01-0.1 nmol/kg), the maximum decrease in blood pressure was significantly higher in pregnant rats (20 days pregnant) than in non-pregnant rats. At high doses, no significant difference was observed between the two groups. Furthermore, the administration of adrenomedullin did not significantly affect the basal mean blood pressure (MBP) at any dose when compared to the non-pregnant group at 6 and 13 days of pregnancy. In the ovariectomized rats, the depressor responses in 17beta-estradiol-treated, progesterone-treated and 17beta-estradiol+progesterone-treated rats were not significantly different from that in the control rats, suggesting that the augmented effect on the depressor response to adrenomedullin in pregnant rats may not be due to hormonal changes during pregnancy. The adrenomedullin receptor mRNA level of the descending thoracic aorta was significantly higher in the late-pregnancy rats (20 days of pregnancy). However, the levels did not show any difference between the early-pregnant rats (6 and 13 days of pregnancy) and the non-pregnant rats. These findings suggested that the changes in the depressor response to adrenomedullin which occur at term in pregnant rats may be mediated by changes of adrenomedullin receptor gene expression rather than by sex hormones.

  5. ATRAZINE INCREASES DIMETHYLBENZ[A]ANTHRACENE-INDUCED MAMMARY TUMOR INCIDENCE IN LONG EVANS OFFSPRING EXPOSED IN UTERO

    Science.gov (United States)

    ATRAZINE INCREASES DIMETHYLBENZ[A]ANTHRACENE-INDUCED MAMMARY TUMOR INCIDENCE IN LONG EVANS OFFSPRING EXPOSED IN UTERO.SE Fenton and CC DavisReproductive Toxicology Division, NHEERL, ORD, USEPA, Durham, NC, USARecently, we found that ATR exposure during ma...

  6. Toluene depresses plasma corticosterone in pregnant rats

    DEFF Research Database (Denmark)

    Hougaard, Karin S; Hansen, Åse Marie; Hass, Ulla

    2003-01-01

    Combined exposure to stressors and chemicals may result in synergistic effects. The effects of prenatal exposure to the organic solvent toluene resemble those observed in offspring of gestationally stressed dams, a possible common mechanism being transfer of stress-/toluene-induced increments...... 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...... being enhanced by maternal stress. A depressant effect of toluene on maternal corticosterone was observed, hence the study does not provide immediate evidence that transfer of elevated levels of corticosterone from the maternal to the foetal compartment mediates the effects of prenatal exposure...

  7. Propolis 長期投与による Otsuka Long-Evans Tokushima Fatty (OLETF) ラットの インスリン抵抗性改善作用

    OpenAIRE

    座間味, 義人; 藤原, 弘喜; 細田, 美穂; 日野, 隼人; 平井, 和浩; 岡本, 和明; 金, 鑫; 高取, 真吾; 高木, 志真; 川﨑, 博己

    2010-01-01

    Propolis is known to have abundant bioactive constituents and a variety of biological activities. To investigate the effect of Brazilian propolis on insulin resistance, 10-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a non-insulin-dependent type 2 diabetic model, were treated for 4 weeks with propolis (100 and 300 mg/kg, p.o.) or vehicle (control). Propolis treatment significantly decreased the plasma levels of insulin and insulin resistance index (Homeostasis Model Assessment-Ins...

  8. Differential effect of neocuproine, a copper(I) chelator, on contractile activity in isolated ovariectomized non-pregnant rat, pregnant rat and pregnant human uterus.

    Science.gov (United States)

    Kumcu, Eda Karabal; Büyüknacar, Hacer Sinem Göktürk; Göçmen, Cemil; Evrüke, Ismail Cüneyt; Onder, Serpil

    2009-03-01

    The study was conducted to examine effects of a selective copper(I) chelator, neocuproine on the spontaneous or oxytocin-induced contractions in isolated ovariectomized non-pregnant rat, pregnant rat and pregnant human uterus. Uterus activity was evaluated in tissues obtained from bilaterally ovariectomized non-pregnant rats on the 21st day of the operation (n = 24), pregnant rats on the 19-21st day of gestation (n = 24) and women undergoing caesarean section at 38-42 weeks of pregnancy (n = 15). Neocuproine (100 microM) significantly suppressed the amplitude and frequency of the spontaneous contractions in the ovariectomized non-pregnant rat uterus while this agent facilitated the frequency of the spontaneous or oxytocin-induced contractions in the pregnant rat and human uterus without altering the amplitude of these contractions. At high concentration of 200 microM, neocuproine could enhance the amplitude of the contractions in the pregnant uterus. These effects were blocked by a purinergic receptor antagonist, suramin (100 microM) and did not occur following the administration of neocuproine-copper(I) complex or copper(II) chelator cuprizone. alpha, beta-methylene ATP increased the amplitude and frequency of contractions in the pregnant uterus, but not affected the contractions in the ovariectomized non-pregnant rat uterus, and neocuproine potentiated this facilitation effect. However, the suppressive effect of neocuproine on the ovariectomized non-pregnant rat uterus increased in the presence of alpha,beta-methylene ATP. Beta-adrenoceptor blocker, propranolol or nitric oxide synthase inhibitor, L-nitroarginine did not affect the responses to neocuproine. These findings suggest that neocuproine can affect the uterus contractile activity by modulation purinergic excitatory responses and that copper(I)-sensitive mechanisms may play a role in this effect.

  9. Carbon tetrachloride-induced hepatotoxicity in pregnant and lactating rats.

    Science.gov (United States)

    Mochizuki, Masahiro; Shimizu, Satomi; Urasoko, Yoshinaka; Umeshita, Kazuhiko; Kamata, Takashi; Kitazawa, Takahiro; Nakamura, Daichi; Nishihata, Yoshito; Ohishi, Takumi; Edamoto, Hiroshi

    2009-04-01

    Carbon tetrachloride (CCl4) is well known to induce hepatotoxicity after being metabolized to trichloromethyl free radical ((.)CCl3) by CYP2E1. In the present study, the hepatotoxicity induced by a single oral dose (2,000 mg/kg) of CCl4 was compared between pregnant (gestation days (GD) 13 and 19) or postpartum (postpartum days (PPD) 1, 13 and 27) and non-pregnant rats. Hepatotoxicity in CCl4-treated pregnant rats evaluated by blood chemistry (alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities) and histopathological finding (area of damaged hepatocytes) was minimal on GD19, being weaker than that in non-pregnant rats. CYP2E1 expression in non-treated pregnant rats decreased as pregnancy progressed and reached minimum level on GD19. Thus, the degree of CCl4-induced hepatotoxicity roughly corresponded to CYP2E1 levels during pregnancy. After delivery, hepatotoxicity in CCl4-treated lactating rats was maximal on PPD13, being stronger than that in non-pregnant rats, and then it decreased slightly on PPD27. The CYP2E1 level in the non-treated lactating rats tended to increase but remained at lower levels until PPD13 compared with that in non-pregnant rats. Thus, the degree of CCl4-induced hepatotoxicity did not correspond to CYP2E1 levels during lactation. This suggests that during lactation, there may be certain factors other than CYP2E1 expression responsible for the degree of CCl4-induced hepatotoxicity.

  10. Disposition of stiripentol in the pregnant and non-pregnant female rat.

    Science.gov (United States)

    Maurizis, J C; Rapp, M; Madelmont, J C; Gillardin, J M; Lepage, F; Labarre, P; Dupuy, J M; Veyre, A

    1993-12-01

    1. The disposition of stiripentol labelled with 14C and 3H on two positions has been studied in the pregnant and non-pregnant female rat after p.o. administration of a 200 mg/kg dose. 2. For both labelled species radioactivity was eliminated mainly in the faeces (69% within 72 h). Urinary excretion was rather low (22% within 72 h). No significant difference was found between the disposition of the two labelled species. 3. For both labelled species concentrations of radioactivity reached a plateau in the plasma and tissues between 1 and 6 h after administration. The liver, fat, mammary gland and adrenal gland were the most extensively-labelled organs. The affinity for the mammary gland was significantly greater in pregnant rats and for the adrenal gland was significantly greater in the non-pregnant rats. The fact that the concentration in the placenta was higher than in the foetus demonstrated that this membrane acts as a barrier for the penetration of the drug in the amniotic fluid. 4. Chromatographic analysis of the faeces and urine showed that an important portion of the dose remained unabsorbed through the gastrointestinal tract. The absorbed fraction undergoes an extensive first-pass metabolism involving mainly the oxidative cleavage of the methylenedioxy ring. Comparison with the results of other work conducted on the non-pregnant rat demonstrated that pregnancy did not affect the disposition and metabolic process.

  11. Histomorphometric changes of small intestine in pregnant rat

    OpenAIRE

    2015-01-01

    Food intake of rats increases during pregnancy. This requires changes in the structure of the small intestine to absorb additional food. The aim of the present study was to investigate the morphological changes in the layers of small intestine in rats during pregnancy. Duodenum, jejunum and ileum of 18 pregnant Sprague-Dawley rats (day 7, 14 and 21 of pregnancy) were collected. Villous height and width and thickness of lamina propria, tunica muscularis entirely and separately (circular and lo...

  12. [Effect of tobacco smoke on permeability of capillary of pregnant and non-pregnant rats].

    Science.gov (United States)

    Florek, Tewa; Ignatowicz, Ewa; Piekoszewski, Wojciech; Wachowiak, Anna; Wrzosek, Jagna

    2006-01-01

    From among 4200 chemical compounds contained in the tobacco smoke, nicotine and carbon monoxide are responsible for changes in the heart-vessel system to the greatest extent. Additionally, other toxic compounds, including the carcinogenic ones, have a significant impact on the biological activity in the tissues of blood vessels. A particularly complex picture of the detrimental impact of the tobacco smoke is presented in case of pregnant women, fetuses and newborns. The aim of the research was to assess the impact of tobacco smoke on the permeability of capillaries in different tissues of rats (lungs, brain, liver, kidneys) and testing of the potentially protective impact of rutine (3-rutinozide of quercetin). The research on the permeability of capillaries has been carried out applying Evans blue. The animals were divided into 8 research groups: pregnant animals--"control", "rutine", "tobacco smoke", "rutine+tobacco smoke", and non-pregnant animals--"control", "rutine", "tobacco smoke", "rutine+tobacco smoke". In the first stage of research (pregnant, non-pregnant-- groups: "rutine" and "rutine+tobacco smoke"), the water rutine solution in a dose of 40 mg/kg of body weight was administered. The non-pregnant and pregnant animals from groups "tobacco smoke" and "rutine+tobacco smoke" were exposed to tobacco smoke via inhalation (1500 mg CO/m3 of air) for 21 days. All the animals were injected with the water Evans blue solution in a dose of 30 mg/kg of body weight. After 30 minutes, the animals were killed by cutting the abdominal aorta, and lungs, brain, liver and kidneys were taken for further testing. The cotinine in the urine was determined by the HPLC method, using norephedrine as the internal standard, after the preceding extraction by means of the liquid-liquid technique. The concentration of cotinine in case of non-pregnant and pregnant females was respectively 11.8 +/- 1.9 pg/ml of urine and 12.0 +/- 2.5 microg/ml of urine. In case of the rats, which

  13. Swimming of pregnant rats at different water temperatures.

    Science.gov (United States)

    Osorio, R A L; Silveira, V L F; Maldjian, S; Morales, A; Christofani, J S; Russo, A K; Silva, A C; Piçarro, I C

    2003-08-01

    We studied the chronic effect of exercise during water immersion, associated with thermal stress (water temperature at 22, 35 and 40 degrees C) at an intensity of 80% of maximal work load supported in pregnant rats (P) and non-pregnant female rats (NP). P and NP were subdivided into three subgroups according to water temperature during exercise (P22 and NP22; P35 and NP35; P40 and NP40). The animals were submitted to daily swimming sessions of 10-15 min, for 19 days of pregnancy (P) or experimental conditions (NP). Plasma concentration of triglycerides, cholesterol, glucose, total protein, albumin and corticosterone were determined 24 h after the last exercise session. Weight gain and rectal temperature pre- and post-swimming session were also determined. The offspring were examined just after caesarian section on the 20th day of pregnancy to check weight, length and litter size. Pregnant rats showed an increase of triglycerides, reduction of glycemia, total protein and albumin and cholesterol (at 35 degrees C) when compared to non-pregnant animals. Such effects probably lead to an adequate delivery of substrate to the fetus and prepare the mother for lactation. Daily thermal stress did not modify metabolic responses to exercise in pregnant rats. Results also show a deleterious effect on offspring when the mother is exposed daily to extreme temperatures during swimming. These results suggest that water temperature (cold and hot) in swimming have to be considered to avoid damage in fetal development.

  14. Dopaminergic modulation of grooming behavior in virgin and pregnant rats

    Directory of Open Access Journals (Sweden)

    A.P. Serafim

    2001-11-01

    Full Text Available Dopamine receptors are involved in the expression of grooming behavior. The pregnancy-induced increase in self-licking observed in rats is important for mammary gland development and lactation. This study focuses on the role of dopamine receptor subtypes in grooming behavior of virgin and pregnant female rats. General and mammary gland grooming were measured in virgin rats treated with 0.25 mg/kg of the D1-like agonist SKF-81297 and antagonist SKF-83566 and the D2-like agonist lisuride and antagonist sulpiride. The effects of 0.01 and 0.25 mg/kg doses of the same agonists and antagonists were evaluated in pregnant rats as well. In virgin animals both SKF-83566 and sulpiride treatments significantly reduced the time spent in general grooming, while none of the dopamine agonists was able to significantly change any parameter of general grooming. Time spent in grooming directed at the mammary glands was not affected significantly by any of the drug treatments in virgin rats. All drugs tested significantly decreased the frequency of and the time spent with general grooming, while SKF-81297 treatment alone did not significantly reduce the duration of mammary gland grooming in pregnant rats. These data show that in female rats the behavioral effects of D1-like and D2-like dopamine receptor stimulation and blockade differ according to physiological state. The results suggest that dopamine receptors may play specific roles modulating grooming behavior in pregnant rats. Since grooming of the mammary gland during pregnancy may influence lactation, this aspect is relevant for studies regarding the perinatal use of dopamine-related drugs.

  15. Exposure to Novelty Weakens Conditioned Fear in Long-Evans Rats

    Science.gov (United States)

    Anderson, Matthew J.; Burpee, Tara E.; Wall, Matthew J.; McGraw, Justin J.

    2013-01-01

    The present study sought to determine whether post-training exposure to a novel or familiar object, encountered in either the location of the original fear conditioning (black compartment of a passive avoidance {PA} chamber) or in a neutral setting (open field where initial object training had occurred) would prove capable of reducing fear at…

  16. Absence of diurnal variation in visceromotor response to colorectal distention in normal Long Evans rats

    NARCIS (Netherlands)

    Botschuijver, Sara; Yu, Zhumei; Welting, Olaf; Cailotto, Cathy; Kalsbeek, A.; van den Wijngaard, Rene

    2016-01-01

    BACKGROUND: Enhanced colorectal sensitivity (i.e. visceral hypersensitivity) is thought to be a pathophysiological mechanism in irritable bowel syndrome (IBS). In healthy men a circadian variation in rectal perception to colonic distention was described. Disturbed day and night rhythms, which occur

  17. Acute triadimefon-induced changes in the EEG of Long-Evans Rats

    Science.gov (United States)

    We have reported that the non-stimulus driven EEG is altered differently by acute treatment with deltamethrin, permethrin, fipronil, or imidacloprid (Lyke and Herr, Lyke et al., Toxicologist, 2010, 2011, 2012) in non-restrained animals. In the current study, we examined the abili...

  18. Effects produced by single and repeated dosages of Fipronil on the EEG of Long Evans Rats

    Science.gov (United States)

    We have previously reported that various classes of pesticides have different effects on the non- stimulus driven EEG after acute treatment, including fipronil (25 or 50 mg/kg) (Lyke et a!., Toxicologist, 2010, 2011, 2012, 2013). In this study, we compared the effects of single a...

  19. IMIDACLOPRID PRODUCES MINIMAL CHANGES IN THE EEG OF LONG-EVANS RATS

    Science.gov (United States)

    We have reported that the non-stimulus driven EEG is differentially altered by deltamethrin or permethrin (Lyke and Herr, Toxicologist, 114(S-1) :265, 2010) as well as fipronil (Lyke and Herr, Toxicologist, 120(S-2) :290, 2011). In the current study, we examined the ability to de...

  20. Effects produced by single and repeated dosages of Fipronil on the EEG of Long Evans Rats

    Science.gov (United States)

    We have previously reported that various classes of pesticides have different effects on the non- stimulus driven EEG after acute treatment, including fipronil (25 or 50 mg/kg) (Lyke et a!., Toxicologist, 2010, 2011, 2012, 2013). In this study, we compared the effects of single a...

  1. Thermoregulatory deficits in adult long evans rat offspring exposed perinatally to the antithyroidal drug, propylthiouracil

    Science.gov (United States)

    Developmental exposure to endocrine disrupting toxicants has been shown to alter a variety of physiological processes in mature offspring. Body (core) temperature (Tc) is a tightly regulated homeostatic system but is susceptible to disruptors of the hypothalamic-pituitary-thyroid...

  2. Toluene Inhalation Exposure for 13 Weeks Causes Persistent Changes in Electroretinograms of Long-Evans Rats

    Science.gov (United States)

    Studies of humans chronically exposed to volatile organic solvents have reported impaired visual functions, including low contrast sensitivity and reduced color discrimination. These reports, however, lacked confirmation from controlled laboratory experiments. To addre...

  3. Phenobarbital (PB)-induced changes in blood coagulationrelated parameters in pregnant rats, lactating rats and pups.

    Science.gov (United States)

    Mochizuki, Masahiro; Shimizu, Satomi; Kidokoro, Yuri; Kamata, Takashi; Kitazawa, Takahiro; Kishi, Daisuke; Okazaki, Emi; Nishihata, Yoshito; Ohishi, Takumi

    2009-12-01

    Effects of repeated administration of phenobarbital (PB) on blood coagulation-related parameters were examined in non-pregnant, pregnant and lactating rats, and also in pups born to PB-treated lactating dams. PB was orally administered at a dose level of 80 mg/kg/day to pregnant (from gestation day (GD) 13), postpartum (from postpartum day (PPD) 7) and non-pregnant rats (from 13 weeks of age) for 7 days. Blood was collected on GD20 or PPD14 to perform blood coagulation examination. Concurrently, the blood coagulation parameters were examined in the pups. Increases in liver weight and/or hepatic cytochrome P450 content were observed in the PB-treated non-pregnant, pregnant and lactating rats. Activated partial thromboplastin time (APTT) was prolonged and anti-thrombin III (ATIII) concentration was increased in the lactating rats, while there were no changes in prothrombin time (PT) or APTT in the non-pregnant and pregnant rats. Moreover, prolongation of PT and APTT and decreases in factors VII and IX activities were observed in their pups. Thus, prolongation of blood coagulation time was confirmed in both dams and their pups following PB-administration to lactating dams. Effects of vitamin K(2) (VK(2)) on PB-induced changes in blood coagulation-related parameters of both dams and their pups were examined by co-administration with PB and VK(2) to lactating dams. PT and APTT were comparable to the control and PB-induced prolongation of blood coagulation time was improved in the pups while APTT was prolonged in dams, suggesting that VK(2) was beneficial to pups but not to dams.

  4. Taurine concentrations in fetal, neonatal and pregnant rats.

    Directory of Open Access Journals (Sweden)

    Akahori,Shuichiro

    1986-04-01

    Full Text Available The concentrations of taurine in the fetal and neonatal organs, and the maternal organs, plasma and urine of rats between the 15th day of gestation and the 21st day after birth were determined using an automatic amino acid analyzer. In the fetal liver and brain and in the placenta, the taurine concentration was the highest of all ninhydrin positive compounds. In the fetal liver and placenta, the concentrations of taurine increased significantly with the gestational days. Concentrations of taurine in the brain were much higher in the fetus and neonate than that in the adult. Moreover, the total amount of taurine per fetus increased markedly after the 15th day of gestation, and near term, reached almost the same amount as in the adult rat liver. In contrast to this, a significant decrease was observed in the taurine concentration in the maternal liver and muscle near term. The concentration of taurine in the urine of pregnant rats decreased near term, but in the plasma of pregnant rats the concentration of taurine did not change during pregnancy.

  5. The Effects of Sugammadex on Progesterone Levels in Pregnant Rats.

    Science.gov (United States)

    Et, Tayfun; Topal, Ahmet; Erol, Atilla; Tavlan, Aybars; Kılıçaslan, Alper; Uzun, Sema Tuncer

    2015-04-01

    Sugammadex has been shown to decrease the efficiency of progesterone-containing oral contraceptive drugs which possess a steroid structure. The aim of the present study was to evaluate the effects of sugammadex on progesterone levels in pregnant rats as well as on the physiological course of the pregnancy. Animal experiment. This study was approved by the Selçuk University Ethical Committee for Experimental Animal Research. Pregnant Winster Albino rats (n=26) were divided into three groups and administered with various intravenous injections on the 7(th) day of pregnancy. The control group (Group K, n=6) received 1.5 mL serum physiologic, the sugammadex group (Group S, n=10) received 30 mg/kg sugammadex and the sugammadex + rocuronium group (Group SR, n=10) received 30 mg/kg sugammadex and 3.5 mg/kg rocuronium. Progesterone levels were measured and the offspring were monitored for morphologic status. Mean progesterone levels were 94.16±15.54 ng/mL in Group K, 87.86±12.48 ng/mL in Group S, and 94.53±16.10 ng/mL in Group SR (p>0.05). No stillbirth or miscarriage was observed in the rats. The mean number of offspring was 6.8±1.47 in Group K, 6.5±1.35 in Group S, and 6.4±1.17 in Group SR. The offspring appeared macroscopically normal. Sugammadex does not appear to affect the progesterone levels in pregnant rats in the first trimester and the clinical course. Successful completion of pregnancy and the absence of stillbirth or miscarriage will guide future studies about the use of sugammadex, particularly in the first trimester of the pregnancy.

  6. Comparative analysis of two different models of swimming applied to pregnant rats born small for pregnant age

    OpenAIRE

    CORVINO,SILVANA B.; Damasceno, Débora C; Yuri K Sinzato; NETTO,ALINE O.; MACEDO,NATHÁLIA C.D.; Zambrano, Elena; Volpato, Gustavo T

    2017-01-01

    ABSTRACT The aim of this study was to compare two models of swimming applied to pregnant rats born small for pregnancy age (SPA). Diabetes was chemically induced in adult female rats to develop an inadequate intrauterine environment, leading to birth of a SPA offspring. In adulthood, the female SPA rats were mated and submitted to different swimming programs. The exercise program 1 (Ex1) consisted of swimming for 15 minutes, followed by 15 minutes of rest and another 15 minutes of swimming, 3...

  7. Neonatally induced diabetes: liver glycogen storage in pregnant rats

    Directory of Open Access Journals (Sweden)

    Isabela Lovizutto Iessi

    2012-04-01

    Full Text Available The aim of this sstudy was to evaluate the liver glycogen storage in pregnant rats presenting neonatal streptozotocin-induced diabetes and to establish a relation with glycemia and insulin levels. Wistar rats were divided in to two groups: 1 Mild Diabetes (STZ - received streptozotocin (glycemia from 120 to 300 mg/dL, 2 Control - received vehicle (glycemia below 120 mg/dL. At days 0, 7, 14 and 21 of the pregnancy, body weight and glycemia were evaluated. At day 21 of the pregnancy, the rats were anesthetized for blood and liver collection so as to determine insulin and liver glycogen, which showed no changes in the STZ group as compared to the controls. In the STZ group, maternal weight gain were lower as compared to those in the control group. Significantly increased glycemia was observed at days 0 and 14 of the pregnancy in the STZ group. Therefore, neonatally induced diabetes in the rats did not cause metabolic changes that impaired insulin and liver glycogen relation in these rats.

  8. Hypertension during chronic exposure to cold: Comparison between Sprague Dawley (SD) and Long Evans (LE) strains

    Energy Technology Data Exchange (ETDEWEB)

    Riesselmann, A.; Baron, A.; Fregly, M.J. (Univ. of Florida, Gainesville (United States))

    1991-03-11

    Hypertension accompanies chronic exposure of SD rats to cold (5-6C), including elevation of systolic, diastolic, and mean blood pressures and cardiac hypertrophy. The renin-angiotensin system may play an important role. Earlier studies suggested that the LE strain may have a decrease in angiotensin I converting enzyme (ACE) activity. Measurement of ACE activity in plasmas of SE and LE strains revealed that basal activity of ACE in the plasma of the LE strain was significantly less than that of the SD strain. A second study was carried out in which both strains were exposed to cold for 7 weeks. There were clear differences between strains. Rats of the SD strain had a significant elevation in their blood pressure; a significantly increased urinary output of norepinephrine (NE) and epinephrine (E); and significant increases in weights of heart, kidneys, adrenals, and brown adipose tissue (IBAT) compared to their controls maintained at 26C. In contrast, rats of the LE strain were less responsive to cold in that blood pressure failed to rise as sharply and to attain as high a level; NE and E outputs, as well as weights of heart and IBAT were significantly less than those of rats of the cold-treated SD strain. Thus, the lower ACE activity in plasma of LE strain, as well as a reduced secretion of catecholamines, may protect these rats against the rise of blood pressure characteristically observed when rats of the SD strain are exposed to cold.

  9. Polyaromatic compounds alter placental protein synthesis in pregnant rats

    Energy Technology Data Exchange (ETDEWEB)

    Shiverick, K.T.; Ogilvie, S.; Medrano, T. (Univ. of Florida, Gainesville (United States))

    1991-03-15

    The administration of the polyaromatic compounds {beta}-naphthoflavone ({beta}NF) and 3-methylcholanthrene (3MC) to pregnant rats during mid-gestation has been shown to produce marked feto-placental growth retardation. This study examined secretory protein synthesis in placental tissue from rats following administration of {beta}NF on gestation days (gd) 11-14 or 3MC on gd 12-14. Explants of placental basal zone tissue were cultured for 24 hours in serum-free medium in the presence of ({sup 3}H)leucine. Secreted proteins were analyzed by two-dimensional SDS-polyacrylamide gel electrophoresis followed by either fluorography or immunostaining. Total incorporation of ({sup 3}H)leucine into secreted proteins was not altered in BZ explants from {beta}NF or 3MC-treated animals. However a selective decrease was observed in ({sup 3}H)leucine incorporation into a major complex of proteins with apparent molecular weight of 25-30,000 and isoelectric point between 5.3 to 5.7. This group of proteins has been further identified as being related to rat pituitary growth hormone (GH) using N-terminal amino acid microsequencing of individual spots from 2-D SDS-PA gels. This is the first report that synthesis of GH-related proteins by rat placenta is decreased following {beta}NF and 3MC administration, a change which may underlie the feto-placental growth retardation associated with these polyaromatic compounds.

  10. Time-course changes of hematology and clinical chemistry values in pregnant rats.

    Science.gov (United States)

    Honda, Tatsuya; Honda, Katsuya; Kokubun, Chisato; Nishimura, Tomonari; Hasegawa, Mina; Nishida, Atsuyuki; Inui, Toshihide; Kitamura, Kazuyuki

    2008-08-01

    The aim of this study is to report how pregnancy alters hematology and clinical chemistry values in rats. Female and male Sprague-Dawley rats were mated; the day of copulation was designated as Day 0. Hematology and clinical chemistry measurements were conducted on Days 7, 14, 17 and 21 in pregnant rats. Measurements were also conducted in non-pregnant rats. Red blood cells (RBC), hemoglobin (Hb), hematocrit (Ht), total protein and albumin decreased on Days 7, 14, 17 and 21; sodium, chloride and glucose decreased on Days 14, 17 and 21; iron decreased on Days 17 and 21; hemoglobin content of reticulocytes (CHr), calcium, inorganic phosphorus and the albumin/globulin ratio decreased on Day 21; and total cholesterol, phospholipid and high-density lipoprotein cholesterol decreased on Day 14 in pregnant rats compared with non-pregnant rats. Reticulocyte increased on Days 7, 14 and 17; mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, neutrophil count and rate increased on Days 14, 17 and 21; platelets, fibrinogen, triglyceride and free fatty acid increased on Days 17 and 21; and activated partial thromboplastin time was prolonged on Days 17 and 21 in pregnant rats compared with non-pregnant rats. The decreased RBC, Hb, Ht, CHr and iron in pregnant rats indicated that they suffered from iron deficiency anemia. These data can be used as background information for effective evaluation in reproductive toxicology studies.

  11. Why does a high-fat diet induce preeclampsia-like symptoms in pregnant rats?*

    Institute of Scientific and Technical Information of China (English)

    Jing Ge; Jun Wang; Dan Xue; Zhengsheng Zhu; Zhenyu Chen; Xiaoqiu Li; Dongfeng Su; Juan Du

    2013-01-01

    Changes in neurotransmitter levels in the brain play an important role in epilepsy-like attacks after pregnancy-induced preeclampsia-eclampsia. Metabotropic glutamate receptor 1 participates in the onset of lipid metabolism disorder-induced preeclampsia. Pregnant rats were fed with a high-fat diet for 20 days. Thus, these pregnant rats experienced preeclampsia-like syndromes such as tension and proteinuria. Simultaneously, metabotropic glutamate receptor 1 mRNA and protein ex-pressions were upregulated in the rat hippocampus. These findings indicate that increased sion of metabotropic glutamate receptor 1 promotes the occurrence of high-fat diet-induced preec-lampsia in pregnant rats.

  12. Histomorphometric changes of small intestine in pregnant rat.

    Science.gov (United States)

    Sabet Sarvestani, Fatemeh; Rahmanifar, Farhad; Tamadon, Amin

    2015-01-01

    Food intake of rats increases during pregnancy. This requires changes in the structure of the small intestine to absorb additional food. The aim of the present study was to investigate the morphological changes in the layers of small intestine in rats during pregnancy. Duodenum, jejunum and ileum of 18 pregnant Sprague-Dawley rats (day 7, 14 and 21 of pregnancy) were collected. Villous height and width and thickness of lamina propria, tunica muscularis entirely and separately (circular and longitudinal layers) were measured on transverse sections. During pregnancy increasing villi length and muscular layer thickness was observed in duodenum. Furthermore, along with the progress of gestation greatest histomorphometric change in small intestine was observed in the jejunum. The reduction in the ileum histomorphologic indices was observed during pregnancy. In conclusion, increase in histomorphologic indices of duodenum and jejunum supplies more capacity of duodenum to digest food intake during pregnancy and decrease in these indices in ileum controls the absorption of excess produced amino acids and glucose by hyperphagia.

  13. The effect of chronic nitric oxide inhibition on vascular reactivity and blood pressure in pregnant rats

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    Nilton Hideto Takiuti

    1999-09-01

    Full Text Available CONTEXT: The exact mechanism involved in changes in blood pressure and peripheral vascular resistance during pregnancy is unknown. OBJECTIVE:To evaluate the importance of endothelium-derivated relaxing factor (EDRF and its main component, nitric oxide, in blood pressure and vascular reactivity in pregnant rats. DESIGN: Clinical trial in experimentation animals. SETTING: University laboratory of Pharmacology. SAMPLE: Female Wistar rats with normal blood pressure, weight (152 to 227 grams and age (90 to 116 days. INTERVENTION: The rats were divided in to four groups: pregnant rats treated with L-NAME (13 rats; pregnant control rats (8 rats; virgin rats treated with L-NAME (10 rats; virgin control rats (12 rats. The vascular preparations and caudal blood pressure were obtained at the end of pregnancy, or after the administration of L-NAME in virgin rats. MAIN MEASUREMENTS: The caudal blood pressure and the vascular response to acetylcholine in pre-contracted aortic rings, both with and without endothelium, and the effect of nitric oxide inhibition, Nw-L-nitro-arginine methyl-ester (L-NAME, in pregnant and virgin rats. The L-NAME was administered in the drinking water over a 10-day period. RESULTS: The blood pressure decreased in pregnancy. Aortic rings of pregnant rats were more sensitive to acetylcholine than those of virgin rats. After L-NAME treatment, the blood pressure increased and relaxation was blocked in both groups. The fetal-placental unit weight of the L-NAME group was lower than that of the control group. CONCLUSION: Acetylcholine-induced vasorelaxation sensitivity was greater in pregnant rats and that blood pressure increased after L-NAME administration while the acetylcholine-induced vasorelaxation response was blocked.

  14. Prenatal Exposure to Nicotine in Pregnant Rat Increased Inflammatory Marker in Newborn Rat

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    Yosouf Mohsenzadeh

    2014-01-01

    Full Text Available This study aimed to investigate any inflammatory effect of nicotine on rat embryo by exposing their mothers to different dosages of nicotine during pregnancy. During this experimental study, 32 pregnant healthy Wistar rats were divided into 4 equal groups, including a control and 3 nicotine exposure groups. Injections were performed subcutaneously starting at the first day of pregnancy until parturition. As the dosages of nicotine were increased, the weight gain by pregnant rats and the mean weight of their newborns were significantly reduced. Mean ± SD of hs-CRP was significantly higher among groups exposed to various dosages of nicotine (2, 4, and 6 mg/kg compared to the control group (P<0.0001 and its increasing rate was also dose dependent. Mean ± SD serum level of IL-6 and TNF-α among all groups exposed to nicotine, except for 2 mg/kg nicotine injected group, was increased significantly (P<0.0001. Mean ± SD of serum level of TGF-β and nitrite oxide among exposure groups showed significant differences compared to the control group only at the dosage of 6 mg/kg (P<0.0001. The current study showed that exposing pregnant rats to nicotine causes a dose dependent increase in the rate of all the studied inflammatory serum markers among their newborns.

  15. Cadmium toxicity in the thyroid gland of pregnant rats

    Energy Technology Data Exchange (ETDEWEB)

    Yoshizuka, M.; Mori, N.; Hamasaki, K.; Tanaka, I.; Yokoyama, M.; Hara, K.; Doi, Y.; Umezu, Y.; Araki, H.; Sakamoto, Y. (Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, Kitakyushu (Japan))

    1991-08-01

    The toxic effects of cadmium on the thyroid gland of pregnant rats were studied with an electron microscope and an X-ray microanalyzer. Serum levels of thyroid hormones (T3 and T4) were also analyzed. Deterioration of the rough-surfaced endoplasmic reticulum occurred in the thyroid follicular epithelium on the fifth day of cadmium treatment. Large intracellular vacuoles, which arose from dilated cisternae of the rough-surfaced endoplasmic reticulum, were fused together, and marked swelling of the mitochondria was also noted. Thyroglobulin-secreting granules at the apical cytoplasm were decreased in number. By energy dispersive X-ray microanalysis, cadmium peaks were preferentially obtained from swollen mitochondria in the follicular epithelial cells. Serum levels of T3 and T4 were significantly decreased in cadmium-treated rats dams when compared to those of controls. In the present experiment, cycloheximide also caused degenerative changes in the rough-surfaced endoplasmic reticulum and the disappearance of thyroglobulin-secreting granules. Cycloheximide is a known inhibitor of protein synthesis on cytosolic ribosomes. These results indicated that accumulated cadmium in the mitochondria of thyroid follicular epithelial cells might disturb the oxidative phosphorylation of this organelle and the loss of energy supply possibly caused the inhibition of the synthesis and release of thyroid hormones.

  16. Surperoxide-mediated glomerulopathy in the endotoxin-treated pregnant rat

    NARCIS (Netherlands)

    Faas, MM; Schuiling, GA; Valkhof, N; Baller, JWF; Bakker, WW

    1998-01-01

    In the present study the role of superoxide in the glomerular damage in the low-dose endotoxin-infused pregnant rats was investigated. On day 14 of pregnancy, 12 rats were infused for 1 h with 1.0 mu g/kg bw endotoxin via a permanent jugular vein cannula. Of these rats, 6 were treated with SOD both

  17. Expression and localization of IL-18 in the hypothalamic-pituitary-ovarian axis of non-pregnant, pregnant, and abortive rats.

    Science.gov (United States)

    Wang, Yuesi; Zhang, Xiuli; Zhang, Yan; Xu, Hui; Fang, Guangli

    2011-12-01

    Cytokines present in the reproductive system play an important role both in the modulation of immune responses to infectious challenge and in the establishment and maintenance of pregnancy. Interleukin 18 (IL-18) has been regarded as an important regulator of innate and acquired immune response, but its expression and distribution in the hypothalamic-pituitary-ovarian axis remain unclear. In this paper, the expression and distribution of IL-18 in non-pregnant, pregnant, and early abortive rats were examined using an ultra-sensitive immunohistochemical streptavidin-peroxidase method, enzyme-linked immunosorbent assay, and reverse transcription-polymerase chain reaction. The results showed that IL-18 expression in the pituitary, in follicular ovaries, and in the corpus luteum of abortive rats were significantly lower than that of pregnant and non-pregnant rats. However, the staining of IL-18 in the hypothalamus, interstitial glands of the ovary, and uterus of abortive rats was strikingly stronger than those of the non-pregnant ones. IL-18 mRNA expression in rat uterus was detected in all groups, whereas IL-18 mRNA content in abortive rat uterus was significantly higher than in normal pregnant rats. Further, IL-18 in the peripheral blood serum of abortive rats was significantly lower than in same-period normal pregnant rats. The differential expression of IL-18 in early abortion suggests that IL-18 may be related to the underlying mechanisms of abortion.

  18. MORPHOLOGICAL STUDIES OF OVARY AND UTERUS OF EARLY PREGNANT RATS AND WOMEN TREATED WITH MIFEPRISTONE

    Institute of Scientific and Technical Information of China (English)

    CHENWen-Jian; ZHANGLong-Sheng; YANGXin-Li; SHENGJi-Yun; ZHOUJie-Ling; WUXi-Rui

    1989-01-01

    In this paper, morphological studies of uterus and ovary during terminating early pregnancy with mifcpristonc Were reported. In the experimental studies, 24 hrs after inhering 10 mg / kg mifcpristonc to early pregnant rats, all embryos wcrc dead, with decidual cells

  19. PRELIMINARY INVESTIGATION ON THE BETA-ADRENO RECEPTORSINNONPREGNANT AND PREGNANT RAT UTERUS

    Institute of Scientific and Technical Information of China (English)

    SHENZhi-Fang; CHENZhi-Chong

    1989-01-01

    The effects of bcta-advenoreceptor agonist isoprenaline on 138 nonpregnant, pregnant and postpartum rat uterus in vitro were observed. The adrenoreceptor response in estrus appeared to be stronger than in diestrus, but not statistically significant, and that in preg-

  20. Interleukin (IL)-1 in rat parturition: IL-1 receptors 1 and 2 and accessory proteins abundance in pregnant rat uterus at term - regulation by progesterone.

    Science.gov (United States)

    Ishiguro, Tomohito; Takeda, Jun; Fang, Xin; Bronson, Heather; Olson, David M

    2016-07-01

    The role of interleukin-1 (IL-1), a pro-inflammatory cytokine, in parturition is typically noted by changes in its concentrations. Studying the expression of its receptor family, IL-1 receptor (IL-1R) 1, IL-1R2, IL-1R accessory protein (IL-1RAcP), and its predominantly brain isoform, IL-1RAcPb, during late gestation in the uterus in the Long-Evans rat is another. We assessed changes in their mRNA and protein relative abundance in the uterus and compared IL-1RAcP and IL-1RAcPb mRNA abundance in uterus, cervix, ovaries, placenta, and whole blood of Long-Evans rats during late gestation or in RU486 and progesterone-treated dams using quantitative real-time PCR and western immunoblotting. IL-1R1, IL-1RAcP, and IL-1RAcPb mRNA abundance significantly increased in the uterus at delivery whereas IL-1R2 mRNA abundance significantly decreased. IL-1R1 protein increased at term and IL-1R2 protein decreased at term compared to nonpregnant uteri. IL1-RAcPb mRNA abundance was less than IL-1RAcP, but in the lower uterine segment it was the highest of all tissues examined. RU486 stimulated preterm delivery and an increase in IL-1R1 mRNA abundance whereas progesterone administration extended pregnancy and suppressed the increase in IL-1R1. These data suggest that changes in uterine sensitivity to IL-1 occur during late gestation and suggest another level of regulation for the control of delivery. The roles for IL-1RAcP and IL-1RAcPb need to be determined, but may relate to different intracellular signaling pathways.

  1. The effect of Bromelia pinguin extract on the pregnant rat uterus.

    Science.gov (United States)

    Matadial, L; West, M E; Gossell-Williams, M; The, T L

    1999-12-01

    A non proteinaceous extract of Bromelia pinguin fruit was examined for activity on the rat uterus in vivo and in vitro. The in vivo experiments involved pregnant rats given the extract intraperitoneally. These rats did not abort nor were any foetal deformities observed. The extract inhibited spontaneous activity of the pregnant rat uterus in vitro. These results do not support the claimed folklore use of the plant as an abortifacient. The extract of Bromelia pinguin fruit may have some utero-active compound which inhibits uterine motility.

  2. Comparative analysis of two different models of swimming applied to pregnant rats born small for pregnant age

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    SILVANA B. CORVINO

    Full Text Available ABSTRACT The aim of this study was to compare two models of swimming applied to pregnant rats born small for pregnancy age (SPA. Diabetes was chemically induced in adult female rats to develop an inadequate intrauterine environment, leading to birth of a SPA offspring. In adulthood, the female SPA rats were mated and submitted to different swimming programs. The exercise program 1 (Ex1 consisted of swimming for 15 minutes, followed by 15 minutes of rest and another 15 minutes of swimming, 3 days a week before and during pregnancy. Another program (Ex2 was applied during 60 minutes uninterrupted a day, 6 days/week during pregnancy. The pregnant rats presented no interference on body weight and glycemia. The rats submitted to Ex2 model showed decreased insulin and blood glucose levels by oral glucose tolerance test, and reduction in area under curve values. The offspring from dams submitted to both exercise protocols presented an increased rate of newborns SPA. However, the offspring from Ex2 dams showed percentage twice higher of newborns SPA than Ex1 offspring. Our data suggests that continuous exercise of 60 min/day ameliorated the enhanced peripheral insulin sensitivity in growth-restricted females. However, this protocol employed at pregnancy leads to intrauterine growth restriction.

  3. Comparative analysis of two different models of swimming applied to pregnant rats born small for pregnant age.

    Science.gov (United States)

    Corvino, Silvana B; Damasceno, Débora C; Sinzato, Yuri K; Netto, Aline O; Macedo, Nathália C D; Zambrano, Elena; Volpato, Gustavo T

    2017-01-01

    The aim of this study was to compare two models of swimming applied to pregnant rats born small for pregnancy age (SPA). Diabetes was chemically induced in adult female rats to develop an inadequate intrauterine environment, leading to birth of a SPA offspring. In adulthood, the female SPA rats were mated and submitted to different swimming programs. The exercise program 1 (Ex1) consisted of swimming for 15 minutes, followed by 15 minutes of rest and another 15 minutes of swimming, 3 days a week before and during pregnancy. Another program (Ex2) was applied during 60 minutes uninterrupted a day, 6 days/week during pregnancy. The pregnant rats presented no interference on body weight and glycemia. The rats submitted to Ex2 model showed decreased insulin and blood glucose levels by oral glucose tolerance test, and reduction in area under curve values. The offspring from dams submitted to both exercise protocols presented an increased rate of newborns SPA. However, the offspring from Ex2 dams showed percentage twice higher of newborns SPA than Ex1 offspring. Our data suggests that continuous exercise of 60 min/day ameliorated the enhanced peripheral insulin sensitivity in growth-restricted females. However, this protocol employed at pregnancy leads to intrauterine growth restriction.

  4. Brain cell apoptosis and enhancement of nervous excitability in pregnant rats with high plasma levels of homocysteine☆

    OpenAIRE

    Wang, Jun; Ge, Jing; YANG, Liu; Zhang, Haiyan; Li, Xuli; Xue, Dan

    2012-01-01

    Hyperhomocysteinemia is an important risk factor for preeclampsia-eclampsia. This study established a pregnant rat model of hyperhomocysteinemia, in which blood plasma homocysteine concentrations were twice or three times greater than that of normal pregnant rats. TUNEL revealed an increase in the number of apoptotic cells in the frontal cortex of pregnant rats with hyperhomocysteinemia. In addition, immunohistochemical staining detected activated nuclear factor-κB-positve cells in the fronta...

  5. Mu opioid modulation of oxytocin secretion in late pregnant and parturient rats. Involvement of noradrenergic neurotransmission.

    Science.gov (United States)

    Kutlu, Selim; Yilmaz, Bayram; Canpolat, Sinan; Sandal, Suleyman; Ozcan, Mete; Kumru, Selahattin; Kelestimur, Haluk

    2004-01-01

    We have investigated effects of micro- and kappa-opioid agonists and antagonists on plasma oxytocin levels and noradrenaline content in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of 20-day pregnant rats. beta-Endorphin, oxytocin, estrogen and progesterone profiles in late pregnant and parturient rats were also sought. Stage of estrous cycle was monitored by vaginal smear, and pro-estrous animals were left overnight with male. In the first set of experiments, pregnant rats were monitored and decapitated on days 20 and 21 and after the delivery of second pup. In the second set, 20-day pregnant rats were intracerebroventricularly infused with morphine (50 microg/10 microl), U50,488H (kappa-agonist; 50 microg/10 microl), clocinnamox (micro-antagonist; 50 microg/10 microl) and norbinaltorphimine (kappa-antagonist; 50 microg/10 microl). Controls received saline alone. Serum estrogen and progesterone levels were measured by enzyme immunoassay, and plasma oxytocin and beta-endorphin by radioimmunoassay. Noradrenaline and its metabolite (3,4-dihydroxyphenylglycol) were determined in micropunched hypothalamic nuclei by HPLC-ECD. In parturient rats, oxytocin levels were increased (p oxytocin levels (p oxytocin secretion. We suggest that noradrenaline may mediate the inhibitory effects of micro-opioids on oxytocin release. Our findings have also shown that kappa-opioid receptors are not involved in modulation of oxytocin neurons in late pregnant rats. Copyright 2004 S. Karger AG, Basel

  6. Corticosterone treatment of pregnant low dose endotoxin-treated rats : Inhibition of the inflammatory response

    NARCIS (Netherlands)

    Faas, MM; Slot, K; Koiter, TR; Schuiling, GA

    2000-01-01

    PROBLEM: Can the endotoxin-induced inflammatory response, underlying experimental pre-eclampsia, in pregnant rats be inhibited by corticosterone? METHOD OF STUDY: On day 10 of pregnancy, rats were implanted with pellets containing 25% corticosterone and 75% cholesterol (n = 10) or with 100% choleste

  7. Effects of L-NAME on morphometric parameters of stomach parietal cells in pregnant rats

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    Seyed Mohammad Hossein Noori Mugahi

    2014-05-01

    Results: Results of this study after analysis showed the significant changes in parietal cells count (mean 61.3±4.32 and its diameters (mean 16.12±1.18 µm in L-NAME group in comparison to control and the sham groups in pregnant rats (P≤0.05. Conclusion: Results of this study showed L-NAME with effects on NO synthesis can reduce the count of parietal cells and increase its diameter in pregnant rats and has destructive effects on structure of stomach parietal cells in pregnancy rats.

  8. Effect of transverse aortic constriction on cardiac structure, function and gene expression in pregnant rats.

    Directory of Open Access Journals (Sweden)

    Nils Thomas Songstad

    Full Text Available BACKGROUND: There is an increased risk of heart failure and pulmonary edema in pregnancies complicated by hypertensive disorders. However, in a previous study we found that pregnancy protects against fibrosis and preserves angiogenesis in a rat model of angiotensin II induced cardiac hypertrophy. In this study we test the hypothesis that pregnancy protects against negative effects of increased afterload. METHODS: Pregnant (gestational day 5.5-8.5 and non-pregnant Wistar rats were randomized to transverse aortic constriction (TAC or sham surgery. After 14.2 ± 0.14 days echocardiography was performed. Aortic blood pressure and left ventricular (LV pressure-volume loops were obtained using a conductance catheter. LV collagen content and cardiomyocyte circumference were measured. Myocardial gene expression was assessed by real-time polymerase chain reaction. RESULTS: Heart weight was increased by TAC (p<0.001 but not by pregnancy. Cardiac myocyte circumference was larger in pregnant compared to non-pregnant rats independent of TAC (p = 0.01, however TAC per se did not affect this parameter. Collagen content in LV myocardium was not affected by pregnancy or TAC. TAC increased stroke work more in pregnant rats (34.1 ± 2.4 vs 17.5 ± 2.4 mmHg/mL, p<0.001 than in non-pregnant (28.2 ± 1.7 vs 20.9 ± 1.5 mmHg/mL, p = 0.06. However, it did not lead to overt heart failure in any group. In pregnant rats, α-MHC gene expression was reduced by TAC. Increased in the expression of β-MHC gene was higher in pregnant (5-fold compared to non-pregnant rats (2-fold after TAC (p = 0.001. Nine out of the 19 genes related to cardiac remodeling were affected by pregnancy independent of TAC. CONCLUSIONS: This study did not support the hypothesis that pregnancy is cardioprotective against the negative effects of increased afterload. Some differences in cardiac structure, function and gene expression between pregnant and non-pregnant rats following TAC indicated that

  9. Selenium-vitamin E combination and melatonin modulates diabetes-induced blood oxidative damage and fetal outcomes in pregnant rats.

    Science.gov (United States)

    Guney, Mehmet; Erdemoglu, Evrim; Mungan, Tamer

    2011-11-01

    Oxidative stress is considered to be the main cause of diabetic complications. In the current study, we investigated the effect of selenium-vitamin E combination and melatonin on lipid peroxidation (LPO) and scavenging enzyme activity in the blood of streptozocin (STZ)-induced diabetic pregnant rats. Forty female Wistar rats were randomly divided into five groups. The first and second groups were used as the non-pregnant control and pregnant control groups, respectively. The third group was the pregnant diabetic group. Vitamin E plus selenium and melatonin were administered to the diabetic pregnant rats consisting fourth and fifth groups, respectively. Diabetes was induced on day 0 of the study by STZ. Blood samples were taken from all animals on the 20th day of pregnancy. LPO level was higher in diabetic pregnant rats than in control, although superoxide dismutase, catalase, and glutathione peroxidase activities were lower in diabetic pregnant animals than in control. LPO levels were lower both in the two treatment groups than in the diabetic pregnant rats, whereas selenium-vitamin E combination and melatonin caused a significant increase in the activities of these antioxidant enzymes (pmelatonin in diabetic pregnant rats. Melatonin did not significantly affect the elevated glucose concentration of diabetic pregnant treated with melatonin group. Vitamin E plus selenium may play a role in preventing diabetes-related diseases of pregnant subjects.

  10. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

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    de Mello Maria

    2002-04-01

    Full Text Available Abstract Background It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. Methods To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein: pregnant (N, tumor-bearing (WN, pair-fed rats (Np. Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine: leucine (L, tumor-bearing (WL and pair-fed with leucine (Lp. Non pregnant rats (C, which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Results Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Conclusions Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones.

  11. Dysregulation of dimethylargininedimethylaminohydrolase/asymmetric dimethylarginine pathway in rat type II diabetic nephropathy.

    Science.gov (United States)

    Lai, Ying-Ling; Aoyama, Sae; Ohata, Miyuki; Otsuka, Nami; Shiokawa, Hidemi; Tomono, Susumu; Fujiwara, Yukio; Kanazawa, Hiroaki; Miyoshi, Noriyuki; Ohshima, Hiroshi

    2012-09-01

    An impaired generation of nitric oxide has been associated with diabetic renal disease. In order to elucidate the underlying molecular mechanisms into how nitric oxide synthesis is impaired in diabetic renal disease, we examined changes in activities and expressions of some renal enzymes involved in nitric oxide production during the development of diabetic nephropathy in type II diabetic Otsuka Long-Evans Tokushima Fatty rats. Ten-week old Otsuka Long-Evans Tokushima Fatty (n = 40) and control Long-Evans Tokushima Otsuka rats (n = 20) were given drinking water containing 20% sucrose to accelerate the development of diabetic nephropathy. Otsuka Long-Evans Tokushima Fatty rats developed diabetic nephropathy in an age-dependent manner. Renal nitric oxide synthase activities in Otsuka Long-Evans Tokushima Fatty rats gradually declined with the progression of diabetic mellitus and were significantly lower than those of age-matched Long-Evans Tokushima Otsuka rats after 22 weeks of age. The lower activities of renal nitric oxide synthase in Otsuka Long-Evans Tokushima Fatty rats were correlated with relatively higher levels of renal free asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, and were also correlated with decreased activities of dimethylargininedimethylaminohydrolase which metabolizes asymmetric dimethylarginine to citrulline. These results imply that dimethylargininedimethylaminohydrolase dysregulation may play an important role in the development of diabetic nephropathy by increasing asymmetric dimethylarginine levels, which leads to inhibition of renal nitric oxide synthesis.

  12. Dysregulation of dimethylargininedimethylaminohydrolase/asymmetric dimethylarginine pathway in rat type II diabetic nephropathy

    Science.gov (United States)

    Lai, Ying-Ling; Aoyama, Sae; Ohata, Miyuki; Otsuka, Nami; Shiokawa, Hidemi; Tomono, Susumu; Fujiwara, Yukio; Kanazawa, Hiroaki; Miyoshi, Noriyuki; Ohshima, Hiroshi

    2012-01-01

    An impaired generation of nitric oxide has been associated with diabetic renal disease. In order to elucidate the underlying molecular mechanisms into how nitric oxide synthesis is impaired in diabetic renal disease, we examined changes in activities and expressions of some renal enzymes involved in nitric oxide production during the development of diabetic nephropathy in type II diabetic Otsuka Long-Evans Tokushima Fatty rats. Ten-week old Otsuka Long-Evans Tokushima Fatty (n = 40) and control Long-Evans Tokushima Otsuka rats (n = 20) were given drinking water containing 20% sucrose to accelerate the development of diabetic nephropathy. Otsuka Long-Evans Tokushima Fatty rats developed diabetic nephropathy in an age-dependent manner. Renal nitric oxide synthase activities in Otsuka Long-Evans Tokushima Fatty rats gradually declined with the progression of diabetic mellitus and were significantly lower than those of age-matched Long-Evans Tokushima Otsuka rats after 22 weeks of age. The lower activities of renal nitric oxide synthase in Otsuka Long-Evans Tokushima Fatty rats were correlated with relatively higher levels of renal free asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, and were also correlated with decreased activities of dimethylargininedimethylaminohydrolase which metabolizes asymmetric dimethylarginine to citrulline. These results imply that dimethylargininedimethylaminohydrolase dysregulation may play an important role in the development of diabetic nephropathy by increasing asymmetric dimethylarginine levels, which leads to inhibition of renal nitric oxide synthesis. PMID:22962534

  13. Utilidad de la Técnica de inmunofluorescencia indirecta en ratas Long Evans nutridas, desnutridas, infectadas con T. spiralis e inmunizadas con el inmunógeno de 45kDa

    Directory of Open Access Journals (Sweden)

    M. en C. José Jesús Muñoz Escobedo

    2011-02-01

    Full Text Available ResumenLa Trichinellosis es una zoonosis endémica, cosmopolita, sus huéspedes son: rata, cerdo y otros mamíferos entre ellos el hombre, la presencia de Trichinellosis se debe a la ingestión de carne de cerdo insuficientemente cocida, afecta a países con bajos recursos económicos. Se han caracterizado Inmunógenos, siendo el inmunodominante el de 45 kDa, efectivo contra T. spiralis, Se han descrito efectos de desnutrición (DN sobre órganos linfáticos. Los mecanismos de defensa del huésped son alterados con DN proteico-calórico (DPC.SummaryThe Trichinellosis is an endemic zoonosis, which cosmopolitan guests are: rat, pig and other mammals including humans. Immunogens have beencharacterized, with the inmunodominant of 45kDa, effective against T.spiralis. Have described effects of malnutrition on lymphatic organs. The host's defense mechanisms are altered by caloric DN protein (DCP.Objective: To evaluate the indirect immunofluorescence technic in LongEvans rats and DN OUR infected immunized with T. spiralis and theimmunogenicity of 45 kDa.

  14. INHIBITION OF BRAIN CHOLINESTERASE AND THE PHOTIC AFTER DISCHARGE OF FLASH EVOKED POTENTIALS PRODUCED BY CARBARYL IN LONG EVANS RATS.

    Science.gov (United States)

    Carbaryl is a widely used N-methyl carbamate pesticide that acts by inhibiting cholinesterases (ChE), which may lead to cholinergic toxicity. Flash evoked potentials (FEPs) are a neurophysiological response often used to detect central nervous system (CNS) changes following expos...

  15. Effects of Exercise Training and Social Environment on Stress Resilience in Male and Female Long-Evans Rats

    Science.gov (United States)

    2010-03-15

    dysfunction. American Journal of Cardiology , 95, 322-326. Alleva, E., & Santucci, D. (2001). Psychosocial vs. “physical” stress situations in rodents and...alleviation of learned helplessness in dogs . Journal of Abnormal Psychology, 73, 256-262. Selye, H. (1946). The general adaptation syndrome and the

  16. Acute and subchronic toxicity of inhaled toluene in male Long Evans rats: oxidative stress markers in brain

    Data.gov (United States)

    U.S. Environmental Protection Agency — Research interested in oxidative stress markers following exposure to VOCs. This dataset is associated with the following publication: Kodavanti , P., J. Royland ,...

  17. Stress facilitates late reversal learning using a touchscreen-based visual discrimination procedure in male Long Evans rats

    OpenAIRE

    Bryce, Courtney A.; Howland, John G.

    2014-01-01

    The stress response is essential to the survival of all species as it maintains internal equilibrium and allows organisms to respond to threats in the environment. Most stress research has focused on the detrimental impacts of stress on cognition and behavior. Reversal learning, which requires a change in response strategy based on one dimension of the stimuli, is one type of behavioral flexibility that is facilitated following some brief stress procedures. The current study investigated a po...

  18. Acute and Subchronic Toxicity of Inhaled Toluene in Male Long-Evans Rats: Oxidative Stress Markers in Brain

    Science.gov (United States)

    The effects of exposure to volatile organic compounds (VOCs), which are of concern to the EPA, are poorly understood, in part because of insufficient characterization of how human exposure duration impacts VOC effects. Two inhalation studies with multiple endpoints, one acute an...

  19. Acute and Subchronic Toxicity of Inhaled Toluene in Male Long-Evans Rats: Oxidative Stress Markers in Brain

    Science.gov (United States)

    The effects of exposure to volatile organic compounds (VOCs), which are of concern to the EPA, are poorly understood, in part because of insufficient characterization of how human exposure duration impacts VOC effects. Two inhalation studies with multiple endpoints, one acute an...

  20. Effect of obesity on the acute inflammatory response in pregnant and cycling female rats.

    Science.gov (United States)

    Pohl, J; Luheshi, G N; Woodside, B

    2013-05-01

    Nonpregnant female rats have a lower inflammatory response to lipopolysaccharide (LPS) than males and, at late stages of gestation, the fever response to this immunogen is almost completely suppressed. We have shown in males that obesity exacerbates sickness responses to pathogenic stimuli. In the present study, we investigated whether obesity would have a similar effect in females and reverse some of the suppressive effects of pregnancy on the innate immune response. Lean and diet-induced obese adult Wistar rats were randomly separated into either cycling or mated groups. On day 18 of pregnancy or in the metestrous/dioestrous phase in cycling rats, a single injection of LPS (100 μg/kg) was administered and rats were sacrificed 8h or 24 h later. In pregnant females, LPS induced a higher increase in body temperature in obese rats only at the 24-h time point and lower hypothalamic interleukin (IL)-1β expression and higher circulating levels of IL-1 receptor antagonist (ra) than their cycling counterparts. Conversely, there was no suppression of inflammatory signals in the white adipose tissue of pregnant rats. At 24 h post LPS, the cell surface marker CD11c and IL-6 mRNA expression were increased in white adipose tissue from obese rats regardless of reproductive state, whereas IL-1ra was highest in the LPS-treated obese pregnant group. In cycling females, LPS induced a higher fever response in obese rats accompanied by higher circulating levels of IL-6 and IL-1ra, as well as an increase in circulating leptin only in the obese cycling group. In the hypothalamus, obese rats showed significantly higher expression of nuclear factor-IL-6 in at the 8-h time point. Collectively, these results show that diet-induced obesity in females is associated with a similar pattern of response to that previously observed in males. On the other hand, obesity had limited effects in pregnant rats, with the exception of white adipose tissue.

  1. Zinc influences on brain development, pituitary an thyroidfunction iniodine-deficient pregnant and neonatal rats

    Institute of Scientific and Technical Information of China (English)

    Xiaoxia Yang; Jianchao Bian; Xin Wang; Haiming Wang; Yongping Liu; Shuzhen Wang; Zhichun Mu; Xinluan Li

    2008-01-01

    BACKGROUND: Zinc (Zn) has been shown to greatly influence brain development. Zn supplements may reduce injury to cell membranes of the thyroid gland due to iodine deficiency. OBJECTIVE: To establish an iodine deficiency rat model using low-iodine food, which was supplemented with compound Zn and Zn gluconate, to observe the effects of Zn on brain development, as well as pituitary gland and thyroid gland function in iodine-deficient rats. DESIGN, TIME AND SETTING: Randomized grouping study of neural development was performed in the central laboratory of Shandong Institute for Prevention and Treatment of Endemic Disease from 1998 to 1999. MATERIALS: A total of 270 Wistar, female rats, one month after weaning, were used in this study, including 150 pregnant and 120 neonatal rats. Rats were randomly divided into six groups: normal control, model, iodine, compound Zn, iodine and compound Zn, and zinc gluconate. Each group contained 25 pregnant rats and 20 nenoatal rats. METHODS: The pregnant rats and 20 neonatal rats, and well as the normal group, were fed standard chow and allowed free access to tap water (containing 5 μ g/L iodine and 1 mg/L Zn). The remaining five groups were fed low-iodine chow. However, the model group received distilled water, the iodine group received potassium-iodide distilled water (containing 300 μ g/L iodine), the compound Zn group received distilled water and intragastrically administrated 10 mL/kg compound Zn solution, once per day, the iodine and compound Zn group received distilled water with 300 p g/L iodine and intragastrically administrated 10 mL/kg compound Zn solution, once per day. All treatments lasted 90 days. MAIN OUTCOME MEASURES: All pregnant rats were sacrificed on the day 21 of pregnancy. Body mass, number and rate of fetal absorption, as well as fetal death and malformation, were determined. Thyroid and pituitary gland weights were measured, as well as serum levels of thyroid hormone, gonadotropin, and sex hormones. In the

  2. Hypothyroid state reduces calcium channel function in 18-day pregnant rat uterus.

    Science.gov (United States)

    Parija, S C; Mishra, S K; Raviprakash, V

    2006-01-01

    Hypothyroidism significantly reduced the mean amplitude and increased the mean frequency of spontaneous rhythmic contractions in 18 day pregnant rat uterus. Nifedipine (10(-12)-10(-9) M) and diltiazem (10(-10)-10(-6) M) caused concentration related inhibition of the myogenic responses of the uterine strips obtained from both pregnant and hypothyroid state. However, nifedipine was less potent (IC50:2.11 x 10(-11) M) in pregnant hypothyroid state as compared to pregnant control (IC50: 3.1 x 10(-12) M). Similarly, diltiazem was less potent (IC50: 3.72 x 10(-9) M) in inhibiting the uterine spontaneous contractions in hypothyroid than in pregnant rat uterus (IC50:5.37 x 10(-10) M). A similar decrease in the sensitivity to nifedipine and diltiazem for reversal of K+ (100 mM)-induced tonic contraction and K(+)-stimulated 45Ca2+ influx was observed with these calcium channel antagonists in uterus obtained from hypothyroid pregnant rats compared to the controls. Nifedipine-sensitive influx of 45Ca(2+)-stimulated either by K+ (100 mM) or by Bay K8644 (1,4-dihydro-2,6-methyl-5-nitro-4-[2'-(trifluromethyl)phenyl]-3-pyridine carboxylic acid methyl ester) (10(-9) M) was significantly less in uterine strips from hypothyroid rats compared to controls. The results suggest that the inhibition of uterine rhythmic contractions may be attributable to a reduction in rat myometrial Ca2+ channel function in the hypothyroid state.

  3. Cadmium toxicity to the cornea of pregnant rats: Electron microscopy and x-ray microanalysis

    Energy Technology Data Exchange (ETDEWEB)

    Yoshizuka, M.; McCarthy, K.J.; Kaye, G.I.; Fujimoto, S. (Univ. of Occupational and Environmental Health, School of Medicine, Kitakyushu (Japan))

    1990-05-01

    Cadmium toxicity to the cornea of pregnant rats was studied using the electron microscope and x-ray microanalyzer. In in-vivo experiments, severe corneal edema occurred in pregnant dams that received intraperitoneal injections of cadmium sulphate for 4 days during gestation, but not in nonpregnant rats. Prominent swelling of mitochondria and the occurrence of intra- and intercellular vacuoles in the corneal endothelium were observed only in pregnant dams. In in-vitro experiments, electron-dense deposits consisting of cadmium-oxine complexes were preferentially found in swollen mitochondria of the endothelial cells. Cadmium peaks were obtained from these deposits with x-ray microanalysis. These data suggest that the corneal edema observed after administration of cadmium may imply the disturbance of pump function and barrier function of the corneal endothelium due to the primary toxic effects of this metal on mitochondria.

  4. Treatment of pregnant rats with oleoyl-estrone slows down pup fat deposition after weaning

    Directory of Open Access Journals (Sweden)

    Vilà Ruth

    2008-06-01

    Full Text Available Abstract Background In rats, oral oleoyl-estrone (OE decreases food intake and body lipid content. The aim of this study was to determine whether OE treatment affects the energy metabolism of pregnant rats and eventually, of their pups; i.e. changes in normal growth patterns and the onset of obesity after weaning. Methods Pregnant Wistar rats were treated with daily intragastric gavages of OE in 0.2 ml sunflower oil from days 11 to 21 of pregnancy (i.e. 10 nmol oleoyl-estrone/g/day. Control animals received only the vehicle. Plasma and hormone metabolites were determined together with variations in cellularity of adipose tissue. Results Treatment decreased food intake and lowered weight gain during late pregnancy, mainly because of reduced adipose tissue accumulation in different sites. OE-treated pregnant rats' metabolic pattern after delivery was similar to that of controls. Neonates from OE-treated rats weighed the same as those from controls. They also maintained the same growth rate up to weaning, but pups from OE-treated rats slowed their growth rate afterwards, despite only limited differences in metabolite concentrations. Conclusion The OE influences on pup growth can be partially buffered by maternal lipid mobilization during the second half of pregnancy. This maternal metabolic "imprinting" may condition the eventual accumulation of adipose tissue after weaning, and its effects can affect the regulation of body weight up to adulthood.

  5. METABOLISM OF PREGNANT-LACTATING RATS IS ADAPTED TO PREGNANCY RATHER THAN TO LACTATION

    NARCIS (Netherlands)

    WIJKSTRA, S; MOES, H; KOITER, TR

    1992-01-01

    In pregnant-lactating rats implantation was induced on day 4 of lactation so that, as an exception, lactation coincided with the period of high fetal growth. The already present suckling litters of these animals lagged behind in growth, but the "second" litters were at birth normal in size and weigh

  6. Endotoxin Treatment of Pregnant Rats Affects Sexual Behavior of the Male Offspring

    NARCIS (Netherlands)

    Wijkstra, S.; Valkhof, N.; Koolhaas, J.M.; Schuiling, G.A.

    1991-01-01

    The offspring of endotoxin-infused pregnant rats (0.2 µg endotoxin, 53.3 min, day 18 of pregnancy) did not exhibit different behavior in the Hebb-Williams-type maze test, but the males showed aberrations in the sexual behavior test. Because endotoxin did not cross the placental barrier, it was concl

  7. Differential expression of uterine NO in pregnant and nonpregnant rats with intrauterine bacterial infection.

    Science.gov (United States)

    Fang, L; Nowicki, B; Yallampalli, C

    2001-05-01

    Previous studies have demonstrated that nitric oxide (NO) is involved in the uterine host defense against bacterial infection. In nonpregnant rats, NO production in the uterus was shown to be lower, and inducible NO synthase (NOS) expression was undetectable. However, studies in pregnant rats show abundant expression of inducible NOS with significant elevation in NO production in the uterus. We have recently reported that intrauterine Escherichia coli infection caused a localized increase in uterine NO production and inducible NOS expression in the nonpregnant rat. In our present study, we examined whether the uterine NO production, NOS expression, and uterine tumor necrosis factor-alpha protein are increased in pregnant rats with intrauterine pathogenic Escherichia coli infection. Unlike the nonpregnant state, the NO production in the infected uterine horn of pregnant rats was not significantly elevated after bacterial inoculation compared with the contralateral uterine horn. The expression of uterine NOS (types II and III) also did not show significant upregulation in the infected horn. This is in contrast to that in nonpregnant animals, in which type II NOS was induced in the uterus on infection. Moreover, intrauterine infection induced an elevated expression of tumor necrosis factor-alpha protein in the infected horn both of nonpregnant and of pregnant rats. These data suggest that the sequential stimulation of NOS expression, especially the inducible isoform, and generation of uterine NO are lacking during pregnancy despite an elevated tumor necrosis factor-alpha after infection. In summary, NO synthesis response may be maximal at pregnancy, and infection may not further induce the NO system. Present studies, together with our previous report that intrauterine infection-induced lethality in pregnancy rats was amplified with the inhibition of NO, suggest that pregnancy is a state predisposed for increased complications associated with intrauterine infection and

  8. Effects of perinatal exposure to nonylphenol on delivery outcomes of pregnant rats and inflammatory hepatic injury in newborn rats

    Directory of Open Access Journals (Sweden)

    J. Yu

    Full Text Available The current study aimed to investigate the effects of perinatal exposure to nonylphenol (NP on delivery outcome of pregnant rats and subsequent inflammatory hepatic injury in newborn rats. The pregnant rats were divided into 2 groups: control group (corn oil and NP exposure group. Thirty-four pregnant rats were administered NP or corn oil by gavage from the sixth day of pregnancy to 21 days postpartum, with blood samples collected at 12 and 21 days of pregnancy and 60 days after delivery. The NP concentration was measured by HPLC, with chemiluminescence used for detection of estrogen and progesterone levels. Maternal delivery parameters were also observed. Liver and blood of the newborn rats were collected and subjected to automatic biochemical detection of liver function and blood lipid analyzer (immunoturbidimetry, and ultrastructural observation of the hepatic microstructure, with the TNF-α and IL-1β hepatic tissue levels evaluated by immunohistochemistry. Compared with the control group, the pregnant and postpartum serum NP and estradiol levels of the mother rats in the NP group were significantly increased, together with lowered progesterone level, increased number of threatened abortion and dystocia, and fewer newborn rats and lower litter weight. Serum and hepatic NP levels of the newborn rats measured 60 days after birth were significantly higher than those of the control group, as well as lower testosterone levels and increased estradiol levels. When observed under electron microscope, the hepatocyte nuclei of the control group were large and round, with evenly distributed chromatin. The chromatin of hepatocytes in the NP group presented deep staining of the nuclei, significant lipid decrease in the cytoplasm, and the majority of cells bonded with lysate. The results of immunohistochemistry showed that there was almost no TNF-α or IL-1β expression in the hepatocytes of the control group, while the number of TNF-α-, PCNA-, and IL-1

  9. Effects of perinatal exposure to nonylphenol on delivery outcomes of pregnant rats and inflammatory hepatic injury in newborn rats

    Science.gov (United States)

    Yu, J.; Luo, Y.; Yang, X.F.; Yang, M.X.; Yang, J.; Yang, X.S.; Zhou, J.; Gao, F.; He, L.T.; Xu, J.

    2016-01-01

    The current study aimed to investigate the effects of perinatal exposure to nonylphenol (NP) on delivery outcome of pregnant rats and subsequent inflammatory hepatic injury in newborn rats. The pregnant rats were divided into 2 groups: control group (corn oil) and NP exposure group. Thirty-four pregnant rats were administered NP or corn oil by gavage from the sixth day of pregnancy to 21 days postpartum, with blood samples collected at 12 and 21 days of pregnancy and 60 days after delivery. The NP concentration was measured by HPLC, with chemiluminescence used for detection of estrogen and progesterone levels. Maternal delivery parameters were also observed. Liver and blood of the newborn rats were collected and subjected to automatic biochemical detection of liver function and blood lipid analyzer (immunoturbidimetry), and ultrastructural observation of the hepatic microstructure, with the TNF-α and IL-1β hepatic tissue levels evaluated by immunohistochemistry. Compared with the control group, the pregnant and postpartum serum NP and estradiol levels of the mother rats in the NP group were significantly increased, together with lowered progesterone level, increased number of threatened abortion and dystocia, and fewer newborn rats and lower litter weight. Serum and hepatic NP levels of the newborn rats measured 60 days after birth were significantly higher than those of the control group, as well as lower testosterone levels and increased estradiol levels. When observed under electron microscope, the hepatocyte nuclei of the control group were large and round, with evenly distributed chromatin. The chromatin of hepatocytes in the NP group presented deep staining of the nuclei, significant lipid decrease in the cytoplasm, and the majority of cells bonded with lysate. The results of immunohistochemistry showed that there was almost no TNF-α or IL-1β expression in the hepatocytes of the control group, while the number of TNF-α-, PCNA-, and IL-1β-positive cells

  10. Red blood cell glutathione peroxidase activity in female nulligravid and pregnant rats

    Directory of Open Access Journals (Sweden)

    Martino Guglielmo

    2009-01-01

    Full Text Available Abstract Background The alterations of the glutathione peroxidase enzyme complex system occur in physiological conditions such as aging and oxidative stress consequent to strenuous exercise. Methods Authors optimize the spectrophotometric method to measure glutathione peroxidase activity in rat red blood cell membranes. Results The optimization, when applied to age paired rats, both nulligravid and pregnant, shows that pregnancy induces, at seventeen d of pregnancy, an increase of both reactive oxygen substance concentration in red blood cells and membrane glutathione peroxidase activity. Conclusion The glutathione peroxidase increase in erythrocyte membranes is induced by systemic oxidative stress long lasting rat pregnancy.

  11. Minor pathological changes are induced by naltrexone-poly(DL-lactide) implants in pregnant rats.

    Science.gov (United States)

    Farid, W O; McCallum, D; Tait, R J; Dunlop, S A; Hulse, G K

    2009-12-15

    Oral naltrexone is used to treat alcohol and heroin dependence but is associated with poor patient compliance. Sustained-release preparations have been developed to overcome noncompliance. Many sustained-release preparations are composed of polymers combined with naltrexone. Limited data indicate that polymers induce variable levels of tissue reactivity and that naltrexone may increase this effect. A slow-release subcutaneous naltrexone-poly (DL-lactide) implant is currently being trialed to treat heroin dependence in Western Australia. A minority of women fall pregnant and, although tissue reactivity in nonpregnant humans is relatively minor, detailed chronological data during pregnancy are lacking. Histological changes in pregnant rats were assessed; a single active tablet containing poly[trans-3,6-dimethyl-1,4-dioxyane-2,5-dione] (DL-lactide) loaded with 25 mg of naltrexone was implanted subcutaneously, and tissue response was compared with inactive polymer implantation. Rats were timed mated at 13-26 days postimplant. Tissue assessment up to 75 days by a pathologist showed that naltrexone induced chronic inflammatory response in a dose-dependent manner, although still at a low level. Furthermore, for inactive implants, minimal foreign body reaction and fibrosis, together with low-level inflammation, suggested good long-term biocompatibility. We conclude that the Australian naltrexone-poly(DL-lactide) implant is tolerated in pregnant rats, reinforcing its potential role for managing alcohol and heroin dependence in pregnant humans.

  12. Attenuated neuroendocrine responses to emotional and physical stressors in pregnant rats involve adenohypophysial changes

    Science.gov (United States)

    Neumann, I D; Johnstone, H A; Hatzinger, M; Liebsch, G; Shipston, M; Russell, J A; Landgraf, R; Douglas, A J

    1998-01-01

    The responsiveness of the rat hypothalamo-pituitary-adrenal (HPA) axis and hypothalamo-neurohypophysial system (HNS) to emotional (elevated plus-maze) and physical (forced swimming) stressors and to administration of synthetic corticotrophin-releasing hormone (CRH) was investigated during pregnancy and lactation. In addition to pregnancy-related adaptations at the adenohypophysial level, behavioural responses accompanying the neuroendocrine changes were studied. Whereas basal (a.m.) plasma corticosterone, but not corticotrophin (adrenocorticotrophic hormone; ACTH), levels were increased on the last day (i.e. on day 22) of pregnancy, the stress-induced rise in both plasma hormone concentrations was increasingly attenuated with the progression of pregnancy beginning on day 15 and reaching a minimum on day 21 compared with virgin control rats. A similar attenuation of responses to both emotional and physical stressors was found in lactating rats. Although the basal plasma oxytocin concentration was elevated in late pregnancy, the stress-induced rise in oxytocin secretion was slightly lower in day 21 pregnant rats. In contrast to vasopressin, oxytocin secretion was increased by forced swimming in virgin and early pregnant rats indicating a differential stress response of these neurohypophysial hormones. The blunted HPA response to stressful stimuli is partly due to alterations at the level of corticotrophs in the adenohypophysis, as ACTH secretion in response to CRH in vivo (40 ng kg−1, i.v.) was reduced with the progression of pregnancy and during lactation. In vitro measurement of cAMP levels in pituitary segments demonstrated reduced basal levels of cAMP and a lower increase after CRH stimulation (10 nm, 10 min) in day 21 pregnant compared with virgin rats, further indicating reduced corticotroph responsiveness to CRH in pregnancy. The reduced pituitary response to CRH in late pregnancy is likely to be a consequence of a reduction in CRH receptor binding as

  13. Barrier Effect of Placenta Membrane of Pregnant Rat on Mixed Rare Earth Changle

    Institute of Scientific and Technical Information of China (English)

    周莉; 陈辉; 黄可欣; 李树蕾; 聂毓秀

    2003-01-01

    To assess the potential health risks of mixed rare earths Changle for human embryo, whether it crosses placenta membrane or placenta barrier should be determined. In order to arrive at the aim placenta tissue was observed after contamination with optical and electron microscope to show distribution and destiny of mixed rare earth Changle in placenta tissue. Meanwhile the amount of rare earths in serum of pregnant rat, amniotic fluid and extract of embryo tissue were measured by using Inductively Coupled Plasma-Mass Spectrometer (ICP-MS). The rats were administered to 0.3, 2, 5 and 20 mg*kg-1 mixed rare earths Changle every day, respectively by oral from the 6th to 18th day after pregnancy. The results show that many particles are found in syncytiotrophoblast around capillaries of placental villi in contaminated groups under light microscope, and there are more particles following increased dose. It also was observed that some dense bodies with the envelope in placenta membrane and to difference extent damages the mitochondria crista within syncytiotrophoblast cytoplasm in contaminated groups under transmission electron microscope (TEM). Results of ICP-MS assay indicate that the level of Ce increases with contamination dose in the serum of pregnant rats, and the level of total rare earth element remarkably rises in amniotic fluid and serum of pregnant rats for 20 mg*kg-1 group as compared with the control without change for the other groups.

  14. The glomerular filtration rate during pregnancy : Saline infusion enhances the glomerular filtration rate in the pregnant rat

    NARCIS (Netherlands)

    Faas, MM; Schuiling, GA; Klok, PA; Valkhof, N; Bakker, WW

    1996-01-01

    The glomerular filtration rate (GFR) of pregnant rats is generally believed to exceed non-pregnant values. This notion is primarily based upon standard inulin clearances. However, the inulin clearance requires continuous infusion of inulin usually dissolved in saline. Since saline infusion per se in

  15. Effect of a leucine-supplemented diet on body composition changes in pregnant rats bearing Walker 256 tumor

    National Research Council Canada - National Science Library

    G. Ventrucci; M.A.R. Mello; M.C.C. Gomes-Marcondes

    2001-01-01

    .... Since leucine is one of the principal amino acids used by skeletal muscle for energy, we investigated the changes in body composition of pregnant tumor-bearing rats after a leucine-supplemented diet...

  16. Brain cell apoptosis and enhancement of nervous excitability in pregnant rats with high plasma levels of homocysteine.

    Science.gov (United States)

    Wang, Jun; Ge, Jing; Yang, Liu; Zhang, Haiyan; Li, Xuli; Xue, Dan

    2012-10-05

    Hyperhomocysteinemia is an important risk factor for preeclampsia-eclampsia. This study established a pregnant rat model of hyperhomocysteinemia, in which blood plasma homocysteine concentrations were twice or three times greater than that of normal pregnant rats. TUNEL revealed an increase in the number of apoptotic cells in the frontal cortex of pregnant rats with hyperhomocysteinemia. In addition, immunohistochemical staining detected activated nuclear factor-κB-positve cells in the frontal cortex. Reverse transcription-PCR detected that mRNA expression of the anti-apoptotic gene bcl-2 diminished in the frontal cortex. In situ hybridization and western blotting revealed that N-methyl-D-aspartate receptor 1 mRNA and protein expression was upregulated in the frontal cortex and hippocampus. These results indicate that hyperhomocysteinemia can induce brain cell apoptosis, increase nerve excitability, and promote the occurrence of preeclampsia in pregnant rats.

  17. Brain cell apoptosis and enhancement of nervous excitability in pregnant rats with high plasma levels of homocysteine

    Institute of Scientific and Technical Information of China (English)

    Jun Wang; Jing Ge; Liu Yang; Haiyan Zhang; Xuli Li; Dan Xue

    2012-01-01

    Hyperhomocysteinemia is an important risk factor for preeclampsia-eclampsia.This study established a pregnant rat model of hyperhomocysteinemia,in which blood plasma homocysteine concentrations were twice or three times greater than that of normal pregnant rats.TUNEL revealed an increase in the number of apoptotic cells in the frontal cortex of pregnant rats with hyperhomocysteinemia.In addition,immunohistochemical staining detected activated nuclear factor-κB-positve cells in the frontal cortex.Reverse transcription-PCR detected that mRNA expression of the anti-apoptotic gene bcl-2diminished in the frontal cortex.In situ hybridization and western blotting revealed that N-methyl-D-aspartate receptor 1 mRNA and protein expression was upregulated in the frontal cortex and hippocampus.These results indicate that hyperhomocysteinemia can induce brain cell apoptosis,increase nerve excitability,and promote the occurrence of preeclampsia in pregnant rats.

  18. Brain cell apoptosis and enhancement of nervous excitability in pregnant rats with high plasma levels of homocysteine☆

    Science.gov (United States)

    Wang, Jun; Ge, Jing; Yang, Liu; Zhang, Haiyan; Li, Xuli; Xue, Dan

    2012-01-01

    Hyperhomocysteinemia is an important risk factor for preeclampsia-eclampsia. This study established a pregnant rat model of hyperhomocysteinemia, in which blood plasma homocysteine concentrations were twice or three times greater than that of normal pregnant rats. TUNEL revealed an increase in the number of apoptotic cells in the frontal cortex of pregnant rats with hyperhomocysteinemia. In addition, immunohistochemical staining detected activated nuclear factor-κB-positve cells in the frontal cortex. Reverse transcription-PCR detected that mRNA expression of the anti-apoptotic gene bcl-2 diminished in the frontal cortex. In situ hybridization and western blotting revealed that N-methyl-D-aspartate receptor 1 mRNA and protein expression was upregulated in the frontal cortex and hippocampus. These results indicate that hyperhomocysteinemia can induce brain cell apoptosis, increase nerve excitability, and promote the occurrence of preeclampsia in pregnant rats. PMID:25538740

  19. C-Psilocin tissue distribution in pregnant rats after intravenous administration

    Directory of Open Access Journals (Sweden)

    Francis C.P. Law

    2014-06-01

    Full Text Available Background: Many species of hallucinogenic mushrooms have been found in the genus Psilocybe. The main psychoactive chemicals of Psilocybe mushrooms are psilocin and its phosphoryloxy derivative, psilocybin. In addition to its psychedelic effects, psilocybin is an effective agent to lift the mood of depressed patients with terminal cancers. Objective: To study the dispositional kinetics of 14C-psilocin in pregnant rats after intravenous injection, to calculate tissue dose surrogates i.e., tissue 14C concentration and area under the concentration-time curve using the experimental data, to quantify trans-placental passage of psilocin and/or its metabolites, and to identify new psilocin metabolite(s in rat urine. Methods: A group of 15 pregnant Wistar rats weighing between 0.30-0.36 kg was used in the study. Each rat was given a single dose of 7.5 mg/kg 14C-psilocin i.v. Three rats were randomly selected and sacrificed at 0.5, 1.0, 2.0, 4.0, and 8.0 hr post-dosing. The maternal and fetal tissues were quickly removed and the radioactivity in these tissues determined by liquid scintillation counting. In a separate study, urine samples were collected from 6 male Wistar rats after administering 15 mg/kg of unlabeled psilocin i.p. The urine samples were collected and extracted by chloroform-methanol (9:1 v/v and analyzed using a gas chromatograph/mass spectrometer. Results: 14C-Psilocin crossed the placental barrier of pregnant rats readily after i.v. administration; maternal tissue 14C concentrations were found to be much higher than those in fetal tissues. The areas under the curve for maternal tissues also were much higher than the fetal tissues. In general, maternal tissues could be divided into the fast eliminating organ group, which included the brain (elimination half-life 13 hr. A new psilocin metabolite tentatively identified as dihydroxyindoleacetic acid was found in the urine. Conclusion: Our study showed that psilocin readily crossed the

  20. The effect of morphine consumption on plasma corticosteron concentration and placenta development in pregnant rats

    OpenAIRE

    Masoomeh Kazemi; Hedayat Sahraei; Mahnaz Azarnia; Leila Dehghani; Hossein Bahadoran; Elaheh Tekieh1

    2011-01-01

    Background: Previous studies have shown that morphine consumption during pregnancy may delay embryo development or cause abnormal nervous system function. Objective: The present study focused on the effect of maternal morphine consumption on development of placenta and blood corticosteron concentration in addictive pregnant mothers. Materials and Methods: 24 female rats, 170-200g weight, were used. The experimental groups after pregnancy received an oral dose of 0.05 mg/ml of morphine by tap ...

  1. [Main factors determining the functional state of pregnant rat's uterus].

    Science.gov (United States)

    Khomasuridze, Kh P; Bekaia, T G; Bekaia, G L

    2009-09-01

    In a review article the authors based on the analysis of the literature, conclude that the Calcitonin Gene-Related Peptide (CGRP) inhibits myometrial contractility at the background of the nonselective Nitric Oxide Synthase inhibitor (L-NAME) action. Along with this, there are evidences that in NOS-deficient rats the process of pregnancy proceeds normally. Thus, literature data indicate that CGRP, independently of Nitric Oxide is included in the myometrium relaxing system, which of course does not exclude its joint action with both Nitric Oxide and other relaxing factors. Moreover, according to our data L-Arginine, causes complete inhibition of spontaneous contractile activity of the rats' myometrial strips, but the administration of L-NAME, eliminates the inhibitory effect - contractile activity was restored.

  2. Adaptive plasticity of vaginal innervation in term pregnant rats.

    Science.gov (United States)

    Liao, Zhaohui; Smith, Peter G

    2011-12-01

    Changes in reproductive status place varied functional demands on the vagina. These include receptivity to male intromission and sperm transport in estrus, barrier functions during early pregnancy, and providing a conduit for fetal passage at parturition. Peripheral innervation regulates vaginal function, which in turn may be influenced by circulating reproductive hormones. We assessed vaginal innervation in diestrus and estrus (before and after the estrous cycle surge in estrogen), and in the early (low estrogen) and late (high estrogen) stages in pregnancy. In vaginal sections from cycling rats, axons immunoreactive for the pan-neuronal marker protein gene product 9.5 (PGP 9.5) showed a small reduction at estrus relative to diestrus, but this difference did not persist after correcting for changes in target size. No changes were detected in axons immunoreactive for tyrosine hydroxylase (sympathetic), vesicular acetylcholine transporter (parasympathetic), or calcitonin gene-related peptide and transient receptor potential vanilloid type 1 (TRPV-1; sensory nociceptors). In rats at 10 days of pregnancy, innervation was similar to that observed in cycling rats. However, at 21 days of pregnancy, axons immunoreactive for PGP 9.5 and each of the subpopulation-selective markers were significantly reduced both when expressed as percentage of sectional area or after correcting for changes in target size. Because peripheral nerves regulate vaginal smooth muscle tone, blood flow, and pain sensitivity, reductions in innervation may represent important adaptive mechanisms facilitating parturition.

  3. Prostaglandin F receptor expression in intrauterine tissues of pregnant rats

    Science.gov (United States)

    Kanca, Halit; Yar, Atiye Seda; Helvacioğlu, Fatma; Menevşe, Sevda; Çalgüner, Engin; Erdoğan, Deniz

    2014-01-01

    In this investigation, we studied the expression and localization of rat prostaglandin F (FP) receptor in uterine tissues of rats on gestational Days 10, 15, 18, 20, 21, 21.5 and postpartal Days 1 and 3 using Western blotting analysis, real-time PCR, and immunohistochemistry. A high level of immunoreactivity was observed on gestational Days 20, 21, and 21.5 with the most significant signals found on Day 20. FP receptor protein was expressed starting on gestational Day 15, and a fluctuating unsteady increase was observed until delivery. Uterine FP receptor mRNA levels were low between Days 10 and 18 of gestation (p < 0.05). The transcript level increased significantly on Day 20 and peaked on Day 21.5 just before labor (p < 0.05). There was a positive correlation between FP receptor mRNA expression and serum estradiol levels (rs = 0.78; p < 0.01) along with serum estradiol/progesterone ratios (rs = 0.79; p < 0.01). In summary, we observed an increase FP receptor expression in rat uterus with advancing gestation, a marked elevation of expression at term, and a concominant decrease during the postpartum period. These findings indicate a role for uterine FP receptors in the mediation of uterine contractility at term. PMID:24136214

  4. The effect of potassium channel opener pinacidil on the non-pregnant rat uterus.

    Science.gov (United States)

    Novakovic, Radmila; Milovanovic, Slobodan; Protic, Dragana; Djokic, Jelena; Heinle, Helmut; Gojkovic-Bukarica, Ljiljana

    2007-09-01

    The effects of the K(+) channel opener, pinacidil on the spontaneous rhythmic contractions and contractions provoked by electrical field stimulation (50 Hz) or by oxytocin were investigated in the isolated uterus of the non-pregnant rat in oestrus. Pinacidil produced more potent inhibition of oxytocin-elicited contractions than of spontaneous rhythmic contractions or electrical field stimulation-induced contractions. Glibenclamide, a selective blocker of adenosine triphosphate (ATP)-sensitive K(+) (K(ATP)) channels, antagonized the pinacidil-induced inhibition of contractions elicited by oxytocin in a competitive manner. However, the pinacidil-induced inhibition of electrical field stimulation-elicited contractions and spontaneous rhythmic contractions was antagonized non-competitively by glibenclamide. In the uterine strips pre-contracted with 80 mM K(+), the pinacidil-induced maximal relaxation was not affected. The present data show that pinacidil exhibits potent relaxant properties in the rat non-pregnant uterus in oestrus and therefore should be taken into account as a possible agent for treatment of dysmenorrhoea. Based on glibenclamide affinity, it appears that the inhibitory response to pinacidil involves K(ATP )channels. We need further investigations to explain why the interaction between glibenclamide and pinacidil in this experimental model depends on the nature of contractions. The ability of pinacidil to completely relax the rat non-pregnant uterus pre-contracted with K(+)-rich solution suggests that K(+) channel-independent mechanism(s) also play a part in its relaxant effect.

  5. Arsenite in drinking water produces glucose intolerance in pregnant rats and their female offspring.

    Science.gov (United States)

    Bonaventura, María Marta; Bourguignon, Nadia Soledad; Bizzozzero, Marianne; Rodriguez, Diego; Ventura, Clara; Cocca, Claudia; Libertun, Carlos; Lux-Lantos, Victoria Adela

    2017-02-01

    Drinking water is the main source of arsenic exposure. Chronic exposure has been associated with metabolic disorders. Here we studied the effects of arsenic on glucose metabolism, in pregnant and post-partum of dams and their offspring. We administered 5 (A5) or 50 (A50) mg/L of sodium arsenite in drinking water to rats from gestational day 1 (GD1) until two months postpartum (2MPP), and to their offspring from weaning until 8 weeks old. Liver arsenic dose-dependently increased in arsenite-treated rats to levels similar to exposed population. Pregnant A50 rats gained less weight than controls and recovered normal weight at 2MPP. Arsenite-treated pregnant animals showed glucose intolerance on GD16-17, with impaired insulin secretion but normal insulin sensitivity; they showed dose-dependent increased pancreas insulin on GD18. All alterations reverted at 2MPP. Offspring from A50-treated mothers showed lower body weight at birth, 4 and 8 weeks of age, and glucose intolerance in adult females, probably due to insulin secretion and sensitivity alterations. Arsenic alters glucose homeostasis during pregnancy by altering beta-cell function, increasing risk of developing gestational diabetes. In pups, it induces low body weight from birth to 8 weeks of age, and glucose intolerance in females, demonstrating a sex specific response. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Coenzyme Q in pregnant women and rats with intrahepatic cholestasis.

    Science.gov (United States)

    Martinefski, Manuela R; Contin, Mario D; Rodriguez, Myrian R; Geréz, Estefanía M; Galleano, Mónica L; Lucangioli, Silvia E; Bianciotti, Liliana G; Tripodi, Valeria P

    2014-08-01

    Intrahepatic cholestasis of pregnancy is a high-risk liver disease given the eventual deleterious consequences that may occur in the foetus. It is accepted that the abnormal accumulation of hydrophobic bile acids in maternal serum are responsible for the disease development. Hydrophobic bile acids induce oxidative stress and apoptosis leading to the damage of the hepatic parenchyma and eventually extrahepatic tissues. As coenzyme Q (CoQ) is considered an early marker of oxidative stress in this study, we sought to assess CoQ levels, bile acid profile and oxidative stress status in intrahepatic cholestasis. CoQ, vitamin E and malondialdehyde were measured in plasma and/or tissues by HPLC-UV method whereas serum bile acids by capillary electrophoresis in rats with ethinyl estradiol-induced cholestasis and women with pregnancy cholestasis. CoQ and vitamin E plasma levels were diminished in both rats and women with intrahepatic cholestasis. Furthermore, reduced CoQ was also found in muscle and brain of cholestatic rats but no changes were observed in heart or liver. In addition, a positive correlation between CoQ and ursodeoxycholic/lithocholic acid ratio was found in intrahepatic cholestasis suggesting that increased plasma lithocholic acid may be intimately related to CoQ depletion in blood and tissues. Significant CoQ and vitamin E depletion occur in both animals and humans with intrahepatic cholestasis likely as the result of increased hydrophobic bile acids known to produce significant oxidative stress. Present findings further suggest that antioxidant supplementation complementary to traditional treatment may improve cholestasis outcome. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Suppression of erythrocyte production in zinc deficient pregnant rats

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, P.N.; Wehr, C.M.; King, J.C. (Univ. of California, Berkeley (United States))

    1991-03-15

    Rat dams fed zinc (Zn) deficient diets during pregnancy accumulate excessive liver iron (Fe) concentrations. In this study, the authors investigated the effect of Zn deficiency on erythropoiesis. Sprague-Dawley rats were fed diets containing 50 {mu}g (ZnAd) or less than 0.5 {mu}g (Zndef) Zn/g diet from d0 to d19 of gestation; food intake and weight were recorded daily. Dams were killed by CO{sub 2} asphyxiation on d19 of pregnancy. Smears were made from dam femur bone marrow and analyzed for erythrocyte (RBC) number and maturity. Plasma, liver and bone were analyzed for Zn and Fe concentrations by AAS. In the ZnAd and Zndef dams, mean ({plus minus}sem) bone Zn was 140 {plus minus} 3 and 104 {plus minus} 2 {mu}g/g; plasma Zn was 112 {plus minus} 3 and 41 {plus minus} 4 {mu}g/dl; and liver Fe was 104 {plus minus} 10 and 185 {plus minus} 16 {mu}g/g, respectively. During gestation, mean weight gain of ZnAd was 91 {plus minus}4 g, and Zndef dams had no weight gain. Mean number of fetuses/dam of ZnAd were 12 {plus minus} 2 and Zndef were 7 {plus minus} 2. Fetal weight was 2.3 {plus minus} 0.1 g in ZnAd and 1.4 {plus minus} 0.1 g in Zndef. Zndef dams resorbed 44% of their implantation sites and 34% of their fetuses had gross teratology. Compared to ZnAd dams, the newly formed RBCs of Zndef dams show marked reduction, indicating suppression of bone marrow erythropoiesis. Thus, severely Zn deficient rat dams were unable to mobilize their excessively high liver Fe stores and could not maintain normal erythropoiesis.

  8. Effect of ether inhalation by adrenalectomized pregnant rats on the adrenal corticosterone concentration in norma, decapitated, and encephalectomized fetuses.

    Science.gov (United States)

    Negellen-Perchellet, E; Cohen, A

    1975-01-01

    The influence of decapitation or encephalectomy (total removal of the brain leaving the pituitary in place) on the adrenal corticosterone concentration of the 20-day-old rat fetus has been studied in normal pregnant rats, in adrenalectomized pregnant rats, and in adrenalectomized pregnant rats subjected to the stress conditions of inhalation of ether for 40 min. Decapitation or encephalectomy of the fetus always results in a drop in adrenal corticosterone concentration within 4 h which is prevented in 15 min by injecting 3.2 mU of hog ACTH into the decapitated fetus. In mothers adrenalectomized in order to avoid a negative feedback reaction of maternal corticosteroids on the fetal pituitary-adrenal system, ether inhalation causes an important rise in adrenal corticosterone concentration in normal fetuses but not in decapitated or encephalectomized ones. Thus ether, which crosses the placental barrier, is a stressor agent for the fetal rat.

  9. Smooth muscle pharmacology in the isolated virgin and pregnant rat uterus and cervix.

    Science.gov (United States)

    Darios, Emma S; Seitz, Bridget; Watts, Stephanie W

    2012-06-01

    Uterine smooth muscle function is established, but comparatively little is known about cervical smooth muscle pharmacology. We performed a proof-of-principle experiment that smooth muscle was expressed in the cervix in both virgin and pregnant rats, using the uterus as a comparator. We tested whether all tissues were pharmacologically responsive to contractile and relaxant agonists. Immunohistochemistry revealed the expression of smooth muscle α-actin in all tissues. The isolated tissue bath was used to measure isometric contractility of uterine strips and whole cervices from virgin and pregnant (day 11 ± 2) female Sprague-Dawley rats. We tested classic activators of uterine smooth muscle contraction and relaxation in both uterus and cervix. All tissues contracted to the depolarizing agent potassium chloride, prostaglandin F2α, muscarinic cholinergic agonist carbachol [2-[(aminocarbonxyl)oxy]-N,N,N-trimethylethanaminium chloride], and 5-hydroxytryptamine. Unlike other tissues, the pregnant cervix did not contract to oxytocin, but the oxytocin receptor was present. Both cervix and uterus (virgin and pregnant) had concentration-dependent, near-complete relaxation to the adrenergic agonist norepinephrine and adenylate cyclase activator forskolin [(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-6,10-10b-trihydroxy-3,4a,7,10a-pentamethyl-1-oxo-3-vinyldodecahydro-1H-benzo[f] chroment-5-yl acetate]. The β-adrenergic receptor agonist isoproterenol was less potent in pregnant cervix versus virgin by ∼10-fold. All tissues, particularly the cervix, responded poorly to the nitric-oxide donor sodium nitroprusside, relaxing ∼20% maximally. These findings support the importance of smooth muscle in the cervix, the use of the isolated cervix in pharmacological studies, and a similarity between smooth muscle pharmacology of the nonpregnant uterus and cervix. This work highlights the unappreciated smooth muscle function of the cervix versus uterus and cervical changes in pharmacology during

  10. Iron deficiency without anemia causes maternal hypothyroxinemia in pregnant rats.

    Science.gov (United States)

    Hu, Xiaona; Teng, Xiaochun; Zheng, Hongzhi; Shan, Zhongyan; Li, Jing; Jin, Ting; Xiong, Chuhui; Zhang, Hongmei; Fan, Chenling; Teng, Weiping

    2014-07-01

    Because of increased total red blood cell mass and the demands of the fetus, iron requirements are greater during pregnancy than at most other times. Previous experiments in nonpregnant women have shown that iron deficiency (ID) can reduce circulating thyroxine and triiodothyronine levels; therefore, we hypothesized that ID before pregnancy can reduce thyroid hormone levels in maternal circulation and in the thyroid gland during pregnancy. In the present study, 2 types of rat models with ID were established using diets with different iron concentrations. Levels of thyroid hormone, hemoglobin, serum iron, liver iron, serum ferritin, serum transferrin receptor, and serum thyroid-stimulating hormone as well as thyroid peroxidase activity were measured throughout pregnancy, and thyroid structure was analyzed. Both mild ID with anemia and ID without anemia resulted in maternal hypothyroxinemia from midgestation to the end of the pregnancy. Thyroid peroxidase activity significantly decreased, even before the reduction of liver iron concentrations in ID groups. Iron deficiency reduced the size of follicular cavities but did not destroy the follicular structure. Linear regressions were performed to compare total levels of maternal serum thyroxine to indices of iron status for individual dams. This is the first rat study to report our results stating that ID can cause maternal hypothyroxinemia during early pregnancy.

  11. Hypothalamic Paraventricular and Arcuate Nuclei Contribute to Elevated Sympathetic Nerve Activity in Pregnant Rats: Roles of Neuropeptide Y and α-Melanocyte-Stimulating Hormone.

    Science.gov (United States)

    Shi, Zhigang; Cassaglia, Priscila A; Gotthardt, Laura C; Brooks, Virginia L

    2015-12-01

    Pregnancy increases sympathetic nerve activity (SNA), but the mechanisms are unknown. Here, we investigated the contributions of the hypothalamic paraventricular and arcuate nuclei in α-chloralose-anesthetized pregnant and nonpregnant rats. Baseline arterial pressure (AP) was lower, and heart rate (HR), lumbar sympathetic activity, and splanchnic SNA were higher in pregnant rats compared with nonpregnant rats. Inhibition of the paraventricular nucleus via bilateral muscimol nanoinjections decreased AP and HR more in pregnant rats than in nonpregnant rats and decreased lumbar SNA only in pregnant rats. Similarly, after arcuate muscimol nanoninjections, the decreases in AP, HR, and lumbar, renal, and splanchnic sympathetic nerve activities were greater in pregnant rats than in nonpregnant rats. Major arcuate neuronal groups that project to the paraventricular nucleus express inhibitory neuropeptide Y (NPY) and excitatory α-melanocyte-stimulating hormone. Inhibition of paraventricular melanocortin 3/4 receptors with SHU9119 also decreased AP, HR, and lumbar SNA in pregnant rats but not in nonpregnant rats. Conversely, paraventricular nucleus NPY expression was reduced in pregnant animals, and although blockade of paraventricular NPY Y1 receptors increased AP, HR, and lumbar sympathetic activity in nonpregnant rats, it had no effects in pregnant rats. Yet, the sympathoinhibitory, depressor, and bradycardic effects of paraventricular NPY nanoinjections were similar between groups. In conclusion, the paraventricular and arcuate nuclei contribute to increased basal SNA during pregnancy, likely due in part to decreased tonic NPY inhibition and increased tonic α-melanocyte-stimulating hormone excitation of presympathetic neurons in the paraventricular nucleus.

  12. High-fat diet induced insulin resistance in pregnant rats through pancreatic pax6 signaling pathway.

    Science.gov (United States)

    Wu, Hao; Liu, Yunyun; Wang, Hongkun; Xu, Xianming

    2015-01-01

    To explore the changes in pancreas islet function of pregnant rats after consumption of high-fat diet and the underlying mechanism. Thirty pregnant Wistar rats were randomly divided into two groups: high-fat diet group and normal control group. Twenty days after gestation, fasting blood glucose concentration (FBG) and fasting serum insulin concentration (FINS) were measured. Then, oral glucose tolerance test (OGTT) and insulin release test (IRT) were performed. Finally, all the rats were sacrificed and pancreas were harvested. Insulin sensitivity index (ISI) and insulin resistance index (HOMA-IR) were calculated according to FBG and FINS. RT-PCR and Real-time PCR were performed to study the expression of paired box 6 transcription factor (Pax6) and its target genes in pancreatic tissues. The body weight was significantly increased in the high-fat diet group compared with that of normal control rats (Pfat diet group was significantly increased compared with that of normal control rats (6.62 mmol/L vs. 4.96 mmol/L, Pinsulin concentration between the two groups. OGTT and IRT were abnormal in the high-fat diet group. The high-fat diet rats were more prone to impaired glucose tolerance and insulin resistance. The level of the expression of Pax6 transcription factor and its target genes in pancreas, such as pancreatic and duodenal homeobox factor-1 (Pdx1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) and glucose transporter 2 (Glut2) were decreased significantly compared with those of normal control group. High-fat diet feeding during pregnancy may induce insulin resistance in maternal rats by inhibiting pancreatic Pax6 and its target genes expression.

  13. Biochemical changes and oxidative stress induced by zearalenone in the liver of pregnant rats.

    Science.gov (United States)

    Zhou, C; Zhang, Y; Yin, S; Jia, Z; Shan, A

    2015-01-01

    The aim of the present research was to examine the toxic influence of different doses of zearalenone (ZEN) on the liver, especially oxidative stress induced by ZEN on the liver. A total of 48 pregnant Sprague-Dawley rats were randomly assigned into 4 treatments groups with 12 animals in each. The rats were fed with a normal diet treated with 0 mg/kg (control), 50 mg/kg (treatment 1), 100 mg/kg (treatment 2), or 150 mg/kg (treatment 3) ZEN in feed on gestation days (GDs) 0-7 and then all the rats were fed with a normal diet on GDs 8-20. The experimental period lasted 21 days. The results showed that exposure to ZEN induced increase in aspartate amino transferase, alanine aminotransferase, and alkaline phosphatase activities and decrease in total protein and albumin content in a dose-dependent manner and also induce decrease in superoxide dismutase and glutathione peroxidase activities and increase in malondialdehyde content in a dose-dependent manner in the serum and the liver. The increased transcription of cytochrome P450 2E1 (CYP2E1) was detected in the liver after exposure to ZEN. These results suggested that ZEN not only caused damage in the liver of pregnant rats in a dose-dependent manner but also induced the messenger RNA expression of CYP2E1 in the liver. © The Author(s) 2014.

  14. Effect of Bauhinia forficata extract in diabetic pregnant rats: maternal repercussions.

    Science.gov (United States)

    Damasceno, D C; Volpato, G T; Calderon, I de Mattos Paranhos; Aguilar, R; Rudge, M V Cunha

    2004-02-01

    Bauhinia forficata, commonly known as "paw-of-cow", is widely used in Brazil folk medicine for the treatment of Diabetes mellitus. The purposes of present study were to determine the repercussions of diabetes on the defense system against oxidative stress in pregnant female rats and to characterize the influence of the treatment with Bauhinia forficata extract on the antioxidant system, glycemic control, hepatic glycogen, cholesterol, triglycerides, total proteins and lipids. Virgin female Wistar rats were injected with 40 mg/kg streptozotocin (STZ) before mating. Oral administration of an aqueous extract of Bauhinia forficata leaves was given to non-diabetic and diabetic pregnant rats in 3 doses: 500 mg/kg from 0 to 4th day of pregnancy, 600 mg/kg from 5th to 14th day and 1000 mg/kg from 15th to 20th day. All the females were killed on the day 21 of pregnancy. A maternal blood sample was collected by venous puncture and the maternal liver was removed for biochemical measurement. The diabetic pregnant rats presented hyperglycemia, hyperlipemia, hypertriglyceridemia, hypercholesterolemia, hyperuricemia, decreased determinations of reduced glutathione (GSH) and superoxide dismutase (SOD). Treatment with B. forficata extract did not interfere in the albumin, total protein and lipid, triglyceride, cholesterol and SOD determinations. Increased hepatic glycogen, decreased uric acid concentration and increased GSH activity was observed. This last fact suggests that the plant may have some action on antioxidant defense system. However, the demonstration of the active component present in B. forficata responsible for its antioxidant effect and the increase in hepatic glycogen deserve further investigation.

  15. Evaluation of developmental toxicity of guaifenesin using pregnant female rats.

    Science.gov (United States)

    Shabbir, Arham; Shamsi, Sadia; Shahzad, Muhammad; Butt, Hajra Ikram; Aamir, Khurram; Iqbal, Javed

    2016-01-01

    Guaifenesin possesses expectorant, muscle relaxant, and anticonvulsive properties. To the best of our knowledge, the promising data regarding the developmental toxicity of guaifenesin are scarce. The current study investigates the developmental toxic effects of guaifenesin in detail using female rats. Twenty-five dams were divided into five groups. Group 1 served as a control, while Group-2, -3, -4, and -5 were administered with 250, 350, 500, and 600 (mg/kg b.w.) doses of guaifenesin, respectively, starting from gestation day 6 to day 17. Half of the total recovered fetuses was subjected to morphologic and morphometric analysis, while other half was subjected to skeletal examination. A significant reduction in maternal weight, and food/water intake, was observed, however, no mortality and morbidity were observed. About 14 dead fetuses were found in Group-3 and -4 each, while 26 in Group 5. Morphological analysis revealed 21.2%, 45.4%, 67.2%, and 86.9% of total fetuses having hemorrhagic spots in Group-2, -3, -4, and -5, respectively. Dropping wrist/ankle and kinky tail were found in Group-4 and -5 only. Morphometric analysis showed a significant decline in fetal weight, full body length, skull length, forelimb length, hindlimb length, and tail length in all guaifenesin treated groups. Skeletal examination displayed that only Group 5 fetuses had increased intercostal space between 7(th) and 8(th) rib. We also observed improper development of carpals, metacarpals, tarsals, and metatarsals of the Group 5 fetuses. Guaifenesin showed a significant developmental toxicity at selected test doses; therefore, a careful use is suggested during pregnancy.

  16. Evaluation of developmental toxicity of guaifenesin using pregnant female rats

    Science.gov (United States)

    Shabbir, Arham; Shamsi, Sadia; Shahzad, Muhammad; Butt, Hajra Ikram; Aamir, Khurram; Iqbal, Javed

    2016-01-01

    Objectives: Guaifenesin possesses expectorant, muscle relaxant, and anticonvulsive properties. To the best of our knowledge, the promising data regarding the developmental toxicity of guaifenesin are scarce. The current study investigates the developmental toxic effects of guaifenesin in detail using female rats. Materials and Methods: Twenty-five dams were divided into five groups. Group 1 served as a control, while Group-2, -3, -4, and -5 were administered with 250, 350, 500, and 600 (mg/kg b.w.) doses of guaifenesin, respectively, starting from gestation day 6 to day 17. Half of the total recovered fetuses was subjected to morphologic and morphometric analysis, while other half was subjected to skeletal examination. Results: A significant reduction in maternal weight, and food/water intake, was observed, however, no mortality and morbidity were observed. About 14 dead fetuses were found in Group-3 and -4 each, while 26 in Group 5. Morphological analysis revealed 21.2%, 45.4%, 67.2%, and 86.9% of total fetuses having hemorrhagic spots in Group-2, -3, -4, and -5, respectively. Dropping wrist/ankle and kinky tail were found in Group-4 and -5 only. Morphometric analysis showed a significant decline in fetal weight, full body length, skull length, forelimb length, hindlimb length, and tail length in all guaifenesin treated groups. Skeletal examination displayed that only Group 5 fetuses had increased intercostal space between 7th and 8th rib. We also observed improper development of carpals, metacarpals, tarsals, and metatarsals of the Group 5 fetuses. Conclusion: Guaifenesin showed a significant developmental toxicity at selected test doses; therefore, a careful use is suggested during pregnancy. PMID:27298495

  17. [Protective Effect of Schisandra Extract on Embryotoxicity and Reproductive Toxicity in Early Pregnant Rats Exposed to Benzo [a] pyrene].

    Science.gov (United States)

    Liang, Jing; Hou, Hai-yan; Sun, Yang; Chen, Ya-qiong

    2016-02-01

    To observe protective effects of Schisandra extract (SE) on embryotoxicity and reproductive toxicity of early pregnant rats exposed to Benzo[a]pyrene (Bap). Pregnant rat model was prepared using periodic screening cage method. Totally 50 female pregnant SD rats were divided into five groups by randomized block design according to the weight, i.e., the BaP model group, the low dose SE group, the middle dose SE group, the high dose SE group, the normal control group, 10 rats in each group. Rats in the BaP model group were administered with BaP at a daily dose of 2 mg/kg by gastrogavage. Rats in low, middle, and high dose SE groups were administered by gastrogavage with BaP (at a daily dose of 2 mg/kg) plus SE at a daily dose of 40, 200, and 1 000 mg/kg, respectively. Equal volume of olive oil was administered to rats in the normal control group by gastrogavage. All medication was performed for 8 successive days. Changes of rat body weight in each period were observed. The uterus embryonic total quality and ovary quality were measured, and organ index calculated. The number of corpus luteum, the number of embryo implantation, and the number of absorbed embryo were statistically calculated respectively. The implantation rate and the absorbed embryos rate were calculated. Serum levels of human chorionic gonadotrophin β (β-HCG) and progesterone (PROG) were detected by ELISA. Compared with the normal control group, the weight of 9-day pregnant rats, the number of embryo implantation, the uterus embryonic total index, ovary index, serum levels of β-HCG and PROG all decreased in the Bap model group with significant difference (P body weight, the uterus embryonic total index, and the PROG level increased in 3 dose SE groups (P pregnant rats exposed to Benzo[a]pyrene.

  18. Effect of Erythromycin on Albendazole-Induced Teratogenicity in Pregnant Rats

    Directory of Open Access Journals (Sweden)

    Reza Ranjbar

    2013-05-01

    Full Text Available Background: Albendazole is utilized as an anthelmentic agent. One its side effect is teratogenicity. This effect apparently is related to its metabolites especially albendazole sulfoxid. The aim of present study was evaluation effect of erythromycin (as enzyme inhibitor in biotransformation on albendazole biotransformation and consequently fetal malformation. Materials and Methods: Four groups of female pregnant wistar rats (8 rats each group were used. First group received normal saline (as control group. A single oral dose 30 mg/kg of albendazole was administered to rats on day 10 of gestation in group 2. Rats in group 3 received albendazole similar group 2 and erythromycin at dose 60 mg/kg. Rats in group 4 received only erythromycin on day 10 of gestation. The rats were euthanatized on day 20 of gestation. The skeletal malformation of fetus was studied by stereomicroscope after staining by Alizarin red-Alcian blue.Results: The length and weight of fetuses were significantly decreased by albendazole but erythromycin did not prevent this effect. In group that received only erythromycin, the length and weight of fetuses was similar to control group. Erythromycin decreased albendazole effect on weight of placenta. There was an increase in resorption by erythromycin when co-administrated with albendazole. The incidence of skeletal malformations (mostly of the limbs, vertebrae and palate decreased significantly by erythromycin when co-administrated with albendazole.Conclusion: Thus, erythromycin may inhibit albendazole biotransformation and decrease teratogenicity of it metabolites; but this subject needs more detailed evaluation.

  19. Role of the availability of substrates on hepatic and renal gluconeogenesis in the fasted late pregnant rat

    Energy Technology Data Exchange (ETDEWEB)

    Zorzano, A.; Lasuncion, M.A.; Herrera, E.

    1986-04-01

    Studies were conducted to examine the role of gluconeogenetic substrate availability on glucose production in the fasted late pregnant rat. Virgin and 21-day pregnant rats were studied after 24 hours' food deprivation. Pregnant animals showed decreased circulating glucose and gluconeogenic amino acid and increased plasma glycerol concentration. Glucose formation was studied in vivo two, five, and ten minutes after the intravenous administration of two concentrations of /sup 14/C-alanine, /sup 14/C-pyruvate, or /sup 14/C-glycerol. Concentrations of 0.2 mmols of /sup 14/C-glycerol or /sup 14/C-pyruvate, but not of /sup 14/C-alanine, enhanced /sup 14/C-glucose production in pregnant rats, whereas 1 mmol of any of the three /sup 14/C-substrates always enhanced /sup 14/C-glucose production in these rats. Both 1 mmol/L and 5 mmol/L /sup 14/C-alanine increased /sup 14/C-glucose formation in 90-minute-incubated liver slices of fasted pregnant rats, in spite of decreased cytosolic activity of alanine aminotransferase. The three substrates enhanced in vitro renal gluconeogenesis in pregnant rats. Under all experimental conditions studied, labeled glycerol was converted more efficiently into glucose than equivalent amounts of any other substrate used, and this difference was greater in pregnant, than in virgin animals. Results indicate that, in spite of enhanced gluconeogenetic activity, maternal glucose production in the fasted state at late gestation is limited by the deficiency of certain substrates, such as amino acids. It is proposed that glycerol derived from enhanced maternal adipose tissue lipolysis constitutes a preferential gluconeogenetic substrate in comparison with others, such as alanine, that are more efficiently transferred through the placenta to the fetus.

  20. Reduced endothelial NO-cGMP vascular relaxation pathway during TNF-alpha-induced hypertension in pregnant rats.

    Science.gov (United States)

    Davis, Justin R; Giardina, Jena B; Green, Gachavis M; Alexander, Barbara T; Granger, Joey P; Khalil, Raouf A

    2002-02-01

    Placental ischemia during pregnancy is thought to release cytokines such as tumor necrosis factor-alpha (TNF-alpha), which may contribute to the increased vascular resistance associated with pregnancy-induced hypertension. We have reported that a chronic twofold elevation in plasma TNF-alpha increases blood pressure in pregnant but not in virgin rats; however, the vascular mechanisms are unclear. We tested the hypothesis that increasing plasma TNF-alpha during pregnancy impairs endothelium-dependent vascular relaxation and enhances vascular reactivity. Active stress was measured in aortic strips of virgin and late-pregnant Sprague-Dawley rats untreated or infused with TNF-alpha (200 ng x kg(-1) x day(-1) for 5 days) to increase plasma level twofold. Phenylephrine (Phe) increased active stress to a maximum of 4.2 +/- 0.4 x 10(3) and 9.9 +/- 0.7 x 10(3) N/m2 in control pregnant and TNF-alpha-infused pregnant rats, respectively. Removal of the endothelium enhanced Phe-induced stress in control but not in TNF-alpha-infused pregnant rats. In endothelium-intact strips, ACh caused greater relaxation of Phe contraction in control than in TNF-alpha-infused pregnant rats. Basal and ACh-induced nitrite/nitrate production was less in TNF-alpha-infused than in control pregnant rats. Pretreatment of vascular strips with 100 microM N(G)-nitro-L-arginine methyl ester, to inhibit nitric oxide (NO) synthase, or 1 microM 1H-[1,2,4]oxadiazolo[4,3-]quinoxalin-1-one, to inhibit cGMP production in smooth muscle, inhibited ACh-induced relaxation and enhanced Phe-induced stress in control but not in TNF-alpha-infused pregnant rats. Phe contraction and ACh relaxation were not significantly different between control and TNF-alpha-infused virgin rats. Thus an endothelium-dependent NO-cGMP-mediated vascular relaxation pathway is inhibited in late-pregnant rats infused with TNF-alpha. The results support a role for TNF-alpha as one possible mediator of the increased vascular resistance

  1. Propofol Exposure in Pregnant Rats Induces Neurotoxicity and Persistent Learning Deficit in the Offspring

    Directory of Open Access Journals (Sweden)

    Ming Xiong

    2014-05-01

    Full Text Available Propofol is a general anesthetic widely used in surgical procedures, including those in pregnant women. Preclinical studies suggest that propofol may cause neuronal injury to the offspring of primates if it is administered during pregnancy. However, it is unknown whether those neuronal changes would lead to long-term behavioral deficits in the offspring. In this study, propofol (0.4 mg/kg/min, IV, 2 h, saline, or intralipid solution was administered to pregnant rats on gestational day 18. We detected increased levels of cleaved caspase-3 in fetal brain at 6 h after propofol exposure. The neuronal density of the hippocampus of offspring was reduced significantly on postnatal day 10 (P10 and P28. Synaptophysin levels were also significantly reduced on P28. Furthermore, exploratory and learning behaviors of offspring rats (started at P28 were assessed in open-field trial and eight-arm radial maze. The offspring from propofol-treated dams showed significantly less exploratory activity in the open-field test and less spatial learning in the eight-arm radial maze. Thus, this study suggested that propofol exposure during pregnancy in rat increased cleaved caspsase-3 levels in fetal brain, deletion of neurons, reduced synaptophysin levels in the hippocampal region, and persistent learning deficits in the offspring.

  2. Renal NCC is unchanged in the midpregnant rat and decreased in the late pregnant rat despite avid renal Na+ retention.

    Science.gov (United States)

    West, Crystal A; McDonough, Alicia A; Masilamani, Shyama M E; Verlander, Jill W; Baylis, Chris

    2015-07-01

    Pregnancy is characterized by plasma volume expansion due to Na(+) retention, driven by aldosterone. The aldosterone-responsive epithelial Na(+) channel is activated in the kidney in pregnancy. In the present study, we investigated the aldosterone-responsive Na(+)-Cl(-) cotransporter (NCC) in mid- and late pregnant rats compared with virgin rats. We determined the abundance of total NCC, phosphorylated NCC (pNCC; pT53, pS71 and pS89), phosphorylated STE20/SPS-1-related proline-alanine-rich protein kinase (pSPAK; pS373), and phosphorylated oxidative stress-related kinase (pOSR1; pS325) in the kidney cortex. We also measured mRNA expression of NCC and members of the SPAK/NCC regulatory kinase network, serum and glucocorticoid-regulated kinase (SGK)1, total with no lysine kinase (WNK)1, WNK3, and WNK4. Additionally, we performed immunohistochemistry for NCC kidneys from virgin and pregnant rats. Total NCC, pNCC, and pSPAK/OSR1 abundance were unchanged in midpregnant versus virgin rats. In late pregnant versus virgin rats, total NCC and pNCC were decreased; however, pSPAK/OSR1 was unchanged. We detected no differences in mRNA expression of NCC, SGK1, total WNK1, WNK3, and WNK4. By immunohistochemistry, NCC was mainly localized to the apical region in virgin rats, and density in the apical region was reduced in late pregnancy. Therefore, despite high circulating aldosterone levels in pregnancy, the aldosterone-responsive transporter NCC is not increased in total or activated (phosphorylated) abundance or in apical localization in midpregnant rats, and all are reduced in late pregnancy. This contrasts to the mineralocorticoid-mediated activation of the epithelial Na(+) channel, which we have previously reported. Why and how NCC escapes aldosterone activation in pregnancy is not clear but may relate to regional differences in aldosterone sensitivity the increased K(+) intake or other undefined mechanisms. Copyright © 2015 the American Physiological Society.

  3. Progesterone and gravidity differentially regulate expression of extracellular matrix components in the pregnant rat myometrium.

    Science.gov (United States)

    Shynlova, Oksana; Mitchell, Jennifer A; Tsampalieros, Anne; Langille, B Lowell; Lye, Stephen J

    2004-04-01

    Myometrial growth and remodeling during pregnancy depends on increased synthesis of interstitial matrix proteins. We hypothesize that the presence of mechanical tension in a specific hormonal environment regulates the expression of extracellular matrix (ECM) components in the uterus. Myometrial tissue was collected from pregnant rats on Gestational Days 0, 12, 15, 17, 19, 21, 22, 23 (labor), and 1 day postpartum and ECM expression was analyzed by Northern blotting. Expression of fibronectin, laminin beta2, and collagen IV mRNA was low during early gestation but increased dramatically on Day 23 during labor. Expression of fibrillar collagens (type I and III) peaked Day 19 and decreased near term. In contrast, elastin mRNA remained elevated from midgestation onward. Injection of progesterone (P4) on Days 20-23 (to maintain elevated plasma P4 levels) delayed the onset of labor, caused dramatic reductions in the levels of fibronectin and laminin mRNA, and prevented the fall of collagen III mRNA levels on Day 23. Treatment of pregnant rats with the progesterone receptor antagonist RU486 on Day 19 induced preterm labor on Day 20 and a premature increase in mRNA levels of collagen IV, fibronectin, and laminin. Analysis of the uterine tissue from unilaterally pregnant rats revealed that most of the changes in ECM gene expression occurred specifically in the gravid horn. Our results show a decrease in expression of fibrillar collagens and a coordinated temporal increase in expression of components of the basement membrane near term associated with decreased P4 and increased mechanical tension. These ECM changes contribute to myometrial growth and remodeling during late pregnancy and the preparation for the synchronized contractions of labor.

  4. Reproductive toxicity study with a novel deoxyguanosine analogue (Metacavir) in pregnant SD rats.

    Science.gov (United States)

    Luo, Qihui; Chen, Zhengli; Cheng, Anchun; Wang, Mingshu; Fang, Jing; Peng, Xi; Tang, Li

    2015-03-01

    Our preliminary studies demonstrated that Metacavir has potential to become a new anti-HBV agent. The main targets of the toxic effects of Metacavir, in rhesus monkeys, were gastrointestinal tracts, liver, blood, and kidneys, which were not related to mitochondrial effects. In this study, the maternal toxicity, embryo-fetal developmental toxicity and teratogenicity were studied in pregnant Sprague-Dawley rats after intragastric administration of Metacavir (200, 100, 50, 0 mg/kg body weight) during the first 6-15 days of pregnancy. Slower weight gain was observed in 5 out of 21 rats subjected to a 200 mg/kg dose, as well as 2 out of 20 subjected to a 100 mg/kg dose. Compared with the solvent control group, the calibration weight gain in the 200 mg/kg and 100 mg/kg dosage groups respectively, during first 6-20 pregnant days were significantly different (P changes were observed. The present research indicated that at a dose of 200 mg/(kg·d) (i.e., 40 times the effective dose in rats), Metacavir shows some maternal toxicity to SD rats. The embryotoxicity in the 200 mg/kg group encompass decreased fetal body weight, and higher fetal mortality rates, compared with the control group. However, the litter incidence showed no statistical difference. All the treated rats displayed normal bone development, no teratogenicity and without adverse effects on fetal development, thus indicating that below a dose of 200 mg/(kg·d) there is no teratogenic side effects.

  5. Gestational Zearalenone Exposure Causes Reproductive and Developmental Toxicity in Pregnant Rats and Female Offspring

    Directory of Open Access Journals (Sweden)

    Xin Gao

    2017-01-01

    Full Text Available Zearalenone (ZEN is an oestrogenic mycotoxin commonly found in food and feed products and can affect reproduction and development in both humans and animals. This study aimed to determine the toxic effects of ZEN on maternal SD rats and the F1 female offspring. Sixty-four pregnant rats were divided into 4 groups and exposed to feed contaminated with ZEN (0, 5, 10, and 20 mg/kg feed on gestational days (GDs 0–21. Compared with the controls, the groups exposed to 10 and 20 mg/kg ZEN showed significantly decreased feed intake and body weight of pregnant rats and/or female offspring. Meanwhile, 20 mg/kg ZEN significantly decreased the birth weight and viability of F1 newborn rats. Moreover, 10 and 20 mg/kg ZEN diets increased follicle-stimulating hormone concentrations but decreased oestradiol in both maternal and F1 adult rats. In the F1 generation, ZEN caused no pathological changes in ovaries and uterus in weaned rats, but significant follicular atresia and a thinning uterine layer were found in F1 female adult rats in the 20 mg/kg ZEN group. These impairments concurred with the inhibited mRNA and protein levels of oestrogen receptor-alpha (Esr1 and 3β-hydroxysteroid dehydrogenase (HSD in the adult uterus and/or ovaries. Furthermore, 10 and/or 20 mg/kg ZEN exposure significantly reduced Esr1, gonadotropin-releasing hormone receptor (GnRHr, and ATP binding cassette transporters b1 and c1 (ABCb1 and ABCc1 in the placenta and foetal and weaned F1 brains, and also produced a dose-dependent increase in 3β-HSD in the placenta. Additionally, 20 mg/kg ZEN significantly upregulated ABCc5 expression in the placenta and ovaries of weaned rats. These results suggested that prenatal ZEN exposure in rats affected maternal and foetal development and may lead to long-term reproductive impairment in F1 adult females.

  6. Gestational Zearalenone Exposure Causes Reproductive and Developmental Toxicity in Pregnant Rats and Female Offspring

    Science.gov (United States)

    Gao, Xin; Sun, Lvhui; Zhang, Niya; Li, Chong; Zhang, Jiacai; Xiao, Zhuohui; Qi, Desheng

    2017-01-01

    Zearalenone (ZEN) is an oestrogenic mycotoxin commonly found in food and feed products and can affect reproduction and development in both humans and animals. This study aimed to determine the toxic effects of ZEN on maternal SD rats and the F1 female offspring. Sixty-four pregnant rats were divided into 4 groups and exposed to feed contaminated with ZEN (0, 5, 10, and 20 mg/kg feed) on gestational days (GDs) 0–21. Compared with the controls, the groups exposed to 10 and 20 mg/kg ZEN showed significantly decreased feed intake and body weight of pregnant rats and/or female offspring. Meanwhile, 20 mg/kg ZEN significantly decreased the birth weight and viability of F1 newborn rats. Moreover, 10 and 20 mg/kg ZEN diets increased follicle-stimulating hormone concentrations but decreased oestradiol in both maternal and F1 adult rats. In the F1 generation, ZEN caused no pathological changes in ovaries and uterus in weaned rats, but significant follicular atresia and a thinning uterine layer were found in F1 female adult rats in the 20 mg/kg ZEN group. These impairments concurred with the inhibited mRNA and protein levels of oestrogen receptor-alpha (Esr1) and 3β-hydroxysteroid dehydrogenase (HSD) in the adult uterus and/or ovaries. Furthermore, 10 and/or 20 mg/kg ZEN exposure significantly reduced Esr1, gonadotropin-releasing hormone receptor (GnRHr), and ATP binding cassette transporters b1 and c1 (ABCb1 and ABCc1) in the placenta and foetal and weaned F1 brains, and also produced a dose-dependent increase in 3β-HSD in the placenta. Additionally, 20 mg/kg ZEN significantly upregulated ABCc5 expression in the placenta and ovaries of weaned rats. These results suggested that prenatal ZEN exposure in rats affected maternal and foetal development and may lead to long-term reproductive impairment in F1 adult females. PMID:28067781

  7. Use of urinary renal biomarkers to evaluate the nephrotoxic effects of melamine or cyanuric acid in non-pregnant and pregnant rats.

    Science.gov (United States)

    Bandele, O J; Stine, C B; Ferguson, M; Black, T; Olejnik, N; Keltner, Z; Evans, E R; Crosby, T C; Reimschuessel, R; Sprando, R L

    2014-12-01

    Although traditional assessments of renal damage detect loss of kidney function, urinary renal biomarkers are proposed to indicate early changes in renal integrity. The recent adulteration of infant formula and other milk-based foods with melamine revealed a link between melamine ingestion and nephropathy. Thus, the effects of melamine and related analogs (e.g., cyanuric acid) should be assessed in other potentially sensitive groups. We evaluated whether urinary Kim-1, clusterin, and osteopontin could detect the effects of high doses of melamine or cyanuric acid in pregnant and non-pregnant female rats gavaged with 1000 mg/kg bw/day for 10 days. We demonstrate that these biomarkers can differentiate the severity of effects induced by melamine or cyanuric acid. All melamine-treated animals experienced adverse effects; however, pregnant rats were most sensitive as indicated by increased SCr, BUN, and kidney weights, decreased body weight, and presence of renal crystals. These effects coincided with elevated urinary biomarker levels as early as day 2 of exposure. One cyanuric acid-treated rat displayed effects similar to melamine, including increased urinary biomarker levels. This work illustrates that these biomarkers can detect early effects of melamine or cyanuric acid crystal-induced nephropathy and further supports the use of urinary protein immunoassays as a powerful, non-invasive method to assess nephrotoxicity.

  8. /sup 1/H-NMR of the uterine muscle in pregnant rat

    Energy Technology Data Exchange (ETDEWEB)

    Muraoka, Eiichi

    1987-09-01

    By using JEOL FX-90Q FT-NMR (observation frequency = 90 MHz) and Bruker pulse NMR minispec pc 20 (observation frequency = 20 MHz), water proton spin-lattice relaxation time (T/sub 1/) and water proton spin-spin relaxation time (T/sub 2/) were measured in pregnant rat uterine muscle and the water content of the subjects were measured, and obtained the following results. 1) The T/sub 1/ and T/sub 2/ value showed the most increased from 4th in pregnancy to 7th. 2) The changes of the relaxation time in pregnancy were observed much greater for T/sub 2/ than for T/sub 1/. 3) The changes in T/sub 1/ and T/sub 2/ were more marked at an observation frequency of 20 MHz than at 90 MHz. 4) The water content of pregnant uterine muscle correlated with their T/sub 1/ and T/sub 2/. 5) There was correlation between observation frequency of 20 MHz and 90 MHz for T/sub 1/ and T/sub 2/ value of the pregnant uterine muscle.

  9. Stimulation of fetal hypothalamus induces uterine contractions in pregnant rats at term.

    Science.gov (United States)

    Endoh, Hisashi; Fujioka, Takashi; Endo, Hideki; Inazuka, Yukiko; Furukawa, Susumu; Nakamura, Shoji

    2008-10-01

    The fetal brain is thought to have a role in the onset and progression of labor. Evidence also exists for fetal oxytocin release just before and during parturition. The present study examined whether activation of the fetal brain could induce uterine myometrial contractions through oxytocin receptors in the dam. Under urethane anesthesia, electrical stimulation of the hypothalamus of fetal rats that were still connected with the dams by an intact umbilical cord induced uterine contractions in term pregnant rats. Intraperitoneal injections of synthetic oxytocin in fetuses induced uterine contractions in the dams similar to those induced by electrical stimulation of the fetal hypothalamus. Maternal intravenous injections of an oxytocin antagonist immediately attenuated uterine contractions induced by fetal oxytocin injections and electrical stimulation of the fetal hypothalamus. These findings suggest the possibility that oxytocin released from the fetal hypothalamus is involved in parturition.

  10. Hepatic bile acids and bile acid-related gene expression in pregnant and lactating rats

    Directory of Open Access Journals (Sweden)

    Qiong N. Zhu

    2013-08-01

    Full Text Available Background. Significant physiological changes occur during pregnancy and lactation. Intrahepatic cholestasis of pregnancy (ICP is a liver disease closely related to disruption of bile acid homeostasis. The objective of this study was to examine the regulation of bile acid synthesis and transport in normal pregnant and lactating rats.Materials and Methods. Livers from timed pregnant SD rats were collected on gestational days (GD 10, 14 and 19, and postnatal days (PND 1, 7, 14 and 21. Total bile acids were determined by the enzymatic method, total RNA was isolated and subjected to real time RT-PCR analysis. Liver protein was extracted for western-blot analysis.Results. Under physiological conditions hepatic bile acids were not elevated during pregnancy but increased during lactation in rats. Bile acid synthesis rate-limiting enzyme Cyp7a1 was unchanged on gestational days, but increased on PND14 and 21 at mRNA and protein levels. Expression of Cyp8b1, Cyp27a1 and Cyp7b1 was also higher during lactation. The mRNA levels of small heterodimer partner (SHP and protein levels of farnesoid X receptor (FXR were increased during pregnancy and lactation. Bile acid transporters Ntcp, Bsep, Mrp3 and Mrp4 were lower at gestation, but increased during lactation. Hepatic Oatp transporters were decreased during pregnancy and lactation.Conclusion. Hepatic bile acid homeostasis is maintained during normal pregnancy in rats, probably through the FXR-SHP regulation. The expression of bile acid synthesis genes and liver bile acid accumulation were increased during lactation, together with increased expression of bile acid efflux transporter Bsep, Mrp3 and Mrp4.

  11. Effects of low doses of alcohol on delta-9-tetrahydrocannabinol's effects in pregnant rats

    Energy Technology Data Exchange (ETDEWEB)

    Abel, E.L.; Subramanian, M.G. (Wayne State Univ., Detroit, MI (USA))

    1990-01-01

    Pregnant rats were intubated with 50 mg/kg of delta-9-tetrahydrocannabinol (THC) or with THC plus alcohol to determine if a low dose of alcohol would significantly increase blood levels of THC. On the basis of this study, a second study was conducted in which pregnant rats were intubated with THC plus alcohol from gestation day six to parturition. THC reduced birth weights but did not significantly affect litter size or passive avoidance learning. Alcohol did not have a significant effect on offspring birth weight nor did it interact with THC to affect offspring.

  12. Effect of a leucine-supplemented diet on body composition changes in pregnant rats bearing Walker 256 tumor

    OpenAIRE

    Ventrucci G.; Mello M.A.R; Gomes-Marcondes M.C.C.

    2001-01-01

    Cancer patients present high mobilization of host protein, with a decrease in lean body mass and body fat depletion occurring in parallel to neoplastic growth. Since leucine is one of the principal amino acids used by skeletal muscle for energy, we investigated the changes in body composition of pregnant tumor-bearing rats after a leucine-supplemented diet. Sixty pregnant Wistar rats divided into six groups were fed a normal protein diet (18%, N) or a leucine-supplemented diet (3% L-leucine, ...

  13. Teratogenicity and metabolism of water-soluble forms of vitamin A in the pregnant rat

    Energy Technology Data Exchange (ETDEWEB)

    Gunning, D.B.; Barua, A.B.; Olson, J.A. (Iowa State Univ., Ames (United States))

    1990-02-26

    Retinoyl {beta}-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 {beta}-glucuronide, retinoyl {beta}-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.

  14. Drotaverine interacts with the L-type Ca(2+) channel in pregnant rat uterine membranes.

    Science.gov (United States)

    Tömösközi, Zsuzsanna; Finance, Olivier; Arányi, Péter

    2002-08-02

    The effect of the isoquinoline derivative, drotaverine on the specific binding of [(3)H]nitrendipine and [(3)H]diltiazem to pregnant rat uterine membranes was examined. Drotaverine inhibited the specific [(3)H]nitrendipine and [(3)H]diltiazem bindings with IC(50) values of 5.6 and 2.6 microM, respectively. Saturation studies showed that diltiazem caused a significant increase in the maximum binding density without changing the K(D) of [(3)H]nitrendipine while drotaverine increased both the K(D) and the B(max) of [3H]nitrendipine. The dissociation kinetics of both [3H]nitrendipine and [(3)H]diltiazem were accelerated by drotaverine. These results suggest that drotaverine has a negative allosteric interaction with the binding sites for 1,4-dihydropyridines and 1,5-benzothiazepines on the L-type Ca(2+) channel in pregnant rat uterine membranes, which may have implications as to the potential usefulness of this drug in aiding child delivery.

  15. The effect of morphine consumption on plasma corticosteron concentration and placenta development in pregnant rats

    Directory of Open Access Journals (Sweden)

    Masoomeh Kazemi

    2011-01-01

    Full Text Available Background: Previous studies have shown that morphine consumption during pregnancy may delay embryo development or cause abnormal nervous system function. Objective: The present study focused on the effect of maternal morphine consumption on development of placenta and blood corticosteron concentration in addictive pregnant mothers.Materials and Methods: 24 female rats, 170-200g weight, were used. The experimental groups after pregnancy received an oral dose of 0.05 mg/ml of morphine by tap water while the control group received only tap water. On 10th and 14th day of pregnancy, rats were anesthetized and placenta removed surgically, 1ml blood was collected from each pregnant mother from retro-orbital sinus, the concentration of blood corticosteron was determined by corticosteron Elisa kit after centrifugation. The fixed tissue was processed, sectioned and stained with hematoxylin and eosin. Placenta was studied microscopically according to the thickness of layers, area of blood cisterns, and the number of cells.Results: Comparing the plasma corticosteron concentration of the treatment and the control groups, not only a severe increase in the treatment group was detected, but also the thickness of maternal and embryonic portions of the placenta at day 10th and 14th of gestation was different significantly (p≤0.05. Furthermore, an increase in number of cells in maternal and embryonic portion of placenta and a decrease in blood cistern area were demonstrated in both the experimental and the control groups.Conclusion: The effects of morphine, including an increase in blood concentration of corticosteron, in dependent pregnant mothers were seen. Development of placenta in the experimental group was delayed.

  16. Reactive oxygen species in pregnant rats: effects of exercise and thermal stress.

    Science.gov (United States)

    Osorio, R A L; Christofani, J S; D'Almeida, V; Russo, A K; Piçarro, I C

    2003-05-01

    With the aim of evaluating the effect of interaction between physical training or exercise only during pregnancy and thermal stress on oxidative stress, and antioxidant mechanism sedentary pregnant rats (PS), exercised pregnant rats only during pregnancy (PE) and trained rats submitted to also exercise during pregnancy (PT) were compared (N=63). Exercise sessions consisted of swimming at 80% of maximal work load supported into water at 28 degrees C (hypothermia, PS 28, PE28, PT28) or 35 degrees C (thermal neutrality, PS35, PE35, PT35) or 39 degrees C (hyperthermia, PS39, PE39, PT39), for 30 min. The initial body weight in all groups of rats was from 177 to 207 g. On the 20th day of pregnancy, 24 h after the last immersion or swimming session venous blood was collected to determine oxidative stress. Plasma concentrations of means malondialdehyde (MDA) values measured as thiobarbituric acid reactive substances (TBARS); total glutathione (GSH) and vitamin E were determined. The oxidative stress index was calculated from the ratio TBARS/GSH and TBARS/Vitamin E. TBARS did not change on the group PE at different temperatures of water; TBARS were higher for PS28 than PS35 and PS39; PT35 had higher values than PT28 and PT39. For GSH, PS39 was lower than PS35; PE28 was higher than PE35 and PE39 and PT35 were lower than PT28 and PT39. Plasma concentration of vitamin E did not present any difference for sedentary rats at different water temperatures, but for PE28, the values were lower than for PE35 and PE39, whereas PT39 was lower than PT35 and PT28. In relation to TBARS/GSH, it was verified an increase in oxidative stress for PS28 (in relation to PS35 and PS39), PE35, and PT35 (in relation to PE28 and PE39 or PT28 and PT39); regarding the ratio TBARS/vitamin E, the highest values were obtained at 35 degrees C for PS and PT groups and at 39 for PE group. These results have shown the great complexity of the interaction between physical training, thermal stress and pregnancy

  17. Characterization of rat lung ICAM-1

    DEFF Research Database (Denmark)

    Beck-Schimmer, B; Schimmer, R C; Schmal, H;

    1998-01-01

    OBJECTIVE AND DESIGN: We expressed soluble rat ICAM-1, generated a polyclonal anti-ICAM-1 antibody, and studied ICAM-1 upregulation in lung inflammatory conditions. Bacterial and baculovirus expression systems were employed. MATERIAL: 250 g adult, male Long Evans rats were used. For in vitro stud...

  18. Reduced endothelial NO-cGMP-mediated vascular relaxation and hypertension in IL-6-infused pregnant rats.

    Science.gov (United States)

    Orshal, Julia M; Khalil, Raouf A

    2004-02-01

    Placental ischemia during pregnancy is associated with increased plasma cytokines such as interleukin-6 (IL-6), which may contribute to increased vascular resistance and hypertension of pregnancy. We tested the hypothesis that an increase in plasma IL-6 during pregnancy is associated with impaired endothelium-dependent relaxation, enhanced vascular contraction, and hypertension. Systolic blood pressure was measured in virgin and pregnant Sprague-Dawley rats non-treated or infused with IL-6 (200 ng/kg per day for 5 days). Isometric contraction was measured in isolated aortic strips, and endothelial nitric oxide (NO) synthase (eNOS) was measured in aortic homogenate using Western blots. Blood pressure was greater in IL-6-infused (146+/-3) than in control pregnant rats (117+/-2 mm Hg). In endothelium-intact vascular strips, phenylephrine (Phe) caused greater increase in active stress in IL-6-infused (maximum: 10.6+/-0.6) than in control pregnant rats (maximum: 4.1+/-0.3x10(4) N/m2). Acetylcholine (ACh)-induced relaxation of Phe contraction and vascular eNOS protein and nitrite/nitrate production were less in IL-6-infused than in control pregnant rats. N(omega)-nitro-L-arginine methyl ester (10(-4) mol/L), inhibitor of NOS, or 1H-[1,2,4]oxadiazolo[4,3]-quinoxalin-1-one (10(-5) mol/L), inhibitor of cGMP production in smooth muscle, inhibited ACh-induced relaxation and enhanced Phe-induced stress in control but not IL-6-infused pregnant rats. Endothelium removal enhanced Phe-induced stress in control but not in IL-6-infused pregnant rats. The blood pressure and vascular Phe-induced contraction, ACh relaxation, and eNOS protein were not different between control and IL-6-infused virgin rats. Thus, an endothelium-dependent NO-cGMP-mediated relaxation pathway is inhibited in systemic vessels of pregnant rats infused with IL-6. The results support a role for IL-6 as a possible mediator of the increased vascular resistance during hypertension of pregnancy.

  19. Suppression by developing ovarian follicles of the low-dose endotoxin-induced glomerular inflammatory reaction in the pregnant rat

    NARCIS (Netherlands)

    Schuiling, GA; Valkhof, N; Faas, MM

    2000-01-01

    OBJECTIVE: In the current study the role of developing ovarian follicles in the control of the endotoxin-induced pregnancy-specific inflammatory reaction was evaluated. STUDY DESIGN: Follicular development was induced in pregnant rats (n = 20) by means of daily intraperitoneal injections of follicle

  20. Moderate Exercise Attenuates Lipopolysaccharide-Induced Inflammation and Associated Maternal and Fetal Morbidities in Pregnant Rats.

    Directory of Open Access Journals (Sweden)

    Karina T Kasawara

    Full Text Available Fetal growth restriction (FGR and coagulopathies are often associated with aberrant maternal inflammation. Moderate-intensity exercise during pregnancy has been shown to increase utero-placental blood flow and to enhance fetal nutrition as well as fetal and placental growth. Furthermore, exercise is known to reduce inflammation. To evaluate the effect of moderate-intensity exercise on inflammation associated with the development of maternal coagulopathies and FGR, Wistar rats were subjected to an exercise regime before and during pregnancy. To model inflammation-induced FGR, pregnant rats were administered daily intraperitoneal injections of E. coli lipopolysaccharide (LPS on gestational days (GD 13.5-16.5 and sacrificed at GD 17.5. Control rats were injected with saline. Maternal hemostasis was assessed by thromboelastography. Moderate-intensity exercise prevented LPS-mediated increases in white blood cell counts measured on GD 17.5 and improved maternal hemostasis profiles. Importantly, our data reveal that exercise prevented LPS-induced FGR. Moderate-intensity exercise initiated before and maintained during pregnancy may decrease the severity of maternal and perinatal complications associated with abnormal maternal inflammation.

  1. Action of phyllanthus niruri on the hormones of pregnant female rats

    Energy Technology Data Exchange (ETDEWEB)

    Souza, G.M.L; Bezerra, A.L; Carvalho, E.F.N.B; Catanho, M.T.J.A. [Pernambuco Univ., Recife, PE (Brazil). Dept. de Biofisica e Radiobiologia]. E-mail: mariajansem@hotmail.com; Galdino, M.F.S. [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Biologia. Dept. de Biofisica e Biometria]. E-mail: egmoura@uerj.br

    2002-07-01

    Phyllanthus niruri is used for treatment of renal diseases, among others. This work aims to evaluate the regulation of the thyroid and estrogenic hormones, under the influence of the extract of Phyllanthus niruri in pregnant female rats. Wistar rats, after copulation and verification of pregnancy, were divided into groups of 10 rats each and were administered 0,05-2,5 mg/mL of aqueous extract of Phyllanthus niruri, intraperitoneally. All the animals after 14 days of treatment, were sacrificed under ether anesthesia, blood was withdrawn by cardiac puncture for attainment of serum, concentrations of T3, T4, 17 {beta}-estradiol, progesterone hormones were determined and macroscopical visualization of the embryos was evaluated. Those hormones serum levels were evaluated by RIA. The extract altered the serum concentration of T{sub 4} , and {beta}-1,7 estradiol, which presented an increase of 333,3 % and more than 272,8%,respectively,when related to group. It is verified that progesterone is reduced of 82,9%,in related to control group. Probably extract of Phyllanthus niruri provokes alterations on the somatic-gonadal development, that modifies the corpus luteum function on synthesis and secretion of estrogenic hormones, a reduction in the number of embryos and morpho physiological dysfunctions are caused, which leads to miscarriage. Chemical study continues to determinate the structure of the active principles isolated. (author)

  2. Safety evaluation of Phytovagex, a pessary formulation of Nigella sativa, on pregnant rats

    Directory of Open Access Journals (Sweden)

    Reza Salarinia

    2016-01-01

    Full Text Available Objective: The possible toxicity of drugs in pregnancy should be tested before their use in pregnant patients. In the present study, we aimed to evaluate the safety of phytovagex, a pessary formulation of Nigella sativa (N. sativa, which is already in clinical use for vaginal fungal infection. Materials and Methods: The pregnant rats were treated intravaginal with physiological saline (vehicle or phytovagex pessary in the first half of their pregnancy (days 1 to 10 of gestation. Duration of pregnancy and health parameters of the newborns were recorded after parturition. Also, cytotoxicity of N. sativa hydroalcoholic extract was tested against ovary Cho cells.  Results: The phytovagex had no significant effect on the duration of pregnancy, number of newborns, weight of neonates, and percent of stillbirth. No deformity or general behavioral abnormality was observed in neonates monitored for 30 days after birth. N. sativa extract had no significant effect on the viability of ovary cells at the concentrations of 12.5-200 µg/mL. Conclusion: Results of this animal study showed that phytovagex has no overall effect on the duration of pregnancy and health parameters of the newborns. Also, its active agent, N. sativa, does not induce any cytotoxic effect on ovary cells.

  3. Hypertension produced by placental ischemia in pregnant rats is associated with increased soluble endoglin expression.

    Science.gov (United States)

    Gilbert, Jeffrey S; Gilbert, Sara A B; Arany, Marietta; Granger, Joey P

    2009-02-01

    Recent clinical studies indicate that an excess of angiostatic factors, such as soluble endoglin (sEng), is related to the occurrence of preeclampsia. Although recent clinical studies report that sEng is increased in preeclamptic women, the mechanisms underlying its overexpression remain unclear. Evidence suggests that hypoxia and induction of heme oxygenase-1 have opposing effects on sEng expression, the former stimulatory and the latter inhibitory. Hence, we hypothesized that placental ischemia because of reduced uterine perfusion pressure (RUPP) in the pregnant rat would increase sEng expression and decrease heme oxygenase-1. Mean arterial pressure was obtained via arterial catheter, and serum and placental proteins were measured by Western blot. Mean arterial pressure was increased (132+/-3 mm Hg versus 102+/-2 mm Hg; Papu] versus 0.05+/-0.01 apu; Papu versus 1.45+/-0.42 apu; Papu versus 0.68+/-0.09 apu; Papu versus 2.5+/-0.1 apu; P<0.05) expression decreased in the RUPP compared with normal pregnant dams. The present findings support our hypothesis that placental ischemia because of RUPP increases the expression of sEng and shifts the balance of angiogenic factors in the maternal circulation toward an angiostatic state. The present study provides further evidence that placental ischemia is a strong in vivo stimulus of angiostatic factors during pregnancy.

  4. Effect of physical training on metabolic responses of pregnant rats submitted to swimming under thermal stress

    Directory of Open Access Journals (Sweden)

    Rodrigo Alexis Lazo-Osorio

    2009-08-01

    Full Text Available

    • BACKGROUND: The aim of this study is to assess the effect of pre-pregnancy physical training on metabolic responses and its effects on offspring.
    • METHODS: Three groups of rats (n = 7 in each group: sedentary pregnant rats (PS, exercised during  regnancy (PE and pregnant rats trained before and during pregnancy (PT were compared. They were separated  nto three subgroups regarding water temperature: 28°C, 35°C or 39°C. Plasma triglycerides and glucose levels,  eight gain during pregnancy and rectal temperature pre and post exercise (swim, as well as the offspring size and weight were analysed.
    • RESULTS: Rectal temperature post exercise was lower than pre exercise at 28°C and 35°C, and higher at 39°C.  eight gain was lower at 39°C for the PT group and at 35°C for the PT and PE groups compared to the PS group. Plasma glucose, at 28°C and 39°C for PS and PE groups, was higher than those obtained at 35°C, while triglycerides  ere lower. For trained rats, plasma glucose and triglycerides were similar at all water temperatures.  rained rats presented lower triglyceride values at 35°C, and higher triglyceride values at 39°C compared to PS  roup. Glucose presented inverse results. None of the groups presented fetal reabsorption. However, in the PS group, the offspring presented lower weight gain at 28

    • T-2 Toxin-induced Toxicity in Pregnant Mice and Rats

      Directory of Open Access Journals (Sweden)

      Shinya Sehata

      2008-11-01

      Full Text Available T-2 toxin is a cytotoxic secondary fungal metabolite that belongs to the trichothecene mycotoxin family. This mycotoxin is a well known inhibitor of protein synthesis through its high binding affinity to peptidyl transferase, which is an integral part of the ribosomal 60s subunit, and it also inhibits the synthesis of DNA and RNA, probably secondary to the inhibition of protein synthesis. In addition, T-2 toxin is said to induce apoptosis in many types of cells bearing high proliferating activity. T-2 toxin readily passes the placenta and is distributed to embryo/fetal tissues, which include many component cells bearing high proliferating activity. This paper reviews the reported data related to T-2 toxin-induced maternal and fetal toxicities in pregnant mice and rats. The mechanisms of T-2 toxin-induced apoptosis in maternal and fetal tissues are also discussed in this paper.

    • Congenital hydrocephalus following X-irradiation of pregnant rats on an early gestational day

      Energy Technology Data Exchange (ETDEWEB)

      Takeuchi, I.K.; Takeuchi, Y.K.

      1986-03-01

      When pregnant rats were X-irradiated at a dose of 100 R on gestational day 9.5, a considerable number of postnatally-viable hydrocephalic offspring resulted, all of which were accompanied with bilateral micro- or anophthalmia. Histological studies revealed that the cerebral aqueduct of the congenital hydrocephalic brain was severely stenosed, and the subcommissural organ was reduced in size and displaced at some distance from the anterior end of the cerebral aqueduct. From embryological studies, it was considered that the maldevelopment of the subcommissural organ in the X-irradiated fetus might cause a reduction in the amount of its secretions which function as a cushion preventing complete closure of the cerebral aqueduct during fetal life, resulting in stenosis of the cerebral aqueduct.

    • Prenatal Ethanol Exposure and Whisker Clipping Disrupt Ultrasonic Vocalizations and Play Behavior in Adolescent Rats

      Directory of Open Access Journals (Sweden)

      Jaylyn Waddell

      2016-09-01

      Full Text Available Prenatal ethanol exposure can result in social deficits in humans and animals, including altered social interaction and poor communication. Rats exposed to ethanol prenatally show reduced play fighting, and a combination of prenatal ethanol exposure and neonatal whisker clipping further reduces play fighting compared with ethanol exposure alone. In this study, we explored whether expression of hedonic ultrasonic vocalizations (USVs correlated with the number of playful attacks by ethanol-exposed rats, rats subjected to postnatal sensory deprivation by whisker clipping or both compared to control animals. In normally developing rats, hedonic USVs precede such interactions and correlate with the number of play interactions exhibited in dyads. Pregnant Long-Evans rats were fed an ethanol-containing liquid diet or a control diet. After birth, male and female pups from each litter were randomly assigned to the whisker-clipped or non-whisker-clipped condition. Animals underwent a social interaction test with a normally developing play partner during early or late-adolescence. USVs were recorded during play. Prenatal ethanol exposure reduced both play and hedonic USVs in early adolescence compared to control rats and persistently reduced social play. Interestingly, ethanol exposure, whisker clipping and the combination abolished the significant correlation between hedonic USVs and social play detected in control rats in early adolescence. This relationship remained disrupted in late adolescence only in rats subjected to both prenatal ethanol and whisker clipping. Thus, both insults more persistently disrupted the relationship between social communication and social play.

    • Estradiol inhibits Ca2+ and K+ channels in smooth muscle cells from pregnant rat myometrium.

      Science.gov (United States)

      Okabe, K; Inoue, Y; Soeda, H

      1999-07-02

      The purpose of this study was to investigate the actions of 17beta-estradiol on the electrical activity of pregnant rat myometrium. The longitudinal layer of the myometrium was dissected from pregnant rats (17 to 19 days of gestation), and single cells were isolated by enzymatic digestion. Calcium currents and potassium currents were recorded by the whole-cell voltage-clamp method, and the single calcium-dependent potassium current was recorded by the outside-out patch-clamp method. The effects of 17beta-estradiol on these currents were investigated. When a myometrial cell was held at -50 mV, depolarization to a potential more positive than -30 mV produced an inward current followed by a slowly developing outward current. Application of tetraethylammonium inhibited the outward current while the inward current was completely abolished in a calcium-free solution. Estradiol at high concentrations (> 3 microM) inhibited both inward and outward currents in a voltage-dependent manner. Removal of estradiol restored the amplitude of the outward but not of the inward current. Estradiol (30 microM) also inhibited the activity of single calcium-dependent potassium channels without changing single channel conductance. In conclusion, estradiol at high concentrations inhibited: (1) voltage-dependent calcium, (2) calcium-dependent potassium and (3) voltage-dependent potassium currents. These actions of estradiol would prevent action potential generation and after-hyperpolarizations. Suppression of the after-hyperpolarization might further prevent spike generation due to slowing of the calcium channel's recovery from the inactivated state.

    • Endocrine Disrupting Effects of Triclosan on the Placenta in Pregnant Rats.

      Directory of Open Access Journals (Sweden)

      Yixing Feng

      Full Text Available Triclosan (TCS is a broad-spectrum antimicrobial agent that is frequently used in pharmaceuticals and personal care products. Reports have shown that TCS is a potential endocrine disruptor; however, the potential effects of TCS on placental endocrine function are unclear. The aim of this study was to investigate the endocrine disrupting effects of TCS on the placenta in pregnant rats. Pregnant rats from gestational day (GD 6 to GD 20 were treated with 0, 30, 100, 300 and 600 mg/kg/d TCS followed by analysis of various biochemical parameters. Of the seven tissues examined, the greatest bioaccumulation of TCS was observed in the placenta. Reduction of gravid uterine weight and the occurrence of abortion were observed in the 600 mg/kg/d TCS-exposed group. Moreover, hormone detection demonstrated that the serum levels of progesterone (P, estradiol (E2, testosterone (T, human chorionic gonadotropin (hCG and prolactin (PRL were decreased in groups exposed to higher doses of TCS. Real-time quantitative reverse transcriptase-polymerase chain reaction (Q-RT-PCR analysis revealed a significant increase in mRNA levels for placental steroid metabolism enzymes, including UDP-glucuronosyltransferase 1A1 (UGT1A1, estrogen sulfotransferase 1E1 (SULT1E1, steroid 5α-reductase 1 (SRD5A1 and steroid 5α-reductase 2 (SRD5A2. Furthermore, the transcriptional expression levels of progesterone receptor (PR, estrogen receptor (ERα and androgen receptor (AR were up-regulated. Taken together, these data demonstrated that the placenta was a target tissue of TCS and that TCS induced inhibition of circulating steroid hormone production might be related to the altered expression of hormone metabolism enzyme genes in the placenta. This hormone disruption might subsequently affect fetal development and growth.

    • 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 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 was not excessive, so the process of apoptosis did not occur excessively, especially in PE models. In this case, Hsp70 served as as an anti-apoptotic and it’s is suggested to further research to observe the relationship of Hsp70 and apoptotic index.

    • Behavioral and Physiological Analyses of Parturition In Pregnant Rats: Insights Derived from Intrauterine Telemetry

      Science.gov (United States)

      Villareal, J.; Mallery, E.; Lynch, A.; Mills, N.; Baer, L.; Wade, C.; Ronca, A.; Dalton, Donnie (Technical Monitor)

      2002-01-01

      During labor and birth, fetuses are exposed to considerable physical stimulation associated with labor contractions and expulsion from the womb These forces are important for the neonates' adaptation to tile extrauterine environment. To further our understanding of the relationship between labor and postpartum outcome, we developed a novel method for measuring intrauterine pressure (IUP) in freely-moving, late pregnant and parturient rats that enables us to make precise, reliable measures of the forces experienced by rat fetuses during parturition. A small (1.25 x 4 cm) telemetric blood pressure sensor was fitted within a fluid-filled balloon, similar in size to a full term rat fetus. On Gestational day (G) 19 of the rats' 22/23 day pregnancy, each dam was anesthetized and a balloon/sensor unit surgically implanted within the uterus following removal of two fetuses. Comparisons were made between sensor-implanted dams (IMPL) and a control conditions: 1) LAP-R, laparotomy with two fetuses removed or 2) LAP-NR, laparotomy with no fetuses removed. IUP signals were sampled at 10s intervals from the IMPL dams during labor and birth. Dams in all three conditions were videorecorded enabling us to analyze the effect of the implant on behavioral expressions of parturition. Contraction frequency, duration, pup-to-pup birth intervals and pup-oriented activities of the dams measured from one hour prior to the first pup birth until the birth of the third pup were unaffected by the sensor implant. Intrauterine telemetry of freely-moving dams offers significant advantages over conventional hardwired IUP measurement techniques. These findings establish and validate intrauterine telemetry as a reliable, non-invasive technique for quantifying pressures associated with parturition.

    • Toxicokinetic assessment of methylphenidate (Ritalin) enantiomers in pregnant rats and rabbits.

      Science.gov (United States)

      Bakhtiar, Ray; Tse, Francis L S

      2004-06-01

      Ritalin or methylphenidate (MPH) is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. The present report describes the determination of plasma concentrations of D-threo- and L-threo-enantiomers of MPH in toxicokinetic (TK) studies in pregnant Wistar Hannover rats and New Zealand white rabbits following repeated daily oral dosing of D,L-MPH (racemate). A previously reported chiral liquid chromatography tandem mass spectrometric (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.09 ng/mL was utilized. Oral (gavage) doses of 7, 25 and 75 mg/kg/day of racemic MPH were selected for the rat study. An over-proportional increase in exposure was observed with increasing doses of MPH racemate, the effect being more profound with the D- than the L-enantiomer. In contrast, Cmax values of both enantiomers were approximately proportional to the dose. Oral (gavage) doses of 20, 60 and 200 mg/kg were selected for the rabbit study. In general, for the D-isomer, an over-proportional increase in exposure was observed with increasing doses of MPH racemate. Conversely, for the L-isomer, a slight under-proportionality was detected in exposure with increasing doses of D,L-MPH. For mean Cmax, while L-isomer exhibited dose proportionality with increasing doses of MPH racemate, the D-isomer appeared to be over-proportional. Herein, the experimental design and observed TK parameters in each study are presented.

    • Developmental toxicity following oral administration of a high-boiling coal liquid to pregnant rats

      Energy Technology Data Exchange (ETDEWEB)

      Hackett, P.L.; Rommereim, D.N.; Sikov, M.R.

      1984-01-01

      Heavy distillate (HD), the highest-boiling coal liquid from the solvent-refined coal-II process (SRC-II), was administered by intragastric (IG) intubation to pregnant rats. Five dose levels of HD (0.09, 0.14, 0.18, 0.36 and 0.74 g kg/sup -1/), were given daily from 12 to 16 days of gestation and the rats were killed at 20 days of gestation. Maternal body weights and weights of the liver, kidneys, spleen, adrenals, thymus, ovaries and the gravid uterus were obtained. Gravid uteri were evaluated for prenatal mortality. Live fetuses were examined for malformations and weighed; fetal lungs were excised and weighed. Maternal (extragestational) weight gains and thymic weights diminished in all groups that received the SRC material. Adrenal weights were increased in all treated animals, except for those in the lowest-dose group (0.9 g kg/sup -1/). There was significant maternal mortality at 0.74 g kg/sup -1/ and increased intrauterine mortality at doses of 0.37 and 0.74 g kg/sup -1/. Placental weight was depressed, and the incidence of fetal anomalies was increased at 0.14 g kg/sup -1/ and all higher dose levels. 19 references, 1 figure, 5 tables.

    • Raising the Pregnant Rate of Rats and Comparison of Methods for Inspecting Pregnant Rats%两种大鼠受孕方法及两种判断受孕方法比较

      Institute of Scientific and Technical Information of China (English)

      毕晓洁; 李兴; 杨国珍; 潘卫

      2012-01-01

      Objective; To investigate the method for increasing pregnant rate of rats, and to explore the methods for judging pregnant rats. Methods; Twenty-four female rats were randomly divided into 2 groups; screening sexual cycle for copulating group (screening group) and prolonging time for copulating group ( prolonging time group). Rats in screening group copulated with male rats for two days in proestrus stage and their sexual cycle was detected with vaginal smear. Rats in prolonging time group copulated with male rats for 10 days directly. Whether female rats were pregnant was judged by 2 methods; vaginal sperm examination method and vaginal sperm combined with cuticular epithelium examination method. Delivery served as judging pregnancy standards. Pregnant rates of rats in screening group and in prolonging time group in the 1 st to 5th days and in the 6th to 10th days were observed. Two judgmental methods were compared. Results: There was significant difference in rat pregnant rates(F 0. 05). The false negative rates of vaginal sperm examination method and vaginal sperm combined with cuticular epithelium examination group were 0 and 11. 76% , and the false positive rates of them were 14. 29% and 0. Conclusions; Screening sexual cycle with vaginal smear method in improving pregnant rate is better than prolonging time method. Vaginal smear combined with screening sexual cycle helps to judging pregnant rats accurately.%目的:探讨提高实验大鼠受孕率的方法及准确判断大鼠受孕的检测方法.方法:24只SD雌鼠随机分为性周期筛选合笼组(筛选组)和延长时间合笼组(延长时间组),筛选组雌鼠根据阴道涂片于发情前期与雄鼠合笼2d,延长时间组雌鼠直接与雄鼠合笼10 d,采用阴道精子检查法和阴道精子合并角化上皮检查法判断合笼后雌鼠是否受孕,以分娩作为受孕成功的标准,观察两组受孕率,并比较两种判断受孕的方法.结果:筛选组受孕率(91.67

    • The effect of exposure to hypergravity on pregnant rat dams, pregnancy outcome and early neonatal development

      Science.gov (United States)

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

      2006-01-01

      We previously reported that hypergravity exposure affects food intake and mass gain during pregnancy. In the present study, we explored the hypothesis that changes in maternal body mass in hypergravity-exposed pregnant rat dams affect pregnancy outcome and early offspring development. Furthermore, we hypothesized that the changes observed at 1.5G will be magnified at higher gravity and by exposure during critical developmental periods. To test this hypothesis, we compared maternal body mass gain, food consumption, birth outcome and early offspring development between Sprague Dawley rat dams exposed to graded (1.5 1.75G) chronic hypergravity (HG) or rotation (rotational control, RC) on a 24-ft centrifuge for 22.5 h starting on gestational day (G) 10 with dams housed under identical conditions but not exposed to hypergravity (SC). We also compared maternal body mass, food consumption, birth outcome and early offspring development between rat dams exposed to 1.65G during different stages of pregnancy and nursing. Exposure to hypergravity resulted in transient loss in body mass and prolonged decrease in food consumption in HG dams, but the changes observed at 1.5G were not magnified at 1.65G or 1.75G. On the other hand RC dams gained more mass and consumed more food than SC dams. Exposure to hypergravity also affected pregnancy outcome as evidenced by decreased litter size, lowered neonatal mass at birth, and higher neonatal mortality; pregnancy outcome was not affected in RC dams. Neonatal changes evidenced by impaired righting response observed at 1.5G was magnified at higher gravity and was dependent on the period of hypergravity exposure. On the other hand, righting response was improved in RC neonates. Hypergravity exposure during early postpartum affected the food consumption of nursing mothers and affected early survival of their offspring. The changes observed in dams and neonates appear to be due to hypergravity exposure since animals exposed to the rotation

    • Cadmium causes delayed effects on renal function in the offspring of cadmium-contaminated pregnant female rats.

      Science.gov (United States)

      Jacquillet, G; Barbier, O; Rubera, I; Tauc, M; Borderie, A; Namorado, M C; Martin, D; Sierra, G; Reyes, J L; Poujeol, P; Cougnon, M

      2007-11-01

      In the adult rat, chronic cadmium intoxication induces nephropathy with Fanconi-like features. This result raises the question of whether intoxication of pregnant rats has any deleterious effects on renal function in their offspring. To test this hypothesis, we measured the renal function of 2- to 60-day-old postnatal offspring from female rats administered cadmium chloride by the oral route (0.5 mg.kg(-1).day(-1)) throughout their entire gestation. Investigations of rat offspring from contaminated pregnant rats showed the presence of cadmium in the kidney at gestational day 20. After birth, the cadmium kidney concentration increased from postnatal day 2 to day 60 (PND2 to PND60), presumably because of 1) milk contamination and 2) neonatal liver cadmium content release. Although the renal parameters (glomerular filtration, U/P inulin, and urinary excretion rate) were not significantly affected until PND45, renal failure appeared at PND60, as demonstrated by a dramatic decrease of the glomerular filtration rate associated with increased excretion of the main ions. In parallel, an immunofluorescence study of tight-junction protein expression of PND60 offspring from contaminated rats showed a disorganization of the tight-junction proteins claudin-2 and claudin-5, specifically expressed in the proximal tubule and glomerulus, respectively. In contrast, expression of a distal claudin protein, claudin-3, was not affected. In conclusion, in utero exposure of cadmium leads to toxic renal effects in adult offspring. These results suggest that contamination of pregnant rats is a serious and critical hazard for renal function of their offspring.

    • Plasma endothelin-1 and tumor necrosis factor-alpha concentrations in pregnant and cyclic rats after low-dose endotoxin infusion

      NARCIS (Netherlands)

      Faas, MM; Bakker, WW; Valkhof, N; Baller, JFW; Schuiling, GA

      1997-01-01

      Plasma endothelin-1 and tumor necrosis factor-alpha were determined in pregnant and cyclic rats after infusion of either endotoxin (1.0 mu g/kg of body weight) or saline solution. After endotoxin, but not after saline solution, administration there was a transient endothelin-1 response in pregnant r

    • Artesunate and artelinic acid: association of embryotoxicity, reticulocytopenia, and delayed stimulation of hematopoiesis in pregnant rats.

      Science.gov (United States)

      Clark, Robert L; Brannen, Kimberly C; Sanders, James E; Hoberman, Alan M

      2011-02-01

      The artemisinin antimalarials cause embryo death and malformations in animals by killing embryonic erythroblasts. Groups of pregnant rats (N = 4) were administered 35 and 48 µmol/kg artesunate and 17.2, 28.7, 48, 96, and 191 µmol/kg artelinic acid as a single oral dose on gestational day (GD) 12. Litters were examined on GD21. The ED(50) for embryo death with artelinic acid (23.4 µmol/kg) was just slightly lower than that for decreased reticulocyte count at 24 hr postdose (33.5 µmol/kg) and both had similarly steep dose responses (maximal effects of total litter loss and ∼60% decreases in reticulocyte count at 48 µmol/kg). Results with artesunate were similar. The correlation coefficient between embryo death and decreased reticulocyte count was 0.82 (pembryotoxicity and reticulocytopenia is suggestive of a common mechanism-artemisinin-induced mitochondrial damage leading to cell death. At 9 days postdose, treatment with artesunate and artelinic acid also caused increases in counts of reticulocytes, lymphocytes, basophils, and monocytes (up to 3.7 ×, 1.7 ×, 4.7 ×, and 1.7 × control, respectively). This stimulation of hematopoiesis may have been mediated by the direct oxidative conversion of artesunate or artelinic acid to the artemisininyl hydroperoxide within the bone marrow cells or by an indirect increase in reactive oxygen species. The high correlation between embryotoxicity and reticulocytopenia further supports the assertion that therapeutic dosage regimens of artemisinins that cause decreases in reticulocyte count in pregnant women during the putative critical period (approximately postconception wk 3 to 9) are at risk of also causing adverse effects on the embryo.

    • Morphological, Biochemical and Ultrastructural Changes in the Pregnant Rat Placenta and the Liver of their Fetuses Treated with Folic Acid and / or Gamma Radiation

      OpenAIRE

      Fatma, L. Ramadan and Seham M. Abu Nour

      2007-01-01

      Backgrounds: The efficacy of antioxidant supplementation and oxidative stress of gamma irradiation for and during pregnancy is poorly established. The present study aimed to detect the toxic effects of high dose of folic acid and / or gamma radiation on the placenta of pregnant rat and the liver of their fetuses. Material and Methods: Pregnant albino rats were divided into four groups. The first group served as a control, the second group received oral intake of folic acid (5 mg/kg) from the ...

    • BRAIN CHOLINESTERASE INHIBITION PRODUCED BY PROPOXUR AND DEPRESSION OF THE PHOTIC AFTER DISCHARGE OF FLASH EVOKED POTENTIALS IN LONG EVANS RATS.

      Science.gov (United States)

      Propoxur is a widely used N-methyl carbamate pesticide that acts by inhibiting cholinesterases (ChE), which may lead to cholinergic toxicity. Flash evoked potentials (FEPs) are a neurophysiological response following stimulation of the visual system with flashes of light. They ar...

  1. Short-term exposure to triclosan decreases thyroxine in vivo via upregulation of hepatic catabolism in young long-evans rats

    Science.gov (United States)

    Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol)is a chlorinated phenolic antibacterial compound used in consumer products. Structural similarity of triclosan to thyroid hormones, in vitro activation ofthe human pregnane X receptor (PXR) and induction of hepatic Phase I enzymes...

  2. SEXUALLY DIMORPHIC LORDOSIS BEHAVIOR IS MORE SENSITIVE TO DISRUPTION BY DEVELOPMENTAL EXPOSURE TO ETHINYL ESTRADIOL THAN IS REPRODUCTIVE MORPHOLOGY IN THE LONG EVANS FEMALE RAT.

    Science.gov (United States)

    Anthropogenic estrogens are pervasive in the environment. Although the effects of these xenoestrogens are controversial in humans, some fish species are adversely affected in contaminated ecosystems. While studies investigating endocrine disruptors typically focus on reproducti...

  3. Cardiovascular Ultrasound of Neonatal Long Evans Rats Exposed Prenatally to Trichloroacetic Acid: Effects on Heart Rate, Ejection Fraction, and Cardiac Output

    Science.gov (United States)

    This abstract describes the use of a relatively new technology, cardiovascular ultrasound (echocardiography) for evaluating developmental toxicity affecting heart development. The abstract describes the effects of two known cardiac teratogens, trichloroacetic acid and dimethadio...

  4. DEVELOPMENT OF A PHYSIOLOGICALLY-BASED PHARMACOKINETIC (PBPK) MODEL FOR THE INHALATION OF 2,2,4-TRIMETHYLPENTANE (TMP) IN LONG EVANS RATS.

    Science.gov (United States)

    TMP (2,2,4-trimethylpentane,“isooctane”) is a colorless liquid used primarily in the alkylation of isobutene and butylene reactions to derive high-octane fuels. TMP is released in the environment through the manufacture, use, and disposal of products associated with the gasoline ...

  5. Mechanisms responsible for hepatic very low density lipoprotein-apoB100 overproduction in Otsuka Long-Evans Tokushima fatty rats

    Science.gov (United States)

    Overproduction of hepatic very low-density lipoprotein (VLDL)1 particles is a major abnormality of lipoprotein dysregulation in type 2 diabetes (T2D). We sought to examine the mechanisms linking systemic/hepatic inflammation associated with insulin resistance and apolipoprotein (apo) B100-containing...

  6. The Effects of Nicotine on Antinociception in Male and Female Sprague-Dawley and Long-Evans Rats With and Without Stress

    Science.gov (United States)

    1998-05-01

    advisor, Dr. Neil Grunberg, and committee member, Dr. Eugene Levine. I also thank Dr. Val Hemming and Dr. Michael Sheridan. These individuals believed in...Etiology of Drug Abuse: Implications for Prevention, [( NIDA Research Monograph 56). Washington, DC: US Department of Health & Human Services

  7. The alpha(2)-adrenoceptors do not modify the activity of tyrosine hydroxylase, corticoliberine, and neuropeptide Y producing hypothalamic magnocellular neurons ion the Long Evans and Brattleboro rats

    DEFF Research Database (Denmark)

    Bundzikova, J; Pirnik, Z; Zelena, D

    2010-01-01

    The hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei are activated by body salt-fluid variations. Stimulation of alpha(2)-adrenoceptors by an agonist-xylazine (XYL) activates oxytocinergic but not vasopressinergic magnocellular neurons. In this study, tyrosine hydroxylase (TH), cort...

  8. The Effects of Female Sexual Hormones on the Expression of Aquaporin 5 in the Late-Pregnant Rat Uterus

    Directory of Open Access Journals (Sweden)

    Adrienn Csányi

    2016-08-01

    Full Text Available Thirteen mammalian aquaporin (AQP water channels are known, and few of them play a role in the mammalian reproductive system. In our earlier study, the predominance of AQP5 in the late-pregnant rat uterus was proven. Our current aim was to investigate the effect of estrogen- and gestagen-related compounds on the expression of the AQP5 channel in the late-pregnant rat uterus. Furthermore, we examined the effect of hormonally-induced preterm delivery on the expression of AQP5 in the uterus. We treated pregnant Sprague-Dawley rats subcutaneously with 17β-estradiol, clomiphene citrate, tamoxifen citrate, progesterone, levonorgestrel, and medroxyprogesterone acetate. Preterm delivery was induced by subcutaneous mifepristone and intravaginal prostaglandin E2. Reverse-transcriptase PCR and Western blot techniques were used for the detection of the changes in AQP5 mRNA and protein expressions. The amount of AQP5 significantly increased after progesterone and progesterone analogs treatment on 18 and 22 days of pregnancy. The 17β-estradiol and estrogen receptor agonists did not influence the AQP5 mRNA level; however, estradiol induced a significant increase in the AQP5 protein level on the investigated days of gestation. Tamoxifen increased the AQP5 protein expression on day 18, while clomiphene citrate was ineffective. The hormonally-induced preterm birth significantly decreased the AQP5 level similarly to the day of delivery. We proved that AQP5 expression is influenced by both estrogen and progesterone in the late-pregnant rat uterus. The influence of progesterone on AQP5 expression is more predominant as compared with estrogen.

  9. The Effects of Female Sexual Hormones on the Expression of Aquaporin 5 in the Late-Pregnant Rat Uterus.

    Science.gov (United States)

    Csányi, Adrienn; Bóta, Judit; Falkay, George; Gáspár, Robert; Ducza, Eszter

    2016-08-22

    Thirteen mammalian aquaporin (AQP) water channels are known, and few of them play a role in the mammalian reproductive system. In our earlier study, the predominance of AQP5 in the late-pregnant rat uterus was proven. Our current aim was to investigate the effect of estrogen- and gestagen-related compounds on the expression of the AQP5 channel in the late-pregnant rat uterus. Furthermore, we examined the effect of hormonally-induced preterm delivery on the expression of AQP5 in the uterus. We treated pregnant Sprague-Dawley rats subcutaneously with 17β-estradiol, clomiphene citrate, tamoxifen citrate, progesterone, levonorgestrel, and medroxyprogesterone acetate. Preterm delivery was induced by subcutaneous mifepristone and intravaginal prostaglandin E2. Reverse-transcriptase PCR and Western blot techniques were used for the detection of the changes in AQP5 mRNA and protein expressions. The amount of AQP5 significantly increased after progesterone and progesterone analogs treatment on 18 and 22 days of pregnancy. The 17β-estradiol and estrogen receptor agonists did not influence the AQP5 mRNA level; however, estradiol induced a significant increase in the AQP5 protein level on the investigated days of gestation. Tamoxifen increased the AQP5 protein expression on day 18, while clomiphene citrate was ineffective. The hormonally-induced preterm birth significantly decreased the AQP5 level similarly to the day of delivery. We proved that AQP5 expression is influenced by both estrogen and progesterone in the late-pregnant rat uterus. The influence of progesterone on AQP5 expression is more predominant as compared with estrogen.

  10. Acute social defeat does not alter cerebral 5-HT2A receptor binding in male Wistar rats

    DEFF Research Database (Denmark)

    Visser, Anniek K D; Meerlo, Peter; Ettrup, Anders;

    2014-01-01

    of stress on this receptor subtype. In this study, we therefore assessed acute and long-term changes in 5HT2A R binding after social defeat stress in rats. Male Wistar rats were subjected to social defeat by placing them in the home cage of an aggressive, dominant Long Evans rat. Acute social defeat...

  11. The celiac ganglion modulates LH-induced inhibition of androstenedione release in late pregnant rat ovaries

    Directory of Open Access Journals (Sweden)

    Rastrilla Ana M

    2006-12-01

    Full Text Available Abstract Background Although the control of ovarian production of steroid hormones is mainly of endocrine nature, there is increasing evidence that the nervous system also influences ovarian steroidogenic output. The purpose of this work was to study whether the celiac ganglion modulates, via the superior ovarian nerve, the anti-steroidogenic effect of LH in the rat ovary. Using mid- and late-pregnant rats, we set up to study: 1 the influence of the noradrenergic stimulation of the celiac ganglion on the ovarian production of the luteotropic hormone androstenedione; 2 the modulatory effect of noradrenaline at the celiac ganglion on the anti-steroidogenic effect of LH in the ovary; and 3 the involvement of catecholaminergic neurotransmitters released in the ovary upon the combination of noradrenergic stimulation of the celiac ganglion and LH treatment of the ovary. Methods The ex vivo celiac ganglion-superior ovarian nerve-ovary integrated system was used. This model allows studying in vitro how direct neural connections from the celiac ganglion regulate ovarian steroidogenic output. The system was incubated in buffer solution with the ganglion and the ovary located in different compartments and linked by the superior ovarian nerve. Three experiments were designed with the addition of: 1 noradrenaline in the ganglion compartment; 2 LH in the ovarian compartment; and 3 noradrenaline and LH in the ganglion and ovarian compartments, respectively. Rats of 15, 19, 20 and 21 days of pregnancy were used, and, as an end point, the concentration of the luteotropic hormone androstenedione was measured in the ovarian compartment by RIA at various times of incubation. For some of the experimental paradigms the concentration of various catecholamines (dihydroxyphenylalanine, dopamine, noradrenaline and adrenaline was also measured in the ovarian compartment by HPLC. Results The most relevant result concerning the action of noradrenaline in the celiac ganglion

  12. Appearance of circulating and tissue /sup 14/C-lipids after oral /sup 14/C-tripalmitate administration in the late pregnant rat

    Energy Technology Data Exchange (ETDEWEB)

    Argiles, J.; Herrera, E.

    1989-02-01

    Studies were performed to determine whether and/or how dietary lipids participate in maternal hypertriglyceridemia during late gestation in the rat. After oral administration of glycerol-tri(1-14C)-palmitate, total radioactivity in plasma increased more rapidly in 20-day pregnant rats than in either 19-day pregnant rats or virgin controls. At the peak of plasma radioactivity, four hours after the tracer was administered, most of the plasma label corresponded to 14C-lipids in triglyceride-rich lipoproteins (d less than 1.006), and when expressed per micromol of triglyceride, values were higher in pregnant than in virgin rats. The difference was less after 24 hours, although at this time the level of 14C-lipids in d less than 1.006 lipoproteins was still higher in 20-day pregnant rats than in virgins. Tissue 14C-lipids, as expressed per gram of fresh weight, were similar in pregnant and virgin rats, but the values in mammary glands were much higher in the former group. Estimated recovery of administered radioactivity four hours after tracer in total white adipose tissue, mammary glands, and plasma lipids was higher in pregnant than in virgin rats. No difference was found between 20-day pregnant and virgin rats either in the label retained in the gastrointestinal tract or in that exhaled as 14C-CO2 during the first four hours following oral administration of 14C-tripalmitate. These findings plus the known maternal hyperphagia, indicate that in the rat at late pregnancy triglyceride intestinal absorption is unchanged or even enhanced and that dietary lipids actively contribute to both maternal hypertriglyceridemia and lipid uptake by the mammary gland.

  13. Functional expression of purinergic P2X7 receptors in pregnant rat myometrium.

    Science.gov (United States)

    Miyoshi, Hiroshi; Yamaoka, Kaoru; Urabe, Satoshi; Kodama, Miho; Kudo, Yoshiki

    2010-04-01

    ATP has been reported to enhance the membrane conductance of myometrial cells and uterine contractility. Purinergic P2 receptor expression has been reported in the myometrium, using molecular biology, but the functional identity of the receptor subtype has not been determined. In this study, ATP-induced currents were recorded and characterized in single myometrial cells from pregnant rats using whole cell patch clamping. Extracellular ATP was applied in the range of 10 muM-1 mM and induced currents with an EC(50) of 74 muM, with no desensitization, time dependency, or voltage dependency. The currents induced carried multiple monovalent cations, with conductances ranked as K(+) > Cs(+) > Li(+) > Na(+). They were activated by P2X receptor agonists, with their effectiveness ranked as 2',3'-O-(4-benzoylbenzoyl)-ATP > ATP > alphabeta-methylene-ATP > 2-methylthio ATP > or = UTP > or = GTP > ADP. These currents were blocked by the selective P2X7 receptor antagonist 3-[5-(2,3-dichlorophenyl)-1 H-tetrazol-1-yl]methyl pyridine (A-438079). We therefore concluded that ATP-induced currents in rat myometrial cells crossed cell membranes via P2X7 receptors. We further showed that the ATP-induced currents were blocked by extracellular Mg(2+) (IC(50) = 0.26 mM). Clinically, administering extracellular Mg(2+) is known to inhibit uterine contraction. It therefore seems likely that uterine contraction may be induced by raised extracellular ATP and suppressed via Mg(2+) inhibiting P2X7 receptors. Further research is needed into the P2X7 receptor as a therapeutic target in abnormal uterine contraction, as a possible treatment for premature labor.

  14. Fate of orally administered radioactive fatty acids in the late-pregnant rat.

    Science.gov (United States)

    López-Luna, Pilar; Ortega-Senovilla, Henar; López-Soldado, Iliana; Herrera, Emilio

    2016-03-01

    To investigate the biodisponibility of placental transfer of fatty acids, rats pregnant for 20 days were given tracer amounts of [(14)C]palmitic (PA), oleic (OA), linoleic (LA), α-linolenic (LNA), or docosahexaenoic acid (DHA) orally and euthanized at 0.5, 1.0, 2.0, or 8.0 h thereafter. Maternal plasma radioactivity in lipids initially increased only to decline at later times. Most of the label appeared first as triacylglycerols (TAG); later, the proportion in phospholipids (PhL) increased. The percentage of label in placental lipids was also always highest shortly after administration and declined later; again, PhL increased with time. Fetal plasma radioactivity increased with time, with its highest value at 8.0 h after DHA or LNA administration. DHA initially appeared primarily in the nonesterified fatty acids (NEFA) and PA, OA, LA, and LNA as TAG followed by NEFA; in all cases, there was an increase in PhL at later times. Measurement of fatty acid concentrations allowed calculation of specific (radio)activities, and the ratio (fetal/maternal) of these in the plasmas gave an index of placental transfer activity, which was LNA > LA > DHA = OA > PA. It is proposed that a considerable proportion of most fatty acids transferred through the placenta are released into the fetal circulation in the form of TAG.

  15. The disposition of /sup 14/C-trimethyltin in the pregnant rat and fetus

    Energy Technology Data Exchange (ETDEWEB)

    Lipscomb, J.C.; Paule, M.G.; Slikker, W. Jr.

    1989-03-01

    Trimethyltin (TMT) is a potent neurotoxicant. For unknown reasons, age at exposure to TMT may dramatically influence the severity of TMT-induced neuropathology. We have demonstrated previously that radiolabel derived from (/sup 14/C)-TMT given to pregnant dams on gestational day (GD) 17 is found in fetal brain and blood. The present study was designed to determine the distribution of radiolabel derived from (14C)-TMT to brain and other tissue in fetuses from dams dosed on either GD 12 or 17 with 7.0 mg/kg TMT chloride. Radioactivity in GD 12 and GD 17 maternal whole blood peaked 1 hour after IP treatment. Whole blood elimination half-lives were 12-15 days. Peak radiolabel concentrations in GD 12 maternal and fetal brain were only 11-30% of those from GD 17 animals, however, peak fetal brain concentrations of radiolabel were not different from their respective maternal brain concentrations. Radiolabel concentrations in liver, kidney, and adrenal of GD 17 dams were higher than those in corresponding GD 12 tissues. Combined urinary and fecal elimination of radiolabel for two weeks after dosing accounted for 31 and 22% of the GD 12 and 17 doses, respectively. It appears that gestational age influences the distribution and elimination of TMT in the rat.

  16. The effect of recombinant aminopeptidase A (APA) on hypertension in pregnant spontaneously hypertensive rats (SHRs).

    Science.gov (United States)

    Ishii, Masakazu; Hattori, Akira; Numaguchi, Yasushi; Ma, Xiuyang; Nagasaka, Tetsuro; Tsujimoto, Masafumi; Murohara, Toyoaki; Kobayashi, Hiroshi; Mizutani, Sigehiko

    2009-09-01

    We have tested the effects of aminopeptidase A (APA), MgSO(4) and various conventional antihypertensive drugs on hypertension in pregnant spontaneously hypertensive rats (SHRs) and examined the effects on both fetal heart and kidney. We used recombinant human APA, which has been recently shown to work as an antihypertensive agent in SHRs (n=5). Each drug was administered from gestational day 10 to day 20 and each dose was increased daily up to 10 fold until the end of treatment except for MgSO(4) (n=5 per each group). Blood pressure (BP) was monitored and fetal kidneys and heart were histologically examined. The antihypertensive effects of the drugs were in the following order: hydralazine>aminopeptidase A and angiotensin receptor blockers (ARBs), candesartan>MgSO(4) and methyldopa. Microscopic examination showed that fetal exposure to candesartan is associated with poor proximal tubular differentiation in the kidney and that to MgSO(4) is associated with poor blood vessel formation in the heart, respectively. Our present study showed that APA is one of the candidates for antihypertensive agents in hypertension during pregnancy.

  17. Histological changes in kidney structure following a long-term administration of paracetamol (acetaminophen) in pregnant Sprague Dawley rats.

    Science.gov (United States)

    Ucheya, R E; Igweh, J C

    2006-01-01

    Histological changes in kidney structure following paracetamol administration in pregnant Sprague - Dawley rats were studied. Ten (10) Sprague-Dawley rats divided into five animals per group were used for the study. They were divided into two groups (A and B). Group A served as a control group, while group B received 7.3 mg x 3/kg/day of paracetamol from 10th day of gestation till the 13th day after parturition. The drug was administered by gavage. They were allowed free access to feed and water ad libitum. The maternal rats were then sacrificed for tissue processing. Three deaths were recorded amongst the maternal rats in the paracetamol treated group during parturition and a prolonged gestation period was also observed in the same animals while two maternal rats had a normal gestation period and a safe parturition. Histopathology results of the maternal control animals showed normal kidney architecture (very minimal capsular spaces and rounded glomeruli intimately surrounded by the Bowman's capsule). Two of the paracetamol treated maternal rats that had a safe parturition at the end of the normal gestation period and showed vascular congestion and glomeruli haemorrhage, while one of the maternal rats that had prolonged gestation period (44 days) with signs of abnormally high bleeding during parturition showed higher degree of kidney derangement which was evidenced by shrunken glomerulus's plus droplets in the tubules, vascular congestion, haemorrhage and tubular necrosis. These findings reflect derangement of kidney architecture. The results suggest that paracetamol though considered safe at a considerable low dose especially in pregnant state, could cause kidney derangement during pregnancy.

  18. Effects of methyl-deficient diets on methionine and homocysteine metabolism in the pregnant rat.

    Science.gov (United States)

    Wilson, Fiona A; Holtrop, Grietje; Calder, A Graham; Anderson, Susan E; Lobley, Gerald E; Rees, William D

    2012-06-15

    Although the importance of methyl metabolism in fetal development is well recognized, there is limited information on the dynamics of methionine flow through maternal and fetal tissues and on how this is related to circulating total homocysteine concentrations. Rates of homocysteine remethylation in maternal and fetal tissues on days 11, 19, and 21 of gestation were measured in pregnant rats fed diets with limiting or surplus amounts of folic acid and choline at two levels of methionine and then infused with L-[1-(13)C,(2)H(3)-methyl]methionine. The rate of homocysteine remethylation was highest in maternal liver and declined as gestation progressed. Diets deficient in folic acid and choline reduced the production of methionine from homocysteine in maternal liver only in the animals fed a methionine-limited diet. Throughout gestation, the pancreas exported homocysteine for methylation within other tissues. Little or no methionine cycle activity was detected in the placenta at days 19 and 21 of gestation, but, during this period, fetal tissues, especially the liver, synthesized methionine from homocysteine. Greater enrichment of homocysteine in maternal plasma than placenta, even in animals fed the most-deficient diets, shows that the placenta did not contribute homocysteine to maternal plasma. Methionine synthesis from homocysteine in fetal tissues was maintained or increased when the dams were fed folate- and choline-deficient methionine-restricted diets. This study shows that methyl-deficient diets decrease the remethylation of homocysteine within maternal tissues but that these rates are protected to some extent within fetal tissues.

  19. Comprehensive Assessment of Oxidatively Induced Modifications of DNA in a Rat Model of Human Wilson's Disease.

    Science.gov (United States)

    Yu, Yang; Guerrero, Candace R; Liu, Shuo; Amato, Nicholas J; Sharma, Yogeshwar; Gupta, Sanjeev; Wang, Yinsheng

    2016-03-01

    Defective copper excretion from hepatocytes in Wilson's disease causes accumulation of copper ions with increased generation of reactive oxygen species via the Fenton-type reaction. Here we developed a nanoflow liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry coupled with the isotope-dilution method for the simultaneous quantification of oxidatively induced DNA modifications. This method enabled measurement, in microgram quantities of DNA, of four oxidative stress-induced lesions, including direct ROS-induced purine cyclonucleosides (cPus) and two exocyclic adducts induced by byproducts of lipid peroxidation, i.e. 1,N(6)-etheno-2'-deoxyadenosine (εdA) and 1,N(2)-etheno-2'-deoxyguanosine (εdG). Analysis of liver tissues of Long-Evans Cinnamon rats, which constitute an animal model of human Wilson's disease, and their healthy counterparts [i.e. Long-Evans Agouti rats] showed significantly higher levels of all four DNA lesions in Long-Evans Cinnamon than Long-Evans Agouti rats. Moreover, cPus were present at much higher levels than εdA and εdG lesions. In contrast, the level of 5-hydroxymethyl-2'-deoxycytidine (5-HmdC), an oxidation product of 5-methyl-2'-deoxycytidine (5-mdC), was markedly lower in the liver tissues of Long-Evans Cinnamon than Long-Evans Agouti rats, though no differences were observed for the levels of 5-mdC. In vitro biochemical assay showed that Cu(2+) ions could directly inhibit the activity of Tet enzymes. Together, these results suggest that aberrant copper accumulation may perturb genomic stability by elevating oxidatively induced DNA lesions, and by altering epigenetic pathways of gene regulation.

  20. 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.

    2016-01-01

    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. PMID:27154534

  1. Distribution and Biomarker of Carbon-14 Labeled Fullerene C60 ([14C(U)]C60) in Pregnant and Lactating Rats and their Offspring after Maternal Intravenous Exposure

    Science.gov (United States)

    Snyder, Rodney W.; Fennell, Timothy R.; Wingard, Christopher J.; Mortensen, Ninell P.; Holland, Nathan A.; Shannahan, Jonathan H.; Pathmasiri, Wimal; Lewin, Anita H.; Sumner, Susan C. J.

    2015-01-01

    A comprehensive distribution study was conducted in pregnant and lactating rats exposed to a suspension of uniformly carbon-14 labeled C60 ([14C(U)]C60). Rats were administered [14C(U)]C60 (~0.2 mg [14C(U)]C60/kg body weight) or 5% polyvinylpyrrolidone (PVP)-saline vehicle via a single tail vein injection. Pregnant rats were injected on gestation day (GD) 11 (terminated with fetuses after either 24h or 8d), GD15 (terminated after 24h or 4d), or GD18 (terminated after 24h). Lactating rats were injected on postnatal day 8 and terminated after 24h, 3d or 11d. The distribution of radioactivity in pregnant dams was influenced by both the state of pregnancy and time of termination after exposure. The percentage of recovered radioactivity in pregnant and lactating rats was highest in liver and lungs. Radioactivity was quantitated in over 20 tissues. Radioactivity was found in placenta and in fetuses of pregnant dams, and in the milk of lactating rats and in pups. Elimination of radioactivity was <2% in urine and feces at each time point. Radioactivity remained in blood circulation up to 11 days after [14C(U)]C60 exposure. Biomarkers of inflammation, cardiovascular injury and oxidative stress were measured to study the biological impacts of [14C(U)]C60 exposure. Oxidative stress were elevated in female pups of exposed dams. Metabolomics analysis of urine showed that [14C(U)]C60 exposure to pregnant rats impacted the pathways of vitamin B, regulation of lipid and sugar metabolism and aminoacyl-tRNA biosynthesis. This study demonstrated that [14C(U)]C60 crosses the placenta at all stages of pregnancy examined, and is transferred to pups via milk. PMID:26081520

  2. Effects of L-arginine oral supplements in pregnant spontaneously hypertensive rats Efeitos da oferta oral de L-arginina em ratas prenhas espontaneamente hipertensas

    OpenAIRE

    José Ricardo Sousa Ayres de Moura; Nelson Sass; Sérgio Botelho Guimarães; Paulo Roberto Leitão de Vasconcelos; Rosiane Mattar; Luis Kulay Jr.

    2006-01-01

    PURPOSE: To evaluate the effects of L-arginine oral supplementation in spontaneously hypertensive pregnant rats (SHR). METHODS: Thirty SHR and ten Wistar-EPM-1 virgin female rats were used in the study. Before randomization, females were caged with males of the same strain (3:1). Pregnancy was confirmed by sperm-positive vaginal smear (Day 0). Wistar-EPM-1 rats served as counterpart control (C-1). SHR rats were randomized in 4 groups (n=10): Group Control 2, non-treated rats; Group L-Arginine...

  3. Interleukin-6 impairs endothelium-dependent NO-cGMP-mediated relaxation and enhances contraction in systemic vessels of pregnant rats.

    Science.gov (United States)

    Orshal, Julia M; Khalil, Raouf A

    2004-06-01

    IL-6 is elevated in plasma of preeclamptic women, and twofold elevation of plasma IL-6 increases vascular resistance and arterial pressure in pregnant rats, suggesting a role of the cytokine in hypertension of pregnancy. However, whether the hemodynamic effects of IL-6 reflect direct effects of the cytokine on the mechanisms of vascular contraction/relaxation is unclear. The purpose of this study was to test the hypothesis that IL-6 directly impairs endothelium-dependent relaxation and enhances vascular contraction in systemic vessels of pregnant rats. Active stress was measured in aortic strips isolated from virgin and late pregnant Sprague-Dawley rats and then nontreated or treated for 1 h with IL-6 (10 pg/ml to 10 ng/ml). In endothelium-intact vascular strips, phenylephrine (Phe, 10(-5) M) caused an increase in active stress that was smaller in pregnant (4.2 +/- 0.3) than virgin rats (5.1 +/- 0.3 x 10(4) N/m(2)). IL-6 (1,000 pg/ml) caused enhancement of Phe contraction that was greater in pregnant (10.6 +/- 0.7) than virgin rats (7.5 +/- 0.4 x 10(4) N/m(2)). ACh and bradykinin caused relaxation of Phe contraction and increases in vascular nitrite production that were greater in pregnant than virgin rats. IL-6 caused reductions in ACh- and bradykinin-induced vascular relaxation and nitrite production that were more prominent in pregnant than virgin rats. Incubation of endothelium-intact strips in the presence of N(omega)-nitro-L-arginine methyl ester (10(-4) M) to inhibit nitric oxide (NO) synthase, or 1H-[1,2,4]oxadiazolo[4,3]-quinoxalin-1-one (ODQ, 10(-5) M) to inhibit cGMP production in smooth muscle, inhibited ACh-induced relaxation and enhanced Phe-induced stress in nontreated but to a lesser extent in IL-6-treated vessels, particularly those of pregnant rats. Removal of the endothelium enhanced Phe-induced stress in nontreated but not IL-6-treated vessels, particularly those of pregnant rats. In endothelium-denuded strips, relaxation of Phe contraction with

  4. Phasic oscillations of extracellular potassium (K(o in pregnant rat myometrium.

    Directory of Open Access Journals (Sweden)

    Roger C Young

    Full Text Available K-sensitive microelectrodes were used to measure K(+ within the extracellular space (K(o of pregnant rat myometrium. Contractile activity was monitored by measuring either force or bioelectrical signals. Single and double-barreled electrodes were used. Double-barreled electrodes allowed monitoring of electrical activity 15 microns from the site of K(o measurement. From double-barreled electrode experiments, the bioelectrical burst started first, and then K(o began to rise 0.6 ± 0.1 seconds later. This delay indicates that K(+ leaves the cells in response to local electrical activity rather than vice versa. Four control experiments were performed to assess the influence of electrical artifacts caused by tissue motion on K(o values. When observed, artifacts were negative and transient, and hence would result in an underestimation of K(o rises. Artifacts were minimized when tissue motion was minimized by fixing the tissue at both ends. At 37°C, 7 single barreled experiments and 45 contractions were analyzed. Resting K(o was within 1 mM of bath K(+ (5 mM at the beginning and end of the experiments. K(o rose during the contraction, fell after the completion of the contraction, and normalized before the next contraction began. Peak K(o values observed during force production were 18.8 ± 5.9 mM, a value high enough to modulate tissue-level electrical activity. K(o required 15.7 ± 2.8 seconds to normalize halfway (t50. Six experiments expressing 38 contractions were performed at 24°C. The contraction period was longer at 24°C. Values for peak K(o (26.2 ± 9.9 mM and t50 (29.8±16.2 sec were both larger than at 37°C (p<0.0003 for both. The direct relationships between peak K(o, t50 and the contraction period, suggest elevations in K(o may modulate contraction frequency. The myometrial interstitial space appears to be functionally important, and K(o metabolism may participate in cell-cell interactions.

  5. Effect of i1 imidazoline receptor agonist, moxonidine, in nitric oxide-deficient hypertension in pregnant rats.

    Science.gov (United States)

    Gairard, Alexis; Lopez-Miranda, Visitacion; Pernot, Fanny; Beck, Jean F; Coumaros, Geneviève; Van Overloop, Bruno; La Roche, Benoît; Koehl, Christian; Christen, Marie O

    2004-05-01

    Decreased nitric oxide production has been reported in preeclampsia, which is also frequently associated with glucose intolerance. It was thus considered of interest to investigate the effects of moxonidine, a centrally acting antihypertensive drug that reduces insulin resistance, in a rat model of preeclampsia. Hypertension was induced in Wistar rats by dietary l-NNA (N(omega)-nitro-L-arginine, 0.063%, 31 mg/kg/d, days 13-19 of gestation) and, over the same period, moxonidine or vehicle was administered orally (2 mg/kg/d by gavage). On day 20, blood pressure was measured in the pentobarbital anesthetized animals, glucose tolerance was tested (2 g/kg glucose i.p.), and morphologic studies were conducted on the litter to determine the benefits with respect to fetal outcome. Hypertension was reduced with daily moxonidine treatment (P < 0.05). Basal plasma insulin and insulin/glucose index were decreased with moxonidine treatment evidencing improved insulin sensitivity in the control and l-NNA-treated pregnant rats (P < 0.05). After glucose challenge, plasma insulin increased in all the groups as expected and plasma insulin and insulin/glucose index were significantly higher in the l-NNA group than in the control, moxonidine, or l-NNA + moxonidine groups (P < 0.05 for time 60 minutes). Thus, moxonidine improved glucose tolerance in l-NNA-treated pregnant rats. Moreover, moxonidine treatment very effectively decreased the number of necroses (1 necrosis in 71 fetuses in the l-NNA + moxonidine group versus 15 necroses in 79 fetuses in the l-NNA group, P < 0.01). In conclusion, the 7-day treatment with moxonidine suppressed hypertension and reduced glucose intolerance and fetal necrosis, thus demonstrating the effectiveness of moxonidine in the preeclamptic model.

  6. 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.

  7. Appetite regulation is independent of the changes in ghrelin levels in pregnant rats fed low-protein diet.

    Science.gov (United States)

    Gao, Haijun; Tanchico, Daren T; Yallampalli, Uma; Balakrishnan, Meena P; Yallampalli, Chandra

    2015-04-01

    Gestational protein restriction causes hypertension in the adult offspring. Very little is known about the food intake regulation and ghrelin signaling in pregnant dams fed a low-protein (LP) diet. We hypothesized that diet intake and ghrelin signaling are altered in pregnant rats fed the low-protein diet. Sprague-Dawley rats were fed a control (CT) or LP diet from Day 3 of pregnancy. Diet intake and body weight were monitored daily. Expression of ghrelin production-related genes in the stomach and appetite-related genes in the hypothalamus was analyzed by real-time PCR. Plasma levels of total and active ghrelin, growth hormone and leptin were measured by ELISA. Main results include: (1) Daily diet intake was greater in the LP group than in the CT group in early pregnancy, but substantially lower in late pregnancy; (2) Daily gain in body weight was substantially lower in the LP group in late pregnancy; (3) Expression of ghrelin production-related genes in the stomach and plasma total ghrelin levels were increased in LP group in late pregnancy; (4) Plasma active ghrelin levels were elevated in the LP group at mid-late pregnancy, but growth hormone and leptin levels were uncorrelated with active ghrelin in late pregnancy; and (5) Hypothalamic expression of ghrelin-stimulated genes in LP rats was unassociated with the changes in both plasma ghrelin levels and the diet intake. Taken together, the appetite in LP rats is greater in early pregnancy but reduced at late pregnancy, possibly due to ghrelin insensitivity in appetite regulation. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  8. 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

  9. Studies on apoptotic changes in combined toxicity of citrinin and endosulfan in pregnant wistar rats and their fetuses.

    Science.gov (United States)

    Singh, N D; Sharma, A K; Dwivedi, P; Telang, A G; Kumar, M; Patil, R D

    2012-05-01

    Citrinin (mycotoxin) and endosulfan (pesticide) both environmental contaminants easily enter the food chain and are caoomon causes of various toxicities. In the present investigation, citrinin (CIT) (10 mg/kg feed) and endosulfan (1 mg/kg body weight) were administered orally alone and in combination to pregnant Wistar rats from gestational day 6 to 20 to study their effect to cause apoptosis in the pregnant Wistar rats and their fetuses. Apoptosis was assessed in dams by agarose gel electrophoresis, flow cytometry and electron microscopy, while in the fetuses it was assessed by flow cytometry only. Citrinin and endosulfan in the combination group caused apoptosis in an additive manner as there was increased number of apoptotic cells as compared to the individual toxin and control groups. The fetuses also showed increased number of apoptotic cells in the combination groups, which also indicated that both the toxins crossed the placental barrier. So it was concluded that apoptosis played a significant role in the pathogenesis of endosulfan and citrinin toxicity.

  10. Extracts from rabbit skin inflamed by the vaccinia virus attenuate bupivacaine-induced spinal neurotoxicity in pregnant rats

    Institute of Scientific and Technical Information of China (English)

    Rui Cui; Shiyuan Xu; Liang Wang; Hongyi Lei; Qingxiang Cai; Hongfei Zhang; Dongmei Wang

    2013-01-01

    Extracts from rabbit skin inflamed by the vaccinia virus can relieve pain and promote repair of nerve injury. The present study intraperitoneally injected extracts from rabbit skin inflamed by the vaccinia virus for 3 and 4 days prior to and following intrathecal injection of bupivacaine into pregnant rats. The pain threshold test after bupivacaine injection showed that the maximum possible effect of tail-flick latency peaked 1 day after intrathecal injection of bupivacaine in the extract-pretreatment group, and gradually decreased, while the maximum possible effect in the bupivacaine group continued to increase after intrathecal injection of bupivacaine. Histological observation showed that after 4 days of intrathecal injection of bupivacaine, the number of shrunken, vacuolated, apoptotic and caspase-9-positive cells in the dorsal root ganglion in the extract-pretreatment group was significantly reduced compared with the bupivacaine group. These findings indicate that extracts from rabbit skin inflamed by the vaccinia virus can attenuate neurotoxicity induced by intrathecal injection of bupivacaine in pregnant rats, possibly by inhibiting caspase-9 protein expression and suppressing nerve cell apoptosis.

  11. Decreased seizure threshold in an eclampsia-like model induced in pregnant rats with lipopolysaccharide and pentylenetetrazol treatments.

    Directory of Open Access Journals (Sweden)

    Qian Huang

    Full Text Available OBJECTIVE: Eclampsia is a poorly understood but potentially fatal complication of pregnancy. Research to date on this disorder has been hampered by the lack of a suitable animal model. To correct this deficiency, this report describes the generation of a rat eclampsia-like model using pentylenetetrazol (PTZ in a previously established rat preeclampsia model. METHOD: Rats were administered lipopolysaccharide (1.0 µg/kg by tail vein injection on gestational day 14 to establish preeclampsia (PE. PE and control rats (non-pregnant, NP; normal-pregnant, P were injected intraperitoneally (i.p. with PTZ (40 mg/kg to induce seizures. In separate experiments, MgSO4 (270 mg/kg IP was injected in advance of PTZ into PE rats to observe its effect on PTZ-induced seizures. RESULTS: PE conditions were verified in rats after LPS administration by significantly higher blood pressure (P<0.01 and urinary albumin excretion (P<0.05, elevated sFlt-1 (P<0.05 and decreased PlGF serum levels (P<0.05, and evidence of hepatic dysfunction compared to control groups. PTZ successfully induced seizure activity in all groups studied. Latency to seizure was significantly (P<0.01 less in the PE-PTZ group (73.2 ± 6.6 sec. than in PTZ-treated controls (107.0 ± 7.4 sec.. Pretreatment with MgSO4 prolonged (P<0.05 latency to seizure, shortened seizure duration and decreased seizure rates. Significant increased (P<0.05 in the serum levels of the inflammatory cytokines TNF-α and IL-1β in PE and PE-PTZ groups, and decreased (P<0.05 in their levels following MgSO4 administration. CONCLUSION: This PTZ-induced eclampsia-like rat model is comparable to the human condition of eclampsia and may serve as a useful research tool for future studies of this disease. The increased inflammatory cytokines in preeclampsia are coincident with a decreased threshold for PTZ-induced seizures, suggesting that an inflammatory mechanism may contribute to the susceptibility to seizure activity and

  12. Oogenesis, fertilisation and early embryonic development in rats. I: Dose-dependent effects of pregnant mare serum gonadotrophins.

    Science.gov (United States)

    Goh, H H; Yang, X F; Tain, C F; Liew, L P; Ratnam, S S

    1992-07-01

    Five hundred and eight mature female Wistar rats divided into 35 different groups were stimulated with pregnant mare serum gonadotrophins (PMSG) (0, 5, 10, 20 & 40 IU) at the late diestrus stage to induce multiple follicular development. No chorionic gonadotrophin (CG) was used for ovulation induction. The quality of oocytes and their in vitro fertilisability, quality of Day 2-embryos, viability of pregnancy and status of fetuses on Day 14 of gestation and status of embryos retrieved on Day 2, 3, 4 and 5 of pregnancy in different subgroups of rats were examined. Results showed that more oocytes and embryos fertilised in in vivo were retrieved from rats supraphysiologically stimulated with 20 IU of PMSG. However, concurrent with the larger number, higher proportions of abnormal oocytes and embryos were found. High doses of PMSG caused lower in vitro fertilisability of oocytes and greater degrees of embryonic degeneration. Although, the number of oocytes and Day 2-embryos were higher in the 20PMGS dose group, the pregnancy rate was significantly reduced to 27%. In the 40PMSG group no viable pregnancy was noted. Most embryo demise occurred by day 3-5 of pregnancy, probably within the oviducts and before the implantation stage. In rats supraphysiologically stimulated with 20 and 40 IU of PMSG, the number of morphologically normal looking embryos was greatly reduced by Day 3-5 of pregnancy. In the 40PMSG group, there were no embryos retrieved by Day 4 and 5.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Differential body weight, blood pressure and placental inflammatory responses to normal versus high-fat diet in melanocortin-4 receptor-deficient pregnant rats.

    Science.gov (United States)

    Spradley, Frank T; Palei, Ana C; Granger, Joey P

    2016-10-01

    Although obesity increases the risk for hypertensive disorders of pregnancy, the mechanisms remain unclear. Neural melanocortin-4 receptor (MC4R) deficiency causes hyperphagia and obesity. Effects of MC4R deficiency on body weight, blood pressure (BP) and placental inflammatory responses to high-fat diet (HFD) are unknown. We tested two hypotheses: MC4R deficiency results in higher body weight, BP and placental inflammation under normal-fat diet (NFD) conditions and HFD exaggerates these responses in MC4R-deficient pregnant rats. MC4R and MC4R rats were maintained on NFD (13% kcal fat) or HFD (40% kcal fat) for ∼15 weeks, then measurements made on gestational day 19. MC4R pregnant rats had greater body mass and total body fat and visceral adipose tissue weights along with greater circulating total cholesterol (TC) and leptin levels than MC4R rats regardless of diet. On NFD, circulating adiponectin levels were lower and placental TNFα levels and BP (conscious with carotid catheter) were higher in these heavier rats. Circulating adiponectin levels were lower and placental TNFα levels and BP were higher in MC4R rats compared with NFD controls. These parameters were not affected by HFD in the already heavier and hypertensive MC4R pregnant rats. Obesity in MC4R deficiency and HFD in MC4R rats result in higher BP and placental inflammation during pregnancy. However, HFD did not exaggerate these responses in already obese MC4R pregnant rats. These data suggest that obesity and HFD are independently related to hypertension and placental inflammation in pregnancy.

  14. Toxic effects of zearalenone on oxidative stress, inflammatory cytokines, biochemical and pathological changes induced by this toxin in the kidney of pregnant rats.

    Science.gov (United States)

    Jia, Zhiqiang; Liu, Min; Qu, Zhe; Zhang, Yuanyuan; Yin, Shutong; Shan, Anshan

    2014-03-01

    An experiment was conducted to determine the toxic effects of zearalenone (ZEN) on oxidative stress, inflammatory cytokines, biochemical and pathological changes in the kidney of pregnant rats, and to explore the possible mechanism in ZEN induced kidney damage. The rats were fed a normal diet treated with 0.3, 48.5, 97.6 or 146 mg/kg ZEN in feed on gestation days (GDs) 0 through 7, and then all the rats were fed with a normal diet on GDs 8 through 20. The results showed that ZEN induced kidney dysfunction, oxidative damage, pathological changes and increased mRNA and protein expression of TLR4 and inflammatory cytokines in kidney in dose-dependent manner. The results indicated that ZEN caused kidney damage of pregnant rats and TLR4-mediated inflammatory reactions signal pathway was one of the mechanisms of ZEN mediated toxicity in kidney. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Response Acquisition and Fixed-Ratio Escalation Based on Interresponse Times in Rats

    Science.gov (United States)

    Taylor, Tracy G.; Galuska, Chad M.; Banna, Kelly; Yahyavi-Firouz-Abadi, Noushin; See, Ronald E.

    2010-01-01

    The effectiveness of a fixed-ratio (FR) escalation procedure, developed by Pinkston and Branch (2004) and based on interresponse times (IRTs), was assessed during lever-press acquisition. Forty-nine experimentally naive adult male Long Evans rats were deprived of food for 24 hr prior to an extended acquisition session. Before the start of the…

  16. Trapped blood elements within the decidua of the rat pregnant uterus generate a lipoxygenase product(s) which inhibits myometrial prostacyclin synthesis

    OpenAIRE

    El Tahir, K.E.H.; Williams, K I

    1981-01-01

    1 Prostacyclin (PGI2) production by chopped segments of rat pregnant uterus was low compared with synthesis by separated myometrial tissue. Incubation of separated myometrium with decidua (2:1 by weight) led to an inhibition of myometrial PGI2 output.

  17. The increased endotoxin-sensitivity of pregnant rats, as reflected by glomerular Ecto-ADP-ase activity, is not dependent on the presence of decidual cells

    NARCIS (Netherlands)

    Faas, MM; Schuiling, GA; Baller, JFW; Valkhof, N; Bakker, WW

    1996-01-01

    In the present study the possible role of decidual cells in the pregnancy-associated increased sensitivity of glomerular ecto-ADP-ase to endotoxin was investigated. Early (day 5) pregnant (E-Pr; n = 10), pseudopregnant (E-PSP; n = 10), (day 5), pseudopregnant rats with a decidualized uterus (E-DEC;

  18. The Role of Clomipramine in Potentiating the Teratogenic Effects of Caffeine in Pregnant Rats: A Histopathological Study

    Directory of Open Access Journals (Sweden)

    Vahid Nikoui

    2013-01-01

    Full Text Available Since little is known about the teratogenic effects of clomipramine used concurrently with caffeine during the organogenesis period, the aim of this study was to test the teratogenic effects of a coadministration of caffeine and clomipramine on rat fetuses. We divided 42 pregnant rats into seven groups, randomly. The first group (control received 0.5 mL of normal saline. Clomipramine was injected at 40 mg/kg and 80 mg/kg to the second and third groups, respectively. The fourth and fifth groups received caffeine in doses of 60 mg/kg and 120 mg/kg, respectively. The sixth group received a combination of 40 mg/kg clomipramine and 60 mg/kg caffeine, and the seventh group was given clomipramine and caffeine at 80 mg/kg and 120 mg/kg, respectively. The fetuses were removed on the 17th day of pregnancy and studied in terms of microscopic and macroscopic morphological features. Fetuses of rats receiving high doses of caffeine or combinations of caffeine and clomipramine showed a significant rate of cleft palate development, open eyelids, mortality, torsion anomalies, shrinkage of skin, and subcutaneous haemorrhage (P≤0.001. This study concludes that caffeine in high doses or the simultaneous administration of caffeine and clomipramine leads to teratogenicity.

  19. [Role of oxytocin in activation of spontaneous electrical activity of uterine body and uterine tubes in non-pregnant rats].

    Science.gov (United States)

    Kazarian, K V; Unanian, N G; Meliksetian, I B; Akopian, R R; Saakian, A A

    2011-01-01

    The work studies effects of various doses of oxytocin (0.01, 0.1, 1 and 10 microg/kg) on duration of discharges of spontaneous electrical activity and frequency of spikes in various parts of uterine tubes and of uterine body of non-pregnant rats. Under these conditions, changes in these parameters for ovarian parts of the uterine tubes had similar character unlike those in cervical parts of the tubes and in the middle part of the uterine body, so the latter parts can be grouped together owing to peculiarities of their changes. The longest duration of genesis of electric discharges has been shown for the ovarian part of uterine tubes at a concentration of 10 microg/kg of oxytocin. Morphological experiments revealed that among all studies areas the ovarian parts of uterine tubes were characterized by the highest amount of atypical cells that have the maximally pronounced functional activity.

  20. The effects of adjuvant arthritis on the myometrial adrenergic functions in the nonpregnant and the late-pregnant rat.

    Science.gov (United States)

    Csik, G; Spiegl, G; Minorics, R; Falkay, G; Zupko, I

    2010-10-01

    The beneficial effects of pregnancy on the symptoms of inflammatory diseases are well documented. The modulation in the uterine functions in the presence of generalized inflammation, however, is much less characterized. The aim of the present study was to explore the modulatory action of adjuvant arthritis on the adrenergic functions of the uterus in nonpregnant and late pregnant rats. Adjuvant arthritis was induced by the subplantar injection of M. butyricum. Presynaptic functions were characterized by a superfusion technique and by registration of the contractions of isolated uterine rings elicited by electric field stimulation. The functions of the adrenoceptors were characterized by constructing concentration-response curves with agonists for both α- and β-receptors. Where these curves differed significantly from the control, the expressions of these receptors at the mRNA level were additionally determined. Adjuvant arthritis substantially decreased the uptake and release of [(3)H]noradrenaline in myometrial samples from nonpregnant rats, but caused no change at term. The electrically induced contractions were decreased by inflammation in both gestational states. Arthritis resulted in decreased β-adrenoceptor-mediated relaxation (in both the nonpregnant and the late-pregnant animals) and an increase in α-mediated contraction at term. It can be concluded that adjuvant arthritis deteriorates the adrenergic innervation of the uterus. The effects of exogenous sympathomimetics are shifted, favoring a state of higher contractility. If similar mechanisms are operative in humans, the present results could imply that β-adrenoceptor agonists are not ideal tocolytics when pregnancy is complicated by generalized inflammation.

  1. The effects of vitamin D3 on lipogenesis in the liver and adipose tissue of pregnant rats.

    Science.gov (United States)

    Kang, Eun-Jin; Lee, Jae-Eon; An, Sung-Min; Lee, Jae Ho; Kwon, Hyeog Soong; Kim, Byoung Chul; Kim, Seon Jong; Kim, Joo Man; Hwang, Dae Youn; Jung, Young-Jin; Yang, Seung Yun; Kim, Seung Chul; An, Beum-Soo

    2015-10-01

    Obesity is a worldwide individual and public health issue, and contributes to the development of numerous chronic diseases. In particular, maternal obesity has harmful effects on both the mother and child during and after pregnancy. The digestion and metabolism of food are controlled by endocrine factors, including insulin, glucagon and estrogen. These hormonal factors are differentially regulated during pregnancy due to the specialized hormonal environment during this period. In the present study, we examined the effects of 1,25-dihydroxyvitamin D3 (VD3), an active hormonal form of nutritional vitamin D3, on lipid metabolism in pregnant rats. The body weight of rats treated with VD3 was significantly reduced compared to that of the rats in the control group. In addition, histological analysis demonstrated that the amount of fat stored in adipocytes was reduced by treatment with VD3. To determine the role of VD3 in lipid metabolism, the expression levels of lipid metabolism‑associated genes were measured in the rat adipose tissue and liver. VD3 negatively regulated the expression of various lipogenic genes, including fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD1) and acetyl-CoA carboxylase 1 (ACC1), in both the adipose tissue and liver. However, the regulators of lipogenic enzymes such as, sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-γ (PPAR-γ) and insulin-induced gene 2 (INSIG2) were differentially regulated by VD3 in a tissue‑specific manner. On the whole, these findings suggest that VD3 regulates lipid metabolism and deposition in the liver and adipose tissue, and thereby reduces fat in pregnant animals, as well as body weight. Our results suggest that the alteration of lipogenesis through the administration of VD3 may help to reduce excessive weight gain during pregnancy and prevent obesity‑related pregnancy complications such as pre-eclampsia, gestational diabetes

  2. Selenium and vitamin E modulates radiation-induced liver toxicity in pregnant and nonpregnant rat: effects of colemanite and hematite shielding.

    Science.gov (United States)

    Gençel, Osman; Naziroglu, Mustafa; Celik, Omer; Yalman, Kadir; Bayram, Dilek

    2010-06-01

    The levels of liver lipid peroxidation, glutathione peroxidase, reduced glutathione, and vitamins A and E were used to follow the level of oxidative damage caused by ionizing radiation in pregnant rats. The possible protective effects of selenium and vitamin E supplemented to rats housed in concrete-protected cages using hematite and colemanite were tested and compared to untreated controls. Ninety-six rats were randomly divided into four main equal groups namely control (A), normal concrete (B), concrete containing colemanite (C), and concrete containing hematite (D). Except group A, all groups exposed to 7 Gy radiation. The four main groups were divided into four subgroups each as follows: subgroups 1 (n = 6): nonpregnant control rats. Subgroups 2 (n = 6): selenium and vitamin E combination was intraperitoneally (i.p.) given to the nonpregnant rats for 20 days. Subgroups 3 (n = 6): pregnant control rats. Subgroups 4 (n = 6): selenium and vitamin E combination was i.p. given to the pregnant rats for concessive 20 days. Lactate dehydrogenate, alkaline phosphates, and lipid peroxidation values were higher in subgroups 1 and 3 than in no radiation group although glutathione peroxidase and vitamin E levels in liver were lower in radiation group than in no radiation group. Lactate dehydrogenate activity and lipid peroxidation levels were found to be decreased in subgroups 2 and 4 protected with concrete containing hematite and colemanite when compared to subgroup 1 and 3 with normal concrete. The radiation doses in rats housed by concrete without colemanite and hematite exposed radiation clearly showed liver degeneration. In conclusion, selenium and vitamin E supplementations and housing by concrete with colemanite was found to offer protection against gamma-irradiation-induced liver damage and oxidative stress in rats, probably by exerting a protective effect against liver necrosis via its free radical scavenging and membrane stabilizing. Protective effects of

  3. Identification of Site of Morphine Action in Pregnant Wistar Rat Placenta Tissue: A C14-Morphine Study

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    Leila Dehghani

    2012-01-01

    Full Text Available Objective: In previous studies it has been emphasized that the site of morphine action may be either in the embryo or the placenta. In the present study, we attempt to identify the site of morphine action on the fetal section of Wistar rat placenta by using C14-morphine.Materials and Methods: In this study (experimental, female Wistar rats (weights: 170-200 g were mated with male rats and their coupling times recorded. Experimental groups received daily doses of 0.05 mg/ml of C14-morphine in their drinking water. On the 9th and14th embryonic days, the pregnant rats were anesthetized and the placenta and uterus surgically removed. Placentas were fixed in 10% formalin for two weeks, then processed, sectioned in 5 μm and 25 μm thicknesses, and fixed on glass slides for further evaluation. The 25 μm sections were delivered to black and white film for three days. Films were processed and evaluated with a digital inverse microscope for possible radiological impression. The 5 μm sections were processed for hematoxylin and eosin (H&E staining, and evaluated by light microscope and MOTIC software.Results: Our results indicated that the site of action of C14-morphine was possibly located on the blood plexus of the fetal portion of the placenta. In addition, oral morphine consumption was shown to inhibit fetal and maternal placental development in the experimental groups.Conclusion: We conclude that morphine’s effectiveness on the reduction of embryo growth and development may be via its effects on the blood plexus of the fetal section of the placenta.

  4. Soy compared with milk protein in a western diet changes fecal microbiota and decreases hepatic steatosis in obese OLETF rats

    Science.gov (United States)

    Soy protein is effective at preventing hepatic steatosis; however, the mechanisms are poorly understood. We tested the hypothesis that soy versus dairy protein-based diet would alter microbiota and attenuate hepatic steatosis in hyperphagic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Male OLETF ...

  5. TIME COURSE OF CHOLINESTERASE INHIBITION IN ADULT RATS TREATED ACUTELY WITH CARBARYL CARBOFURAN, FORMETANATE, METHOMYL, METHIOCARB, OXAMYL ON PROPOXUR.

    Science.gov (United States)

    To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n=4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); ...

  6. Obesity-related changes in bone structural and material properties in hyperphagic OLETF rats and protection by voluntary wheel running

    Science.gov (United States)

    We conducted a study to examine how the development of obesity and the associated insulin resistance affect bone structural and material properties, and bone formation and resorption markers in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat model. This was a 36-week study of sedentary, hyperphag...

  7. Placental Protein 13 Administration to Pregnant Rats Lowers Blood Pressure and Augments Fetal Growth and Venous Remodeling.

    Science.gov (United States)

    Gizurarson, Sveinbjorn; Sigurdardottir, Elisabet Run; Meiri, Hamutal; Huppertz, Berthold; Sammar, Marei; Sharabi-Nov, Adi; Mandalá, Maurizio; Osol, George

    2016-01-01

    Reduced first-trimester concentrations of placental protein 13 (PP13) are associated with subsequent development of preeclampsia, a major pregnancy disorder. We previously showed that PP13 has a vasodilatory effect, reduces blood pressure and augments expansive remodeling of the uteroplacental vasculature in pregnant rats. In this study, slow-release osmotic pumps were implanted in gravid rats (on day 8) to provide 1 week of PP13 supplementation. Treatment was associated with a reversible blood pressure reduction that returned to normal on day 15. In addition, PP13 caused venous expansion that is larger in the venous branches closer to the placenta. Then, it increased placental and pup weights. Similar administration of a truncated PP13 variant (DelT221) that is unable to bind carbohydrates (a rare spontaneous mutation associated with a high frequency of severe early preeclampsia among Blacks in South Africa) produced a hypotensive effect similar to the full-length molecule, but without venous remodeling and increased placental and pup weights. These results indicate the importance of PP13 carbohydrate binding for inducing vascular remodeling and improving reproductive outcome. Future studies are needed to determine whether beneficial effects would be evident in animal models of preeclampsia or in women predisposed to the development of preeclampsia.

  8. Effects of Electroacupuncture at Different Acupoints on Changes of Uterine Myoelectricity Induced by Oxytocin and Progesterone in Pregnant Rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To observe the effects of electroacupuncture (EA) at different acupoints on abnormal changes of uterine myoelectric activities in pregnant rats so as to analyze the specificity of regulative effects of the acupoint. Methods: Forty-eight pregnant (18-20 days) Wistar rats were randomly divided into control group (n=10), "Sanyinjiao" (SP 6) group (n=9), "Neiguan" (PC 6) group (n=10), "Hegu" (LI 4) group (n=8), and "Sanyinjiao plus Hegu" group (n=11). These rats were anesthetized by intraperitoneal injection of a mixture solution of 1.5% chloralose (50mg/kg) and 25% urethane (420mg/kg). Electrohysterogram (EHG) was recorded by using a pair of stainless steel electrodes inserted into the subserous layer of the left mid part of the uterus. The reference electrode was placed in the adjoining subcutaneous tissue of the incision. Oxytocin and progesterone were given to the local uterus nearby the recording electrode to induce excitement and suppression of myoelectric activities of the uterus respectively. EA (2mA, 5/15Hz) was carried out at the above-mentioned acupoints separately for 20min, and the influence of EA on changes (amplitude and frequency) of fast waves and slow waves of the uterine myoelectric activity was analyzed. Results: As compared with control group, EA at SP6 plus LI4 and at SP6 alone had a significantly inhibitory effect on oxytocin-induced increase in the frequency and amplitude of both fast and slow waves (P0.05). Compared with control group, EA at SP6 plus LI4 and at SP6 alone could relieve or significantly relieve progesterone-induced suppression of the frequency and amplitude of both fast and slow waves (P0.05). Conclusion: EA at SP6 plus LI4 and at SP6 alone has a dual-directional regulative effect on abnormal EHG, the effect of EA at SP6 plus LI4 is the strongest, EA at SP6 the secondary, EA at LI4 the weakest, and EA at PC6 shows no effect. In short, EA at different acupoints have their own relative specificity in regulating abnormal

  9. Respiratory Tract Lung Geometry and Dosimetry Model for Male Sprague-Dawley Rats

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Frederick J.; Asgharian, Bahman; Schroeter, Jeffry D.; Price, Owen; Corley, Richard A.; Einstein, Daniel R.; Jacob, Rick E.; Cox, Timothy C.; Kabilan, Senthil; Bentley, Timothy

    2015-07-24

    While inhalation toxicological studies of various compounds have been conducted using a number of different strains of rats, mechanistic dosimetry models have only had tracheobronchial (TB) structural data for Long-Evans rats, detailed morphometric data on the alveolar region of Sprague-Dawley rats and limited alveolar data on other strains. Based upon CT imaging data for two male Sprague-Dawley rats, a 15-generation, symmetric typical path model was developed for the TB region. Literature data for the alveolar region of Sprague-Dawley rats were analyzed to develop an eight-generation model, and the two regions were joined to provide a complete lower respiratory tract model for Sprague-Dawley rats. The resulting lung model was used to examine particle deposition in Sprague-Dawley rats and to compare these results with predicted deposition in Long-Evans rats. Relationships of various physiologic variables and lung volumes were either developed in this study or extracted from the literature to provide the necessary input data for examining particle deposition. While the lengths, diameters and branching angles of the TB airways differed between the two Sprague-Dawley rats, the predicted deposition patterns in the three major respiratory tract regions were very similar. Between Sprague-Dawley and Long-Evans rats, significant differences in TB and alveolar predicted deposition fractions were observed over a wide range of particle sizes, with TB deposition fractions being up to 3- to 4-fold greater in Sprague-Dawley rats and alveolar deposition being significantly greater in Long-Evans rats. Thus, strain-specific lung geometry models should be used for particle deposition calculations and interspecies dose comparisons.

  10. Inflammatory processes enhance cAMP-mediated uterus relaxation in the pregnant rat: the role of TNF-alpha.

    Science.gov (United States)

    Klukovits, Anna; Márki, Arpád; Páldy, Eszter; Benyhe, Sándor; Gálik, Márta; Falkay, George; Gáspár, Róbert

    2009-05-01

    The objective of this study was to assess the in vitro uterus relaxing potency of beta(2)-adrenergic receptor (beta(2)-AR) agonists in pregnant rats after in utero administration of the bacterial lipopolysaccharide, Escherichia coli endotoxin (LPS). The LPS (100 microg/kg) was injected into the uterine lumen on day 16 of pregnancy. The effects of beta(2)-AR agonist terbutaline was tested in vitro, in isolated uterine rings precontracted by electric field stimulation. Uterine beta(2)-AR densities were detected by radioligand binding assay, the activated G-protein levels were investigated by a radiolabelled GTP binding assay. Uterine cAMP accumulation and the serum tumor necrosis factor-alpha (TNF-alpha) levels were measured by enzyme immunoassay. The endotoxin-evoked preterm delivery occurred on day 21. Higher pD(2) values of terbutaline (p 0.05) in LPS-treated vs. control animals. Serum TNF-alpha level rose threefold after LPS treatment, but this rise was abolished by thalidomide. In LPS + thalidomide-treated rats, the effect of terbutaline became similar to that in sham-operated controls. By the measurement of myometrial cAMP levels, we documented that the concentration-response curve of terbutaline on cAMP accumulation was shifted to the left in the LPS-treated rats, with a significant rise in the pD(2). We concluded that in the case of uterine inflammation, the in vitro uterus-relaxing potency of beta(2)-agonists enhances, which is possibly mediated by TNF-alpha and uterine cAMP levels and that may serve as a rationale for the use of beta(2)-AR agonists in the attenuation of preterm uterine contractions on an inflammatory basis.

  11. The metabolic clearance of progesterone in the pregnant rat: Absence of a physiological role for the lung

    Energy Technology Data Exchange (ETDEWEB)

    Waddell, B.J.; Bruce, N.W. (Univ. of Western Australia, Nedlands)

    1989-06-01

    The metabolic clearance rate (MCR) of progesterone is among the highest for all steroid hormones studied, yet it is difficult to apportion this high MCR to specific organ contributions. The isolated lung has been shown to metabolize progesterone, and since this tissue receives the entire cardiac output, potentially it could make a major contribution to the overall MCR. This possibility was examined in the present study by measuring lung extraction of (3H)progesterone under steady-state conditions in the intact pregnant rat. Anesthetized rats (n = 6) were infused with (3H)progesterone via a femoral vein for 100 min on Day 16 of pregnancy. After the onset of steady state (40 min), four blood samples were obtained at 20-min intervals from the right ventricle and from the aorta, and the concentrations of (3H)progesterone and its metabolites were determined. Throughout the sampling period, mean arterial pressure and heart rate remained stable (two-way analysis of variance), as did the production rate (3.76 +/- 0.35 mg/day; mean +/- SEM) and the MCR (34.8 +/- 3.5 ml/min) of progesterone. Despite this high rate of clearance, there was no difference between the concentration of (3H)progesterone in arterial and right ventricular blood, indicating no net extraction of progesterone during passage through the lung. Furthermore, there was no change in the concentration of either lipid-soluble or aqueous-soluble (3H)progesterone metabolites during trans-lung passage. These observations demonstrate that the lung does not contribute to the MCR of progesterone when measured under physiological and steady-state conditions. Therefore, the relationship, MCR (ml/min) = whole-body extraction (%) x cardiac output (ml/min), is upheld for progesterone in the rat.

  12. Effects of rosiglitazone treatment on TGF-β1/JNK signaling pathways in otsuka long-evans tokushima fatty ratspulmonary%罗格列酮对OLETF大鼠肺组织TGF-β1/JNK信号转导途径的影响

    Institute of Scientific and Technical Information of China (English)

    赵伟; 陈晓琴; 朱梦瑜; 张宏

    2011-01-01

    Objective To approach effects of rosiglitazone treatment on transforming growth factor-β1/c-Jun NH2-terminal kinases(TGF-β1/JNK) signaling pathways in otsuka long-evans tokushima fatty(OLETF) rats. Methods Experimental rats were divided into three groups: OLETF group, rosiglitazone-treated group(OLETF/L group), and long evans tokushima otsuka(LETO group) as control. The expression of TGF-β1, p-JNK, collagen type Ⅰ in pulmonary of rats were examined by immunohistochemistry. Results The expression of TGF-β1, p-JNK and mean optical density, the ratio of positive area and total area of, collagen type Ⅰ were increased in pulmonary of OLETF rats than those of LETO rats(7.4438±0.6397 vs 1.1844±0.2066,5.7025±0.5530 vs 1.5875±0.1727 and 0.1195±0.0183 vs 0.0154±0.0016,0.0322±0.0058 vs 0.0033±0.0010;0.2628±0.0279 vs 0.0831±0.0096,0.0909±0.0138 vs 0.0385±0.0082, P<0.01). The expression of TGF-β1,p-JNK and mean optical density, the ratio of positive area and total area of, collagen type Ⅰ were decreased in OLETF/L group as compared with OLETF group(1.8398±0.3591 vs 7.4438±0.6397,1.7500±0.1690 vs 5.7025±0.5530 and 0.0223±0.0053 vs 0.1195±0.0183,0.0052±0.0019 vs 0.0322±0.0058;0.1152±0.0313 vs 0.2628±0.0279,0.0535±0.0119 vs 0.0909±0.0138, P<0.01). Conclusions Rosiglitazone may improve diabetic pulmonary fibrosis probably by regulating TGF-β1/JNK signaling pathways.%目的 探讨罗格列酮对自发性2型糖尿病OLETF 大鼠肺组织转化生长因子-β1(TGF-β1)/c-Jun氨基末端激酶(JNK)信号转导途径的影响.方法 将16只30周龄成模OLETF大鼠分为OLETF组和罗格列酮治疗组(OLETF/L组),设LETO大鼠8只为对照组.免疫组织化学分析肺组织TGF-β1、磷酸化(p)-JNK、Ⅰ型胶原表达.结果 与LETO组大鼠相比,OLETF组大鼠肺组织TGF-β1、p-JNK表达(7.4438±0.6397 vs 1.1844±0.2066、5.7025±0.5530 vs 1.5875±0.1727)及Ⅰ型胶原的阳性面积比、平均光密度(0.1705±0.0110 vs 0.0550±0.0048

  13. Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring.

    Science.gov (United States)

    Axelstad, Marta; Boberg, Julie; Vinggaard, Anne Marie; Christiansen, Sofie; Hass, Ulla

    2013-09-01

    Thyroid disrupting chemicals can potentially disrupt brain development. Two studies investigating the effect of the antibacterial compound triclosan on thyroxine (T₄) levels in rats are reported. In the first, Wistar rat dams were gavaged with 75, 150 or 300 mg triclosan/kg bw/day throughout gestation and lactation. Total T₄ serum levels were measured in dams and offspring, and all doses of triclosan significantly lowered T₄ in dams, but no significant effects on T₄ levels were seen in the offspring at the end of the lactation period. Since this lack of effect could be due to minimal exposure through maternal milk, a second study using direct per oral pup exposure from postnatal day 3-16 to 50 or 150 mg triclosan/kg bw/day was performed. This exposure pointed to significant T₄ reductions in 16 day old offspring in both dose groups. These results corroborate previous studies showing that in rats lactational transfer of triclosan seems limited. Since an optimal study design for testing potential developmental neurotoxicants in rats, should include exposure during both the pre- and postnatal periods of brain development, we suggest that in the case of triclosan, direct dosing of pups may be the best way to obtain that goal.

  14. Prior reproductive experience alters prolactin-induced macrophage responses in pregnant rats.

    Science.gov (United States)

    Carvalho-Freitas, Maria Isabel Roth; Anselmo-Franci, Janete A; Palermo-Neto, João; Felicio, Luciano F

    2013-09-01

    Reproductive experience (i.e., pregnancy and lactation) induces physiological changes in mammals. A previous reproductive experience was recently shown to modulate the activity of dopaminergic hypothalamic systems while decreasing serum prolactin levels and oxidative burst activity in peritoneal macrophages. Dopamine receptor antagonists increase serum prolactin levels, and both prolactin and dopamine receptors may be involved in the modulation of macrophage activity, providing a means of communication between the nervous and immune systems. The present study evaluated the in vitro effects of prolactin and a dopamine D2 receptor antagonist on the peritoneal activity of macrophages from primigravid and multigravid female rats during the third trimester of pregnancy. Oxidative bursts and phagocytosis in peritoneal macrophages were evaluated by flow cytometry. Primigravid and multigravid Wistar rats, during the third trimester of pregnancy (i.e., days 17-21), were used. Peritoneal fluid samples from these rats were first incubated with prolactin (10 and 100 nM) for different periods of time. The same procedure was repeated to evaluate the effects of domperidone (10 and 100 nM) on macrophage activity. Our results showed that macrophages from multigravid rats responded more effectively to in vitro incubation with prolactin, especially with regard to the intensity and percentage of phagocytosis. Additionally, these effects were more pronounced after incubation periods of 30 min or 4 h. These data suggest that macrophages during a second pregnancy become more sensitive to the phagocytotic effects of prolactin.

  15. ARGININE STIMULATED GLUCAGON AND INSULIN-SECRETION BY ISLETS OF LANGERHANS OF PREGNANT AND LACTATING RATS

    NARCIS (Netherlands)

    MOES, H; SCHUILING, GA; KOITER, TR

    Glucagon secretion by isolated pancreatic rat islets was not affected by an increase of the glucose concentration from 2.5 to 5.0 mM, but was stimulated by 25 mM arginine. This stimulation was only slightly increased by pregnancy and lactation. Insulin secretion increased, when the glucose

  16. Correlative Analysis of Behavioral and Physiological Concomitants of Labor in Pregnant Rats

    Science.gov (United States)

    Baer, L. A.; Wade, C. E.; Ronca, A. E.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    During parturition, rats exhibit characteristic behavioral expressions of labor. Lordosis contractions, consisting of an elongation of the dams body, are observed beginning several hours prior to neonate births, whereas vertical contractions, repeated rapid lifts of the abdomen, occur immediately preceding the birth of each neonate. We analyzed underlying changes in intrauterine pressure (IUP) using a telemetric sensor that we modified for use in freely-moving rats. This technique enabled us to correlate behavioral expressions of labor contractions with IUP. A small telemetric blood pressure sensor was fitted within a fluid-filled balloon, similar in size to a full term rat fetus. On Gestational day 19 of the rats' 22-day pregnancy, a unit was surgically implanted within the uterus. The dams were simultaneously videotaped, enabling us to directly correlate IUP signals with behavioral expressions of labor contractions. Earlier phases of labor, consisting predominantly of lordosis contractions were characterized by lower pressures relative to later phases during which higher pressures and vertical contractions were frequently observed.

  17. ARGININE STIMULATED GLUCAGON AND INSULIN-SECRETION BY ISLETS OF LANGERHANS OF PREGNANT AND LACTATING RATS

    NARCIS (Netherlands)

    MOES, H; SCHUILING, GA; KOITER, TR

    1993-01-01

    Glucagon secretion by isolated pancreatic rat islets was not affected by an increase of the glucose concentration from 2.5 to 5.0 mM, but was stimulated by 25 mM arginine. This stimulation was only slightly increased by pregnancy and lactation. Insulin secretion increased, when the glucose concentra

  18. Effect of Diabetes on Circulating Pancreatic Hormones in Pregnant Rats and Their Offspring

    DEFF Research Database (Denmark)

    Iessi, I L; Sinzato, Y K; Gallego, F Q

    2016-01-01

    into: control (C); mildly diabetic (MD); and severely diabetic (SD). The rats were mated and distributed into 2 subgroups: euthanasia at day 21 of pregnancy and at day 10 postpartum. Both MD and SD dams showed impaired oral glucose tolerance. SD dams had lower body weight and insulin levels compared...

  19. REGULATION OF PERIPHERAL GLUCAGON CONCENTRATIONS IN CYCLIC, PREGNANT, AND LACTATING RATS

    NARCIS (Netherlands)

    KOITER, TR; FAAS, MM; VISSCHER, A; KIEVIT, C; STEFFENS, AB; SCHUILING, GA

    1992-01-01

    In the rat, peripheral glucagon concentrations were studied throughout pregnancy and lactation. Basal glucose concentrations were decreased during late pregnancy and during lactation. but basal glucagon concentrations were not affected. Infusion of glucose (7.4 mg/min) caused an elevation of the glu

  20. Influence of caffeine used at various temperature ranges on the concentrations of glucose and total serum protein as well as body weight gain in pregnant rats

    Directory of Open Access Journals (Sweden)

    Cendrowska-Pinkosz Monika

    2014-06-01

    Full Text Available Caffeine (120 mg/kg was administered intragastrically to pregnant rats daily on gestational days 8-21. An increase in serum concentration of glucose and total protein was found in animals, which were given caffeine. The protein content proved to be highly significant in the experimental group of animals. The control group showed a negative interdependence between body weight gain and glucose concentration. No correlation was found between body weight gain and total protein concentration, yet the glucose concentration significantly influenced the total protein concentration in this group of animals. Among animals which received caffeine, correlations between total protein and glucose concentrations were observed. The analysis did not show that the glucose or total protein concentration significantly influenced the body weight gain of pregnant female rats in the experimental group. The research conducted suggests the possibility of modulating effects of caffeine on adaptive processes during pregnancy.

  1. Cumulated activities determined from biodistribution data in pregnant rats ranging from 13 to 21 days gestation. I. Tc-/sup 99m/ pertechnetate

    Energy Technology Data Exchange (ETDEWEB)

    Wegst, A.V.; Goin, J.E.; Robinson, R.G.

    Cumulated activity estimates for Tc-/sup 99m/ pertechnetate were determined using biodistribution data from pregnant and nonpregnant rats. The pregnant rats were studied at 13, 15, 17, 19, and 21 days gestation. The results indicate that maternal organ cumulated activities are not a simple function of gestational age. The organs into which Tc-/sup 99m/ pertechnetate enters through passive diffusion follow the pattern established by the blood, generally resulting in an increase from the 13th through the 17th day with a decrease on the 19th and 21st day. The organs dominated by active transport follow unique and different patterns. The fetal cumulated activity estimates increased exponentially with gestational age and the placental estimates increased linearly.

  2. Cumulated activities determined from biodistribution data in pregnant rats ranging from 13 to 21 days gestation. I. Tc-99m pertechnetate.

    Science.gov (United States)

    Wegst, A V; Goin, J E; Robinson, R G

    1983-01-01

    Cumulated activity estimates for Tc-99m pertechnetate were determined using biodistribution data from pregnant and nonpregnant rats. The pregnant rats were studied at 13, 15, 17, 19, and 21 days gestation. The results indicate that maternal organ cumulated activities are not a simple function of gestational age. The organs into which Tc-99m pertechnetate enters through passive diffusion follow the pattern established by the blood, generally resulting in an increase from the 13th through the 17th day with a decrease on the 19th and 21st day. The organs dominated by active transport follow unique and different patterns. The fetal cumulated activity estimates increased exponentially with gestational age and the placental estimates increased linearly.

  3. Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring

    DEFF Research Database (Denmark)

    Petersen, Marta Axelstad; Boberg, Julie; Vinggaard, Anne Marie

    2013-01-01

    Thyroid disrupting chemicals can potentially disrupt brain development. Two studies investigating the effect of the antibacterial compound triclosan on thyroxine (T4) levels in rats are reported. In the first, Wistar rat dams were gavaged with 75, 150 or 300 mg triclosan/kg bw/day throughout...... gestation and lactation. Total T4 serum levels were measured in dams and offspring, and all doses of triclosan significantly lowered T4 in dams, but no significant effects on T4 levels were seen in the offspring at the end of the lactation period. Since this lack of effect could be due to minimal exposure...... through maternal milk, a second study using direct per oral pup exposure from postnatal day 3–16 to 50 or 150 mg triclosan/kg bw/day was performed. This exposure pointed to significant T4 reductions in 16 day old offspring in both dose groups. These results corroborate previous studies showing...

  4. Effects of quercetin on predator stress-related hematological and behavioral alterations in pregnant rats and their offspring

    Indian Academy of Sciences (India)

    Mohamed L Toumi; Sameha Merzoug; Abdelkrim Tahraoui

    2016-06-01

    This study aims at investigating the effect of a psychogenic stress during gestation on the behaviour and haematological indices in dams as well as on the neonatal haematological status and periadolescent behaviour in their offspring. Moreover, the ability of quercetin, a natural flavonoid, to prevent the stress-induced changes was estimated. Pregnant Wistar rats were pretreated with quercetin before the exposure to a predator stress on gestational day 19. Post-stress maternal anxiety-like behaviour was assessed with a concomitant haematological analysis. In the offspring, haematological analysis and behavioural testing were performed during the postnatal stage. Our results revealed that predator stress causes an anxiety-like behaviour in dams along with a decrease in erythrocytes, a microcytosis, and a thrombocytosis. Prenatally stressed neonates manifested microcytosis and thrombocytosis with a significant polycythemia. Signs of motor hyperactivity, anxiety-like behaviour, and memory dysfunction were detected at periadolescence. Quercetin pretreatment alleviated the stress-induced behavioural and haematological impairments in dams but failed to attenuate the haematological changes in neonates. A sex-dependent effect of quercetin on behaviour was found at periadolescence. Our findings suggest that, besides a beneficial effect on haematological and behavioural anomalies in traumatized dams, quercetin may lastingly modulate the behaviour of their progeny.

  5. Effect of restricted food supply to pregnant rats inhaling carbon monoxide on fetal weight, compared with cigarette smoke exposure

    Energy Technology Data Exchange (ETDEWEB)

    Tachi, N.; Aoyama, M.

    1986-12-01

    Although many studies have shown that cigarette smoking during gestation retarded the intrauterine fetal growth, resulting in the decreased birth weight in babies born to smoking mothers, neither causal substance nor mechanism of action to disturb fetal growth has been firmly established yet. Based on the human and animal studies, researchers have implied that fetal hypoxia induced by carbon monoxide (CO) in the cigarette smoke to be responsible for the event. A shortage in energy intake in smoking mothers also has been suspected to cause the retardation in fetal development. In the previous results (Tachi and Aoyama 1983), the weight increment in CO exposed animals was greater than that in the smoke exposed group. The phenomenon seemed to indicate that the reduction in the food intake occurs in animals which inhale the cigarette smoke, and induces the disturbance of fetal development in association with CO. In the present study, so as to evaluate the role of energy intake upon the fetal development in utero, the experiment of paired feeding with pregnant rats exposed to cigarette smoke is designed in animals which inhale the cigarette smoke, CO, or room air, following after the observation of the quantity of food taken by mothers exposed to cigarette smoke, CO, or room air.

  6. Effect of valproic acid on /sup 65/Zn distribution in the pregnant rat

    Energy Technology Data Exchange (ETDEWEB)

    Keen, C.L.; Peters, J.M.; Hurley, L.S.

    1989-04-01

    The effect of valproic acid on the distribution of gavaged /sup 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 /sup 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 /sup 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.

  7. Effects of Hypergravity Exposure On Plasma Oxytocin Concentrations In Pregnant and Lactating Rat Dams

    Science.gov (United States)

    Baer, Lisa A.; Wade, Charles E.; Ronca, April E.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    Rat dams and offspring were exposed to 1.5-g, 1.75-g or 2.0-g hypergravity (hg) from Gestational day (G) 11 until Postnatal day (P) 10. To ascertain the role of maternal factors in reduced postnatal body weights of offspring developed in hg, the dams' lactational hormones were measured. Oxytocin (OT), the major hormone responsible for milk ejection, was reduced in hg dams whereas prolactin (Prl), involved in milk production, was unchanged. Video analyses of nursing behavior revealed that hg dams spent more time nursing relative to 1-g controls. We hypothesized impaired milk transfer from dam to pup, however pup body weight gains following a discrete suckling episode were comparable across conditions. Changes in lactational hormones and nursing behavior by dams exposed to hg do not account for reduced body masses of their offspring.

  8. Proteomic analysis of amniotic fluid of pregnant rats with spina bifida aperta.

    Science.gov (United States)

    Shan, Liping; Fan, Yang; Li, Hui; Liu, Wei; Gu, Hui; Zhou, Fenghua; Yuan, Zhengwei

    2012-02-02

    Congenital spina bifida aperta is a common congenital malformation in children and has an incidence of 1‰ to 5‰ in China. However, we currently lack specific biomarkers for screening or prenatal diagnosis and there is no method to entirely cure or prevent such defects. In this study, we used two-dimensional gel electrophoresis (2-DE)/mass spectrometry (MS) to characterize differentially expressed proteins in amniotic-fluid samples (AFSs) of embryonic day (E) 17.5 rat fetuses with spina bifida aperta induced by retinoic acid (RA). We identified five proteins differentially expressed in AFSs of spina bifida aperta, including three upregulated proteins (transferrin, alpha-1 antiproteinase and signal recognition particle receptor, B subunit [SRPRB] 55 kDa), two downregulated proteins (apolipoprotein A IV [APO A4] and Srprb 77 kDa). Specifically, we found 11 alpha-1 fetoprotein (AFP) fragments that were downregulated and 35 AFP fragments that were upregulated in AFSs from embryos with spina bifida aperta. Of the downregulated AFP fragments, 72.7% (8/11) were confined to the AFP N-terminus (amino acids [aas] 25-440) and 77.1% (27/35) of upregulated AFP fragments were confined to the AFP C-terminus (aas 340-596). We also confirmed APO A4 and AFP by immunoblot analysis. This is the first comparative proteomic study of AFSs from rat fetuses with spina bifida aperta. We demonstrate proteomic alterations in the AFS of spina bifida aperta, which may provide new insights in neural tube defects and contribute to the prenatal screening.

  9. Maternal immune activation during pregnancy in rats impairs working memory capacity of the offspring.

    Science.gov (United States)

    Murray, Brendan G; Davies, Don A; Molder, Joel J; Howland, John G

    2017-05-01

    Maternal immune activation during pregnancy is an environmental risk factor for psychiatric illnesses such as schizophrenia in the offspring. Patients with schizophrenia display an array of cognitive symptoms, including impaired working memory capacity. Rodent models have been developed to understand the relationship between maternal immune activation and the cognitive symptoms of schizophrenia. The present experiment was designed to test whether maternal immune activation with the viral mimetic polyinosinic:polycytidylic acid (polyI:C) during pregnancy affects working memory capacity of the offspring. Pregnant Long Evans rats were treated with either saline or polyI:C (4mg/kg; i.v.) on gestational day 15. Male offspring of the litters (2-3months of age) were subsequently trained on a nonmatching-to-sample task with odors. After a criterion was met, the rats were tested on the odor span task, which requires rats to remember an increasing span of different odors to receive food reward. Rats were tested using delays of approximately 40s during the acquisition of the task. Importantly, polyI:C- and saline-treated offspring did not differ in performance of the nonmatching-to-sample task suggesting that both groups could perform a relatively simple working memory task. In contrast, polyI:C-treated offspring had reduced span capacity in the middle and late phases of odor span task acquisition. After task acquisition, the rats were tested using the 40s delay and a 10min delay. Both groups showed a delay-dependent decrease in span, although the polyI:C-treated offspring had significantly lower spans regardless of delay. Our results support the validity of the maternal immune activation model for studying the cognitive symptoms of neurodevelopmental disorders such as schizophrenia. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Effects of the Electromagnetic field, 60 Hz, 3 µT, on the hormonal and metabolic regulation of undernourished pregnant rats

    Directory of Open Access Journals (Sweden)

    CWSF. Anselmo

    Full Text Available Epidemiological studies have implicated maternal protein-calorie deficiency as an important public health problem in developing countries. Over the last decades, a remarkable diffusion of electricity and an increased level of the electromagnetic field (EMF in the environment have characterized modern societies. Therefore, researchers are concerned with the biological effects of 50-60 Hz, EMF. The aim of this paper is to show the effects of EMF of 60 Hz, 3 μT, exposure for two hours per day in the regulation of the hormonal and metabolic concentrations in pregnant rats, which were fed by Regional Basic Diet (RBD during their pregnancy as compared with pregnant rats fed a standard diet. Pregnant rats exposed to EMF of 60 Hz, 3 μT, over the pregnancy and fed with RBD presented an increase in glucose release when compared with the Group subjected only to the RBD ration. Rats fed RBD presented a decrease in their insulin and cortisol serum levels when compared with the Group fed with casein. The T3 and T4 concentrations presented the greatest variation among the Groups. The relation T4:T3 was much exaggerated in the Group subjected to RDB and exposed to EMF when compared to the others. In conclusion, the group subjected to the association of EMF and undernutrition suffered a decrease in its serum concentration of T4 and T3 when compared to the well-nourished group and the relationship T4:T3 in the former group was almost eighteen-fold the later one.

  11. Ameliorating effect of vitamin C and selenium against nicotine induced oxidative stress and changes of p53 expression in pregnant albino rats

    Directory of Open Access Journals (Sweden)

    Khadiga A. Hassan

    2016-12-01

    Full Text Available Objective: This study was aimed to evaluate the effects of daily intake of vitamin C or selenium against deleterious effects of nicotine toxicity on pregnant albino rats. Materials and methods: Forty albino pregnant rats were equally distributed into four groups. Group A was considered as control. Group B was administered with nicotine dosed at 1 mg/kg body weight (bwt daily for 7 weeks (wks from 1st day of gestation until the postnatal 4 wks. Group C was treated with nicotine and vitamin C dosed at 1 mg/kg bwt orally for 7 wks, group D was treated with nicotine and sodium selenite dosed at 1 ug/100 g bwt concurrently for 7 wks. The levels of catalase (CAT, superoxide dismutase (SOD, protein carbonyl (PC and thiobarbituric acid reactive substances (TBARS, were estimated in homogenates of the lung, kidney and liver. Histopathological studies using hematoxylin and eosin as well as immunohistochemical studies using p53 antibody were also done. Results: Nicotine significantly elevated the levels of TBARS and PC as compared to control rats. Groups C and D showed decrease in these levels significantly. CAT and SOD activities of group B were decreased significantly. Significant elevation of CAT and SOD activities was detected in both groups C and D. Vitamin C elevated the antioxidant enzymes activities to normal levels, however selenium administration improved these levels but still lower than those of group A. Expression of p53 was decreased in group B as compared to group A. Vitamin C completely reversed the expression of p53 as group A. However, group D did not showed any significant changes in expressions as compared to group B. Conclusion: It is concluded that vitamin C intake was useful than selenium in prevention against nicotine-induced oxidative stress including p53 expression in the lung, kidney and liver of pregnant rats. [J Adv Vet Anim Res 2016; 3(4.000: 321-331

  12. Metagenomic analysis of antibiotic-induced changes in gut microbiota in a pregnant rat model

    Directory of Open Access Journals (Sweden)

    Imran eKhan

    2016-04-01

    Full Text Available Food and Drug Administration (FDA, USA-approved category B antibiotics are commonly prescribed to treat infections during pregnancy. The aim of this study was to investigate antibiotic-induced changes in gut microbiota (GM that occur during pregnancy. The 16S rRNA amplicon deep-sequencing method was used to analyse the effect of category B antibiotics (azithromycin, amoxicillin and cefaclor on GM during pregnancy using a rat model. The GM composition was substantially modulated by pregnancy and antibiotics administration. Firmicutes, Bacteroidetes, Proteobacteria, Chlamydiae, Actinobacteria and Cyanobacteria were the dominant phyla. Antibiotic treatment during pregnancy increased the relative abundance of Proteobacteria and reduced Firmicutes. The genera Shigella, Streptococcus, Candidatus Arthromitus and Helicobacter were significantly (p<0.05 more abundant during pregnancy. Antibiotics significantly (p<0.05 reduced the relative abundance of Lactobacillus but increased that of Enterobacter. There was a significant (p<0.05 decrease in Lactobacillus sp., Lactobacillus gallinarum and Lactobacillus crispatus during pregnancy. Antibiotic treatment reduced bacterial diversity; the lowest number of operational taxonomic units (OTUs were detected in the cefaclor-treated groups. Antibiotics significantly (p<0.05 promoted weight gain during pregnancy, and increased relative abundance of Shigella sonnei, Enterococcus hormaechei and Acinetobacter sp. GM perturbations were accompanied by increases in Proteobacteria abundance and weight gain in pregnancy following antibiotic treatment

  13. Disposition of intravenously or orally administered silver nanoparticles in pregnant rats and the effect on the biochemical profile in urine.

    Science.gov (United States)

    Fennell, Timothy R; Mortensen, Ninell P; Black, Sherry R; Snyder, Rodney W; Levine, Keith E; Poitras, Eric; Harrington, James M; Wingard, Christopher J; Holland, Nathan A; Pathmasiri, Wimal; Sumner, Susan C J

    2017-05-01

    Few investigations have been conducted on the disposition and fate of silver nanoparticles (AgNP) in pregnancy. The distribution of a single dose of polyvinylpyrrolidone (PVP)-stabilized AgNP was investigated in pregnant rats. Two sizes of AgNP, 20 and 110 nm, and silver acetate (AgAc) were used to investigate the role of AgNP diameter and particle dissolution in tissue distribution, internal dose and persistence. Dams were administered AgNP or AgAc intravenously (i.v.) (1 mg kg(-1) ) or by gavage (p.o.) (10 mg kg(-1) ), or vehicle alone, on gestation day 18 and euthanized at 24 or 48 h post-exposure. The silver concentration in tissues was measured using inductively-coupled plasma mass spectrometry. The distribution of silver in dams was influenced by route of administration and AgNP size. The highest concentration of silver (μg Ag g(-1) tissue) at 48 h was found in the spleen for i.v. administered AgNP, and in the lungs for AgAc. At 48 h after p.o. administration of AgNP, the highest concentration was measured in the cecum and large intestine, and for AgAc in the placenta. Silver was detected in placenta and fetuses for all groups. Markers of cardiovascular injury, oxidative stress marker, cytokines and chemokines were not significantly elevated in exposed dams compared to vehicle-dosed control. NMR metabolomics analysis of urine indicated that AgNP and AgAc exposure impact the carbohydrate, and amino acid metabolism. This study demonstrates that silver crosses the placenta and is transferred to the fetus regardless of the form of silver. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Physiological increases in lactate inhibit intracellular calcium transients, acidify myocytes and decrease force in term pregnant rat myometrium.

    Science.gov (United States)

    Hanley, Jacqui-Ann; Weeks, Andrew; Wray, Susan

    2015-10-15

    Lactate is increased in myometrial capillary blood from women in slow or non-progressive labour (dystocia), suggesting that it is detrimental to uterine contractions. There are, however, no studies of the effect of lactate on the myometrium. We therefore investigated its effects and mechanism of action on myometrial strips from term pregnant rats. The effects on spontaneous and oxytocin-induced contractility in response to sodium lactate and other weak acids (1-20 mM) were studied. In some experiments, simultaneous force and intracellular Ca(2+) or pH (pH(i)) were measured with Indo-1 or Carboxy-SNARF, respectively. Statistical differences were tested using non-parametric tests. Lactate significantly decreased spontaneous contractility with an EC50 of 3.9 mM. Propionate, butyrate and pyruvate also reduced contractions with similar potency. The effects of lactate were reduced in the presence of oxytocin but remained significant. Lactate decreased pH(i) and nulling the decrease in pH(i) abolished its effects. We also show that lactate inhibited Ca(2+) transients, with these changes mirroring those produced on force. If Ca(2+) entry was enhanced by depolarization (high KCl) or applying the Ca(2+) channel agonist, Bay K 4644, the effects of lactate were abolished. Taken together, these data show that lactate in the physiological range potently decreases myometrial contractility as a result of its inhibition of Ca(2+) transients, which can be attributed to the induced acidification. The present study suggests that the accumulation of extracellular lactate will reduce myometrial contractions and could therefore contribute to labour dystocia.

  15. Effect of the ethanolic extract of Nauclea latifolia (Family: Rubiaceae on the isolated uterus of non-pregnant rats

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    Nworgu Z.A.M.

    2010-01-01

    Full Text Available The plant Nauclea latifolia has been reported to be used by traditional healers to arrest pre-term labour. The ethanolic extract of the root of N. latifolia was screened for activity via agonist-induced contractions of uterine smooth muscles in non-pregnant female albino rats. The extract, at 0.1 and 0.2 mg/ml (final bath concentration, was tested against oxytocin (4×10 -5 to 8×10 -2 I.U/ml: final bath concentration, acetylcholine (0.04 to 40 µg/ml: final bath concentration and ergometrine (0.05 to 100 µg/ml: final bath concentration induced contractions invitro. The effect of the extract was compared to that of (0.004 µg/ml: final bath concentration salbutamol and (0.004 µg/ml: final bath concentration atropine. Both concentrations of the extract significantly shifted the concentration response curves of oxytocin ( P < 0.01, acetylcholine ( P < 0.0001 and ergometrine ( P < 0.0001 to the right with a slight depression of the Emax. This shift was more with the 0.2 mg/ml concentration, thus suggesting the possibility of a dose dependent action. There was no statistical significant decrease in Emax by 0.1 mg/ml of the extract, while the 0.2 mg/ml produced a significant depression ( P < 0.05 of the Emax, which like salbutamol could not be overwhelmed by higher concentrations of oxytocin. Similarly a significant reduction of the Emax of acetylcholine induced contractions was produced by 0.2 mg/ml, while both concentrations (0.1 and 0.2 mg/ml produced significant ( P < 0.0001 reduction in Emax of ergometrine. It can thus be concluded that N latifolia root extract reduces oxytocin, acetylcholine and ergometrine-induced uterine contractions. These inhibitions were non-competitive. The result indicates an anti-abortifacient property.

  16. Effects of iron polymaltose complex, ferrous fumarate and ferrous sulfate treatments in anemic pregnant rats, their fetuses and placentas.

    Science.gov (United States)

    Toblli, Jorge E; Cao, Gabriel; Oliveri, Leda; Angerosa, Margarita

    2013-06-01

    Although oral iron preparations are widely prescribed to prevent and to treat iron deficiency anemia in pregnancy, comparative data on their effects to the mother, fetus and placenta are limited. In this study, the effects of oral iron polymaltose complex (IPC), ferrous fumarate (FF) and ferrous sulfate (FS) were compared in anemic pregnant rats, their fetuses and placentas. Hematological variables and oxidative stress markers in the liver, heart and kidneys of the dams and fetuses as well as the markers for oxidative stress, inflammation and hypoxia in placentas were assessed. Pregnancy outcome was measured by number of fetuses, and by neonate and placental weight. All therapies were comparably effective in correcting anemia. FS and FF, but not IPC, resulted in liver damage in dams and oxidative stress in dams, fetuses and placentas. FS group presented the highest catalase and GPx levels in dams, fetuses and placentas. IPC, but not FF or FS, restored normal TNF-α and IL6 expression levels in placentas whereas FS-treated animals presented the highest cytokine levels, suggesting a local inflammatory reaction. Anemia-induced high levels of HIF-1α were partially lowered by IPC and FF but further elevated by FS. Most of the negative effects associated with IDA were resolved by IPC treatment. Especially FS treatment was found to elicit hepatic damage in the dams, oxidative stress in the dams, fetuses and placenta as well as inflammation and high levels of HIF-1α in the placenta. Pregnancy outcome of FFand FS-treated animals was worse than that of IPC-treated animals.

  17. Effect of long term exposure of low doses of lambda- cyhalothrin on the level of lipid peroxidation and antioxidant enzymes of the pregnant rats and their offspring

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    Kadir Tukhtaev

    2012-12-01

    Full Text Available Lambda- cyhalothrin (LCT is a pyrethroid insecticide class, which is widely used for pest control in agriculture, public health, home and garden. In the present study we investigated the effect of long term exposure of low doses of the LCT on the state of lipid peroxidation and antioxidant protection of pregnant rats and their offspring. It was revealed, that prolonged exposure of lambda-cyhalothrin leads to the development of oxidative stress in both of pregnant females and their offspring. The highest level of lipid peroxidation detected on 14-21 days of pregnancy, which was accompanied by a reduction in activity of antioxidant enzymes. In the offspring highest level of oxidative stress observed on 7-14 days of lactation. The degree of oxidative stress in offspring decreases as the cessation of receipt of a pesticide or its toxic metabolites in breast milk.

  18. Effect of sodium benzoate on DNA breakage, micronucleus formation and mitotic index in peripheral blood of pregnant rats and their newborns

    Directory of Open Access Journals (Sweden)

    Cetin Saatci

    2016-11-01

    Full Text Available Sodium benzoate (SB is one of the most widely used additives in food products in the world. The aim of this study was to assess the effect of three different concentrations of SB on the DNA breakage in liver cells and on the micronuclei formation and the mitotic index in lymphocytes of pregnant rats and their fetuses, as well as to evaluate the effects of SB on the fetus development. The results showed that general genomic injuries were present in almost all the liver cell samples obtained from the SB group compared with the control (non-treated group. This indicates that SB usage may cause DNA damage and increase micronuclei formation. We recommend that pregnant women should avoid consuming foodstuffs containing SB as an additive.

  19. Use of novel inhalation kinetic studies to refine physiologically-based-pharmacokinetic models for ethanol in non-pregnant and pregnant rats

    Science.gov (United States)

    Ethanol (EtOH) exposure induces a variety of concentration-dependent neurological and developmental effects in the rat. Physiologically-based pharmacokinetic (PBPK) models have been used to predict the inhalation exposure concentrations necessary to produce blood EtOH concentrat...

  20. Antidepressant-like effects of nicotine and transcranial magnetic stimulation in the olfactory bulbectomy rat model of depression

    OpenAIRE

    2008-01-01

    In this study, we compared the depression–like symptoms induced by olfactory bulbectomy (OBX) in the two inbred Wistar and Long Evans rat strains. We also analyzed the self-regulated oral intake of nicotine in these strains and the effect of nicotine on the depression-like symptoms of olfactory bulbectomy. Furthermore, we compared the antidepressant-like effects of nicotine on Wistar rats to those of transcranial magnetic stimulation (TMS), which has emerged as a therapeutic alternative for d...

  1. Antidiabetic, antihyperlipidemic and antioxidant properties of ethanol extract of Grewia asiatica Linn. bark in alloxan-induced diabetic rats

    OpenAIRE

    2016-01-01

    Background Inspite of introduction of oral hypoglycemic agents, diabetes and its related complications remains to be a major clinical problem. The aim of this study was to investigate the antidiabetic, antihyperlipidemic and antioxidant activities of Grewia asiatica (Linn) stem bark in alloxan induced diabetic rats. Methods Diabetes was induced by a single dose of intraperitoneal injection of alloxan (110 mg/kg) in Norwegian Long Evans rats. Ethanol extract of barks from Grewia asiatica (GAE ...

  2. Sensitization of sexual behavior in ovariectomized rats by chronic estradiol treatment.

    Science.gov (United States)

    Jones, Sherri Lee; Farrell, Sara; Gregory, James Gardner; Pfaus, James G

    2013-06-01

    The ovariectomized (OVX) rat treated with estradiol benzoate (EB) is used to elucidate neuroendocrine mechanisms of sexual behavior. Chronic behavioral and pharmacological manipulations can be confounded by rising baselines, since females are behaviorally more sensitive to repeated EB injections. The literature lacks a systematic examination of chronic effects of EB administered alone to the sexually experienced OVX rat. Long-Evans rats were repeatedly treated (8 tests) with s.c. injections of 2, 5, or 10 μg EB at different time intervals (4 or 8 days). Female sexual behaviors as well as receipt of mounts, intromissions and ejaculations from the male were observed in the unilevel 4-hole pacing chamber. The effects of adrenalectomy (ADX) and strain (Long-Evans vs. Wistar) were also assessed. Long-Evans OVX rats treated with 5 μg EB every 8 days showed persistently low levels of sexual behavior. Sensitization was most robust following 10 μg EB at 4-day intervals. Very few sexual behaviors were ever induced by 2 μg EB. ADX did not affect the development of behavioral sensitization by 10μg EB. Therefore, to achieve a low steady state of sexual behaviors in sexually experienced Long-Evans OVX rats 5μg of EB administered every 8days is optimal, whereas a persistently high level of sexual behaviors is induced with 10 μg EB administered every 4 days. OVX Wistar rats are behaviorally more sensitive to EB. Behavioral sensitization to EB may serve as a mechanism to optimize reproductive success.

  3. Regional haemodynamic effects of noradrenaline injected into the hypothalamic paraventricular nuclei of conscious, unrestrained rats: possible mechanisms of action.

    Science.gov (United States)

    Bachelard, H; Harland, D; Gardiner, S M; Kemp, P A; Bennett, T

    1992-01-01

    The cardiovascular effects of noradrenaline bilaterally injected into the hypothalamic paraventricular nuclei were investigated in conscious, unrestrained Long-Evans rats and homozygous, vasopressin-deficient Brattleboro rats, chronically instrumented with pulsed Doppler probes for measurement of regional haemodynamics. In Long-Evans rats, incremental doses of noradrenaline (0.01-10 nmol) caused dose-related increases in blood pressure and a substantial, dose-related, superior mesenteric vasoconstriction. These changes were accompanied by bradycardia and reductions in renal and hind-quarter vascular conductances. In Brattleboro rats, noradrenaline (10 nmol) had no effect on blood pressure, heart rate, or renal or superior mesenteric vascular conductances. However, there was a slight vasodilatation in the vascular bed of the hindquarters. In Long-Evans rats, intravenous pretreatment with phentolamine had no effect on the bradycardia but partly inhibited the pressor response to noradrenaline injected into the paraventricular nuclei. These effects were associated with a smaller superior mesenteric vasoconstriction and an abolition of the vasoconstriction in the hindquarters. Combined intravenous pretreatment with phentolamine and propranolol had no effect on the heart rate or pressor responses to noradrenaline injected into the paraventricular nuclei, but reduced the superior mesenteric vasoconstriction, potentiated the vasoconstriction in the hindquarters and eliminated the renal vasoconstriction. These results suggest that, in untreated Long-Evans rats, alpha-adrenoceptor-mediated constriction in the mesenteric vascular bed and beta-adrenoceptor-mediated dilatation in the vascular bed of the hindquarters have important influences on the pressor response to noradrenaline injected into the paraventricular nuclei. In the presence of the vasopressin V1-receptor antagonist, d(CH2)5[Tyr(Et)]DAVP, the pressor and heart rate responses to noradrenaline injected into the

  4. Pregnant growth restricted female rats have bone gains during late gestation which contributes to second generation adolescent and adult offspring having normal bone health.

    Science.gov (United States)

    Anevska, Kristina; Gallo, Linda A; Tran, Melanie; Jefferies, Andrew J; Wark, John D; Wlodek, Mary E; Romano, Tania

    2015-05-01

    Low birth weight, due to uteroplacental insufficiency, results in programmed bone deficits in the first generation (F1). These deficits may be passed onto subsequent generations. We characterized the effects of being born small on maternal bone health during pregnancy; and aimed to characterize the contribution of the maternal environment and germ line effects to bone health in F2 offspring from mothers born small. Bilateral uterine vessel ligation (or sham) surgery was performed on female F0 WKY rats on gestational day 18 (term 22days) to induce uteroplacental insufficiency and fetal growth restriction. Control and Restricted F1 female offspring were allocated to a non-pregnant or pregnant group. To generate F2 offspring, F1 females were allocated to either non-embryo or embryo transfer groups. Embryo transfer was performed on gestational day 1, where second generation (F2) embryos were gestated (donor-in-recipient) in either a Control (Control-in-Control, Restricted-in-Control) or Restricted (Control-in-Restricted, Restricted-in-Restricted) mother. Restricted F1 females were born 10-15% lighter than Controls. Restricted non-pregnant females had shorter femurs, reduced trabecular and cortical bone mineral contents, trabecular density and bone geometry measures determined by peripheral quantitative computed tomography (pQCT) compared to non-pregnant Controls. Pregnancy restored the bone deficits that were present in F1 Restricted females. F2 non-embryo transfer male and female offspring were born of normal weight, while F2 embryo transfer males and females gestated in a Control mother (Control-in-Control, Restricted-in-Control) were heavier at birth compared to offspring gestated in a Restricted mother (Restricted-in-Restricted, Control-in-Restricted). Male F2 Restricted embryo groups (Restricted-in-Control and Restricted-in-Restricted) had accelerated postnatal growth. There was no transmission of bone deficits present at 35days or 6months in F2 offspring. Embryo

  5. Investigation on the role of Spirulina platensis in ameliorating behavioural changes, thyroid dysfunction and oxidative stress in offspring of pregnant rats exposed to fluoride.

    Science.gov (United States)

    Banji, David; Banji, Otilia J F; Pratusha, N Gouri; Annamalai, A R

    2013-09-01

    The study investigated the role of Spirulina platensis in reversing sodium fluoride-induced thyroid, neurodevelopment and oxidative alterations in offspring of pregnant rats. The total antioxidant activity, phycocyanins, and β carotene content were quantified in Spirulina. Thirty female pregnant rats were allocated to six groups and treatment initiated orally from embryonic day (ED) 6 to postnatal day (PND) 15. Treatment groups included control, Spirulina alone, sodium fluoride (20 mg/kg) alone, and sodium fluoride along with Spirulina (250 and 500 mg/kg). Serum fluoride levels were determined on ED 20 and PND 11. Offspring were subjected to behavioural testing, estimation of thyroid levels, oxidative measurements in brain mitochondrial fraction and histological evaluation of the cerebellum. Fluoride-induced alterations in thyroid hormones, behaviour and increased oxidative stress. Spirulina augmented the displacement of fluoride, facilitated antioxidant formation, improved behaviour and protected Purkinje cells. Supplementing Spirulina during pregnancy could reduce the risk of fluoride toxicity in offspring. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. BRAIN CHOLINESTERASE INHIBITION AND DEPRESSION OF THE PHOTIC AFTER DISCHARGE (PHAD) OF FLASH EVOKED POTENTIALS (FEPS) IN LONG EVANS RATS FOLLOWING ACUTE OR REPEATED EXPOSURES TO A MIXTURE OF CARBARYL AND PROPOXUR.

    Science.gov (United States)

    Carbaryl and propoxur are N-methyl carbamate pesticides (NMCs) which are part of the EPA’s cumulative risk assessments for NMCs. These NMCs inhibit cholinesterase (ChE) activity and may lead to cholinergic disruption of CNS function. We used decreases in the PhAD of FEPs to indic...

  7. Gestational and Lactational Exposure to Ethinyl Estradiol, but not Bisphenol A, Decreases Androgen-Dependent Reproductive Organ Weights and Epididymal Sperm Abundance in the Male Long Evans Hooded Rat.

    Science.gov (United States)

    Many chemicals released into the environment are capable of disrupting normal sex steroid balance, including the oral contraceptive ethinyl estradiol (EE) and the plastic monomer bisphenol A (BPA). EE and BPA are reported to impair reproductive organ development in laboratory ani...

  8. Effects of selective antagonism or depletion of the cholinergic system on visual discrimination performance in rats

    NARCIS (Netherlands)

    Drinkenburg, W.H.I.M.; Sondag, H.N.P.M.; Coenders, C.J.H.; Andrews, J.S.; Vossen, J.M.H.

    1995-01-01

    A two-lever simultaneous visual discrimination task was used to study the effects on performance in Long-Evans rats of the muscarinic antagonists scopolamine (0.0125, 0.05, 0.2 and 0.8mg/kg s.c.), the M(1) antagonist pirenzepine, the M(2) antagonist AF-DX 116, the M(3) antagonist UH-AH 37 (each 3.2,

  9. Emergency Interventions After Severe Traumatic Brain Injury in Rats: Effect on Neuropatholgy and Functional Outcome.

    Science.gov (United States)

    1999-01-01

    brain of male Long-Evans rats (225-250 gm) via intracerebroventricular infusion. The distribution of bio-rncfosriis was detected using antibodies...Please check one: □ A. Administration /Education D B. Burns/Trauma D C. CPR D D. Cardiovascular O E. Computers/Technology O F. Ethics □ G. Immunology...therapies. Dietrich et aP reported that combination of 3 hours of moderate hypothermia with sustained administration of the glu- tamate antagonist

  10. Androgen receptor expression in the rat prostate is down-regulated by dietary phytoestrogens

    OpenAIRE

    Handa Robert J; Adlercreutz Herman; Lund Trent D; Munson Daniel J; Lephart Edwin D

    2004-01-01

    Abstract Background It is well established that the growth of the prostate gland is a hormone-dependent phenomenon involving both androgenic and estrogenic control. Proliferation of prostate cells is, at least in part, under control of estrogen receptor beta (ER-beta). Phytoestrogens bind ER-beta with high affinity and therefore may have antiproliferative effects in the prostate. Methods The prostates of male Long-Evans rats fed a diet high in phytoestrogens (Phyto-600) or very low levels of ...

  11. Effects of rifampicin, dexamethasone, St. John's Wort and Thyroxine on maternal and foetal expression of Abcb1 and organ distribution of talinolol in pregnant rats.

    Science.gov (United States)

    Saljé, Karen; Lederer, Kirstin; Oswald, Stefan; Dazert, Eike; Warzok, Rolf; Siegmund, Werner

    2012-08-01

    It is well accepted that ABCB1 plays a critical role in absorption, distribution and elimination of many xenobiotics and drugs. Only little is known about the regulation and function of ABCB1 during pregnancy. Thus, the aim of this study is to investigate maternal, placental and foetal Abcb1 expression and function in pregnant rats after induction with rifampicin, dexamethasone, St. John's wort (SJW) or thyroxine. Wistar rats were orally treated with rifampicin (250 mg/kg), SJW (1.0 g/kg), thyroxine (9 μg/kg), dexamethasone (1 mg/kg) or 0.5% methylcellulose suspension (control) for 9 days during late pregnancy (each N = 5). Afterwards, organ mRNA expression and protein content of Abcb1a were determined. Tissue concentrations of the ABCB1 probe drug talinolol were measured after repeated administration of the drug (100 mg/kg, 9 days) and after induction with oral rifampicin (250 mg/kg, 9 days, N = 5). Abcb1 expression was substantially lower in foetal than in maternal organs. Abcb1 was significantly induced by SJW in the maternal jejunum and placenta, by dexamethasone in foetal brain and liver and by thyroxine in the placenta and maternal and foetal brain. Rifampicin induced Abcb1 in all maternal and foetal organs. However, organ distribution of talinolol was not influenced by comedication of rifampicin. In conclusion, maternal and foetal Abcb1 organ expression in pregnant rats is inducible by nuclear receptor agonists. Although rifampicin regulates maternal and foetal Abcb1 expression, organ distribution of talinolol remains unchanged most likely caused by the known inhibitory effect of rifampicin on Abcb1 function.

  12. A New Slow Releasing, H2S Generating Compound, GYY4137 Relaxes Spontaneous and Oxytocin-Stimulated Contractions of Human and Rat Pregnant Myometrium

    Science.gov (United States)

    Robinson, Hayley; Wray, Susan

    2012-01-01

    Better tocolytics are required to help prevent preterm labour. The gaseotransmitter Hydrogen sulphide (H2S) has been shown to reduce myometrial contractility and thus is of potential interest. However previous studies used NaHS, which is toxic and releases H2S as a non-physiological bolus and thus alternative H2S donors are sought. GYY4137 has been developed to slowly release H2S and hence better reflect endogenous physiological release. We have examined its effects on spontaneous and oxytocin-stimulated contractility and compared them to NaHS, in human and rat myometrium, throughout gestation. The effects on contractility in response to GYY4137 (1 nM–1 mM) and NaHS (1 mM) were examined on myometrial strips from, biopsies of women undergoing elective caesarean section or hysterectomy, and from non-pregnant, 14, 18, 22 day (term) gestation or labouring rats. In pregnant rat and human myometrium dose-dependent and significant decreases in spontaneous contractions were seen with increasing concentrations of GYY4137, which also reduced underlying Ca transients. GYY4137 and NaHS significantly reduced oxytocin-stimulated and high-K depolarised contractions as well as spontaneous activity. Their inhibitory effects increased as gestation advanced, but were abruptly reversed in labour. Glibenclamide, an inhibitor of ATP-sensitive potassium (KATP) channels, abolished the inhibitory effect of GYY4137. These data suggest (i) H2S contributes to uterine quiescence from mid-gestation until labor, (ii) that H2S affects L-type calcium channels and KATP channels reducing Ca entry and thereby myometrial contractions, (iii) add to the evidence that H2S plays a physiological role in relaxing myometrium, and thus (iv) H2S is an attractive target for therapeutic manipulation of human myometrial contractility. PMID:23029460

  13. A new slow releasing, H₂S generating compound, GYY4137 relaxes spontaneous and oxytocin-stimulated contractions of human and rat pregnant myometrium.

    Directory of Open Access Journals (Sweden)

    Hayley Robinson

    Full Text Available Better tocolytics are required to help prevent preterm labour. The gaseotransmitter Hydrogen sulphide (H(2S has been shown to reduce myometrial contractility and thus is of potential interest. However previous studies used NaHS, which is toxic and releases H(2S as a non-physiological bolus and thus alternative H(2S donors are sought. GYY4137 has been developed to slowly release H(2S and hence better reflect endogenous physiological release. We have examined its effects on spontaneous and oxytocin-stimulated contractility and compared them to NaHS, in human and rat myometrium, throughout gestation. The effects on contractility in response to GYY4137 (1 nM-1 mM and NaHS (1 mM were examined on myometrial strips from, biopsies of women undergoing elective caesarean section or hysterectomy, and from non-pregnant, 14, 18, 22 day (term gestation or labouring rats. In pregnant rat and human myometrium dose-dependent and significant decreases in spontaneous contractions were seen with increasing concentrations of GYY4137, which also reduced underlying Ca transients. GYY4137 and NaHS significantly reduced oxytocin-stimulated and high-K depolarised contractions as well as spontaneous activity. Their inhibitory effects increased as gestation advanced, but were abruptly reversed in labour. Glibenclamide, an inhibitor of ATP-sensitive potassium (K(ATP channels, abolished the inhibitory effect of GYY4137. These data suggest (i H(2S contributes to uterine quiescence from mid-gestation until labor, (ii that H(2S affects L-type calcium channels and K(ATP channels reducing Ca entry and thereby myometrial contractions, (iii add to the evidence that H(2S plays a physiological role in relaxing myometrium, and thus (iv H(2S is an attractive target for therapeutic manipulation of human myometrial contractility.

  14. Extracellular ATP decreases trophoblast invasion, spiral artery remodeling and immune cells in the mesometrial triangle in pregnant rats

    NARCIS (Netherlands)

    Spaans, F.; Melgert, B. N.; Chiang, C.; Borghuis, T.; Klok, P. A.; de Vos, P.; van Goor, H.; Bakker, W.W.; Faas, M. M.

    2014-01-01

    Introduction: Preeclampsia is characterized by deficient trophoblast invasion and spiral artery remodeling, a process governed by inflammatory cells. High levels of the danger signal extracellular adenosine triphosphate (ATP) have been found in women with preeclampsia and infusion of ATP in pregnant

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

    Directory of Open Access Journals (Sweden)

    Tadashi Okamura

    2013-01-01

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

  16. Relaxant effect of the calcitonin gene-related peptide (CGRP) on the nonpregnant and pregnant rat uterus. Comparison with vascular tissue.

    Science.gov (United States)

    Anouar, A; Schirar, A; Germain, G

    1998-04-01

    To explore the role of calcitonin gene-related peptide (CGRP) in rat pregnancy, we determined the density of myometrial CGRP-encoded nerve fibre terminals and examined, in an organ bath, the relaxant effect of the peptide on uterine strips near parturition. Comparisons were made with the uterus and aorta of nonpregnant rats. In the myometrium, CGRP immunoreactive nerve fibers were abundant in nonpregnant rats and scarce at the parturient stage. In the aorta there was no variation in the density of CGRP fibres with gestation. In nonpregnant rats only, CGRP relaxed spontaneous and tetrodotoxin (TTX)-sensitive electrically-evoked uterine contractions (EC50 40 nM, Emax 80%). The effect was antagonized by CGRP[8-37] (pKB 6.47) but was not affected by either blockers of nitricoxid synthase or ATP-sensitive potassium channels. CGRP was also able to relax contractions evoked by direct depolarization of the cells (TTX-insensitive contractions) (EC50, 2 nM, Emax 70%). In aorta contracted with arginine vasopressin, CGRP-induced relaxation was the same in nonpregnant and parturient animals. It was antagonized by CGRP [8-371 (pKB 6.90) and was abolished in presence of the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). Amylin neither relaxed the uterus nor the aorta. In pregnant rats, the relaxant effect of CGRP on the uterus was limited on day 21 and was totally absent on day 22 of gestation. We conclude that the primary relaxant effect of CGRP on the uterus occurs at the level of myometrial smooth muscle cells. In the myometrium, gestation decreases CGRP innervation and impairs the relaxant responses to CGRP. Such changes are not observed in vascular tissues like aorta.

  17. [Comparative study of the distribution of 7,12-dimethylbenz(a)anthracene in the organs of pregnant rats and their fetuses].

    Science.gov (United States)

    Baranova, L N; Aleksandrov, V A

    1980-03-01

    On the 21st day of pregnancy rats were injected intravenously with 7,12-dimethylbenz(a)anthracene (DMBA) in a dose of 15 mg/kg. After 30, 60 and 180 min the content of the preparation was determined by the fluorescent-spectral method in the organs of females (liver, kidneys, lungs, brain, spleen and placenta) and in their fetuses (liver, kidneys, lungs, brain, intestine, "carcasses" and intact fetus). In the course of all experimental periods the female rats showed the highest concentration of DMBA in the lungs. The concentration of DMBA in all organs of pregnant rats diminished while in the brain it increased with time elapsed after injection. The fetuses showed uneven distribution of the carcinogen in the organs only 60 min after DMBA injection, the highest content being recorded in the liver. The maximum content of the carcinogen was detected in all organs of the fetus by the 60th minute. DMBA accumulation in fetal organs did not correlate with the evidence on predominant occurrence of tumours in the kidneys and the nervous system of the progeny in transplacental effect of DMBA administered in the same dose.

  18. Effects of uteroplacental restriction on the relaxin-family receptors, Lgr7 and Lgr8, in the uterus of late pregnant rats.

    Science.gov (United States)

    Vodstrcil, Lenka A; Wlodek, Mary E; Parry, Laura J

    2007-01-01

    The peptide hormone relaxin stimulates uterine growth and endometrial angiogenesis and inhibits myometrial contractions in a variety of species. The receptor for relaxin is a leucine-rich repeat containing G-protein-coupled receptor Lgr7 (RXFP1) that is highly expressed in the myometrium of late pregnant mice, with a significant decrease in receptor density observed at term. The present study first compared the expression of Lgr7 with another relaxin-family receptor Lgr8 (RXFP2) in the uterus and placenta of late pregnant rats. The uterus was separated into endometrial and myometrial components, and the myometrium into fetal and non-fetal sites, for further analysis. We then assessed the response of these receptors to uteroplacental restriction (UPR). Expression of the Lgr7 gene was significantly higher in the uterus compared with the placenta. Within the uterus, on Day 20 of gestation, there was equivalent expression of Lgr7 in fetal and non-fetal sites of the myometrium, as well as in the endometrium v. myometrium. The second receptor investigated, Lgr8, was also expressed in the endometrium and myometrium, but at significantly lower levels than Lgr7. Bilateral ligation of the maternal uterine blood vessels on Day 18 of gestation resulted in uteroplacental restriction, a decrease in fetal weight and litter size, and a significant upregulation in uterine, but not placental, Lgr7 and Lgr8 gene expression in UPR animals compared with controls. These data suggest that both relaxin family receptors are upregulated in response to a reduction in uteroplacental blood flow in rats.

  19. Liver and Kidney Functional Indices of Pregnant Rats Following the Administration of the Crude Alkaloids from Senna alata (Linn. Roxb Leaves

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    Musa Toyin Yakubu

    2012-05-01

    Full Text Available Background: Alkaloids from Senna alata leaves implicated as the active constituents of abortifacient are yet to be investigated for their effects on the normal functioning of the maternal liver and kidney. Therefore, the effects of crude alkaloids on some biochemical indices of kidney and liver damage were investigated in pregnant rats. Methods: Pregnant rats were randomized into 4 groups: A (control, B, C, and D and were orally administered 0.5 ml of distilled water, 250, 500 and 1000 mg/kg body weight of the alkaloids respectively once daily on days 10-18 post coitum. Results: Thin-layer chromatographic separation gave five spots with Rf values of 0.28, 0.33, 0.39, 0.47, and 0.55 that produced creamy precipitate and reddish-brown colour, respectively, with Mayer’s and Wagner’s reagents. Quantitative determination gave 0.30 g which corresponded to a percentage yield of 1.50 % of the alkaloids. The decreases in the activities of alkaline phosphatase (ALP, gamma glutamyl transferase (GGT, aspartate (AST and alanine transaminases in the liver and kidney of the animals by the alkaloids were accompanied by corresponding increases in the serum enzymes. The alkaloids reduced liver- and kidney-body weight ratios, serum globulin, urea, uric acid, and phosphate ions while the serum concentrations of albumin, bilirubin, creatinine, potassium ions, AST/ALT ratio, blood urea nitrogen: creatinine increased. The levels of sodium, calcium, and chloride ions did not change significantly (P>0.05. Conclusion: Overall, the alkaloid at doses of 250-1000 mg/kg body weight produced permeability changes in the plasma membrane of the organs and adversely affected the normal secretory, synthetic, and excretory functions of these organs.

  20. Zinc supplementation decreases hepatic copper accumulation in LEC rat: a model of Wilson's disease.

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    Gonzalez, Blanca P Esparza; Niño Fong, Rodolfo; Gibson, Candace J; Fuentealba, I Carmen; Cherian, M George

    2005-01-01

    The effect of dietary zinc (Zn) supplementation on copper (Cu)-induced liver damage was investigated in Long-Evans Cinnamon rats (LEC), a model for Wilson's disease (WD). Four-week-old LEC (N=64) and control Long-Evans (LE) (N=32) female rats were divided into two groups; one group was fed with a Zn-supplemented diet (group I) and the other was given a normal rodent diet (group II). LEC rats were killed at 6, 8, 10, 12, 18, and 20 wk of age; the LE control rats were killed at 6, 12, 18, and 20 wk of age. Cu concentration in the liver was reduced in LEC rats fed the Zn-supplemented diet compared with LEC rats on the normal diet between 6 and 18 wk of age. Metallothionein (MT) concentration in the livers of LEC rats in group I increased between 12 and 20 wk of age, whereas hepatic MT concentration in LEC rats from group II decreased after 12 wk. Hepatocyte apoptosis, as determined by TUNEL, was reduced in Zn-supplemented LEC rats at all ages. Cholangiocellular carcinoma was observed only in LEC rats in group II at wk 20. These results suggest that Zn supplementation can reduce hepatic Cu concentration and delay the onset of clinical and pathological changes of Cu toxicity in LEC rats. Although the actual mechanism of protection is unknown, it could be explained by sequestration of dietary Cu by intestinal MT, induced by high dietary Zn content.

  1. Pre- and neonatal exposure to lipopolysaccharide or the enteric metabolite, propionic acid, alters development and behavior in adolescent rats in a sexually dimorphic manner.

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    Foley, Kelly A; Ossenkopp, Klaus-Peter; Kavaliers, Martin; Macfabe, Derrick F

    2014-01-01

    Alterations in the composition of the gut microbiome and/or immune system function may have a role in the development of autism spectrum disorders (ASD). The current study examined the effects of prenatal and early life administration of lipopolysaccharide (LPS), a bacterial mimetic, and the short chain fatty acid, propionic acid (PPA), a metabolic fermentation product of enteric bacteria, on developmental milestones, locomotor activity, and anxiety-like behavior in adolescent male and female offspring. Pregnant Long-Evans rats were subcutaneously injected once a day with PPA (500 mg/kg) on gestation days G12-16, LPS (50 µg/kg) on G15-16, or vehicle control on G12-16 or G15-16. Male and female offspring were injected with PPA (500 mg/kg) or vehicle twice a day, every second day from postnatal days (P) 10-18. Physical milestones and reflexes were monitored in early life with prenatal PPA and LPS inducing delays in eye opening. Locomotor activity and anxiety were assessed in adolescence (P40-42) in the elevated plus maze (EPM) and open-field. Prenatal and postnatal treatments altered behavior in a sex-specific manner. Prenatal PPA decreased time spent in the centre of the open-field in males and females while prenatal and postnatal PPA increased anxiety behavior on the EPM in female rats. Prenatal LPS did not significantly influence those behaviors. Evidence for the double hit hypothesis was seen as females receiving a double hit of PPA (prenatal and postnatal) displayed increased repetitive behavior in the open-field. These results provide evidence for the hypothesis that by-products of enteric bacteria metabolism such as PPA may contribute to ASD, altering development and behavior in adolescent rats similar to that observed in ASD and other neurodevelopmental disorders.

  2. Pre- and neonatal exposure to lipopolysaccharide or the enteric metabolite, propionic acid, alters development and behavior in adolescent rats in a sexually dimorphic manner.

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    Kelly A Foley

    Full Text Available Alterations in the composition of the gut microbiome and/or immune system function may have a role in the development of autism spectrum disorders (ASD. The current study examined the effects of prenatal and early life administration of lipopolysaccharide (LPS, a bacterial mimetic, and the short chain fatty acid, propionic acid (PPA, a metabolic fermentation product of enteric bacteria, on developmental milestones, locomotor activity, and anxiety-like behavior in adolescent male and female offspring. Pregnant Long-Evans rats were subcutaneously injected once a day with PPA (500 mg/kg on gestation days G12-16, LPS (50 µg/kg on G15-16, or vehicle control on G12-16 or G15-16. Male and female offspring were injected with PPA (500 mg/kg or vehicle twice a day, every second day from postnatal days (P 10-18. Physical milestones and reflexes were monitored in early life with prenatal PPA and LPS inducing delays in eye opening. Locomotor activity and anxiety were assessed in adolescence (P40-42 in the elevated plus maze (EPM and open-field. Prenatal and postnatal treatments altered behavior in a sex-specific manner. Prenatal PPA decreased time spent in the centre of the open-field in males and females while prenatal and postnatal PPA increased anxiety behavior on the EPM in female rats. Prenatal LPS did not significantly influence those behaviors. Evidence for the double hit hypothesis was seen as females receiving a double hit of PPA (prenatal and postnatal displayed increased repetitive behavior in the open-field. These results provide evidence for the hypothesis that by-products of enteric bacteria metabolism such as PPA may contribute to ASD, altering development and behavior in adolescent rats similar to that observed in ASD and other neurodevelopmental disorders.

  3. Long-term exposure to electromagnetic radiation from mobile phones and Wi-Fi devices decreases plasma prolactin, progesterone, and estrogen levels but increases uterine oxidative stress in pregnant rats and their offspring.

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    Yüksel, Murat; Nazıroğlu, Mustafa; Özkaya, Mehmet Okan

    2016-05-01

    We investigated the effects of mobile phone (900 and 1800 MHz)- and Wi-Fi (2450 MHz)-induced electromagnetic radiation (EMR) exposure on uterine oxidative stress and plasma hormone levels in pregnant rats and their offspring. Thirty-two rats and their forty newborn offspring were divided into the following four groups according to the type of EMR exposure they were subjected to: the control, 900, 1800, and 2450 MHz groups. Each experimental group was exposed to EMR for 60 min/day during the pregnancy and growth periods. The pregnant rats were allowed to stand for four generations (total 52 weeks) before, plasma and uterine samples were obtained. During the 4th, 5th, and 6th weeks of the experiment, plasma and uterine samples were also obtained from the developing rats. Although uterine lipid peroxidation increased in the EMR groups, uterine glutathione peroxidase activity (4th and 5th weeks) and plasma prolactin levels (6th week) in developing rats decreased in these groups. In the maternal rats, the plasma prolactin, estrogen, and progesterone levels decreased in the EMR groups, while the plasma total oxidant status, and body temperatures increased. There were no changes in the levels of reduced glutathione, total antioxidants, or vitamins A, C, and E in the uterine and plasma samples of maternal rats. In conclusion, although EMR exposure decreased the prolactin, estrogen, and progesterone levels in the plasma of maternal rats and their offspring, EMR-induced oxidative stress in the uteri of maternal rats increased during the development of offspring. Mobile phone- and Wi-Fi-induced EMR may be one cause of increased oxidative uterine injury in growing rats and decreased hormone levels in maternal rats. TRPV1 cation channels are the possible molecular pathways responsible for changes in the hormone, oxidative stress, and body temperature levels in the uterus of maternal rats following a year-long exposure to electromagnetic radiation exposure from mobile phones and

  4. Hypothalamic galanin and plasma leptin and ghrelin in the maintenance of energy intake in the Brattleboro rat.

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    Beck, Bernard; Max, Jean-Pierre

    2007-12-07

    Galanin, ghrelin, and leptin are three peptides involved in feeding regulation and more particularly in fat intake. The Brattleboro (di/di) rat is a genetic model of diabetes insipidus characterized by a preference for fat when it is in a food choice situation. Here, we measured hypothalamic galanin concentrations, plasma ghrelin and leptin and dietary preferences of adult di/di Brattleboro rats, di/+ and Long-Evans controls. The Brattleboro rats weighed significantly less than the di/+ rats (-18%; Pdiet and a high-carbohydrate diet. Galanin concentrations were significantly lower in di/di rats than in di/+ rats in the paraventricular nucleus (-56%; P<0.001), but not in the arcuate nucleus. Plasma leptin was significantly lower in the di/di rats than in the di/+ rats (3.49+/-0.20 vs. 6.94+/-0.49 ng/ml; P<0.001). Plasma ghrelin concentrations were significantly lower in Long-Evans rats than in the di/di rats (-21%; P< 0.01). Given that galanin mRNA is overexpressed in the paraventricular nucleus of Brattleboro rats, these data are consistent with increased release of the peptide. In the Brattleboro rat, this overactive galanin system and the variations of ghrelin and leptin maintain an orexigenic drive favoring a preferential intake of fat which provides the animal with enough energy for its metabolism.

  5. Region-specific growth effects in the developing rat prostate following fetal exposure to estrogenic ultraviolet filters.

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    Hofkamp, Luke; Bradley, Sarahann; Tresguerres, Jesus; Lichtensteiger, Walter; Schlumpf, Margret; Timms, Barry

    2008-07-01

    Exposure to environmental endocrine disruptors is a potential risk factor for humans. Many of these chemicals have been shown to exhibit disruption of normal cellular and developmental processes in animal models. Ultraviolet (UV) filters used as sunscreens in cosmetics have previously been shown to exhibit estrogenic activity in in vitro and in vivo assays. We examined the effects of two UV filters, 4-methylbenzylidene camphor (4-MBC) and 3-benzylidene camphor (3-BC), in the developing prostate of the fetal rat. Pregnant Long Evans rats were fed diets containing doses of 4-MBC and 3-BC that resulted in average daily intakes of these chemicals corresponding to the lowest observed adverse effects level (LOAEL) and the no observed adverse effects level (NOAEL) doses in prior developmental toxicity studies. Using digital photographs of serial sections from postnatal day 1 animals, we identified, contoured, and aligned the epithelial ducts from specific regions of the developing prostate, plus the accessory sex glands and calculated the total volume for each region from three-dimensional, surface-rendered models. Fetal exposure to 4-MBC (7.0 mg/kg body weight/day) resulted in a significant increase (p < 0.05) in tissue volume in the prostate and accessory sex glands. Treated males exhibited a 62% increase in the number of ducts in the caudal dorsal prostate. Increased distal branching morphogenesis appears to be a consequence of exposure in the ventral region, resulting in a 106% increase in ductal volume. 4-MBC exposure during development of the male reproductive accessory sex glands exhibited classical growth effects associated with estrogenic endocrine disruptors. The different regional responses suggest that the two developmental processes of ductal outgrowth and branching morphogenesis are affected independently by exposure to the environmental chemicals.

  6. Uterine stretch regulates temporal and spatial expression of fibronectin protein and its alpha 5 integrin receptor in myometrium of unilaterally pregnant rats.

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    Shynlova, Oksana; Williams, S Joy; Draper, Haley; White, Bryan G; MacPhee, Daniel J; Lye, Stephen J

    2007-11-01

    The adaptive growth of the uterus during pregnancy is a critical event that involves increased synthesis of extracellular matrix (ECM) proteins and dynamic remodeling of smooth muscle cell (SMC)-ECM interactions. We have previously found a dramatic increase in the expression of the mRNAs that encode fibronectin (FN) and its alpha5-integrin receptor (ITGA5) in pregnant rat myometrium near to term. Since the myometrium at term is exposed to considerable mechanical stretching of the uterine wall by the growing fetus(es), the objective of the present study was to examine its role in the regulation of FN and ITGA5 expression at late gestation and during labor. Using myometrial tissues from unilaterally pregnant rats, we investigated the temporal changes in Itga5 gene expression in gravid and empty uterine horns by Northern blotting and real-time PCR, in combination with immunoblotting and immunofluorescence analyses of the temporal/spatial distributions of the FN and ITGA5 proteins. In addition, we studied the effects of early progesterone (P4) withdrawal on Itga5 mRNA levels and ITGA5 protein detection. At all time-points examined, the Itga5 mRNA levels were increased in the gravid uterine horn, compared to the empty horn (P < 0.05). Immunoblot analysis confirmed higher ITGA5 and FN protein levels in the myometrium, associated with gravidity (P < 0.05). Immunodetection of ITGA5 was consistently high in the longitudinal muscle layer, increased with gestational age in the circular muscle layer of the gravid horn, and remained low in the empty horn. ITGA5 and FN immunostaining in the gravid horn exhibited a continuous layer of variable thickness associated directly with the surfaces of individual SMCs. In contrast to the effects of stretch, P4 does not appear to regulate ITGA5 expression. We speculate that the reinforcement of the FN-ITGA5 interaction: 1) contributes to myometrial hypertrophy and remodeling during late pregnancy; and 2) facilitates force transduction

  7. Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hormones of energy balance in a TCDD-sensitive and a TCDD-resistant rat strain.

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    Lindén, Jere; Lensu, Sanna; Pohjanvirta, Raimo

    2014-08-12

    One of the hallmarks of the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a drastically reduced feed intake by an unknown mechanism. To further elucidate this wasting syndrome, we followed the effects of a single large dose (100 μg/kg) of TCDD on the serum levels of several energy balance-influencing hormones, clinical chemistry variables, and hepatic aryl hydrocarbon receptor (AHR) expression in two rat strains that differ widely in their TCDD sensitivities, for up to 10 days. TCDD affected most of the analytes in sensitive Long-Evans rats, while there were few alterations in the resistant Han/Wistar strain. However, analyses of feed-restricted unexposed Long-Evans rats indicated several of the perturbations to be secondary to energy deficiency. Notable increases in ghrelin and glucagon occurred in TCDD-treated Long-Evans rats alone, which links these hormones to the wasting syndrome. The newly found energy balance regulators, insulin-like growth factor 1 and fibroblast growth factor 21 (FGF-21), appeared to function in concert in body weight loss-induced metabolic state, and FGF-21 was putatively linked to increased lipolysis induced by TCDD. Finally, we demonstrate a reverse set of changes in the AHR protein and mRNA response to TCDD and feed restriction, suggesting that AHR might function also as a physiological regulator, possibly involved in the maintenance of energy balance.

  8. Effect of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD on Hormones of Energy Balance in a TCDD-Sensitive and a TCDD-Resistant Rat Strain

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    Jere Lindén

    2014-08-01

    Full Text Available One of the hallmarks of the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD is a drastically reduced feed intake by an unknown mechanism. To further elucidate this wasting syndrome, we followed the effects of a single large dose (100 μg/kg of TCDD on the serum levels of several energy balance-influencing hormones, clinical chemistry variables, and hepatic aryl hydrocarbon receptor (AHR expression in two rat strains that differ widely in their TCDD sensitivities, for up to 10 days. TCDD affected most of the analytes in sensitive Long-Evans rats, while there were few alterations in the resistant Han/Wistar strain. However, analyses of feed-restricted unexposed Long-Evans rats indicated several of the perturbations to be secondary to energy deficiency. Notable increases in ghrelin and glucagon occurred in TCDD-treated Long-Evans rats alone, which links these hormones to the wasting syndrome. The newly found energy balance regulators, insulin-like growth factor 1 and fibroblast growth factor 21 (FGF-21, appeared to function in concert in body weight loss-induced metabolic state, and FGF-21 was putatively linked to increased lipolysis induced by TCDD. Finally, we demonstrate a reverse set of changes in the AHR protein and mRNA response to TCDD and feed restriction, suggesting that AHR might function also as a physiological regulator, possibly involved in the maintenance of energy balance.

  9. Effects of Hyperbaric Oxygen on Metabolic Capacity of the Skeletal Muscle in Type 2 Diabetic Rats with Obesity

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    Naoto Fujita

    2012-01-01

    Full Text Available We investigated whether hyperbaric oxygen enhances the oxidative metabolic capacity of the skeletal muscle and attenuates adipocyte hypertrophy in type 2 diabetic rats with obesity. Five-week-old male Otsuka Long-Evans Tokushima fatty (OLETF and Long-Evans Tokushima Otsuka (LETO rats were used as diabetic animals and nondiabetic controls, respectively, and assigned to control and hyperbaric oxygen groups. Animals in the hyperbaric oxygen group were exposed to an atmospheric pressure of 1.25 with an oxygen concentration of 36% for 3 h daily. The glucose level at 27 weeks of age was significantly higher in OLETF rats than in LETO rats, but the elevation was inhibited in OLETF rats exposed to hyperbaric oxygen. The slow-to-fast fiber transition in the skeletal muscle was observed in OLETF rats, but the shift was inhibited in OLETF rats exposed to hyperbaric oxygen. Additionally, the oxidative enzyme activity of muscle fibers was increased by hyperbaric oxygen. The adipocyte size was larger in OLETF rats than in LETO rats, but hypertrophied adipocytes were not observed in OLETF rats exposed to hyperbaric oxygen. Hyperbaric oxygen enhances glucose and lipid metabolism in the skeletal muscle, indicating that hyperbaric oxygen can prevent elevation of glucose and adipocyte hypertrophy in diabetic rats with obesity.

  10. Defective copper binding to apo-ceruloplasmin in a rat model and patients with Wilson's disease.

    Science.gov (United States)

    Kojimahara, N; Nakabayashi, H; Shikata, T; Esumi, M

    1995-06-01

    To examine the mechanism of decrease in serum ceruloplasmin (Cp) in Long-Evans Cinnamon (LEC) rats, a proposed model of Wilson's disease, we analyzed Cp products at the stages of transcription and translation. Northern blot analysis and immunoblot analysis showed that the level and the molecular size of Cp mRNA and protein in LEC rats were similar to those in control Long-Evans-Agouti (LEA) rats. However, the ferroxidase activity of Cp was significantly decreased in LEC rats. We separated serum Cp into two forms by native polyacrylamide gel electrophoresis with pH modification: one was a holo-Cp with copper and ferroxidase activity, and the other was an inactive apo-Cp without copper. Holo-Cp was the predominant form in LEA rats and normal humans, whereas apo-Cp was the major form in LEC rats and patients with Wilson's disease. The cosegregation of apo-Cp predominance with the disease in LEC rats was analyzed using backcross rats. Apo-Cp was dominant in 8 of 11 offspring with disease but in none of 19 normal offspring. These results indicate that a genetic disturbance of copper binding to apo-Cp may be closely associated with the pathogenesis in LEC rats, and probably in Wilson's disease.

  11. Effects of ligature-induced periodontitis in pregnant Wistar rats Efeito da doença periodontal induzida por ligadura na prenhez de ratas Wistar

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    Mariane Ponzio de Azevedo Galvão

    2003-03-01

    Full Text Available The aim of this study was to evaluate the influence of ligature-induced periodontal disease in pregnant rats on their newborn's health parameters. Twenty-four female adult Wistar rats were divided into two groups: the control group (G1 and the group that was submitted to dental ligatures around second upper molars (G2. After the four week period of development of periodontitis, the female animals were mated with male adult Wistar rats. There were no differences in the body weight of females between the two groups during mating and pregnancy. No differences were observed among the groups in relation to the viable newborn index. However, there were differences in newborn birth weight, explained by the diverse size of the litters. In this study, ligature-induced periodontal disease did not promote changes during pregnancy that resulted in low birth weight in newborn Wistar rats.O objetivo do presente estudo foi avaliar a influência da periodontite induzida por ligadura em ratas prenhes sobre parâmetros de saúde geral de seus filhotes. Vinte e quatro ratas Wistar de idade adulta foram divididas em dois grupos: grupo controle (G1 e grupo experimental, que recebeu ligaduras ao redor dos segundos molares superiores (G2. Após o período de indução de periodontite (quatro semanas, as ratas foram colocadas para cruzamento com ratos Wistar machos, adultos. Não houve diferença no peso corporal das fêmeas durante os períodos de cruzamento e prenhez. Também não foram observadas diferenças entre os grupos quanto à taxa de recém-nascidos viáveis. No entanto, houve diferença quanto ao peso dos recém-nascidos, sendo tal diferença explicada pela variação no tamanho das ninhadas. No presente estudo, doença periodontal induzida por ligadura não promoveu mudanças durante a prenhez que resultassem em baixo peso ao nascer dos filhotes Wistar.

  12. The Effect of Pregnant Rat Swimming on Hypoxia-Inducible Factor-1α Levels of Neonatal Lung

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    Hajizade A

    2012-03-01

    Full Text Available Background: Uterine environment and fetal period can profoundly affect health of the neonat. Hypoxia-inducible factor-1α (HIF-1α is a transcription factor that regulates cellular stress responses and its activity is essential in both embryogenesis and postnatal life. The aim of the present study was to investigate the effects of maternal swimming on rat Pups' HIF-1α levels as a key regulator of oxygen in lungs.Methods: Sixteen female Wistar rats weighing 180- 200 grams were acclimated to a new environment consisting of equal light-darkness cycle and ad lib access to chow and adapted to the stress caused by water for two weeks. The rats were divided into two swimming and control groups. Swimming training began on the first day of pregnancy in a pool and continued for 3 weeks (1 h/day, 5 days/wk. Pups' lungs were removed two days after birth and their HIF-1α concentration was determined with enzyme-linked immunosorbent assay (ELISA. Statistical analysis of the data was done using independent t-test. A p-value smaller than 0.05 was considered statistically significant. Results: Swimming lead to a significant (P<0.001 increase in the Pups' lung HIF-1α levels compared with the control group. Although 3-wk period of swimming training, showed no significant increase in weight and also lung weight of newborns. Thus it can be concluded that swimming endurance training in pregnancy, can be considered as appropriate alternative in order to embryos development. Conclusion: Our research suggests that HIF-1α level is an essential element for the development of the lungs of embryos. Moreover, further studies on the lung HIF-1α levels at post-natal period with different modes of exercise will provide more clear insight into the mechanisms of the findings resulting from this study.

  13. Altered object-in-place recognition memory, prepulse inhibition, and locomotor activity in the offspring of rats exposed to a viral mimetic during pregnancy.

    Science.gov (United States)

    Howland, J G; Cazakoff, B N; Zhang, Y

    2012-01-10

    Infection during pregnancy (i.e., prenatal infection) increases the risk of psychiatric illnesses such as schizophrenia and autism in the adult offspring. The present experiments examined the effects of prenatal immune challenge on behavior in three paradigms relevant to these disorders: prepulse inhibition (PPI) of the acoustic startle response, locomotor responses to an unfamiliar environment and the N-methyl-d-aspartate antagonist MK-801, and three forms of recognition memory. Pregnant Long-Evans rats were exposed to the viral mimetic polyinosinic-polycytidylic acid (PolyI:C; 4 mg/kg, i.v.) on gestational day 15. Offspring were tested for PPI and locomotor activity before puberty (postnatal days (PNDs)35 and 36) and during young adulthood (PNDs 56 and 57). Four prepulse-pulse intervals (30, 50, 80, and 140 ms) were employed in the PPI test. Recognition memory testing was performed using three different spontaneous novelty recognition tests (object, object location, and object-in-place recognition) after PND 60. Regardless of sex, offspring of PolyI:C-treated dams showed disrupted PPI at 50-, 80-, and 140-ms prepulse-pulse intervals. In the prepubescent rats, we observed prepulse facilitation for the 30-ms prepulse-pulse interval trials that was selectively retained in the adult PolyI:C-treated offspring. Locomotor responses to MK-801 were significantly reduced before puberty, whereas responses to an unfamiliar environment were increased in young adulthood. Both male and female PolyI:C-treated offspring showed intact object and object location recognition memory, whereas male PolyI:C-treated offspring displayed significantly impaired object-in-place recognition memory. Females were unable to perform the object-in-place test. The present results demonstrate that prenatal immune challenge during mid/late gestation disrupts PPI and locomotor behavior. In addition, the selective impairment of object-in-place recognition memory suggests tasks that depend on prefrontal

  14. Hypothermic protection in rat focal ischemia models: strain differences and relevance to "reperfusion injury".

    Science.gov (United States)

    Ren, Yubo; Hashimoto, Megumi; Pulsinelli, William A; Nowak, Thaddeus S

    2004-01-01

    Hypothermic protection was compared in Long-Evans and spontaneously hypertensive rat (SHR) strains using transient focal ischemia, and in Wistar and SHR strains using permanent focal ischemia. Focal ischemia was produced by distal surgical occlusion of the middle cerebral artery and tandem occlusion of the ipsilateral common carotid artery (MCA/CCAO). Moderate hypothermia of 2 hours' duration was produced by systemic cooling to 32 degrees C, with further cooling of the brain achieved by reducing to 30 degrees C the temperature of the saline drip superfusing the exposed occlusion site. Infarct volume was determined from serial hematoxylin and eosin-stained frozen sections obtained routinely at 24 hours, or in some cases after 3 days' survival. In the SHR, moderate hypothermia was only effective when initiated before recirculation after a 90-minute occlusion period. In contrast, the same intervention was strikingly effective in the Long-Evans rat even when initiated after as long as 30-minute reperfusion after a 3-hour occlusion. This magnitude and duration of cooling was not protective in permanent MCA/CCAO in the SHR, but such transient hypothermia did effectively reduce infarct volume after permanent occlusions in Wistar rats. These results show striking differences in the temporal window for hypothermic protection among rat focal ischemia models. As expected, "reperfusion injury" in the Long-Evans strain is particularly responsive to delayed cooling. The finding that the SHR can be protected by hypothermia initiated immediately before recirculation suggests a rapidly evolving component of injury occurs subsequent to reperfusion in this model as well. Hypothermic protection after permanent occlusion in Wistar rats identifies a transient, temperature-sensitive phase of infarct evolution that is not evident in the unreperfused SHR. These observations confirm that distinct mechanisms can underlie the temporal progression of injury in rat stroke models, and emphasize

  15. Effects of Microwave Irradiation on Embryonic Brain Tissue.

    Science.gov (United States)

    1979-03-01

    pregnant. The groups thus were too small to permit any valid comparisons. A third experiment on short-term irradiation of dated pregnancy rats morning...and afternoon was carried out from 14 and 15 January to .4 and 5 February 1976. Twenty-one Long-Evans dated pregnancy rats (mated on 1-14- 76) were

  16. Effects of L-arginine oral supplements in pregnant spontaneously hypertensive rats Efeitos da oferta oral de L-arginina em ratas prenhas espontaneamente hipertensas

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    José Ricardo Sousa Ayres de Moura

    2006-08-01

    Full Text Available PURPOSE: To evaluate the effects of L-arginine oral supplementation in spontaneously hypertensive pregnant rats (SHR. METHODS: Thirty SHR and ten Wistar-EPM-1 virgin female rats were used in the study. Before randomization, females were caged with males of the same strain (3:1. Pregnancy was confirmed by sperm-positive vaginal smear (Day 0. Wistar-EPM-1 rats served as counterpart control (C-1. SHR rats were randomized in 4 groups (n=10: Group Control 2, non-treated rats; Group L-Arginine treated with L-arginine 2%; Group Alpha-methyldopa treated with Alpha-methyldopa 33mg/Kg; Group L-Arginine+Alpha-methyldopa treated with L-arginine 2%+Alpha-methyldopa 33mg/Kg. L-arginine 2% solution was offered ad libitum in drinking water and Alpha-methyldopa was administered by gavage twice a day during the length of pregnancy (20 days. Blood pressure was measured by tailcuff plethysmography on days 0 and 20. Body weight was measured on days 0, 10 and 20. Results were expressed as mean ± SD (Standard Deviation. One-Way ANOVA/Tukey (or Kruskal-Wallis/Dunn, as appropriate was used for group comparisons. Statistical significance was accepted as pOBJETIVO: Avaliar os efeitos da oferta oral de L-arginina em ratas prenhas espontaneamente hipertensivas (SHR. MÉTODOS: 30 SHR e 10 Wistar-EPM-1 ratas virgens foram utilizadas no estudo. Antes da distribuição, as fêmeas foram acasaladas com machos da mesma linhagem (3:1; a prenhez foi confirmada pela presença de espermatozóides no esfregaço vaginal. As ratas Wistar-EPM-1 foram utilizadas como controles. As ratas SHR foram aleatoriamente distribuídas em 4 grupos (n=10: Grupo Controle-2, não-tratado; Grupo L-Arginina, tratado com L-arginina; Grupo Alfa-metildopa, tratado com alfa-metildopa; Grupo L-Arginina+Alfa-metildopa, tratado com arginina+Alfa-metildopa. L-arginina (2% foi oferecida ad libitum na água de beber e a Alfa-metildopa (33 mg/Kg foi administrada por gavagem, duas vezes ao dia, durante toda a

  17. Ameliorative effect of Morus alba leaves extract against developmental retinopathy in pups of diabetic and aluminum intoxicated pregnant albino rats

    Institute of Scientific and Technical Information of China (English)

    Hassan; El-Sayyed; Gamal; Badawy; Sobhy; Hassab; Elnabi; Ibrahim; El-Elaimy; Eman; Al; Shehari

    2015-01-01

    Objective: To investigate the possible ameliorative effect of crude water extract of Morus alba(M. alba) leaves on retinopathy of rat pups maternally subjected to diabetes and/or Al intoxication.Methods: Both control and experimental groups were subjected to certain integrated approaches, namely, biochemical assessments, light microscopic investigation, transmission electron microscopic investigation, single cell gel electrophoresis(comet assay) and determination of DNA fragmentation.Results: The retina of pups of diabetic and/or Al-intoxicated mothers exhibited abnormal alterations in retinal cell layers including retinal pigmented epithelium, photoreceptor inner segment and ganglion cells. Increased incidence of DNA fragmentation and apoptosis were evident in pups of diabetic and/or Al-intoxicated mothers. However, retina of pups maternally received M. alba extract plus diabetes or Al-intoxicated alone or in combination showed marked amelioration. Less degree of ameliorations was seen in retina of pups maternally subjected to combined treatment. Furthermore, application of crude water extract of M.alba resulted in amelioration of the alterations of maternal serum glucose as well as Al concentration.Conclusions: Based on the results of the present study, M. alba extract is effective against experimentally diabetic and Al-induced developmental retinopathy.

  18. Choline supplementation mitigates trace, but not delay, eyeblink conditioning deficits in rats exposed to alcohol during development.

    Science.gov (United States)

    Thomas, Jennifer D; Tran, Tuan D

    2012-03-01

    Children exposed to alcohol prenatally suffer from a range of physical, neuropathological, and behavioral alterations, referred to as fetal alcohol spectrum disorders (FASD). Both the cerebellum and hippocampus are affected by alcohol exposure during development, which may contribute to behavioral and cognitive deficits observed in children with FASD. Despite the known neuropathology associated with prenatal alcohol exposure, many pregnant women continue to drink (heavy drinkers, in particular), creating a need to identify effective treatments for their children who are adversely affected by alcohol. We previously reported that choline supplementation can mitigate alcohol's effects on cognitive development, specifically on tasks which depend on the functional integrity of the hippocampus. The present study examined whether choline supplementation could differentially mitigate alcohol's effects on trace eyeblink classical conditioning (ECC, a hippocampal-dependent task) and delay ECC (a cerebellar-dependent task). Long-Evans rats were exposed to 5.25 g/kg/day alcohol via gastric intubation from postnatal days (PD) 4-9, a period of brain development equivalent to late gestation in humans. A sham-intubated control group was included. From PD 10-30, subjects received subcutaneous injections of 100 mg/kg choline chloride or vehicle. Beginning on PD 32-34, subjects were trained on either delay or trace eyeblink conditioning. Performance of subjects exposed to alcohol was significantly impaired on both tasks, as indicated by significant reductions in percentage and amplitude of conditioned eyeblink responses, an effect that was attenuated by choline supplementation on the trace, but not delay conditioning task. Indeed, alcohol-exposed subjects treated with choline performed at control levels on the trace eyeblink conditioning task. There were no significant main or interactive effects of sex. These data indicate that choline supplementation can significantly reduce the

  19. Effects of Post-coital Administration of Alkaloids from Senna alata (Linn. Roxb) Leaves on some Fetal and Maternal Outcomes of Pregnant Rats.

    Science.gov (United States)

    Yakubu, Musa Toyin; Musa, Isa Fakai

    2012-10-01

    The abortifacient claim of Senna alata (S. alata) was scientifically validated recently with alkaloids speculated to be the bioactive agent. This speculation is yet to be substantiated or refuted by scientific evidence. The present study was aimed to investigate the pregnancy terminating effects of the alkaloids from S. alata leaves. Twenty four Pregnant rats (143.99±1.21 g) allocated randomly to four groups: A, B, C and D respectively received, 0.5 ml of distilled water, 250, 500 and 1000 mg/kg body weight of the S. alata extracted alkaloids orally, once daily from day 10 until day 18 post-coitum. The indices of abortifacient were evaluated at the end of the exposure period. The results were analyzed by both the analysis of variance and Duncan's multiple range test and p < 0.05 was considered as statistically significant. Thin-layer chromatographic separation produced five spots with Rf values of 0.28, 0.33, 0.39, 0.47 and 0.55 which gave positive reaction with Meyer's and Wagner's reagents, respectively. The number of implantation sites and corpora lutea, as well as the concentrations of FSH, LH, progesterone, weight of uterus, uterine/ body weight ratio, glucose and cholesterol decreased significantly (p < 0.05) whereas the resorption index, pre- and post-implantation losses, uterine protein content and alkaline phosphatase activity increased significantly. None of the alkaloid treated animals presented with provoked vaginal opening or bleeding except fetal deaths. The alkaloid decreased the maternal weight gain, as well as feed and water intake. Overall, the alkaloids from S. alata leaves exhibited anti-implantation, anti-gonadotropic, anti-progesteronic, embryonic resorptive, feto-maternal toxic activities but not complete abortifacient. The alkaloids alone may not be the sole abortifacient bioactive agent in the leaf extract.

  20. A toxicidade do Hypericum perforatum administrado a ratas prenhes Evaluation of Hypericum perforatum toxicity when administered to pregnant rats

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    Luciana Valente Borges

    2005-08-01

    Full Text Available OBJETIVO: No presente trabalho foi avaliada a toxicidade do H. perforatum administrado a ratas no período de organogênese (9º ao 15º dia de gestação. MÉTODOS: Trinta ratas Wistar inseminadas foram distribuídas aleatoriamente nos grupos controle e tratado, que receberam, respectivamente, 0,5 mL de solução fisiológica e 36 mg/kg de extrato seco de Jarsin diluídos em 0,5 mL de solução fisiológica por gavagem. A toxicidade materna foi avaliada por: consumo de água e ração, peso corporal, piloereção, deambulação, diarréia e ocorrência de mortes. As ratas foram sacrificadas no 21º dia de gestação, quando foram removidos e pesados: rins, fígado e ovários. Foram calculados os índices de implantação e de reabsorção e foi verificado o número médio de fetos por rata. RESULTADOS: Não foram observados sinais clínicos de toxicidade materna e nenhuma das variáveis analisadas apresentou diferenças estatisticamente significativas entre os grupos experimentais. CONCLUSÃO: Na dose administrada e no modelo experimental utilizado, o Hypericum perforatum não apresenta manifestações tóxicas para ratas prenhas no período de organogênese.BACKGROUND: Saint John's wort (Hypericum perforatum is a medicinal plant used in the treatment of depression and other psychiatric disorders. OBJECTIVE: In the present paper, the toxicity of H. perforatum administered to female rats during organogenesis (9th to 15th day of pregnancy was evaluated. METHODS: Thirty inseminated Wistar rats were randomly distributed into Control and Treated groups, which received by gavage, respectively, 0.5 ml of saline and 36 mg/Kg body weight of Jarsin dried extract diluted into 0.5 ml of saline. Maternal toxicity was evaluated by means of: water and food intake, body weight, piloerection, walking activity, diarrhea and death. Animals were killed on the 21st day of pregnancy, when kidneys, liver and ovaries were weighed. Implantation and reabsorption indices

  1. Ação crônica do napsilato de propoxifeno na prenhez da rata Chronic effects of propoxyphene napsylate on pregnant rats

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    Eliane T. R. Mendes

    1998-03-01

    Full Text Available O objetivo deste trabalho é avaliar os efeitos do napsilato de propoxifeno sobre a prenhez da rata albina. Para tanto utilizamos 50 ratas prenhes divididas ao acaso em cinco grupos iguais. Todas receberam diariamente, por gavagem, o volume de 1 ml, desde os dias 0 (zero até o 20 de prenhez, com as seguintes características: grupo I - somente água destilada (controle; grupo II - solução aquosa de acácia 2% (veículo; grupos III, IV e V - respectivamente, 5, 15 e 45 mg/kg de peso de napsilato de propoxifeno dissolvido em solução de acácia a 2%. Os pesos maternos foram anotados nos dias 0 (zero, 7, 14 e 20 de prenhez; no 20º dia as matrizes foram sacrificadas. Nossos resultados mostraram que os animais tratados com 45 mg/kg do fármaco apresentaram redução dos pesos individuais dos fetos como também dos pesos das ninhadas e das placentas. Quanto às outras variáveis apreciadas: número de reabsorções, de implantações e de placentas não houve diferença significante entre os grupos tratados em relação ao grupo controle.The purpose of this study is to evaluate the effects of propoxyphene napsylate on the pregnancy of the rat. We used fifty pregnant rats divided into five groups. All the animals received daily 1 ml of the solution by gavage from day 0 to the 20th day of pregnancy. Group I - only distilled water (control; group II - aqueous solution of acacia 2% (vehicle; groups III, IV and V - respectively, 5, 15 and 45 mg/kg of weight of propoxyphene napsylate diluted in 2% acacia solution. The animals were weighed on days 0, 7, 14 and 20 of pregnancy. All animals were sacrificed on the 20th day of pregnancy. Our results showed that the animals treated with 45 mg/kg of propoxyphene napsylate presented reduction of the individual weights of the fetuses, as well as of the weights of the newborns and placentas. The difference betewwn number of resorptions, implantations and placentas of the treated groups was shown to be non

  2. Toxicological assessments of rats exposed prenatally to inhaled vapors of gasoline and gasoline-ethanol blends.

    Science.gov (United States)

    Bushnell, Philip J; Beasley, Tracey E; Evansky, Paul A; Martin, Sheppard A; McDaniel, Katherine L; Moser, Virginia C; Luebke, Robert W; Norwood, Joel; Copeland, Carey B; Kleindienst, Tadeusz E; Lonneman, William A; Rogers, John M

    2015-01-01

    The primary alternative to petroleum-based fuels is ethanol, which may be blended with gasoline in the United States at concentrations up to 15% for most automobiles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ethanol vapors from these fuels. The well-known sensitivity of the developing nervous and immune systems to ingested ethanol and the lack of information about the neurodevelopmental toxicity of ethanol-blended fuels prompted the present work. Pregnant Long-Evans rats were exposed for 6.5h/day on days 9-20 of gestation to clean air or vapors of gasoline containing no ethanol (E0) or gasoline blended with 15% ethanol (E15) or 85% ethanol (E85) at nominal concentrations of 3000, 6000, or 9000 ppm. Estimated maternal peak blood ethanol concentrations were less than 5mg/dL for all exposures. No overt toxicity in the dams was observed, although pregnant dams exposed to 9000 ppm of E0 or E85 gained more weight per gram of food consumed during the 12 days of exposure than did controls. Fuel vapors did not affect litter size or weight, or postnatal weight gain in the offspring. Tests of motor activity and a functional observational battery (FOB) administered to the offspring between post-natal day (PND) 27-29 and PND 56-63 revealed an increase in vertical activity counts in the 3000- and 9000-ppm groups in the E85 experiment on PND 63 and a few small changes in sensorimotor responses in the FOB that were not monotonically related to exposure concentration in any experiment. Neither cell-mediated nor humoral immunity were affected in a concentration-related manner by exposure to any of the vapors in 6-week-old male or female offspring. Systematic concentration-related differences in systolic blood pressure were not observed in rats tested at 3 and 6 months of age in any experiment. No systematic differences were observed in serum glucose or glycated hemoglobin A1c (a marker of long-term glucose

  3. The effect of resveratrol on contractility of non-pregnant rat uterus: the contribution of K(+) channels.

    Science.gov (United States)

    Novakovic, R; Ilic, B; Beleslin-Cokic, B; Radunovic, N; Heinle, H; Scepanovic, R; Gojkovic-Bukarica, L

    2013-12-01

    This study was aimed to evaluate resveratrol (1-100 μM) effect on the spontaneous rhythmic contractions (SRC), oxytocin-induced (0.2 nM, POxC) phasic and tonic (20 nM, TOxC) contractions of isolated rat uterus. The SRC and POxC were more sensitive to resveratrol than TOxC (pD2 values: 4.53 and 4.66 versus 4.06). Different blockers of K(+) channels (glibenclamide, tetraethylamonium, iberiotoxin, 4-aminopyridine) antagonized the response to resveratrol on the SRC and phasic contractions, but did not antagonize the effect of resveratrol on the TOxC. In order to compare the relaxant activities of resveratrol on the TOxC with that of potassium channel openers, a separate experiments with NS 1619, a highly specific big Ca(2+)-sensitive K(+) (BKCa) channels opener and pinacidil, a predominant opener of ATP-sensitive K(+) (KATP) channels were done. NS 1619 (10-100 μM) and pinacidil (10-100 μM) produced more potent inhibition of TOxC than resveratrol (pD2 values were 6.00 and 5.29). Iberiotoxin, a highly selective BKCa channels blocker, antagonized the response to NS 1619 and glibenclamide, a highly selective KATP channels blocker, antagonized the response to pinacidil on the TOxC. To test K(+)- and extracellular Ca(2+)- independent mechanism(s) of resveratrol on TOxC, a K(+)-rich, Ca(2+)-free solution was used. Under this condition, only high concentrations (≥30 μM) of resveratrol inhibited TOxC. Western blots analysis confirmed expression of Kir6.1, Kir6.2, KCa1.1, Kv2.1 and Kv4.2. channel proteins in myometrium. Thus, the effect of resveratrol is dependent on the types of contractions. The inhibitory response of resveratrol on the SRC and phasic contractions involves different myometrial K(+)- channels. When applied in high concentrations, resveratrol has an additional K(+)- channels independent mechanism(s) of action. As the effects of NS 1619, pinacidil and resveratrol on the TOxC are different, we can conclud that resveratrol does not behave as a classical

  4. Oxytocic effects of the aqueous leaf extract of Costus lucanusianus - family Costaceae on isolated non-pregnant rat uterus.

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    Owolabi, Omonkhelini J; Omogbai, Eric K I; Falodun, Abiodun

    2010-04-01

    Costus lucanusianus J. Braun (Costaceae) is a climbing herb, found mainly in the Niger Delta region of Nigeria. This plant is locally used in situations of pains, inflammation, dysmenorrhoea and in pyrexia. The purpose of this study was to investigate this claim with view to validating scientifically the ethno-medicinal usage. The aqueous extract was subjected to pharmacological testing in vitro on a piece of isolated rat uterus previously pretreated with 1 mg/kg stilbestrol for 24 h. The dose response curves of oxytocin and that of the extract were first obtained. The effects of antagonists like atropine (1 mg) and salbutamol (2 microg) on the dose response curve of the extract were also investigated. Possible synergy was investigated via co-administration of the extract and oxytocin. Finally the proximate analysis of the extract was investigated. The aqueous extract of C. lucanusianus and oxytocin both produced a dose dependent contraction of the uterus. An effect of 0.63+/-0.06 g force of uterine contraction produced by 12.5 mg of the extract was increased to 1.37+/-0.09 g when 200 mg of the extract was administered. Oxytocin at 0.16 i.u was observed to produce a similar force of contraction with 200 mg of the aqueous extract. Synergy was established as co administration of the extract at 200 mg and oxytocin at 0.08 i.u, produced higher contractile effect, significantly higher (p<0.05) than when either the extract (200mg) or oxytocin (0.08 i.u) was administered alone. Both atropine and salbutamol significantly (p<0.0001) inhibited the contractile effect produced by the extract. The inhibitory effect showed by atropine on the contractile effect of the extract seems to suggest the involvement of muscarinic receptors. The proximate analysis carried out in this study is used to establish the identity of the crude drug sample. A moisture content of 10.047 % was obtained. The total ash is a measure of the non-volatile inorganic constituents remaining after ashing. The

  5. The nuclear factor-κB inhibitor pyrrolidine dithiocarbamate reduces polyinosinic-polycytidilic acid-induced immune response in pregnant rats and the behavioral defects of their adult offspring

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    Song Xueqin

    2011-12-01

    Full Text Available Abstract Background Epidemiological studies have indicated that maternal infection during pregnancy may lead to a higher incidence of schizophrenia in the offspring. It is assumed that the maternal infection increases the immune response, leading to neurodevelopmental disorders in the offspring. Maternal polyinosinic-polycytidilic acid (PolyI:C treatment induces a wide range of characteristics in the offspring mimicking some schizophrenia symptoms in humans. These observations are consistent with the neurodevelopmental hypothesis of schizophrenia. Methods We examined whether suppression of the maternal immune response could prevent neurodevelopmental disorders in adult offspring. PolyI:C or saline was administered to early pregnant rats to mimic maternal infection, and the maternal immune response represented by tumor necrosis factor alpha (TNF-α and interleukin-10 (IL-10 levels was determined by enzyme-linked immunosorbent assays (ELISA. The NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC was used to suppress the maternal immune response. Neurodevelopmental disorders in adult offspring were examined by prepulse inhibition (PPI, passive avoidance, and active avoidance tests. Results PolyI:C administration to early pregnant rats led to elevated serum cytokine levels as shown by massive increases in serum TNF-α and IL-10 levels. The adult offspring showed defects in prepulse inhibition, and passive avoidance and active avoidance tests. PDTC intervention in early pregnant rats suppressed cytokine increases and reduced the severity of neurodevelopmental defects in adult offspring. Conclusions Our findings suggest that PDTC can suppress the maternal immune response induced by PolyI:C and partially prevent neurodevelopmental disorders of adult offspring.

  6. Adolescent rats are more prone to binge eating behavior: a study of age and obesity as risk factors.

    Science.gov (United States)

    Bekker, Liza; Barnea, Royi; Brauner, Akiva; Weller, Aron

    2014-08-15

    Binge eating (BE) is characterized by repeated, intermittent over-consumption of food in a brief period of time. This study aims to advance the understanding of potential risk factors for BE such as obesity, overeating and adolescence as an age group. We used the Otsuka Long Evans Tokushima Fatty (OLETF) rat, a genetic overeating-induced obesity model with increased preferences for sweet and fat. Adolescent and adult rats from both strains (OLETF and the lean control strain, Long Evans Tokushima Otsuka [LETO]) received limited access to a palatable liquid diet (Ensure vanilla) for three weeks. Water and chow were available throughout the study, but access to Ensure was limited to two hours, three times a week (3TW group) or every work day (5TW group). As expected, OLETF rats consumed more Ensure and were more BE-prone (BEP) than LETO rats at both ages. Adolescent rats showed a significantly larger binge size as demonstrated by a greater increase in Ensure intake, compared to adults. Furthermore, while the adults reduced their chow intake, compensating for increased Ensure intake, the adolescents increased their chow intake too. Finally, the adolescent rats showed binge like behavior earlier in the study and they tended to be BEP more than the adults. Our findings in rats suggest that adolescents and in particular obese adolescents are at risk for BE, and BE can lead to overweight, thus providing the basis for examination of biological mechanisms of this process in animal models.

  7. The influence of aging on the number of neurons and levels of non-phosporylated neurofilament proteins in the central auditory system of rats

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    Jana eBurianová

    2015-03-01

    Full Text Available In the present study, an unbiased stereological method was used to determine the number of all neurons in Nissl stained sections of the inferior colliculus (IC, medial geniculate body (MGB and auditory cortex (AC in rats (strains Long Evans and Fischer 344 and their changes with aging. In addition, using the optical fractionator and western blot technique, we also evaluated the number of SMI-32-immunoreactive(-ir neurons and levels of non-phosphorylated neurofilament proteins in the IC, MGB, AC, and visual cortex (VC of young and old rats of the two strains. The SMI-32 positive neuronal population comprises about 10% of all neurons in the rat IC, MGB and AC and represents a prevalent population of large neurons with highly myelinated and projecting processes. In both Long Evans and Fischer 344 rats, the total number of neurons in the IC was roughly similar to that in the AC. With aging, we found a rather mild and statistically non-significant decline in the total number of neurons in all three analyzed auditory regions in both rat strains. In contrast to this, the absolute number of SMI-32-ir neurons in both Long Evans and Fischer 344 rats significantly decreased with aging in all the examined structures. The western blot technique also revealed a significant age-related decline in the levels of non-phosphorylated neurofilaments in the auditory brain structures, 30-35%. Our results demonstrate that presbycusis in rats is not likely to be primarily associated with changes in the total number of neurons. On the other hand, the pronounced age-related decline in the number of neurons containing non-phosphorylated neurofilaments as well as their protein levels in the central auditory system may contribute to age-related deterioration of hearing function.

  8. 莪术对正常和血瘀证孕大鼠血液流变学的影响%Effect of Curcumae Rhizoma on Hemorheological Parameters in Normal and Blood-stasis Pregnant Rats

    Institute of Scientific and Technical Information of China (English)

    徐天娇; 赵学梅; 郭丽娜; 洪博; 王晓丽; 李晓明; 李刚; 牛英才

    2014-01-01

    目的:观察莪术对正常和血瘀证孕大鼠血液流变学的影响。方法采用皮下注射盐酸肾上腺素与冷刺激的方法制备血瘀证模型,造模后将正常组随机分为空白对照组和高、中、低剂量莪术组,将血瘀证模型组随机分为模型对照组和高、中、低剂量莪术组。受孕后第6~19 d给予不同剂量的莪术水煎液。检测受孕雌鼠血液流变学指标。结果莪术高、中、低剂量组均能降低正常组与血瘀证模型组在不同切变率下全血黏度。与正常对照组相比较,正常+莪术高剂量组在不同切变率下全血黏度有显著性差异(P<0.05),而在中切变率下,各剂量血瘀+莪术组的全血黏度与正常对照组相比较均有显著性差异(P<0.05)。结论莪术+血瘀证模型组能使全血黏度降至正常孕大鼠水平,证明了中医“有故无殒,亦无殒”的中药辨证减毒理论。%Objective This study aims at evaluating the effect of curcumae rhizoma on hemorheological parameters between normal and blood -stasis pregnant rats .Methods A model of blood -stasis in rats was established by injecting adrenalin and being immersed in ice water .Normal Wistar female rats were randomly divided into blank control group and low , medium and large dose curcumae rhizoma groups , blood-stasis model rats were divided into model control group , low, medium and large dose curcumae rhizoma groups .Curcumae Rhizoma was orally administered to pregnant rats from gestational day ( GD) 6 through 19 at different doses .The hemorheological parameters were used to monitor the pregnant rats .Results Curcumae rhizoma could significantly reduce the hemorheological indexes in whole blood viscosity .Compared with normal group , whole blood viscosity at high , middle and low shear rate were decreased in rats of normal group treated with Curcumae Rhizoma(P<0.05), and We only could find blood viscosity changes at middle shear

  9. Influence of Hyperhomocysteinemia on Embryo Development of Pregnant Rats%高同型半胱氨酸血症对孕鼠胚胎发育的影响

    Institute of Scientific and Technical Information of China (English)

    卢艳; 王新; 王海琴

    2011-01-01

    [Objective] To explore the influence of hyperhomocysteinemia (HHE) on rat pregnancy. [Methods] According to the level of homocysteine ( HCY) , 30 SD pregnant rats were randomly divided into high dose group(group H) , low dose group(group L) and control group(group C) with 10 in each. From d7 to d20 of pregnancy before uterine-incision delivery, group A was intraperitoneally injected with 200mg/(kg. D) , and group L was injected with 100mg/(kg. D) , and group C was injected the equal volume of normal saline. The number of young rats and the dead fetus were counted. The weight and the height of young rats were measured. High performance liquid chromatography and electrochemical method were used to detect plasma HCY levels of pregnant rats before and d20 of pregnancy. [Results]Plasma HCY levels of pregnant rats in group H, L and C at d20 of pregnancy were 30. 47 ± 1. 12, 20. 90 ± 1. 08 and 10. 98 ± 0. 77umol/L respectively, which were higher than those before the pregnancy, and there were significant differences among groups (all P <0. 01). As the dose of HCY increased, the number, weight and height of young rats in group H and L decreased, and the rate of dead and malformation fetus increased. There were significant differences between group H or L and group C(all P <0. 05). There was also significant difference between group H and group L ( P <0. 05). [Conclusion] HHE may exert the toxic effect on embryo development of pregnant rats and there is dose-effect relationship, which mainly shows the decreasing of the number of young rats, growth retardation, malformation and dead fetus.%[目的]探讨高同型半胱氨酸血症(Hhe)对大鼠妊娠的影响.[方法]将30只SD孕鼠按同型半胱氨酸(HCY)浓度高低随机分为 高剂量组(H组)、低剂量组(L组)、对照组(C组),每组10只.从妊娠d7起,H组腹腔内注 HCY 200 mg/(kg·d),L组注射100 mg/(kg·d),C组腹腔内注射同等体积的生理盐水,直至孕d20剖宫取胎.计算各组仔鼠

  10. Periodontitis contributes to aberrant metabolism in type 2 diabetes mellitus rats by stimulating the expression of adipokines.

    Science.gov (United States)

    Luo, S; Yang, X; Wang, D; Ni, J; Wu, J; Xu, Z; Xuan, D; Zhang, J

    2016-08-01

    Periodontitis has been associated with type 2 diabetes mellitus. We investigated the effects of local aberrant secretion of adipokines in diabetic rats on systemic metabolism. Otsuka Long-Evans Tokushima Fatty (OLETF) and non-diabetic Long-Evans Tokushima Otsuka rats were used as a diabetic model and associated control, respectively. Periodontitis was induced using a silk ligature for 36 wk. Rats were grouped into OLETF with (OP+) or without (OP-) periodontitis and Long-Evans Tokushima Otsuka with (LP+) or without (LP-) periodontitis. Alveolar bone resorption and destruction were evaluated by micro-computed tomography and hematoxylin and eosin staining. After 20 wk of periodontitis induction, lipids, insulin, interleukin-1, leptin and plasminogen activator inhibitor-1 were analyzed, and mRNA expressions of NF-κB, Mark8, TLR2 and -4, IKBKB and Nampt were evaluated by quantitative polymerase chain reaction in adipose tissue. After ligation, OLETF rats exhibited typical periodontitis lesions with the clinical features of type 2 diabetes mellitus. When compared with the OP(-) group, the area under curve of the oral glucose tolerance test and homeostatic model assessment-insulin resistance values were significantly higher in the OP(+) group. Micro-computed tomography showed that the OP(+) group had more bone resorption than the OP(-) group. When compared with the OP(-) group, the OP(+) group also exhibited higher total cholesterol (p 0.05) and higher expression of Nampt (p periodontitis can alter lipid profiles in affected rats, elevate adipose tissue expression of Nampt and affect the metabolism of adipose tissue through the NF-κB pathway to inflame diabetes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Ingestion of carbohydrate-rich supplements during gestation programs insulin and leptin resistance but not body weight gain in adult rat offspring

    Directory of Open Access Journals (Sweden)

    Bernard eBeck

    2012-06-01

    Full Text Available Prenatal nutritional conditions can predispose to development of obesity and metabolic syndrome in adulthood. Gestation with its important hormonal status modification is a period of changes in usual feeding habits with pulses or avoidance for certain categories of food. We tried to mimic in an animal model some changes in food consumption patterns observed in pregnant women. For this purpose, Long-Evans female rats were fed during the dark period, their usual pre-gestational food quantity, and were allowed to complete their intake with either a control (Cr, high-fat (HF, or high-carbohydrate (HC diet available ad libitum during the light period. Dams fed a control diet ad libitum (Ca served as controls. Body weight and composition, food intake, and metabolic hormones (insulin, leptin were recorded in male offspring until 20 weeks after birth. Cr and HC females ate less than Ca females ( -16%; p<0.001 and their offspring presented a weight deficit from birth until 6 (HC group and 10 (Cr group weeks of age (p<0.05 or less. Plasma leptin corresponded to low body weight in Cr offspring, but was increased in HC offspring that in addition, had increased plasma insulin, blood glucose and subcutaneous adipose tissue mass. HF dams ate more than Ca dams (+13%;p<0.001, but plasma leptin and insulin were similar in their offspring. Hypothalamic Ob-Rb expression was increased in Cr, HC and HF offspring (+33-100% vs. Ca; p<0.05 or less. HC supplement ingestion during gestation leads therefore to insulin and leptin resistance in adult offspring independently of lower birth weight. These hormonal changes characterize obesity-prone animals. We therefore suggest to be heedful of the carbohydrate content in the diet during the last weeks (or months preceding delivery to limit development of later metabolic disorders in offspring.

  12. Early exposure to bisphenol A alters neuron and glia number in the rat prefrontal cortex of adult males, but not females.

    Science.gov (United States)

    Sadowski, R N; Wise, L M; Park, P Y; Schantz, S L; Juraska, J M

    2014-10-24

    Previous work has shown that exposure to bisphenol A (BPA) during early development can alter sexual differentiation of the brain in rodents, although few studies have examined effects on areas of the brain associated with cognition. The current study examined if developmental BPA exposure alters the total number of neurons and glia in the medial prefrontal cortex (mPFC) in adulthood. Pregnant Long-Evans rats were orally exposed to 0, 4, 40, or 400-μg/kg BPA in corn oil throughout pregnancy. From postnatal days 1 to 9, pups were given daily oral doses of oil or BPA, at doses corresponding to those given during gestation. Brains were examined in adulthood, and the volume of layers 2/3 and layers 5/6 of the mPFC was parcellated. The density of neurons and glia in these layers was quantified stereologically with the optical disector, and density was multiplied by volume for each animal. Males exposed to 400-μg/kg BPA were found to have increased numbers of neurons and glia in layers 5/6. Although there were no significant effects of BPA in layers 2/3, the pattern of increased neuron number in males exposed to 400-μg/kg BPA was similar to that seen in layers 5/6. No effects of BPA were seen in females or in males exposed to the other doses of BPA. This study indicates that males are more susceptible to the long-lasting effects of BPA on anatomy of the mPFC, an area implicated in neurological disorders.

  13. Long-term melatonin administration reduces hyperinsulinemia and improves the altered fatty-acid compositions in type 2 diabetic rats via the restoration of Delta-5 desaturase activity.

    Science.gov (United States)

    Nishida, Shigeru; Segawa, Toshiko; Murai, Ichiro; Nakagawa, Shigeki

    2002-01-01

    The objective of this study was to investigate the effect of long-term melatonin administration on plasma levels of triglycerides, insulin and leptin, and on the fatty-acid metabolism of plasma and hepatic lipids in type 2 diabetic rats. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes mellitus, were divided into two groups: one untreated (n=6), and one implanted with time-releasing melatonin pellets (1.1 mg/day for 30 wk) under the abdominal skin (n=6). Age-matched Long-Evans Tokushima Otsuka (LETO) rats (n=6) were used as healthy controls. The untreated diabetic rats had the increased plasma levels of triglycerides, cholesterol, insulin and leptin at 35 wk, as compared with the healthy control rats (n=6). The diabetic rats also had augmented ratios of 20:3n-6/20:4n-6 fatty acids, owing to diminished activity of Delta-5 desaturase, an insulin-permissive enzyme, in the liver. Melatonin administration to OLETF rats reduced the hypertriglyceridemia (-39%, P melatonin-releasing pellet thus resulted in improved lipid metabolism in diabetic rats, probably through restored insulin resistance.

  14. Conditioned preference for sweet stimuli in OLETF rat: effects of food deprivation.

    Science.gov (United States)

    De Jonghe, Bart C; Hajnal, Andras; Covasa, Mihai

    2007-05-01

    The Otsuka Long-Evans Tokushima Fatty (OLETF) rat, an outbred strain of Long- Evans Tokushima Otsuka rat (LETO) that lacks CCK-1 receptor expression, is hyperphagic and develops obesity and type-2 diabetes. The present study sought to assess how OLETF rats alter intake, preference, and conditioned preference of palatable solutions after acute food deprivation. Our results show that after 24 h chow restriction, LETO rats increase both sucrose intake and two-bottle sucrose preference relative to their free-fed baseline, whereas OLETF rats do not increase sucrose intake (0.3 M or 1.0 M sucrose) or preference (1.0 M vs. 0.3 M sucrose) when they are food deprived. In contrast, OLETF rats exhibit a higher conditioned flavor preference when sucrose is used as unconditioned stimulus (US) relative to LETO rats, whether overnight food restricted (81% vs. 71% for OLETF and LETO rats, respectively) or free fed (82% vs. 54% for OLETF and LETO rats, respectively) during the test. When a noncaloric saccharin solution is used as US, OLETF rats show a higher preference for the saccharin-associated flavor relative to LETO rats when nondeprived (76% vs. 58% for OLETF and LETO rats, respectively); however, neither strain shows differential conditioned flavor preference for saccharin in the deprivation state during the test. These findings suggest that OLETF rats fail to integrate postabsorptive and orosensory effects of sucrose in a conditioning setting to influence intake. Thus, it appears that OLETF rats form preferences for sucrose based largely on orosensory and hedonic properties of the solution, rather than caloric value.

  15. Inhibition and recovery of maternal and fetal cholinesterase enzyme activity following a single cutaneous dose of methyl parathion and diazinon, alone and in combination, in pregnant rats.

    Science.gov (United States)

    Abu-Qare, A W; Abou-Donia, M B

    2001-01-01

    Pregnant Sprague-Dawley rats (14-18 days of gestation) were treated with a single cutaneous subclinical dose(s) of 10 mg kg(-1) (15% of LD(50)) of methyl parathion (O,O-dimethyl O-4-nitrophenyl phosphorothioate) and 65 mg kg(-1) (15% of LD(50)) of diazinon (O,O)-diethyl O-2-isopropyl-6-methylpyrimidinyl phosphorothioate, and their combination. Animals were sacrificed at 1, 2, 4, 12, 24, 48, 72, and 96 h after dosing. Inhibition of maternal and fetal cholinesterase enzyme activity has been determined. Methyl parathion significantly inhibited maternal and fetal brain acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BuChE) activity within 24 h after dosing. Diazinon and a mixture of methyl parathion and diazinon caused lesser inhibition compared with methyl parathion alone. Recovery of maternal and fetal brain AChE activity was in the order of diazinon > combination of diazinon and methyl parathion > methyl parathion 96 h after dosing. Although fetal plasma BuChE activity recovered to 100% of control within 96 h of application, maternal BuChE activity remained inhibited to 55% and 32% of control 96 h after application of methyl parathion and a mixture of methyl parathion and diazinon, respectively. Following a single dermal dose of methyl parathion, the activity of maternal liver BuChE was 63% of control 2 h after dosing, whereas inhibition of placental AChE or BuChE activity occurred 12 and 1 h following a single dose of methyl parathion, corresponding to activities of 63% and 54% of control, respectively. Diazinon, alone or in combination with methyl parathion, did not inhibit significantly the maternal liver BuChE or placental AChE and BuChE activity. The results suggest that dermal application of a single dose of methyl parathion and diazinon, alone or in combination, has an easy access into maternal and fetal tissues, resulting in inhibition of cholinesterase enzymes. The lower inhibitory effect of the combination of methyl parathion and diazinon

  16. Oral administration of green algae, Euglena gracilis, inhibits hyperglycemia in OLETF rats, a model of spontaneous type 2 diabetes.

    Science.gov (United States)

    Shimada, Ryoko; Fujita, Miho; Yuasa, Masahiro; Sawamura, Hiromi; Watanabe, Toshiaki; Nakashima, Ayaka; Suzuki, Kengo

    2016-11-09

    In the present study, the effects of Euglena and paramylon on hyperglycemia were examined in Otsuka Long-Evans Tokushima fatty (OLETF; type 2 diabetes mellitus model) rats. OLETF rats were fed an AIN-93 M diet containing cellulose, Euglena, or paramylon for 10 weeks. Long-Evans Tokushima Otsuka (LETO) rats were used as nondiabetic controls. An oral glucose-tolerance test (OGTT) was performed at 0 and 10 weeks. OLETF control rats were obese because of bulimia and showed abdominal fat accumulation and hyperglycemia. Euglena supplementation improved hyperglycemia and decreased food intake, body weight gain, and abdominal fat. However, there were no changes in the paramylon-supplemented group compared to the OLETF control group. Triglyceride concentrations in the serum and liver were lower in Euglena-supplemented rats than in OLETF control rats. There was a correlation between hepatic triglyceride concentration and the area under the curve (AUC) of OGTT at 10 weeks. This suggests that the improvement in glycemic control in the Euglena-supplemented group may depend on substances other than paramylon present in Euglena.

  17. Uso da Ciprofloxacina durante a Prenhez de Ratas: efeitos sobre a Mãe e Fetos Use of Ciprofloxacin in Pregnant Rats: effects on Mother and Fetuses

    Directory of Open Access Journals (Sweden)

    Mário Silva Approbato

    2000-12-01

    , divided into three groups: D50-treated (ciprofloxacin, 50 mg/kg; D100-treated (ciprofloxacin 100 mg/kg and control group which received physiological saline per os, from the 1st to the 7th day after mating. We studied abortion percentage, maternal weight gain during pregnancy, fetal and maternal death, gross fetal malformation, newborn number and weight at 1st, 3rd, 5th and 10th day of life and newborn neurological reflexes at 1st, 3rd, 5th and 10th day of life. Results: there was no difference between groups in the number of rats that became pregnant. The same was found for maternal weight gain and newborn number. There was a difference in newborn mean weight on day 3rd, 5th and 10th (p = 0.006, 0.01 and 0.03, respectively. The D100 newborn group was the one with less weight gain up to the 10th day of life. We found a significant difference (p = 0.002 in the newborn orientation reflex on the 1st day of life, that disappeared afterwards. No abortion or gross malformation was found in this study. Conclusions: ciprofloxacin modified the newborn weight and reflex on the first days of life. In conclusion, we consider that the use of ciprofloxacin should be restricted during the pregnancy.

  18. The effects of taurine on vigabatrin, high light intensity and mydriasis induced retinal toxicity in the pigmented rat.

    Science.gov (United States)

    Rasmussen, Allan D; Truchot, Nathalie; Pickersgill, Nigel; Thale, Zia Irene; Rosolen, Serge G; Botteron, Catherine

    2015-01-01

    The overall purpose of this study was to establish a model that may be used for examining the effect of Vigabatrin-induced retinal toxicity in pigmented rats, and subsequently examine the possible effects of taurine on the retinal toxicity. In the first part of the study, pigmented Long Evans rats were subjected to combinations of induced mydriasis, low/high light intensities (40/2000 lx) and oral administration of near-MTD (Maximum Tolerated Dose) doses (200 mg/kg/day) of Vigabatrin for up to 6 weeks. The combination of mydriasis and high light intensity applied to Long Evans rats resulted in retinal damage that was increased by the administration of Vigabatrin. In the second part of the study Long Evans rats were subjected to combinations of induced mydriasis and high/low light intensity (40/2000 lx) while being orally administered low (30 mg/kg/day) or high (200 mg/kg/day) doses of Vigabatrin for up to 6 weeks. In addition, selected groups of animals were administered taurine via the drinking water (20 mg/ml), resulting in systemic taurine concentrations of approximately threefold the endogenous concentration. The combined results of the studies demonstrate that retinal damage can be induced in pigmented animals when combining mydriasis and high light intensity. Retinal damage was functionally evaluated by electroretinography (ERG), then confirmed by histopathology. While depending on mydriasis and high light intensity, administration of Vigabatrin increased the retinal toxicity and resulted in the formation of rosette-like structures in the retina in a dose-related manner. Administration of taurine did not alleviate the Vigabatrin-induced retinal toxicity, as demonstrated either functionally by ERG or morphologically, although systemic concentrations of 3-fold the endogenous levels were reached, and it was thus not possible to demonstrate a protective effect of taurine in these pigmented animals. Copyright © 2014 Elsevier GmbH. All rights reserved.

  19. Study on ingredients of Scutellaria Radix extract penetrable through placental barrier of pregnant rat%黄芩水提液透过妊娠大鼠胎盘屏障的药物成分研究

    Institute of Scientific and Technical Information of China (English)

    邓丽丽; 宋殿荣; 郭锦明; 王跃飞

    2012-01-01

    目的:对不同孕期妊娠大鼠给予黄芩水提液,采用HPLC-MS研究透过胎盘屏障的药物成分.方法:早、中、晚孕期Wistar大鼠灌胃黄芩水提液,连续给药5d,末次给药后1.5,12 h,取母体血浆(母血)及胚胎组织,检测生物样品中所含药物成分.结果:实验剂量下,各孕期孕鼠血浆中均检测到了7个化合物,明确归属的化合物有黄芩苷、汉黄芩苷、黄芩素、汉黄芩素、千层纸素A.各孕期胚胎组织中,早期检测到7个化合物,包括已归属的5个化合物;中期未检测到待测成分;晚期检测到除黄芩素以外的6个化合物.结论:大鼠妊娠不同时期给药黄芩后,除孕中期外,孕早、晚期胚胎组织中均可检测到黄芩中的药物成分,提示在妊娠期应用黄芩可以造成胎儿的宫内暴露,应对其进一步进行胚胎毒性研究.%Objective: To study ingredients penetrable through placental barrier by administering pregnant rats with Scutellaria Radix extract using HPLC-MS. Method: Rats in early, middle and late pregnancy were intragastrically administered with Scutellaria Radix extract for 5 days. Maternal plasma and embryonic tissues were obtained at 1. 5 , 12 h after the final administration of Scutellaria Radix extract to determine ingredients of biological specimens. Result: Under the optimum experimental conditions, seven compounds were detected in all pregnant rat plasma, specifically including baicalin, wogonoside, baicalein, wogonin and oroxylin A. The seven compounds were also discovered in embryonic tissues of rats in early pregnancy, including the five detected compounds. But they were not detected in embryonic tissues of rats in middle pregnancy, and six compounds except baicalein were detected embryonic tissues of rats in late pregnancy. Conclusion: Ingredients contained in Scutellaria Radix are detected in pregnant rats at different stages, except those in middle pregnancy, indicating a potential in utero exposure in case

  20. Matching the neural adaptation in the rat ventral cochlear nucleus produced by artificial (electric) and acoustic stimulation of the cochlea

    OpenAIRE

    Loquet, Gérard; Pelizzone, Marco; Valentini, Gregory; Rouiller, Eric M

    2005-01-01

    To investigate neural adaptive properties, near-field evoked potentials were recorded from a chronically implanted electrode in the ventral cochlear nucleus in awake Long-Evans rats exposed to acoustic stimuli or receiving intracochlear electric stimulation. Stimuli were 250-ms trains of repetitive acoustic clicks (10, 30 and 50 dB SPL) or biphasic electric pulses (30, 50 and 70 µA) with intratrain pulse rates ranging from 100 to 1000 pulses per second (pps). The amplitude of the first negati...

  1. Placental lactogen administration reverses the effect of low-protein diet on maternal and fetal serum somatomedin levels in the pregnant rat.

    OpenAIRE

    1984-01-01

    Female rats were studied on day 20 of pregnancy after being fed either a 5% lactalbumin (low protein) diet or a 20% lactalbumin (adequate) diet for the last 2 weeks of pregnancy. Rats on the lower intake of protein showed decreased serum levels of rat placental lactogen and reduced numbers of lactogenic receptors in the maternal liver. These changes were accompanied by much reduced serum levels of somatomedins IGF I(insulin-like growth factor) and II (multiplication-stimulating activity, MSA)...

  2. 寒冷刺激诱发孕鼠妊娠高血压综合征动物模型研究%Cold-stress stimulates pregnancy-induced hypertension syndrome in pregnant rats

    Institute of Scientific and Technical Information of China (English)

    俞丽丽; 李力; 陈鸣; 吴国萍; 胡春秀; 祝之明

    2001-01-01

    目的 探讨寒冷刺激是否能诱发孕鼠妊娠高血压综合征样的改变。方法 将成年Wistar雌鼠随机分为4组:非孕对照组(NN)、非孕寒冷组(NC)、妊娠对照组(PN)、妊娠寒冷组(PC),从妊娠第1天至妊娠第19天每天分别置于(4±2) ℃ 4 h(寒冷组)及25 ℃ (对照组),测定大鼠血压、尿蛋白、体重、红细胞压积,测量胎盘重量、胎鼠重量及身长,观察胎盘、肾脏组织学改变。结果 NC及PC组刺激两周后血压升高、尿蛋白增加,与NN及PN组相比,均有统计学意义。PC组与PN组相比,胎盘重量、胎鼠重量及身长均显著降低,其肾脏及胎盘各层均有明显的缺血、缺氧的组织学表现。结论 反复寒冷刺激可诱发孕鼠妊娠高血压综合征样的改变,为妊娠高血压综合征的动物模型制作提供了一种新的非侵袭性方法。%Objective To determine whether cold-stress stimulation could lead to pregnancy-induced hypertension syndrome (PIH) in rats. Methods Female adult Wistar female rats were randomly divided into 4 groups: non-pregnant control group (NN), non-pregnant cold-stress group (NC), pregnant control group (PN) and pregnant cold-stress group (PC). The rats were kept in (4±2) ℃ for 4 h (cold-stress groups) every day or remained in 25 ℃ (control groups) from the 1 st day to 19 th day of pregnancy. The blood pressure, urine protein, body weight, haematocrit (HCT), weight of placenta, length and weight of fetus were all measured. The histological change of the placenta and kidneys were also observed. Results After cold-stress stimulation for 2 weeks, the blood pressure, urine protein in NC and PC group increased significantly compared with that in control group, while the weight of placenta and fetus, the length of fetus in PC decreased significantly than that in PN. Obvious ischemic and anoxic histological changes in kidneys and all layers of placenta were

  3. Differential effects of strain, circadian cycle, and stimulation pattern on LTP and concurrent LTD in the dentate gyrus of freely moving rats.

    Science.gov (United States)

    Bowden, Jared B; Abraham, Wickliffe C; Harris, Kristen M

    2012-06-01

    Because long-term potentiation (LTP) and long-term depression (LTD) are thought to be involved in learning and memory, it is important to delineate factors that modulate their induction and persistence, especially as studied in freely moving animals. Here, we investigated the effects of rat strain, circadian cycle, and high-frequency stimulation (HFS) pattern on LTP and concurrently induced LTD in the dentate gyrus (DG). Comparison of two commonly used rat strains revealed that medial perforant path field EPSP-population spike (E-S) coupling and LTP were greater in Long-Evans than Sprague-Dawley rats. Circadian cycle experiments conducted in Long-Evans rats revealed greater E-S coupling and enhanced LTP during the dark phase. Interestingly, concurrent LTD in the lateral perforant path did not significantly differ across strains or circadian cycle. Testing HFS protocols during the dark phase revealed that theta burst stimulation (100 Hz bursts at 5 Hz intervals) was ineffective in eliciting either LTP or concurrent LTD in DG, whereas 400 Hz bursts delivered at theta (5 Hz) or delta (1 Hz) frequencies produced substantial LTP and concurrent LTD. Thus, these natural and experimental factors regulate granule cell excitability, and differentially affect LTP and concurrent LTD in the DG of freely moving rats. © 2011 Wiley Periodicals, Inc.

  4. Systemic administration of the neurotensin NTS₁-receptor agonist PD149163 improves performance on a memory task in naturally deficient male brown Norway rats.

    Science.gov (United States)

    Keiser, Ashley A; Matazel, Katelin S; Esser, Melissa K; Feifel, David; Prus, Adam J

    2014-12-01

    Agonists for the neurotensin NTS₁ receptor consistently exhibit antipsychotic effects in animal models without producing catalepsy, suggesting that NTS₁-receptor agonists may be a novel class of drugs to treat schizophrenia. Moreover, studies utilizing NTS₁ agonists have reported improvements in some aspects of cognitive functioning, including prepulse inhibition and learning procedures, which suggest an ability of NTS₁-receptor agonists to diminish neurocognitive deficits. The present study sought to assess both baseline delay-induced memory performance and the effects of NTS₁-receptor activation on learning and memory consolidation in male Long-Evans and Brown Norway rats using a delayed nonmatch-to-position task radial arm-maze task. In the absence of drugs, Brown Norway rats displayed a significant increase in spatial memory errors following 3-, 7-, and 24-hr delay, whereas Long-Evans rats exhibited an increase in spatial memory errors following only a 7-, and 24-hr delay. With Brown Norway rats, administration of PD149163 before or after an information trial significantly reduced errors during a retention trial after a 24 hr delay. Administration of the NTS(1/2)-receptor antagonist SR142948 prior to the information trial did not affect retention-trial errors. These data are consistent with previous findings that Brown Norway rats have natural cognitive deficits and that they may be useful for assessing putative antipsychotic drugs for cognitive efficacy. Moreover, the results of this study support previous findings suggesting that NTS₁-receptor agonists may improve some aspects of cognitive functioning.

  5. Nerve excitability in the rat forelimb

    DEFF Research Database (Denmark)

    Arnold, Ria; Moldovan, Mihai; Rosberg, Mette Romer;

    2017-01-01

    Background Nerve excitability testing by threshold-tracking is the only available method to study axonal ion channel function and membrane potential in the clinical setting. The measures are, however, indirect and the interpretation of neuropathic changes remains challenging. The same multiple...... measures of axonal excitability were adapted to further explore the pathophysiological changes in rodent disease models under pharmacologic and genetic manipulations. These studies are typically limited to the investigation of the “long nerves” such as the tail or the tibial nerves. New method We introduce...... a novel setup to explore the ulnar nerve excitability in rodents. We provide normative ulnar data in 11 adult female Long Evans rats under anaesthesia by comparison with tibial and caudal nerves. Additionally, these measures were repeated weekly on 3 occasions to determine the repeatability of these tests...

  6. Effects of lithium on water intake and renal concentrating ability in rats with vasopressin-deficient diabetes insipidus (Brattleboro strain).

    Science.gov (United States)

    Christensen, S

    1983-02-01

    Male and female Long Evan rats and Brattleboro rats with ADH-deficient diabetes insipidus were treated with lithium administered in the diet for 12 weeks. The plasma lithium level was about 1 mmol/l in all groups. Lithium caused polydipsia and polyuria and lowering of renal concentrating ability in normal rats. In rats with ADH deficiency lithium tended to increase water intake, but did not influence spontaneous urine osmolality or maximal urine osmolality during water deprivation. The results indicate that the renal concentrating defect caused by lithium in rats can be explained by ADH-blockade as the only mechanism. However, there is circumstantial evidence that lithium in addition may stimulate thirst mechanisms by an ADH-independent action.

  7. Influence of dietary melatonin on photoreceptor survival in the rat retina: an ocular toxicity study.

    Science.gov (United States)

    Wiechmann, Allan F; Chignell, Colin F; Roberts, Joan E

    2008-02-01

    Previous studies have shown that melatonin treatment increases the susceptibility of retinal photoreceptors to light-induced cell death. The purpose of this study was to evaluate under various conditions the potential toxicity of dietary melatonin on retinal photoreceptors. Male and female Fischer 344 (non-pigmented) and Long-Evans (pigmented) rats were treated with daily single doses of melatonin by gavage for a period of 14 days early in the light period or early in the dark period. In another group, rats were treated 3 times per week with melatonin early in the light period, and then exposed to high intensity illumination (1000-1500 lx; HII) for 2h, and then returned to the normal cyclic lighting regime. At the end of the treatment periods, morphometric measurements of outer nuclear layer thickness (ONL; the layer containing the photoreceptor cell nuclei) were made at specific loci throughout the retinas. In male and female non-pigmented Fischer rats, melatonin administration increased the degree of photoreceptor cell death when administered during the nighttime and during the day when followed by exposure to HII. There were some modest effects of melatonin on photoreceptor cell death when administered to Fischer rats during the day or night without exposure to HII. Melatonin treatment caused increases in the degree of photoreceptor cell death when administered in the night to male pigmented Long-Evans rats, but melatonin administration during the day, either with or without exposure to HII, had little if any effect on photoreceptor cell survival. In pigmented female Long-Evans rats, melatonin administration did not appear to have significant effects on photoreceptor cell death in any treatment group. The results of this study confirm and extend previous reports that melatonin increases the susceptibility of photoreceptors to light-induced cell death in non-pigmented rats. It further suggests that during the dark period, melatonin administration alone (i.e., no

  8. Aroclor 1254, a developmental neurotoxicant, alters energy metabolism- and intracellular signaling-associated protein networks in rat cerebellum and hippocampus

    Energy Technology Data Exchange (ETDEWEB)

    Kodavanti, Prasada Rao S., E-mail: kodavanti.prasada@epa.gov [Neurotoxicology Branch, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina (United States); Osorio, Cristina [Systems Proteomics Center, University of North Carolina at Chapel Hill, North Carolina (United States); Program on Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, North Carolina (United States); Royland, Joyce E.; Ramabhadran, Ram [Genetic and Cellular Toxicology Branch, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina (United States); Alzate, Oscar [Department of Cellular and Developmental Biology, University of North Carolina at Chapel Hill, North Carolina (United States); Systems Proteomics Center, University of North Carolina at Chapel Hill, North Carolina (United States); Program on Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, North Carolina (United States)

    2011-11-15

    The vast literature on the mode of action of polychlorinated biphenyls (PCBs) indicates that PCBs are a unique model for understanding the mechanisms of toxicity of environmental mixtures of persistent chemicals. PCBs have been shown to adversely affect psychomotor function and learning and memory in humans. Although the molecular mechanisms for PCB effects are unclear, several studies indicate that the disruption of Ca{sup 2+}-mediated signal transduction plays significant roles in PCB-induced developmental neurotoxicity. Culminating events in signal transduction pathways include the regulation of gene and protein expression, which affects the growth and function of the nervous system. Our previous studies showed changes in gene expression related to signal transduction and neuronal growth. In this study, protein expression following developmental exposure to PCB is examined. Pregnant rats (Long Evans) were dosed with 0.0 or 6.0 mg/kg/day of Aroclor-1254 from gestation day 6 through postnatal day (PND) 21, and the cerebellum and hippocampus from PND14 animals were analyzed to determine Aroclor 1254-induced differential protein expression. Two proteins were found to be differentially expressed in the cerebellum following PCB exposure while 18 proteins were differentially expressed in the hippocampus. These proteins are related to energy metabolism in mitochondria (ATP synthase, sub unit {beta} (ATP5B), creatine kinase, and malate dehydrogenase), calcium signaling (voltage-dependent anion-selective channel protein 1 (VDAC1) and ryanodine receptor type II (RyR2)), and growth of the nervous system (dihydropyrimidinase-related protein 4 (DPYSL4), valosin-containing protein (VCP)). Results suggest that Aroclor 1254-like persistent chemicals may alter energy metabolism and intracellular signaling, which might result in developmental neurotoxicity. -- Highlights: Black-Right-Pointing-Pointer We performed brain proteomic analysis of rats exposed to the neurotoxicant

  9. Differential body weight and feeding responses to high-fat diets in rats and mice lacking cholecystokinin 1 receptors.

    Science.gov (United States)

    Bi, Sheng; Chen, Jie; Behles, R Ryan; Hyun, Jayson; Kopin, Alan S; Moran, Timothy H

    2007-07-01

    Prior data demonstrated differential roles for cholecystokinin (CCK)1 receptors in maintaining energy balance in rats and mice. CCK1 receptor deficiency results in hyperphagia and obesity of Otsuka Long-Evans Tokushima Fatty (OLETF) rats but not in mice. To ascertain the role of CCK1 receptors in high-fat-diet (HFD)-induced obesity, we compared alterations in food intake, body weight, fat mass, plasma glucose, and leptin levels, and patterns of hypothalamic gene expression in OLETF rats and mice lacking CCK1 receptors in response to a 10-wk exposure to HFD. Compared with Long-Evans Tokushima Otsuka (LETO) control rats, OLETF rats on HFD had sustained overconsumption over the 10-wk period. High fat feeding resulted in greater increases in body weight and plasma leptin levels in OLETF than in LETO rats. In situ hybridization determinations revealed that, while HFD reduced neuropeptide Y (NPY) mRNA expression in both the arcuate nucleus (Arc) and the dorsomedial hypothalamus (DMH) of LETO rats, HFD resulted in decreased NPY expression in the Arc but not in the DMH of OLETF rats. In contrast to these results in OLETF rats, HFD increased food intake and induced obesity to an equal degree in both wild-type and CCK1 receptor(-/-) mice. NPY gene expression was decreased in the Arc in response to HFD, but was not detectable in the DMH in both wild-type and CCK1 receptor(-/-) mice. Together, these data provide further evidence for differential roles of CCK1 receptors in the controls of food intake and body weight in rats and mice.

  10. Metabolic dose-effect relationships of different Pt compounds on growing, pregnant, and lactating rats; Metabolische Dosis-Wirkungsbeziehungen verschiedener Pt-Verbindungen bei wachsenden, graviden und laktierenden Ratten (VPT 04)

    Energy Technology Data Exchange (ETDEWEB)

    Eder, K.; Kirchgessner, M. [Technische Univ. Muenchen, Freising (Germany). Lehrstuhl fuer Tierernaehrung

    1997-12-31

    The fact that humans can take up platinum via the food chain calls for an investigation of the effects of platinum ingestion on the organism. For this purpose a study was carried out on the dose-effect relationships of various platinum compounds using the rat as a model. To take due account of different physiological stages the study included growing, pregnant, and lactating rats. According to present knowledge platinum is primarily emitted in its elemental form by the catalytic converter, i.e. with the formal oxidation number zero, and to a lesser degree in ionic form. Beside elemental platinum the study therefore also involved exposure to PtCl{sub 2} and PtCl{sub 4}. Furthermore, to do justice to the fact that humans and animals take up platinum not only from its primary source but also from plants in the food chain, platinum was also administered as a Pt-II-phytochelatin complex previously isolated from Pt-contaminated material. Study criteria were chosen with a view to obtaining a general indication of potential toxic effects and included parameters such as the live weight curve, haematological status, and platinum accumulation in the body or in specific organs. Of particular interest in pregnant and lactating rats were platinum levels in foetuses and milk. [Deutsch] Ueber die Nahrungskette ist eine alimentaere Aufnahme von Platin durch den Menschen moeglich und erfordert, die Auswirkungen der ingestiven Platinzufuhr auf den Organismus zu untersuchen. Deshalb wurden am Modelltier Ratte Studien zur Dosis-Wirkungsbeziehung verschiedener Platinverbindungen durchgefuehrt. Um den verschiedenen physiologischen Stadien gerecht zu werden, wurden sowohl wachsende wie auch gravide und laktierende Ratten in die Studien einbezogen. Soweit bislang bekannt, wird Platin vorwiegend in der formalen Oxidationsstufe Null als elementares Platin, zu einem geringeren Anteil aber auch in ionischer Form aus der Katalysatoreinheit ausgetragen. Deshalb wurden in den vorliegenden

  11. Early Treatment With Olmesartan Prevents Juxtamedullary Glomerular Podocyte Injury and the Onset of Microalbuminuria in Type 2 Diabetic Rats

    Science.gov (United States)

    Sofue, Tadashi; Kiyomoto, Hideyasu; Kobori, Hiroyuki; Urushihara, Maki; Nishijima, Yoko; Kaifu, Kumiko; Hara, Taiga; Matsumoto, Sachiko; Ichimura, Atsuhiko; Ohsaki, Hiroyuki; Hitomi, Hirofumi; Kawachi, Hiroshi; Hayden, Melvin R.; Whaley-Connell, Adam; Sowers, James R.; Ito, Sadayoshi; Kohno, Masakazu; Nishiyama, Akira

    2012-01-01

    Background Studies were performed to determine if early treatment with an angiotensin II (Ang II) receptor blocker (ARB), olmesartan, prevents the onset of microalbuminuria by attenuating glomerular podocyte injury in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with type 2 diabetes mellitus. Methods OLETF rats were treated with either a vehicle, olmesartan (10 mg/kg/day) or a combination of nonspecific vasodilators (hydralazine 15 mg/kg/day, hydrochlorothiazide 6 mg/kg/day, and reserpine 0.3 mg/kg/day; HHR) from the age of 7–25 weeks. Results OLETF rats were hypertensive and had microalbuminuria from 9 weeks of age. At 15 weeks, OLETF rats had higher Ang II levels in the kidney, larger glomerular desmin-staining areas (an index of podocyte injury), and lower gene expression of nephrin in juxtamedullary glomeruli, than nondiabetic Long-Evans Tokushima Otsuka (LETO) rats. At 25 weeks, OLETF rats showed overt albuminuria, and higher levels of Ang II in the kidney and larger glomerular desmin-staining areas in superficial and juxtamedullary glomeruli compared to LETO rats. Reductions in mRNA levels of nephrin were also observed in superficial and juxtamedullary glomeruli. Although olmesartan did not affect glucose metabolism, it decreased blood pressure and prevented the renal changes in OLETF rats. HHR treatment also reduced blood pressure, but did not affect the renal parameters. Conclusions This study demonstrated that podocyte injury occurs in juxtamedullary glomeruli prior to superficial glomeruli in type 2 diabetic rats with microalbuminuria. Early treatment with an ARB may prevent the onset of albuminuria through its protective effects on juxtamedullary glomerular podocytes. PMID:22318512

  12. Cerebral antioxidant enzyme increase associated with learning deficit in type 2 diabetes rats.

    Science.gov (United States)

    Suge, Rie; Shimazu, Tomokazu; Hasegawa, Hajime; Inoue, Ikuo; Hayashibe, Hidemasa; Nagasaka, Hironori; Araki, Nobuo; Katayama, Shigehiro; Nomura, Masahiko; Watanabe, Shu-Ichi

    2012-10-24

    In this study, we examined alterations in the enzymatic antioxidant defenses associated with learning deficits induced by type 2 diabetes, and studied the effects of the peroxisome proliferator-activated receptor γ agonist pioglitazone on these learning deficits. Learning ability was assessed by visual discrimination tasks in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, as a model of spontaneous type 2 diabetes. Levels of the antioxidant enzymes glutathione peroxidase (GPx), Cu(2+)-Zn(2+) superoxide dismutase (CuZn-SOD) and manganese SOD were measured in the cortex, hippocampus and striatum. Half the rats received oral pioglitazone (20mg/kg/day) from the early stage of diabetes (22 weeks old) to 27 weeks old. OLETF rats showed learning deficits compared with control, Long-Evans Tokushima Otsuka (LETO) rats. GPx levels in the cortex and hippocampus were increased in OLETF rats compared with LETO rats, with an inverse correlation between GPx in the hippocampus and learning score. CuZn-SOD levels were also increased in the hippocampus in OLETF rats. Pioglitazone reduced blood glucose and increased serum adiponectin levels, but had no effect on learning tasks or antioxidant enzymes, except for CuZn-SOD. These results suggest that an oxidative imbalance reflected by increased brain antioxidant enzymes plays an important role in the development of learning deficits in type 2 diabetes. Early pioglitazone administration partly ameliorated diabetic symptoms, but was unable to completely recover cerebral oxidative imbalance and functions. These results suggest that diabetes-induced brain impairment, which results in learning deficits, may have occurred before the appearance of the symptoms of overt diabetes.

  13. Dehydration-induced changes in the secretion of atrial natriuretic factor in Brattleboro rats: effect of water-drinking.

    Science.gov (United States)

    Januszewicz, P; Gutkowska, J; Thibault, G; Garcia, R; Mercure, C; Jolicoeur, F; Genest, J; Cantin, M

    1986-06-18

    The secretion of atrial natriuretic factor (ANF) was measured in Brattleboro rats (DI) subjected to 20-h dehydration and in normal Long-Evans rats (LE) subjected to 72-h dehydration and 7 times within the hour following voluntary rehydration by drinking water. In these rats, water deprivation caused a large, significant drop in plasma immunoreactive ANF (IR-ANF). Drinking water did not restore plasma IR-ANF values within one hour, even when indirect indices of intravascular volume such as serum osmolality, sodium and hematocrit returned to normal. The dehydration-induced decrease in plasma IR-ANF and its very low secretion after restoring drinking may be essential for the homeostasis of water conservation in both DI and LE rats.

  14. Evaluation of the effect of music given to pregnant rats on the development of brain functions in offspring rats%音乐刺激孕鼠对子代鼠大脑功能影响的系统评价

    Institute of Scientific and Technical Information of China (English)

    范尧; 潘国强; 雷迅; 高佳; 谭毅

    2017-01-01

    Objectives To systematically evaluate the effect of music given to pregnant rats on the development of brain functions in the offspring rats and to provide scientific evidence for the application of antenatal musical training and the promotion of welfare for laboratory animals.Methods We comprehensively retrieved and collected the research literatures related to the effect of music on brain function development in offsprings of the pregnant rats from Pubmed,Web of Science,Cochrane Library,Wanfang,Weipu,CNKI and CBMdisc.The retrieval time was set from the foundation date of databases to 2 April,2016.We selected literatures according to the inclusion and exclusion criteria,evaluated their utilities,then extracted and qualitatively described the data.Results Seven experimental studies were selected in this study including 4 published in Chinese and 3 in English.The object laboratory animals of those studies were Wistar or SD rats.Music materials involved comfort music,classic music,violin concerto(Liangzhu/The butterfly lovers).Intervention were given to the pregnant rats roundly from the gestation until parturition.These results showed that,to some extent,music stimulations during gestation may promote the development of brain function and improve spatial memory of the offspring rats.However,expressions of some functional receptors were not significantly altered.Conclusions Appropriate music provided to the pregnant rats promote the development of brain functions in their offspring.%目的 系统评价音乐刺激孕鼠对子代鼠大脑功能的影响效果,为促进实验动物的福利以及音乐胎教的应用发展提供科学依据.方法 计算机检索Pubmed、Web of Science、Cochrane Library、万方、维普、中国知网和中国生物医学文献数据库,全面收集有关音乐刺激孕鼠对子代鼠大脑功能影响效果的研究文献,检索时限为建库至2016年4月2日.按照纳入与排除标准选择文献、评价文献质量和提取

  15. Polarization properties of single layers in the posterior eyes of mice and rats investigated using high resolution polarization sensitive optical coherence tomography.

    Science.gov (United States)

    Fialová, Stanislava; Augustin, Marco; Glösmann, Martin; Himmel, Tanja; Rauscher, Sabine; Gröger, Marion; Pircher, Michael; Hitzenberger, Christoph K; Baumann, Bernhard

    2016-04-01

    We present a high resolution polarization sensitive optical coherence tomography (PS-OCT) system for ocular imaging in rodents. The system operates at 840 nm and uses a broadband superluminescent diode providing an axial resolution of 5.1 µm in air. PS-OCT data was acquired at 83 kHz A-scan rate by two identical custom-made spectrometers for orthogonal polarization states. Pigmented (Brown Norway, Long Evans) and non-pigmented (Sprague Dawley) rats as well as pigmented mice (C57BL/6) were imaged. Melanin pigment related depolarization was analyzed in the retinal pigment epithelium (RPE) and choroid of these animals using the degree of polarization uniformity (DOPU). For all rat strains, significant differences between RPE and choroidal depolarization were observed. In contrast, DOPU characteristics of RPE and choroid were similar for C57BL/6 mice. Moreover, the depolarization within the same tissue type varied significantly between different rodent strains. Retinal nerve fiber layer thickness, phase retardation, and birefringence were mapped and quantitatively measured in Long Evans rats in vivo for the first time. In a circumpapillary annulus, retinal nerve fiber layer birefringence amounted to 0.16°/µm ± 0.02°/µm and 0.17°/µm ± 0.01°/µm for the left and right eyes, respectively.

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

    Science.gov (United States)

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

    2017-01-01

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

  17. The strain of an accompanying conspecific affects the efficacy of social buffering in male rats.

    Science.gov (United States)

    Nakamura, Kayo; Ishii, Akiko; Kiyokawa, Yasushi; Takeuchi, Yukari; Mori, Yuji

    2016-06-01

    Social buffering is a phenomenon in which stress in an animal is ameliorated when the subject is accompanied by a conspecific animal(s) during exposure to distressing stimuli. We previously reported that in male Wistar rats, the presence of another Wistar rat mitigates conditioned fear responses to an auditory conditioned stimulus (CS). Subsequent analyses revealed several characteristics of this social buffering of conditioned fear responses. However, information regarding the specificity of accompanying conspecifics is still limited. In the present study, we assessed whether rats of other strains could induce social buffering in Wistar rats. When a fear-conditioned Wistar subject was re-exposed to the CS alone, we observed increased freezing and decreased investigation and walking, as well as elevated corticosterone levels. The presence of a Wistar, Sprague-Dawley, or Long-Evans rat blocked these responses, suggesting that social buffering was induced by these strains of rats. In contrast, a Fischer 344 rat did not induce social buffering in the Wistar subject. We further found that an inbred Lewis rat induced social buffering whereas a Brown Norway rat, a strain that has been established independently from Wistar rats, did not. These results suggest that the difference in origin, rather than the inbred or outbred status of the associate rat, seemed to account for the lack of social buffering induced by the F344 rats. Based on these findings, we conclude that strains of an accompanying conspecific can affect the efficacy of social buffering in rats.

  18. Comparison of Ankle Proprioception Between Pregnant and Non Pregnant Women

    OpenAIRE

    Preetha R; John Solomon M

    2011-01-01

    Pregnant women report falls especially during their third trimester. Physiological changes along with ligament laxity can affect the joint proprioception in this population. This study was conducted to compare the ankle proprioception between pregnant and non pregnant women. Thirty pregnant and 30 non pregnant women were included in the study and the position of ankles were recorded by a digital camera placed 60 cms away from the feet of the subject. UTHSCSA Image tool software version 3.0. w...

  19. Regulation of ingestive behaviors in the rat by GSK1521498, a novel micro-opioid receptor-selective inverse agonist.

    Science.gov (United States)

    Ignar, Diane M; Goetz, Aaron S; Noble, Kimberly Nichols; Carballo, Luz Helena; Stroup, Andrea E; Fisher, Julie C; Boucheron, Joyce A; Brainard, Tracy A; Larkin, Andrew L; Epperly, Andrea H; Shearer, Todd W; Sorensen, Scott D; Speake, Jason D; Hommel, Jonathan D

    2011-10-01

    μ-Opioid receptor (MOR) agonism induces palatable food consumption principally through modulation of the rewarding properties of food. N-{[3,5-difluoro-3'-(1H-1,2,4-triazol-3-yl)-4-biphenylyl]methyl}-2,3-dihydro-1H-inden-2-amine (GSK1521498) is a novel opioid receptor inverse agonist that, on the basis of in vitro affinity assays, is greater than 10- or 50-fold selective for human or rat MOR, respectively, compared with κ-opioid receptors (KOR) and δ-opioid receptors (DOR). Likewise, preferential MOR occupancy versus KOR and DOR was observed by autoradiography in brain slices from Long Evans rats dosed orally with the drug. GSK1521498 suppressed nocturnal food consumption of standard or palatable chow in lean and diet-induced obese (DIO) Long Evans rats. Both the dose-response relationship and time course of efficacy in lean rats fed palatable chow correlated with μ receptor occupancy and the plasma concentration profile of the drug. Chronic oral administration of GSK1521498 induced body weight loss in DIO rats, which comprised fat mass reduction. The reduction in body weight was equivalent to the cumulative reduction in food consumption; thus, the effect of GSK1521498 on body weight is related to inhibition of food consumption. GSK1521498 suppressed the preference for sucrose-containing solutions in lean rats. In operant response models also using lean rats, GSK1521498 reduced the reinforcement efficacy of palatable food reward and enhanced satiety. In conclusion, GSK1521498 is a potent, MOR-selective inverse agonist that modulates the hedonic aspects of ingestion and, therefore, could represent a pharmacological treatment for obesity and binge-eating disorders.

  20. Protein deficiency in pregnant rats causes decreased levels of plasma somatomedin and its carrier protein associated with reduced plasma levels of placental lactogen and hepatic lactogenic receptor number.

    Science.gov (United States)

    Pilistine, S J; Munro, H N

    1984-03-01

    Rats were fed either a 20% lactalbumin (control) or a 5% lactalbumin (low protein) diet for the last 2 weeks of pregnancy. At day 20 of gestation, rat serum placental lactogen levels, measured by radioreceptor assay, were significantly decreased by the low protein diet, thus confirming our earlier findings. The number of microsomal membrane lactogenic receptors, measured on the maternal livers at the end of pregnancy, was severely reduced in the livers of the low protein group, whereas protein deficiency did not affect binding affinity. Serum concentrations of somatomedin, measured by a competitive binding assay after acid treatment of the serum to remove endogenous carrier protein, were extensively reduced in the low protein group. The amounts of the somatomedin carrier proteins in the serum were assayed by separation on Sephacryl-S300 columns into higher- and lower-molecular-weight fractions peak 2 and peak 3, respectively. For the low protein diet group, both fractions showed a reduction in binding capacity, more marked in the case of peak 2. Since placental lactogen is known to influence output of somatomedin by the liver, we hypothesize that protein deficiency during pregnancy causes a fall in serum somatomedin level by reducing secretion of placental lactogen, which regulates its production by the liver.

  1. Transcriptional profiling of rat hypothalamus response to 2,3,7,8-tetrachlorodibenzo-ρ-dioxin.

    Science.gov (United States)

    Houlahan, Kathleen E; Prokopec, Stephenie D; Moffat, Ivy D; Lindén, Jere; Lensu, Sanna; Okey, Allan B; Pohjanvirta, Raimo; Boutros, Paul C

    2015-02-03

    In some mammals, halogenated aromatic hydrocarbon (HAH) exposure causes wasting syndrome, defined as significant weight loss associated with lethal outcomes. The most potent HAH in causing wasting is 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD), which exerts its toxic effects through the aryl hydrocarbon receptor (AHR). Since TCDD toxicity is thought to predominantly arise from dysregulation of AHR-transcribed genes, it was hypothesized that wasting syndrome is a result of to TCDD-induced dysregulation of genes involved in regulation of food-intake. As the hypothalamus is the central nervous systems' regulatory center for food-intake and energy balance. Therefore, mRNA abundances in hypothalamic tissue from two rat strains with widely differing sensitivities to TCDD-induced wasting syndrome: TCDD-sensitive Long-Evans rats and TCDD-resistant Han/Wistar rats, 23h after exposure to TCDD (100μg/kg) or corn oil vehicle. TCDD exposure caused minimal transcriptional dysregulation in the hypothalamus, with only 6 genes significantly altered in Long-Evans rats and 15 genes in Han/Wistar rats. Two of the most dysregulated genes were Cyp1a1 and Nqo1, which are induced by TCDD across a wide range of tissues and are considered sensitive markers of TCDD exposure. The minimal response of the hypothalamic transcriptome to a lethal dose of TCDD at an early time-point suggests that the hypothalamus is not the predominant site of initial events leading to hypophagia and associated wasting. TCDD may affect feeding behaviour via events upstream or downstream of the hypothalamus, and further work is required to evaluate this at the level of individual hypothalamic nuclei and subregions. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  2. Angiotensin receptor blockade recovers hepatic UCP2 expression and aconitase and SDH activities and ameliorates hepatic oxidative damage in insulin resistant rats.

    Science.gov (United States)

    Montez, Priscilla; Vázquez-Medina, José Pablo; Rodríguez, Rubén; Thorwald, Max A; Viscarra, José A; Lam, Lisa; Peti-Peterdi, Janos; Nakano, Daisuke; Nishiyama, Akira; Ortiz, Rudy M

    2012-12-01

    Metabolic syndrome (MetS) is commonly associated with elevated renin-angiotensin system, oxidative stress, and steatohepatitis with down-regulation of uncoupling proteins (UCPs). However, the mechanisms linking renin-angiotensin system, steatosis, and UCP2 to hepatic oxidative damage during insulin resistance are not described. To test the hypothesis that angiotensin receptor activation contributes to decreased hepatic UCP2 expression and aconitase activity and to increased oxidative damage after increased glucose intake in a model of MetS, lean and obese Long Evans rats (n = 10/group) were randomly assigned to the following groups: 1) untreated Long Evans Tokushima Otsuka (lean, strain control), 2) untreated Otsuka Long Evans Tokushima Fatty (OLETF) (MetS model), 3) OLETF + angiotensin receptor blocker (ARB) (10 mg olmesartan/kg·d × 6 wk), 4) OLETF + high glucose (HG) (5% in drinking water × 6 wk), and 5) OLETF + ARB + HG (ARB/HG × 6 wk). HG increased body mass (37%), plasma triglycerides (TGs) (35%), plasma glycerol (87%), plasma free fatty acids (28%), and hepatic nitrotyrosine (74%). ARB treatment in HG decreased body mass (12%), plasma TG (15%), plasma glycerol (23%), plasma free fatty acids (14%), and hepatic TG content (42%), suggesting that angiotensin receptor type 1 (AT1) activation and increased adiposity contribute to the development of obesity-related dyslipidemia. ARB in HG also decreased hepatic nitrotyrosine and increased hepatic UCP2 expression (59%) and aconitase activity (40%), as well as antioxidant enzyme activities (50-120%), suggesting that AT1 activation also contributes to protein oxidation, impaired lipid metabolism, and antioxidant metabolism in the liver. Thus, in addition to promoting obesity-related hypertension, AT1 activation may also impair lipid metabolism and antioxidant capacity, resulting in steatosis via decreased UCP2 and tricarboxylic acid cycle activity.

  3. 自发2型糖尿病模型OLETF大鼠不同病程脂肪组织水通道蛋白7 mRNA的表达%Expression of Aquaporin 7 mRNA in different duration of diabetes stage adipose tissue of Otsuka Long-Evans Tokushima fatty rats

    Institute of Scientific and Technical Information of China (English)

    段玉敏; 袁振芳; 郭晓蕙

    2010-01-01

    目的 观察自发性2型糖尿病动物模型OLETF大鼠不同病程阶段皮下及肾周脂肪水通道蛋白7(AQP7)mRNA的表达.方法 以OLETF大鼠为研究对象,同种系非糖尿病LETO大鼠为正常对照.分别在8、14、22周龄行口服葡萄糖耐量试验,试验后取皮下及肾周脂肪组织,采用实时PCR方法测定其AQP7 mRNA的表达.结果 LETO组皮下及肾周脂肪组织均随肥胖增加表达上调,OLETF组皮下及肾周脂肪组织则呈先上调后下调趋势,且与血清甘油变化趋势一致.结论 AQP7可能在腹型肥胖的发生中发挥重要作用.

  4. Gestational Day-Dependent Expression of Interleukin-10 and Tumor Necrosis Factor-alpha in Porphyromonas gingivalis-infected Pregnant Rats

    Directory of Open Access Journals (Sweden)

    Banun Kusumawardani

    2014-04-01

    Full Text Available Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 Fetal growth restriction remains a major cause of neonatal morbidity and mortality. Porphyromonas gingivaliscan induce placental inflammatory response resulting in fetal growth restriction. Objective: This study aimed to evaluate the potential utility of the pro-inflammatory cytokine TNF-α and anti-inflammatory cytokine IL-10 in rat placental tissues to understand whether these events were causally related. Methods: Female rats were infected with live-Porphyromonas gingivalis at concentration of 2x109 cells/ml into subgingival sulcus area of the maxillary first molar before and/or during pregnancy. They were sacrificed on gestational day (GD-14 and GD20. The expression of TNF-α and IL-10 in macrophages and trophoblast cells were detected by immunohistochemistry. Results: A higher expression of TNF-α was found in spongiotrophoblast of the Pg-BD group on GD14 (6.30±1.16, and in trophoblastic giant cells of Pg-D group on GD20 (5.50±1.35. Furthermore, a higher expression of IL-10 was found in trophoblastic giant cells of the Pg-BD group on GD14 (4.50±1.51 and in syncytiotrophoblasts of Pg-BD group on GD20 (8.70±2.67. Conclusion: The expression of TNF-α on GD14 and GD20 were accompanied by increased expression of IL-10. The placental pathologic conditions induced by Porphyromonas gingivalis can be inhibited by elevated expression of IL-10 in macrophages and trophoblast cells.DOI: 10.14693/jdi.v20i3.199

  5. Concentration-time interactions in hydrogen sulphide toxicity in rats.

    Science.gov (United States)

    Prior, M G; Sharma, A K; Yong, S; Lopez, A

    1988-01-01

    Concentration-time interactions were investigated in young male and female Sprague-Dawley, Long Evans and Fischer-344 rats exposed to hydrogen sulphide for two, four or six hours. Higher concentrations caused more deaths, with no significant difference for duration of exposure. A significant sex effect was noted with 30% mortality in males and 20% in females, with no significant difference among strains. Changes in weight were significant: increasing with concentration, higher in males than in females, different among strains (Fischer-344 less than Sprague Dawley less than Long Evans), and affected by duration of exposure. Lethal concentration values (LC50 and LC10) were estimated, for the pooled data set (n = 456); the probit equation was Y = -5.74749 + 3.8259X where X is log10 dose of hydrogen sulphide in parts per million. The LC50/LC10 values were 644/298 parts per million (902/417 mg m-3) respectively. Individual probit analyses were also performed for strain, hours of exposure and sex. The LC50 and LC10 values for male, female and strain were not different. Significant differences were observed among LC50/LC10 values for hours of exposure (2 h = 587/549 parts per million, 822/769 mg m-3; 4 h = 501/422 parts per million, 701/591 mg m-3; 6 h = 335/299 parts per million, 469/491 mg m-3). There was no effect of spatial position in the exposure chamber on the distribution of mortality. All rats of all strains dying had severe pulmonary edema. PMID:3167719

  6. serum lipid profile in non-pregnant and pregnant hausa

    African Journals Online (AJOL)

    DR. AMINU

    Body weight and height of each subject were taken to calculate body mass index ... contribute in unraveling the serum lipid profile among pregnant and non pregnant Hausa - Fulani women in ... Changes in loudness were not considered.

  7. 妊娠与非妊娠大鼠子宫内膜促性腺激素释放激素及其受体的免疫组织化学研究%IMMUNOHISTOCHEMICAL LOCALIZATION OF GnRH AND GnRH RECEPTOR IN THE ENDOMETRIUM OF PREGNANT RATS AND UNPREGNANT RATS

    Institute of Scientific and Technical Information of China (English)

    夏永娟; 黄威权

    2001-01-01

    目的:研究促性腺激素释放激素(GnRH)及其受体在妊娠与非妊娠大鼠子宫内膜中的分布及相对含量,为了解促性腺激素释放激素对子宫内膜的可能功能提供依据。方法:免疫组织化学ABC法及图像分析技术。结果:非妊娠大鼠子宫内促性腺激素释放激素及促性腺激素释放激素受体阳性反应发生在内膜上皮、腺上皮及基质细胞。妊娠大鼠子宫内这二者阳性反应主要发生在内膜上皮及基蜕膜的蜕膜细胞,妊娠大鼠子宫上皮细胞中的促性腺激素释放激素及其受体的相对含量明显高于非妊娠大鼠子宫内膜。结论:妊娠与非妊娠大鼠子宫内膜均能表达促性腺激素释放激素及其受体。%Objective: To study the distribution and relative contents of GnRH and GnRH receptor in the endometrium in pregnant rats and unpregnant rat. Methids: Immunohistochemical ABC method and image analysis were used in the experiment. Results: GnRH and GnRH recepter positive immunoreaction occured in the endometrium epithelium and the glandular epithelium of unpregnant rats, and in the endometrium epithelium and deciduate cells of the basal decidua of rpegnant rat.Conclusion: The GnRH may take partin regulating endometrial function through its receptor, its effect on endometrium may be strong in pregnant uterine than in unpregnant.

  8. 单次氯胺酮注射对孕鼠子代认知功能的研究%The effects of ketamine on learning and memory function in the pregnant rat' s offspring

    Institute of Scientific and Technical Information of China (English)

    于俊芳; 蒋奕红; 岳毅刚; 林高翔; 田小琳

    2011-01-01

    Objective To investigate whether pregnant rats exposure to ketamine cause offspring changes in space cognitive abilities and exploration abilities.Methods 3-month Sprague-Dawley female rats ( n =24)were randomly divided into four groups:group N (control group),group K1 (small doses of ketamine group),group K2 ( clinical anesthesia dose of ketamine group),group K3 ( large doses of ketamine group).3-month Sprague-Dawley male rats ( n =4) and female rats were mated at the same cage by the proportion of 2∶ 1.Pregnant mice were treated at tenth day:group N were treated saline with equal-volume to ketamine vein injection; group K1,group K2,group K3 administered vein injection 3,8,20mg/kg of ketamine.Then the 20-day offspring rats'learning and memory were assessed used Open Field Test ( record the time of the offspring in the central case through the number of grid within 2 min ) and Hole Board Test ( Counting the times of offspring stretch into the hole in 5 min) at postnatal days 20.Results In the Open Field Test,the retention time in central check of group N,group K2 and group K3 were (2.45 ± 1.23)s,(6.42 ±2.50)s,(6.41 ±2.19)s.Compared with group N,the retention time in central check of group K2 and group K3 were significantly higher (F=13.42,P<0.01 ),and group K1 were not significant different ( t =1.33,P>0.01 ),and the locomotion of group K1,group K2,group K3 were significantly reduced( ( 15.33 ± 6.81 ),( 13.75 ± 5.93 ),( 16.92 ± 6.54 ),F =4.24,P < 0.05 ).In the Hole Board Test,the times of offspring stretch into the hole were not significant different comparing with the control group(F=2.17,P > 0.05 ).Conclusion The dose of ketamine that equivalented clinical anesthesia can affect offspring rats' space cognitive abilities; but the exploring cognitive ability were not significantly influenced.%目的 探讨单次氯胺酮注射对孕鼠子代在空间认知能力、探索能力方面的行为学改变.方法 3月龄SD同胞雌大鼠12对,

  9. Activation of the NLRP3 inflammasome induces vascular dysfunction in obese OLETF rats

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Penghao [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Xie, Qihai [Department of Cardiology, Shanghai Jiading District Central Hospital, Shanghai (China); Wei, Tong [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Chen, Yichen [Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Chen, Hong, E-mail: hchen100@shsmu.edu.cn [Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Shen, Weili, E-mail: wlshen@sibs.ac.cn [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)

    2015-12-04

    Objective: Obesity-induced vascular dysfunction is related to chronic low-grade systemic inflammation. Recent studies indicate that NLRP3, a multiprotein complex formed by NOD-like receptor (NLR) family members, is a key component mediating internal sterile inflammation, but the role in obesity-related vascular dysfunction is largely unknown. In the present study, we investigate whether NLRP3 activation is involved in vascular inflammation in obese Otsuka Long-Evans Tokushima Fatty rats (OLETF). Methods and results: Male OLETF with their control Long-Evans Tokushima Otsuka rats (LETO) were studied at 3 and 12 months of age. Aortic relaxation in response to acetylcholine decreased gradually with age in both strains, with early and persistent endothelium dysfunction in obese OLETF compared with age-matched LETO controls. These changes are associated with parallel changes of aortic endothelial nitric oxide synthase (eNOS) content, macrophage accumulation and intimal thickening. NLRP3 increased in OLETF rats compared to LETO. Consistent with inflammasome activation, the conversion of procaspase-1 to cleaved and activated forms as well as IL-1β markedly increased in OLETF rats. Additionally, we observed increased expression of dynamin-related protein-1 (Drp1) and decreased fusion-relative protein optic atropy-1(OPA1). Altered mitochondrial dynamics was associated with elevated oxidative stress level in OLETF aortas. Conclusions: These results demonstrate that obesity seems to accelerate endothelial dysfunction in OLETFs via the activation of NLRP3 and mitochondrial dysfunction. - Highlights: • NLRP3 is involved in obesity-induced vascular dysfunction. • Impaired mitochondrial dynamics may have been linked to mitochondrial defect and inflammasome activation. • Obesity seems to accelerate vascular dysfunction via NLRP3 activation and mitochondrial dysfunction.

  10. Travelers' Health: Pregnant Travelers

    Science.gov (United States)

    ... Zika is present and take precautions to avoid sexual transmission of the virus. If travel cannot be avoided, pregnant women should strictly follow steps to prevent mosquito bites. Additional information, including the most current list of countries and territories where Zika virus is a risk, ...

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

    Directory of Open Access Journals (Sweden)

    Sarah M. DeNucci

    2010-01-01

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

  12. Consumption of sucrose, but not high fructose corn syrup, leads to increased adiposity and dyslipidaemia in the pregnant and lactating rat.

    Science.gov (United States)

    Toop, C R; Muhlhausler, B S; O'Dea, K; Gentili, S

    2015-02-01

    Excess consumption of added sugars, including sucrose and high fructose corn syrup (HFCS-55), have been implicated in the global epidemics of obesity and type 2 diabetes. This study aimed to investigate and compare the impact of maternal consumption of sucrose or HFCS-55 during pregnancy and lactation on the metabolic health of the dam and her offspring at birth. Female Albino Wistar rats were given access to chow and water, in addition to a sucrose or HFCS-55 beverage (10% w/v) before, and during pregnancy and lactation. Maternal glucose tolerance was determined throughout the study, and a postmortem was conducted on dams following lactation, and on offspring within 24 h of birth. Sucrose and HFCS-55 consumption resulted in increased total energy intake compared with controls, however the increase from sucrose consumption was accompanied by a compensatory decrease in chow consumption. There was no effect of sucrose or HFCS-55 consumption on body weight, however sucrose consumption resulted in increased adiposity and elevated total plasma cholesterol in the dam, while HFCS-55 consumption resulted in increased plasma insulin and decreased plasma non-esterified fatty acids (NEFA). Maternal HFCS-55 consumption was associated with decreased relative liver weight and plasma NEFA in the offspring at birth. There was no effect of either treatment on pup weight at birth. These findings suggest that both sucrose and HFCS-55 consumption during pregnancy and lactation have the potential to impact negatively on maternal metabolic health, which may have adverse consequences for the long-term health of the offspring.

  13. The effect of iron deficiency on the temporal changes in the expression of genes associated with fat metabolism in the pregnant rat.

    Science.gov (United States)

    Hay, Susan M; McArdle, Harry J; Hayes, Helen E; Stevens, Valerie J; Rees, William D

    2016-11-01

    Iron is essential for the oxidative metabolism of lipids. Lipid metabolism changes during gestation to meet the requirements of the growing fetus and to prepare for lactation. The temporal effects of iron deficiency during gestation were studied in female rats fed complete or iron-deficient diets. Plasma triglycerides were elevated in the iron-deficient group throughout gestation. There were time-dependent changes in the triglyceride content of the maternal liver, falling at the midpoint of gestation and then increasing on d21.5. Compared to the control, triglycerides in the maternal liver were not different in the iron-deficient group prior to pregnancy and on d12.5, but were markedly reduced by d21.5. The abundance of mRNAs in the maternal liver suggests that lipogenesis is unchanged and beta-oxidation is reduced on d21.5 by iron deficiency. On d21.5 of gestation, the expression of placental lipase was unchanged by iron deficiency, however, the abundance of mRNAs for SREBP-1c, FABP4 were reduced, suggesting that there were changes in fatty acid handling. In the fetal liver, iron deficiency produced a marked decrease in the abundance of the L-CPT-1 mRNA, suggesting that beta-oxidation is reduced. This study shows that the major effect of iron deficiency on maternal lipid metabolism occurs late in gestation and that perturbed lipid metabolism may be a common feature of models of fetal programming. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  14. Establishment of rat cerebral palsy model by intraperitoneal injection of lipopolysaccharide combined with hypoxia in pregnant rat%应用孕鼠腹腔注射脂多糖合并缺氧方法制作脑瘫动物模型的实验研究

    Institute of Scientific and Technical Information of China (English)

    高峰; 杨小朋; 陈刚

    2011-01-01

    Objective To establish and evaluate the rat cerebral palsy model by intraperitoneal injection of lipopolysaccharide ( LPS )comhined with hypoxia in pregnant rat. Methods The experimental rats were divided into LPS - hypoxia group, hypoxia group and control group.In LPS - hypoxia group, the pregnant rats were intraperitoneally injected with LPS on gestational flay 17 , then exposed to hypoxic environment in 12 h for 2. 5 h and followed by the second LPS injection in 4 h. In hypoxia group, the rats had the left carotid artery ligated followed by hypoxia for 2 h on postnatal day 7. In control group, the pregnant rats were intraperitoneally injected with same amount of normal saline on gestational day 17. Footprints gait repeat spacing analysis, balance heam test and pathological examinations were performed in postnatal 4 wk rats. Results Compared with control group, poor footprints repeatability, increased footprints spacing and the instable spacing ( P <0. 05 ) were found in LPS - bypoxia group and hypoxia group. The footprints gait repeat spacing , balance beam test were no significant difference LPS - hypoxia group and hypoxia group( P >0. 05 ). Pathological examination revealed structural damage, local cystic degeneration and inflammatory cells accumulation in the tissue adjacent to cerehral ventricle. Conclusion The rat cerebral palsy model hy intraperitoneal injection of LPS comhined with hypoxia in pregnant rat is of advantages of easy to operate, minimally invasive and more closely simulate fetal hrain damage caused by perinatal infection, hypoxia and ischemia in comparison with the model by unilateral carotid artery ligation induced hypoxia.%目的 探讨孕鼠腹腔注射脂多糖宫内感染合并缺氧致幼鼠脑瘫的模型制作及评价方法.方法 实验分为3组:脂多糖缺氧组,受孕17 d的健康Wistar孕鼠脂多糖腹腔注射,12 h后置于缺氧环境中2.5 h,4 h后再次腹腔注射脂多糖;颈动脉结扎缺氧组,7 d龄Wistar幼鼠

  15. Can low-level ethanol exposure during pregnancy influence maternal care? An investigation using two strains of rat across two generations.

    Science.gov (United States)

    Popoola, Daniel O; Borrow, Amanda P; Sanders, Julia E; Nizhnikov, Michael E; Cameron, Nicole M

    2015-09-01

    Gestational alcohol use is well documented as detrimental to both maternal and fetal health, producing an increase in offspring's tendency for alcoholism, as well as in behavioral and neuropsychological disorders. In both rodents and in humans, parental care can influence the development of offspring physiology and behavior. Animal studies that have investigated gestational alcohol use on parental care and/or their interaction mostly employ heavy alcohol use and single strains. This study aimed at investigating the effects of low gestational ethanol dose on parental behavior and its transgenerational transmission, with comparison between two rat strains. Pregnant Sprague Dawley (SD) and Long Evans (LE) progenitor dams (F0) received 1g/kg ethanol or water through gestational days 17-20 via gavage, or remained untreated in their home cages. At maturity, F1 female offspring were mated with males of the same strain and treatment and were left undisturbed through gestation. Maternal behavior was scored in both generations during the first six postnatal days. Arch-back nursing (ABN) was categorized as: 1, when the dam demonstrated minimal kyphosis; 2, when the dam demonstrated moderate kyphosis; and 3, when the dam displayed maximal kyphosis. Overall, SD showed greater amounts of ABN than LE dams and spent more time in contact with their pups. In the F0 generation, water and ethanol gavage increased ABN1 and contact with pups in SD, behaviors which decreased in treated LE. For ABN2, ethanol-treated SD dams showed more ABN2 than water-treated dams, with no effect of treatment on LE animals. In the F1 generation, prenatal exposure affected retrieval. Transgenerational transmission of LG was observed only in the untreated LE group. Strain-specific differences in maternal behavior were also observed. This study provides evidence that gestational gavage can influence maternal behavior in a strain-specific manner. Our results also suggest that the experimental procedure during

  16. Acupuncture Alters Expression of Insulin Signaling Related Molecules and Improves Insulin Resistance in OLETF Rats

    Directory of Open Access Journals (Sweden)

    Xin-Yu Huang

    2016-01-01

    Full Text Available To determine effect of acupuncture on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF rats and to evaluate expression of insulin signaling components. Rats were divided into three groups: Sprague-Dawley (SD rats, OLETF rats, and acupuncture+OLETF rats. Acupuncture was subcutaneously applied to Neiguan (PC6, Zusanli (ST36, and Sanyinjiao (SP6; in contrast, acupuncture to Shenshu (BL23 was administered perpendicularly. For Neiguan (PC6 and Zusanli (ST36, needles were connected to an electroacupuncture (EA apparatus. Fasting blood glucose (FPG was measured by glucose oxidase method. Plasma fasting insulin (FINS and serum C peptide (C-P were determined by ELISA. Protein and mRNA expressions of insulin signaling molecules were determined by Western blot and real-time RT-PCR, respectively. OLETF rats exhibit increased levels of FPG, FINS, C-P, and homeostasis model assessment-estimated insulin resistance (HOMA-IR, which were effectively decreased by acupuncture treatment. mRNA expressions of several insulin signaling related molecules IRS1, IRS2, Akt2, aPKCζ, and GLUT4 were decreased in OLETF rats compared to SD controls. Expression of these molecules was restored back to normal levels upon acupuncture administration. PI3K-p85α was increased in OLETF rats; this increase was also reversed by acupuncture treatment. Acupuncture improves insulin resistance in OLETF rats, possibly via regulating expression of key insulin signaling related molecules.

  17. Dietary fat and bile juice, but not obesity, are responsible for the increase in small intestinal permeability induced through the suppression of tight junction protein expression in LETO and OLETF rats

    Directory of Open Access Journals (Sweden)

    Suzuki Takuya

    2010-03-01

    Full Text Available Abstract Background An increase in the intestinal permeability is considered to be associated with the inflammatory tone and development in the obesity and diabetes, however, the pathogenesis of the increase in the intestinal permeability is poorly understood. The present study was performed to determine the influence of obesity itself as well as dietary fat on the increase in intestinal permeability. Methods An obese rat strain, Otsuka Long Evans Tokushima Fatty (OLETF, and the lean counter strain, Long Evans Tokushima Otsuka (LETO, were fed standard or high fat diets for 16 weeks. Glucose tolerance, intestinal permeability, intestinal tight junction (TJ proteins expression, plasma bile acids concentration were evaluated. In addition, the effects of rat bile juice and dietary fat, possible mediators of the increase in the intestinal permeability in the obesity, on TJ permeability were explored in human intestinal Caco-2 cells. Results The OLETF rats showed higher glucose intolerance than did the LETO rats, which became more marked with the prolonged feeding of the high fat diet. Intestinal permeability in the OLETF rats evaluated by the urinary excretion of intestinal permeability markers (Cr-EDTA and phenolsulfonphthalein was comparable to that in the LETO rats. Feeding the high fat diet increased intestinal permeability in both the OLETF and LETO rats, and the increases correlated with decreases in TJ proteins (claudin-1, claudin-3, occludin and junctional adhesion molecule-1 expression in the small, but not in the large intestine (cecum or colon. The plasma bile acids concentration was higher in rats fed the high fat diet. Exposure to bile juice and the fat emulsion increased TJ permeability with concomitant reductions in TJ protein expression (claudin-1, claudin-3, and junctional adhesion molecule-1 in the Caco-2 cell monolayers. Conclusion Excessive dietary fat and/or increased levels of luminal bile juice, but not genetic obesity, are

  18. Effect of sodium loading on the urinary excretion of prostaglandins E2 and F2 alpha in rats with hereditary diabetes insipidus (Brattleboro rats).

    Science.gov (United States)

    Rathaus, M; Kariv, N; Shapira, J; Bernheim, J

    1985-01-01

    Current evidence suggests that the antidiuretic hormone (ADH) and changes in sodium balance influence renal prostaglandins (PGs). To separate these two mechanisms, the effect of sodium loading on the urinary excretion of PGE2 and PGF2 alpha was studied in female Brattleboro rats with diabetes insipidus (DIHO) and compared with that in female, age matched, heterozygous Long Evans controls (LEHE). Ten DIHO and ten LEHE rats had a normal sodium intake. In ten DIHO rats a 0.16% NaCl solution was supplied instead of drinking water for either 8 days (n = 5) or 14 days (n = 5). In two groups of LEHE rats, sodium loading was obtained with a 0.80% NaCl solution for the same study periods. Urine PGs were measured by radioimmunoassay in three 24 h urine collections for each rat. Urine PGs were significantly increased in the 8 day loaded but not in the 14 day loaded LEHE rats. In DIHO rats, a non-significant increase in both PGE2 and PGF2 alpha was present after 8 days of sodium loading, while PGE2 and the E/F ratio were decreased after 14 days of salt loading. The findings suggest that the natriuresis induced by sodium loading in the rat may be mediated in part by increased production of PGs. In addition, it seems that ADH plays a role in this response.

  19. Physical activity maintains aortic endothelium-dependent relaxation in the obese type 2 diabetic OLETF rat.

    Science.gov (United States)

    Bunker, Aaron K; Arce-Esquivel, Arturo A; Rector, R Scott; Booth, Frank W; Ibdah, Jamal A; Laughlin, M Harold

    2010-06-01

    We tested the hypothesis that physical activity can attenuate the temporal decline of ACh-induced endothelium-dependent relaxation during type 2 diabetes mellitus progression in the Otsuka Long-Evans Tokushima fatty (OLETF) rat. Sedentary OLETF rats exhibited decreased ACh-induced abdominal aortic endothelium-dependent relaxation from 13 to 20 wk of age (20-35%) and from 13 to 40 wk of age (35-50%). ACh-induced endothelium-dependent relaxation was maintained in the physically active OLETF group and control sedentary Long-Evans Tokushima Otsuka (LETO) group from 13 to 40 wk of age. Aortic pretreatment with N(G)-nitro-l-arginine (l-NNA), indomethacin (Indo), and l-NNA + Indo did not alter the temporal decline in ACh-induced endothelium-dependent relaxation. Temporal changes in the protein expression of SOD isoforms in the aortic endothelium or smooth muscle did not contribute to the temporal decline in ACh-induced endothelium-dependent relaxation in sedentary OLETF rats. A significant increase in the 40-wk-old sedentary LETO and physically active OLETF rat aortic phosphorylated endothelial nitric oxide (p-eNOS)-to-eNOS ratio was observed versus 13- and 20-wk-old rats in each group that was not seen in the 40- versus 13- and 20-wk-old sedentary OLETF rats. These results suggest that temporal changes in the antioxidant system, EDHF, and cycloxygenase metabolite production in sedentary OLETF rat aortas do not contribute to the temporal decline in sedentary OLETF rat aortic ACh-induced endothelium-dependent relaxation seen with type 2 diabetes mellitus progression. We also report that physical activity in conjunction with aging in the OLETF rat results in a temporal increase in the aortic endothelial p-eNOS-to-eNOS ratio that was not seen in sedentary OLETF rats. These results suggest that the sustained aortic ACh-induced endothelium-dependent relaxation in aged physically active OLETF rats may be the result of an increase in active aortic eNOS.

  20. Drug gastrointestinal absorption in rat: Strain and gender differences.

    Science.gov (United States)

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

    2015-10-12

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

  1. Stereological method for objectively quantifying myelin sheaths in the rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    Lei Zhang; Wei Lu; Shu Yang; Lin Chen; Xuan Qiu; Guohua Cheng; Yong Tang

    2011-01-01

    In the present study, tissue blocks were randomly sampled from the entire hippocampus of 6-week-old Long-Evans rats. Isotropic, uniform and random sections, 60 nm thick, were prepared by isector. Fifteen fields of view were randomly selected for each section and photographed using a transmission electron microscope. The mean internal and external diameters of the myelin sheaths were obtained by measuring the longest profile diameter perpendicular to its longest axis.The inner and outer perimeters of the myelin sheaths were estimated using the equidistant parallel test lines. The thickness of the myelin sheaths was estimated by direct orthogonal measurements in uniform, random locations. These stereological methods should permit an unbiased quantitative assessment of changes in the myelin sheaths of myelinated fibers in the hippocampus.

  2. THE PREGNANT MAN

    Directory of Open Access Journals (Sweden)

    M.Arulmani

    2014-09-01

    Full Text Available This scientific research article focus that the “Human Ancestor” lived in “Mars Planet‟ in the early universe shall be considered having distinguished genetic characteristics compared to “Modern Human” living in earth Planet especially in reproduction of population. This research further focus that MALE PARENT shall be considered as “become pregnant” and responsible for child birth. During the course of “Space” and “Time” of expanding universe the mars populations consider have descended to Earth planet due to varied climatic condition and FEMALE PARENT become pregnant and responsible for child birth at later stage of “Nuclear age”

  3. Vitamin D3 supplementation in pregnant and lactating rats on vitamin D receptor expression in the lung of baby rats with asthma%孕期哺乳期大鼠补充维生素D3对子代大鼠哮喘模型肺组织维生素D受体表达的影响

    Institute of Scientific and Technical Information of China (English)

    陈凌燕; 周小建; 李霞; 李臻; 洪建国

    2012-01-01

    目的 探讨给予孕期及哺乳期大鼠不同剂量1,25-二羟维生素D3,对其子代大鼠哮喘模型肺组织维生素D受体(VDR)表达的影响.方法 雌性Wistar大鼠32只,随机分配到维生素D低、中、高剂量组,在孕期及哺乳期给予不同剂量的1,25-二羟维生素D2,并设对照组.子代大鼠断乳后,各组随机取8只,用卵清蛋白致敏并激发,建立哮喘模型.采用real-time PCR和免疫组织化学方法分别从mRNA和蛋白水平检测子代大鼠VDR的表达.结果 与对照组相比,中剂量组子代大鼠支气管痉挛收缩、管壁增厚、管腔内黏液分泌增加、肺部炎症浸润等变化最轻,低剂量组其次,高剂量组反而较对照组严重.免疫组织化学染色显示,与对照组相比,低剂量组和巾剂量组子代大鼠的VDR表达明显减少,且中剂量组较低剂量组更明显,差异有统计学意义(P均< 0.01);高剂量组的VDR表达则较对照组增多,差异亦有统计学意义(P<0.01).real-time PCR结果显示,与对照组比较,低剂量组和中剂量组子代大鼠肺组织中VDR mRNA水平降低,而高剂量组的VDR mRNA水平增高,差异均有统计学意义(P< 0.01).结论 孕期及哺乳期补充适量维生素D可减少子代大鼠哮喘模型VDR的表达,减轻气道炎症反应,而过量补充维生素D则增加VDR表达,可能加重气道炎症反应.%Objective To investigate the effect of vitamin D supplementation in pregnant and lactating rats on vitamin D receptor (VDR) expression in the lung of baby rats with asthma. Methods Thirty two sexually matured female Wistar rats were randomly divided into low dose group, medium dose group and high dose group. During the gestation and lactation period, rats of each group were given different doses of 1, 25-(OH)2D3 while the control group was given normal saline. After the newborn rats were weaned, 8 baby rats were chose.n from each group randomly. Then the rats were challenged with aerosol ovalbumin to

  4. Reactive Protein Synthesis in Pregnant Rats

    African Journals Online (AJOL)

    olayemitoyin

    to exert anti-obesity effects with prompt weight reduction and reduced ... and leptin, closely linked to body metabolism and food consumption. ... chow was provided ad libitum throughout the ..... food intake, body weight, and fat pad weight and.

  5. Toluene depresses plasma corticosterone in pregnant rats

    DEFF Research Database (Denmark)

    Hougaard, K. S.; Hansen, A. M.; Hass, Ulla

    2003-01-01

    Combined exposure to stressors and chemicals may result in synergistic effects. The effects of prenatal exposure to the organic solvent toluene resemble those observed in offspring of gestationally stressed dams, a possible common mechanism being transfer of stress-/toluene-induced increments of ...

  6. The Legal Rights of Pregnant Students and Pregnant Employees.

    Science.gov (United States)

    Evers, Irving C.

    This speech presents an analysis of court cases dealing with the rights of pregnant students and pregnant employees. The discussion of these rights, such as the right to maternity leave, focuses around the Civil Rights Act of 1964 and its implications for equal employment opportunity. The court cases discussed consider the application of the equal…

  7. Oral Mucosal Disorders in Pregnant versus Non-Pregnant Women

    Directory of Open Access Journals (Sweden)

    Fahimeh Rezazadeh

    2014-12-01

    Full Text Available The effects of pregnancy on the Oral Mucosa Disorder (OMD have been sporadically documented in some developed countries. Less known is the status of OMD during pregnancy in less developed/developing countries. Iran is no exception. This study assesses the prevalence of OMD in 200 pregnant women and compares the findings with the findings from a 200 non-pregnant woman of similar age distribution in Iran. The participants had been referred to a clinic to receive reproductive age-related services. Participants suffering from systemic chronic diseases, those on medications/drugs, smokers, needing biopsies, and those with urgent Oral Mucosal Lesion (OML treatments were excluded from the study. Oral mucosal of all 400 participants were examined. The participants’ age ranges were from 17 to 47; with the average age of 33.14 for one group; and 30.23 for the other group. Both groups had the same level of formal education. Out of 400 examined women; 62 had lesions, including 47 pregnant (23.5%; and 15 non-pregnant (7.5% women. This result shows that the OMD rate of occurrence was significantly higher among the pregnant women. Higher OML prevalence in pregnant women, as compared to the non-pregnant women, indicates the importance of timely oral examination of pregnant women and subsequent treatment plans for them.

  8. Vaccinations for pregnant women.

    Science.gov (United States)

    Swamy, Geeta K; Heine, R Phillips

    2015-01-01

    In the United States, eradication and reduction of vaccine-preventable diseases through immunization has directly increased life expectancy by reducing mortality. Although immunization is a public priority, vaccine coverage among adult Americans is inadequate. The Institute of Medicine, the Community Preventive Services Task Force, and other public health entities have called for the development of innovative programs to incorporate adult vaccination into routine clinical practice. Obstetrician-gynecologists are well suited to serve as vaccinators of women in general and more specifically pregnant women. Pregnant women are at risk for vaccine-preventable disease-related morbidity and mortality and adverse pregnancy outcomes, including congenital anomalies, spontaneous abortion, preterm birth, and low birth weight. In addition to providing direct maternal benefit, vaccination during pregnancy likely provides direct fetal and neonatal benefit through passive immunity (transplacental transfer of maternal vaccine-induced antibodies). This article reviews: 1) types of vaccines; 2) vaccines specifically recommended during pregnancy and postpartum; 3) vaccines recommended during pregnancy and postpartum based on risk factors and special circumstances; 4) vaccines currently under research and development for licensure for maternal-fetal immunization; and 5) barriers to maternal immunization and available patient and health care provider resources.

  9. How I Got Pregnant

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    Dwyer, James

    2014-04-01

    Full Text Available This short story raises ethical issues about a woman’s request for medical assistance to get pregnant. In this fictional account, a 34-year-old woman has been trying to get pregnant for the last year. Her husband would like to keep trying for one more year, but the woman loses patience. She visits an ob-gyn and requests artificial insemination. She does not intend to tell her husband about this medical assistance. The doctor has helped single women, lesbian couples, and married couples with pregnancies, but he feels conflicted by this request. The doctor and the woman discuss their concerns and plans. Then they decide on a course of action. In a creative way, this story aims to bring to life ethical issues about assisted reproduction, complex relationships, individual choice, non- judgmental attitudes, deception, confidentiality, genetic connections, and social parents. But this story is not a textbook case that illustrates a clearly defined ethical issue. On the contrary, the story shows that some common ethical ideas don’t quite fit the characters’ experiences and the readers’ reactions.

  10. The effects of antidiuretic hormone and state of potassium balance on the renin-angiotensin system in rats with diabetes insipidus.

    Science.gov (United States)

    Fernández-Repollet, E; Maldonado, M M; Opava-Stitzer, S

    1982-02-01

    1. The influence of ADH and the state of potassium balance on the renin-angiotensin system was studied in rats with hereditary diabetes insipidus (DI rats). 2. Plasma renin concentration in DI rats was higher than in control Long-Evans rats. 3. Spontaneous reversal of the hypokalaemia normally found in DI rats did not reduce plasma renin concentration (p.r.c.), suggesting that potassium deficiency does not contribute significantly to the elevation of p.r.c. in DI rats. Similarly, a low potassium diet failed to further increase p.r.c. in DI rats. 4. In contrast, the p.r.c. of DI rats was significantly diminished by a high potassium intake both in the presence and absence of ADH. A highly significant inverse correlation was found between p.r.c. and urinary potassium excretion in both ADH-treated and untreated DI rats on low, normal and high potassium diets. 5. Plasma renin concentration was significantly lower in ADH-treated than in untreated DI rats on a high potassium intake, suggesting that the inhibitory effects of ADH and potassium are additive. 6. ADH consistently reduced p.r.c. in DI rats independent of the state of potassium balance. 7. ADH and potassium may inhibit renin secretion via different mechanisms of action.

  11. Expression of Estrogen Receptor mRNA and Genes Related to Regulation of Bile acid Metabolism in Fetal Rat Liver of Pregnant Rats with Intrahepatic Cholestasis%雌激素受体及胆汁酸代谢相关基因在胆汁淤积孕鼠胎鼠肝脏中的表达

    Institute of Scientific and Technical Information of China (English)

    时青云; 赵晋; 林宇庚; 闫时; 周新; 林颖奇

    2011-01-01

    gene related to regulation of bile acid metabolism in fetal rat liver of pregnant rats with intrahepafic cholestasis. Methods Sixty clean SD pregnant rats were selected and divided into two groups at random. ① Since the 13th day of pregnancy after taking blood, the rats in control group were injected subcutaneously with refined vegetable oil 2. 5mL · kg -1 · d -1, study group was injected subcutaneously with the 17-a-ethynylestradiol(EE) 1.25 mg· kg -1 · d-1 till the 17th day. ② On the 21st day, all rats were killed. Then the fetus livers were collected for study. ③) The levels of serum total bile acid(TBA) were examined by ELISA. The expression of ER, CYP7A1, CYP27AI, CYP8B1 (mRNA) in fetal rat liver was examined by real-time PCR. Results ② The levels of TBA were significanfiy higher in study group mother rats(58.7 ±3.2) μmol/L than that of control group(24. 6 ± 1.3 ) μmol/L on the ITs day ( P < 0.05 ); The levels of TBA were higher in study group mother rats (66.4 ± 2.7 ) μnol/L than that of control group ( 26.5 ± 3.1 ) μmoL/L on the 21 st day ( P < O. 05 ). The levels of TBA were higher in study group fetus rats(28.4 ±2.6) μ mol/L than that of control group( 10.5 ± 3.1 ) μ moL/L on the 21st day. ③ The expression of CYP7AI mRNA( 1.25 ± 0 01 ), CYP27A1 mRNA ( 2.05 ± 0. 03 ), CYPSB1 mRNA ( 1.85 ± 0. 01 ) in study group fetus liver increased as compared to control group(0.35 ± 0.02, 0.75 ± 0.03, 0. 85 ± 0.02, respectively) ( P < O. 05 ). 3) The expression of ERα mRNA in study group ( 0.75 ± 0.02 ) was higher than that ofcontrol group ( 0.45 ± 0.01 ) ( P< 0.05 ) . Conclusion The expression of ERα,CYP7AI, CYP27A1, CYPSBI(mRNA ) increased in the fetal rat liver of pregnant rots with intrahepatic cholestasis, resulting in increased synthesis of bile acids, which may be one of the mechanisms of perinatal death of the fetal rats.

  12. Effect of Pre-treatment with Moringa oleifera (Drumstick Leaves on Diabetogenesis Produced by Alloxan in Rats

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    Shamsun Nahar

    2015-07-01

    Full Text Available Background: Medicinal plants constitute an important source of potential therapeutic agents for diabetes. Objective: In the study, we aimed to investigate the pre-treatment effect or preventive effects of Moringa oleifera (MO leaves on blood sugar of rats. Materials and method: This experimental study was carried out in the department of Pharmacology and Therapeutics of Sir Salimullah Medical College in collaboration with Bangladesh Council of Scientific and Industrial Research (BCSIR, Dhaka. A total 24 long Evans rats were included in this study and divided in to four groups. Hyperglycemia was induced on rats using alloxan (100 mg/kg body weight, intraperitioneally. Blood sample was collected from tail vein by tail tipping method. Pre-treatment effect or preventive role of Moringa oleifera (drumstick leaf powder on diabetogenesis produced by Alloxan in rats was tested by giving 50 mg/rat/day Moringa oleifera leaf powder for 14 days orally as pre-treatment along with standard rat feed. Then alloxan was administered intraperitoneally on 15th day of the experiment and 50mg/rat/day Moringa oleifera leaf powder was given for 7 days as post-treatment. Results: No significant effect of MO on blood glucose level was observed on normal rats and non significant hypoglycaemic effect was found in rats that were pretreated with MO. Conclusion: The present study suggests that Moringa oleifera leaf powder did not produce any significant protective effect in diabetogenesis produced by alloxan though it has hypoglycaemic effect.

  13. Thermoregulation in cold- and noncold-acclimated rats cold exposed in hypergravic fields

    Science.gov (United States)

    Horowitz, J. M.; Horwitz, B. A.; Monson, C. B.

    1983-01-01

    The effect of hypergravity on thermoregulation processes is investigated experimentally in rats. Hooded male Long-Evans rats were kept for 6 weeks at 5 or 23 C (cold-acclimated and noncold-acclimated groups, CA and NCA) prior to testing. One test protocol comprised sequential 1-h exposures to 23 C at 1 G, 23 C at 3 G (in a 2.1-m radius centrifuge; -Gx), 8 C at 3 G, 8 C at 1 G, and finally 23 C at 1 G, with continuous measurement of the oxygen consumption. In a second protocol, restrained rats were exposed to 23 C at 1 G, 23 C at 3 G, and 10 C at 3 G, and core temperature changes were monitored. The results are presented in graphs and a table. Oxygen consumption doubled in both CA and NCA rats on exposure to cold at 1 G, but at 3 G NCA consumption decreased while CA consumption remained high. The CA rats were also more able to maintain core temperature at 3 G than the NCA rats. These differences are attributed to the nonshivering thermogenic processes developed in CA rats, which appear to be unaffected by hypergravity.

  14. Circadian rhythm of outside-nest activity in wild (WWCPS, albino and pigmented laboratory rats.

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    Rafał Stryjek

    Full Text Available The domestication process of the laboratory rat has been going on for several hundred generations in stable environmental conditions, which may have affected their physiological and behavioural functions, including their circadian system. Rats tested in our ethological experiments were laboratory-bred wild Norway rats (WWCPS, two strains of pigmented laboratory rats (Brown Norway and Long Evans, and two strains of albino rats (Sprague-Dawley and Wistar. Rats were placed in purpose-built enclosures and their cycle of activity (time spent actively outside the nest has been studied for one week in standard light conditions and for the next one in round-the-clock darkness. The analysis of circadian pattern of outside-nest activity revealed differences between wild, pigmented laboratory, and albino laboratory strains. During daytime, albino rats showed lower activity than pigmented rats, greater decrease in activity when the light was turned on and greater increase in activity when the light was switched off, than pigmented rats. Moreover albino rats presented higher activity during the night than wild rats. The magnitude of the change in activity between daytime and nighttime was also more pronounced in albino rats. Additionaly, they slept outside the nest more often during the night than during the day. These results can be interpreted in accordance with the proposition that intense light is an aversive stimulus for albino rats, due to lack of pigment in their iris and choroid, which reduces their ability to adapt to light. Pigmented laboratory rats were more active during lights on, not only in comparison to the albino, but also to the wild rats. Since the difference seems to be independent of light intensity, it is likely to be a result of the domestication process. Cosinor analysis revealed a high rhythmicity of circadian cycles in all groups.

  15. Role of water balance in the enhanced potassium excretion and hypokalaemia of rats with diabetes insipidus.

    Science.gov (United States)

    Fernández-Repollet, E; Martínez-Maldonado, M; Opava-Stitzer, S

    1980-08-01

    1. The role of water balance in the hypokalaemia of rats with diabetes insipidus (DI rats) was studied. 2. After a 3-day balance study DI rats had a lower muscle potassium content, and plasma [K+], and the urinary excretion of potassium in response to oral KCl loading was reduced when compared to normal rats. The hypokalaemia was found to be associated with elevated concentrations of potassium in renal medulla and papilla when compared to values in normal Long-Evans rats. 3. During a 9-day balance study urinary potassium excretion was higher than that of normal rats on days 1-3, but not different on days 4-9; this transient elevation was observed in DI rats on normal, high and low potassium diets. On a low potassium diet the urinary potassium excretion of DI rats fell to minimal levels, making unlikely the existence of a renal defect in potassium handling. 4. Muscle potassium content and plasma [K+] were normal after 9 days in metabolism cages. This spontaneous reversal of the hypokalaemia of DI rats was associated with increased water content of renal medulla and papilla, and decreased potassium concentration in these zones. 5. The effect of acute mild dehydration on potassium handling of DI rats was evaluated. Water deprivation for 1-8 hr was sufficient to raise the urinary potassium excretion of DI rats above that of DI rats drinking ad lib. Renal tissue [K+] was significantly increased after 8 hr of dehydration. Water deprivation also enhanced the response of DI rats to an oral KCl load. Two days of chronic dehydration in the form of water rationing also significantly enhanced the urinary potassium excretion of DI rats. 6. These data suggest that chronic mild dehydration may be responsible for the modest potassium deficiency observed in DI rats via alterations in renal tissue [K+] and consequently in urinary potassium excretion. Correction of dehydration during prolonged periods in metabolism cages may account for the spontaneous reversal of the hypokelaemic

  16. The expression and significance of NKx2.5 in the embryos heart defects induced by pregnant rat obesity%NKx2.5基因在孕鼠肥胖致胚胎心脏畸形中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    刘伟; 陶芳标; 汪思应; 黄德武; 王晓红

    2013-01-01

    Objective To explore the expression and significance of NKx2. 5 gene mRNA and its protein in the embryos heart defects induced by pregnant rat obesity. Methods 100 three-week old SD female rats were randomly divided into control group( n =40 ) and high-fat group( n =60 ). The rats in the control group were fed with stand- ard forage and the rats in the high fat group were fed with high-fat diet. After 8 weeks, the rats in the high-fat group with body weight more than 20% of average body weight of control group and total cholesterol, triglyceride level were significantly higher than control group were selected as the obese rats. Random choice of obese rats( n = 20 ) and normal rats( n = 20 ) mate with male counterparts to access to pregnancy. All the embryos were removed on the thirteenth, fifteenth, seventeenth and nineteenth day and cut section for microscopic examination to observe heart malformation. The expression of NKx2. 5 mRNA by RT-PCR was observed. The expression of NKx2. 5 protein by Western blot was investigated. Results The number of rats with the embryonic heart defects in obese pregnant rat group were significantly higher than those in the control group( P < 0. 01 ). The expression of NKx2. 5 mRNA and protein was significantly decreased in the embryonic heart defects rats of obese rats versus the normal heart rats of the control group ( P <0. 05 ). Conclusion Pregnant rat obesity can increase the incidence of embryonic heart defects. Pregnant rat obesity can restrain the expression of NKx2. 5 mRNA and protein in the embryos heart, which might lead to the morphological changes of heart and congenital heart defects.%目的 探讨NKx2.5基因mRNA及其蛋白在肥胖孕鼠胚胎畸形心脏中的表达水平及相关意义.方法 3周龄SPF级SD雌鼠100只,随机分为两组:正常组(40只)给予基础饲料;高脂组(60只)给予高脂饲料.8周后,以高脂组体重超过正常组平均体重的20%且血清总胆固醇(TC)、甘油三酯(TG)含量

  17. A warmer ambient temperature increases the passage of interleukin-1β into the brains of old rats

    Science.gov (United States)

    Buchanan, Jessica B.; Peloso, Elizabeth; Satinoff, Evelyn

    2008-01-01

    We have demonstrated that after intraperitoneal lipopolysaccharide (LPS) injection, old rats mount fevers similar to those of young rats at an ambient temperature (Ta) of 31°C, but not at 21°C. The same is true for intraperitoneal or intravenous IL-1β administration. The underlying mechanism responsible for blunted fever in old rats may be a deficiency in communication between the periphery and the brain. Possibly, peripheral cytokine actions are altered in old rats, such that the signal that reaches the brain is diminished. Here, we hypothesized that at standard laboratory temperatures, not enough IL-1β is reaching the brain for fever to occur and that a warmer Ta would increase the influx of IL-1β into the brain, enabling old rats to generate fever. Young (3–5 mo) and old (23–29 mo) Long-Evans rats were maintained for 3 days at either Ta 21 or 31°C prior to intravenous injection with radiolabeled IL-1β to measure passage across the blood-brain barrier. Young rats showed similar influx of IL-1β into the brain at the two Tas, but old rats showed significant influx only at the warmer Ta. These data suggest that the lack of fever at a cool Ta may be due to a reduced influx of IL-1β into the brain. PMID:18448612

  18. Perineuronal nets increase inhibitory GABAergic currents during the critical period in rats

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    Zheng-Qin Yin

    2013-04-01

    Full Text Available AIM: To investigate inhibitory γ-aminobutyric acid (GABA ergic postsynaptic currents (IPSCs and postsynaptic currents (PSCs in layer IV of the rat visual cortex during the critical period and when plasticity was extended through dissolution of the perineuronal nets (PNNs.METHODS:We employed 24 normal Long-Evans rats to study GABAA-PSC characteristics of neurons within layer IV of the visual cortex during development. The animals were divided into six groups of four rats according to ages at recording:PW3 (P21-23d, PW4 (P28-30d, PW5 (P35-37d, PW6 (P42-44d, PW7 (P49-51d, and PW8 (56-58d. An additional 24 chondroitin sulfate proteoglycan (CSPG degradation rats (also Long-Evans were generated by making a pattern of injections of chondroitinase ABC (chABC into the visual cortex 1 week prior to recording at PW3, PW4, PW5, PW6, PW7, and PW8. Immunohistochemistry was used to identify the effect of chABC injection on CSPGs. PSCswere detected with whole-cell patch recordings, and GABAA receptor-mediated IPSCs were pharmacologically isolated.RESULTS:IPSC peak current showed a strong rise in the age-matched control group, peaked at PW5 and were maintained at a roughly constant value thereafter. Although there was a small increase in peak current for the chABC group with age, the peak currents continued to decrease with the delayed highest value at PW6, resulting in significantly different week-by-week comparison with normal development. IPSC decay time continued to increase until PW7 in the control group, while those in the chABC group were maintained at a stable level after an initial increase at PW4. Compared with normal rats, the decay times recorded in the chABC rats were always shorter, which differed significantly at each age. We did not observe any differences in IPSC properties between the age-matched control and penicillinase (P-ase group.However, the change in IPSCs after chABC treatment was not reflected in the total PSCs or in basic membrane

  19. Drug specificity in drug versus food choice in male rats.

    Science.gov (United States)

    Tunstall, Brendan J; Riley, Anthony L; Kearns, David N

    2014-08-01

    Although different classes of drug differ in their mechanisms of reinforcement and effects on behavior, little research has focused on differences in self-administration behaviors maintained by users of these drugs. Persistent drug choice despite available reinforcement alternatives has been proposed to model behavior relevant to addiction. The present study used a within-subjects procedure, where male rats (Long-Evans, N = 16) were given a choice between cocaine (1.0 mg/kg/infusion) and food (a single 45-mg grain pellet) or between heroin (0.02 mg/kg/infusion) and food in separate phases (drug order counterbalanced). All rats were initially trained to self-administer each drug, and the doses used were based on previous studies showing that small subsets of rats tend to prefer drug over food reinforcement. The goal of the present study was to determine whether rats that prefer cocaine would also prefer heroin. Choice sessions consisted of 2 forced-choice trials with each reinforcer, followed by 14 free-choice trials (all trials separated by 10-min intertrial interval). Replicating previous results, small subsets of rats preferred either cocaine (5 of the 16 rats) or heroin (2 of the 16 rats) to the food alternative. Although 1 of the 16 rats demonstrated a preference for both cocaine and heroin to the food alternative, there was no relationship between degree of cocaine and heroin preference in individual rats. The substance-specific pattern of drug preference observed suggests that at least in this animal model, the tendencies to prefer cocaine or heroin in preference to a nondrug alternative are distinct behavioral phenomena.

  20. Effects of cyclophosphamide on the kaolin consumption (pica behavior) in five strains of adult male rats.

    Science.gov (United States)

    Tohei, Atsushi; Kojima, Shu-ichi; Ikeda, Masashi; Hokao, Ryoji; Shinoda, Motoo

    2011-07-01

    It is known that pica, the consumption of non-nutritive substances such as kaolin, can be induced by administration of toxins or emetic agents in rats. In the present study, we examined the effects of intraperitoneal (i.p.) administration of cyclophosphamide on pica behavior and on the concentration of 5-hydroxyindoleacetic acids (5HIAA) in cerebrospinal fluid (CSF) in the following five strains of adult male rats: Sprague Dawley (SD), Wistar, Fischer 344 (F344), Wistar-Imamichi (WI) and Long Evans (LE). Cyclophosphamide (25 mg or 50 mg/kg) was injected (i.p.) into the rats and kaolin and food intake were measured at 24 hr after injection. The animals were anesthetized with urethane (1 g/kg) at 3 hr after injection of cyclophosphamide, and CSF was collected from the cisterna magna. WI and LE rats clearly showed pica behavior as compared with the other strains. In LE rats, the concentration of 5HIAA in CSF also increased in a dose-dependent manner of cyclophosphamide. The pretreatment with ondansetron (5-HT(3) antagonist) restored both changes (kaolin consumption and 5HIAA levels) induced by cyclophosphamide. These results suggest that the LE rat is sensitive to cyclophosphamide, that pica induced by cyclophosphamide mimics many aspects of emesis including the serotonergic response in the central nervous system and that use of the pica model would be a practical method for evaluating the effects of antiemetic drugs in addition to the mechanism of emesis.

  1. Sudden or Gradual Sound Onset Differentially Affects Audiogenic Seizure Severity in Developmentally Primed Rats

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    Mark Zrull

    2005-01-01

    Full Text Available In a rat model of reflex epilepsy, sound-induced or audiogenic seizures (AGS are initiated by and propagated though excessive activity of inferior colliculus neurons. Because more auditory system neurons respond to onset of sound rather than a continuing sound, we examined the effect of sudden (SO and gradual (GO onset intensity of seizure-triggering sound on AGS severity. Long-Evans rats were primed for AGS using loud sound when they were 18 days old and were tested for seizures using loud noise when 32 days old. SO and GO groups of 10 rats, matched for AGS severity, were then tested three times for AGS. Overall, rated seizure activity was 39% more severe in GO than SO rats (p<.05, and the duration of clonus for GO animals was 28% longer than for SO rats (p<.05. While latency to clonic seizures was 24% longer in GO than SO rats, this was an artifact of the sound gradually reaching AGS-inducing intensity for the GO group. Because sensory neurons respond to change, sudden onset sound may allow more adaptation of AGS-prone inferior colliculus neurons than a gradual onset seizure-inducing stimulus. Ramping to a maximum intensity sound may produce greater seizure severity due to a greater number of neurons remaining active.

  2. Sudden or gradual sound onset differentially effects audiogenic seizure severity in developmentally primed rats

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    Mary Dravland

    2005-08-01

    Full Text Available In a rat model of reflex epilepsy, sound-induced or audiogenic seizures (AGS are initiated by and propagated though excessive activity of inferior colliculus neurons. Because more auditory system neurons respond to onset of than a continuing sound, we examined the effect of sudden (SO and gradual (GO onset intensity of seizure-triggering sound on AGS severity. Long-Evans rats were primed for AGS using loud sound when they were 18 days old and were tested for seizures using loud noise when 32 days old. SO and GO groups of 10 rats, matched for AGS severity, were then tested 3 times for AGS. Overall, rated seizure activity was 39% more severe in GO than SO rats (p<.05, and the duration of clonus for GO animals was 28% longer than for SO rats (p<.05. While latency to clonic seizures was 24% longer in GO than SO rats, this was an artifact of the sound gradually reaching AGS-inducing intensity for the GO group. Because sensory neurons respond to change, sudden onset sound may allow more adaptation of AGSprone inferior colliculus neurons than a gradual onset seizure-inducing stimulus. Ramping to a maximum intensity sound may produce greater seizure severity due to a greater number of neurons remaining.

  3. Emblica officinalis improves glycemic status and oxidative stress in STZ induced type 2 diabetic model rats

    Institute of Scientific and Technical Information of China (English)

    Aneesa Ansari; Md Shahed Zaman Shahriar; Md Mehedi Hassan; Shukla Rani Das; Begum Rokeya; Md Anwarul Haque; Md Enamul Haque; Nirupam Biswas; Tama Sarkar

    2014-01-01

    Objective: To evaluate the antidiabetic and antioxidant potential of Emblica officinalis (E. officinalis) fruit on normal and type 2 diabetic rats. Methods: Type 2 diabetes was induced into the male Long-Evans rats. The rats were divided